The peripheral blood proteome signature of idiopathic pulmonary fibrosis is distinct from normal and is associated with novel immunological processes.

PubMed

O'Dwyer, David N; Norman, Katy C; Xia, Meng; Huang, Yong; Gurczynski, Stephen J; Ashley, Shanna L; White, Eric S; Flaherty, Kevin R; Martinez, Fernando J; Murray, Susan; Noth, Imre; Arnold, Kelly B; Moore, Bethany B

2017-04-25

Idiopathic pulmonary fibrosis (IPF) is a progressive and fatal interstitial pneumonia. The disease pathophysiology is poorly understood and the etiology remains unclear. Recent advances have generated new therapies and improved knowledge of the natural history of IPF. These gains have been brokered by advances in technology and improved insight into the role of various genes in mediating disease, but gene expression and protein levels do not always correlate. Thus, in this paper we apply a novel large scale high throughput aptamer approach to identify more than 1100 proteins in the peripheral blood of well-characterized IPF patients and normal volunteers. We use systems biology approaches to identify a unique IPF proteome signature and give insight into biological processes driving IPF. We found IPF plasma to be altered and enriched for proteins involved in defense response, wound healing and protein phosphorylation when compared to normal human plasma. Analysis also revealed a minimal protein signature that differentiated IPF patients from normal controls, which may allow for accurate diagnosis of IPF based on easily-accessible peripheral blood. This report introduces large scale unbiased protein discovery analysis to IPF and describes distinct biological processes that further inform disease biology.

Finding viable models in SUSY parameter spaces with signal specific discovery potential

NASA Astrophysics Data System (ADS)

Burgess, Thomas; Lindroos, Jan Øye; Lipniacka, Anna; Sandaker, Heidi

2013-08-01

Recent results from ATLAS giving a Higgs mass of 125.5 GeV, further constrain already highly constrained supersymmetric models such as pMSSM or CMSSM/mSUGRA. As a consequence, finding potentially discoverable and non-excluded regions of model parameter space is becoming increasingly difficult. Several groups have invested large effort in studying the consequences of Higgs mass bounds, upper limits on rare B-meson decays, and limits on relic dark matter density on constrained models, aiming at predicting superpartner masses, and establishing likelihood of SUSY models compared to that of the Standard Model vis-á-vis experimental data. In this paper a framework for efficient search for discoverable, non-excluded regions of different SUSY spaces giving specific experimental signature of interest is presented. The method employs an improved Markov Chain Monte Carlo (MCMC) scheme exploiting an iteratively updated likelihood function to guide search for viable models. Existing experimental and theoretical bounds as well as the LHC discovery potential are taken into account. This includes recent bounds on relic dark matter density, the Higgs sector and rare B-mesons decays. A clustering algorithm is applied to classify selected models according to expected phenomenology enabling automated choice of experimental benchmarks and regions to be used for optimizing searches. The aim is to provide experimentalist with a viable tool helping to target experimental signatures to search for, once a class of models of interest is established. As an example a search for viable CMSSM models with τ-lepton signatures observable with the 2012 LHC data set is presented. In the search 105209 unique models were probed. From these, ten reference benchmark points covering different ranges of phenomenological observables at the LHC were selected.

miRvestigator: web application to identify miRNAs responsible for co-regulated gene expression patterns discovered through transcriptome profiling.

PubMed

Plaisier, Christopher L; Bare, J Christopher; Baliga, Nitin S

2011-07-01

Transcriptome profiling studies have produced staggering numbers of gene co-expression signatures for a variety of biological systems. A significant fraction of these signatures will be partially or fully explained by miRNA-mediated targeted transcript degradation. miRvestigator takes as input lists of co-expressed genes from Caenorhabditis elegans, Drosophila melanogaster, G. gallus, Homo sapiens, Mus musculus or Rattus norvegicus and identifies the specific miRNAs that are likely to bind to 3' un-translated region (UTR) sequences to mediate the observed co-regulation. The novelty of our approach is the miRvestigator hidden Markov model (HMM) algorithm which systematically computes a similarity P-value for each unique miRNA seed sequence from the miRNA database miRBase to an overrepresented sequence motif identified within the 3'-UTR of the query genes. We have made this miRNA discovery tool accessible to the community by integrating our HMM algorithm with a proven algorithm for de novo discovery of miRNA seed sequences and wrapping these algorithms into a user-friendly interface. Additionally, the miRvestigator web server also produces a list of putative miRNA binding sites within 3'-UTRs of the query transcripts to facilitate the design of validation experiments. The miRvestigator is freely available at http://mirvestigator.systemsbiology.net.

Identification of E-cadherin signature motifs functioning as cleavage sites for Helicobacter pylori HtrA

NASA Astrophysics Data System (ADS)

Schmidt, Thomas P.; Perna, Anna M.; Fugmann, Tim; Böhm, Manja; Jan Hiss; Haller, Sarah; Götz, Camilla; Tegtmeyer, Nicole; Hoy, Benjamin; Rau, Tilman T.; Neri, Dario; Backert, Steffen; Schneider, Gisbert; Wessler, Silja

2016-03-01

The cell adhesion protein and tumour suppressor E-cadherin exhibits important functions in the prevention of gastric cancer. As a class-I carcinogen, Helicobacter pylori (H. pylori) has developed a unique strategy to interfere with E-cadherin functions. In previous studies, we have demonstrated that H. pylori secretes the protease high temperature requirement A (HtrA) which cleaves off the E-cadherin ectodomain (NTF) on epithelial cells. This opens cell-to-cell junctions, allowing bacterial transmigration across the polarised epithelium. Here, we investigated the molecular mechanism of the HtrA-E-cadherin interaction and identified E-cadherin cleavage sites for HtrA. Mass-spectrometry-based proteomics and Edman degradation revealed three signature motifs containing the [VITA]-[VITA]-x-x-D-[DN] sequence pattern, which were preferentially cleaved by HtrA. Based on these sites, we developed a substrate-derived peptide inhibitor that selectively bound and inhibited HtrA, thereby blocking transmigration of H. pylori. The discovery of HtrA-targeted signature sites might further explain why we detected a stable 90 kDa NTF fragment during H. pylori infection, but also additional E-cadherin fragments ranging from 105 kDa to 48 kDa in in vitro cleavage experiments. In conclusion, HtrA targets E-cadherin signature sites that are accessible in in vitro reactions, but might be partially masked on epithelial cells through functional homophilic E-cadherin interactions.

Fishing for Features

ScienceCinema

Heredia-Langner, Alejandro; Cort, John; Bailey, Vanessa

2018-01-16

The Fishing for Features Signature Discovery project developed a framework for discovering signature features in challenging environments involving large and complex data sets or where phenomena may be poorly characterized or understood. Researchers at PNNL have applied the framework to the optimization of biofuels blending and to discover signatures of climate change on microbial soil communities.

Fishing for Features

DOE Office of Scientific and Technical Information (OSTI.GOV)

Heredia-Langner, Alejandro; Cort, John; Bailey, Vanessa

2016-07-21

The Fishing for Features Signature Discovery project developed a framework for discovering signature features in challenging environments involving large and complex data sets or where phenomena may be poorly characterized or understood. Researchers at PNNL have applied the framework to the optimization of biofuels blending and to discover signatures of climate change on microbial soil communities.

The discovery of the prokaryotic cytoskeleton: 25th anniversary.

PubMed

Erickson, Harold P

2017-02-01

The year 2017 marks the 25th anniversary of the discovery of homologues of tubulin and actin in prokaryotes. Before 1992, it was largely accepted that tubulin and actin were unique to eukaryotes. Then three laboratories independently discovered that FtsZ, a protein already known as a key player in bacterial cytokinesis, had the "tubulin signature sequence" present in all α-, β-, and γ-tubulins. That same year, three candidates for bacterial actins were discovered in silico. X-ray crystal structures have since confirmed multiple bacterial proteins to be homologues of eukaryotic tubulin and actin. Tubulin and actin were apparently derived from bacterial precursors that had already evolved a wide range of cytoskeletal functions. © 2017 Erickson. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0).

Capability of detecting ultraviolet counterparts of gravitational waves with GLUV

NASA Astrophysics Data System (ADS)

Ridden-Harper, Ryan; Tucker, B. E.; Sharp, R.; Gilbert, J.; Petkovic, M.

2017-12-01

With the discovery of gravitational waves (GWs), attention has turned towards detecting counterparts to these sources. In discussions on counterpart signatures and multimessenger follow-up strategies to the GW detections, ultraviolet (UV) signatures have largely been neglected, due to UV facilities being limited to SWIFT, which lacks high-cadence UV survey capabilities. In this paper, we examine the UV signatures from merger models for the major GW sources, highlighting the need for further modelling, while presenting requirements and a design for an effective UV survey telescope. Using the u΄-band models as an analogue, we find that a UV survey telescope requires a limiting magnitude of m_{u^' }}(AB)≈ 24 to fully complement the aLIGO range and sky localization. We show that a network of small, balloon-based UV telescopes with a primary mirror diameter of 30 cm could be capable of covering the aLIGO detection distance from ∼60 to 100 per cent for BNS events and ∼40 per cent for the black hole and a neutron star events. The sensitivity of UV emission to initial conditions suggests that a UV survey telescope would provide a unique data set, which can act as an effective diagnostic to discriminate between models.

Flow-Signature Analysis of Water Consumption in Nonresidential Building Water Networks Using High-Resolution and Medium-Resolution Smart Meter Data: Two Case Studies

NASA Astrophysics Data System (ADS)

Clifford, Eoghan; Mulligan, Sean; Comer, Joanne; Hannon, Louise

2018-01-01

Real-time monitoring of water consumption activities can be an effective mechanism to achieve efficient water network management. This approach, largely enabled by the advent of smart metering technologies, is gradually being practiced in domestic and industrial contexts. In particular, identifying water consumption habits from flow-signatures, i.e., the specific end-usage patterns, is being investigated as a means for conservation in both the residential and nonresidential context. However, the quality of meter data is bivariate (dependent on number of meters and data temporal resolution) and as a result, planning a smart metering scheme is relatively difficult with no generic design approach available. In this study, a comprehensive medium-resolution to high-resolution smart metering program was implemented at two nonresidential trial sites to evaluate the effect of spatial and temporal data aggregation. It was found that medium-resolution water meter data were capable of exposing regular, continuous, peak use, and diurnal patterns which reflect group wide end-usage characteristics. The high-resolution meter data permitted flow-signature at a personal end-use level. Through this unique opportunity to observe water usage characteristics via flow-signature patterns, newly defined hydraulic-based design coefficients determined from Poisson rectangular pulse were developed to intuitively aid in the process of pattern discovery with implications for automated activity recognition applications. A smart meter classification and siting index was introduced which categorizes meter resolution in terms of their suitable application.

Challenges in Biomarker Discovery: Combining Expert Insights with Statistical Analysis of Complex Omics Data

PubMed Central

McDermott, Jason E.; Wang, Jing; Mitchell, Hugh; Webb-Robertson, Bobbie-Jo; Hafen, Ryan; Ramey, John; Rodland, Karin D.

2012-01-01

Introduction The advent of high throughput technologies capable of comprehensive analysis of genes, transcripts, proteins and other significant biological molecules has provided an unprecedented opportunity for the identification of molecular markers of disease processes. However, it has simultaneously complicated the problem of extracting meaningful molecular signatures of biological processes from these complex datasets. The process of biomarker discovery and characterization provides opportunities for more sophisticated approaches to integrating purely statistical and expert knowledge-based approaches. Areas covered In this review we will present examples of current practices for biomarker discovery from complex omic datasets and the challenges that have been encountered in deriving valid and useful signatures of disease. We will then present a high-level review of data-driven (statistical) and knowledge-based methods applied to biomarker discovery, highlighting some current efforts to combine the two distinct approaches. Expert opinion Effective, reproducible and objective tools for combining data-driven and knowledge-based approaches to identify predictive signatures of disease are key to future success in the biomarker field. We will describe our recommendations for possible approaches to this problem including metrics for the evaluation of biomarkers. PMID:23335946

The Chandra Strong Lens Sample: Revealing Baryonic Physics In Strong Lensing Selected Clusters

NASA Astrophysics Data System (ADS)

Bayliss, Matthew

2017-08-01

We propose for Chandra imaging of the hot intra-cluster gas in a unique new sample of 29 galaxy clusters selected purely on their strong gravitational lensing signatures. This will be the first program targeting a purely strong lensing selected cluster sample, enabling new comparisons between the ICM properties and scaling relations of strong lensing and mass/ICM selected cluster samples. Chandra imaging, combined with high precision strong lens models, ensures powerful constraints on the distribution and state of matter in the cluster cores. This represents a novel angle from which we can address the role played by baryonic physics |*| the infamous |*|gastrophysics|*| in shaping the cores of massive clusters, and opens up an exciting new galaxy cluster discovery space with Chandra.

The Chandra Strong Lens Sample: Revealing Baryonic Physics In Strong Lensing Selected Clusters

NASA Astrophysics Data System (ADS)

Bayliss, Matthew

2017-09-01

We propose for Chandra imaging of the hot intra-cluster gas in a unique new sample of 29 galaxy clusters selected purely on their strong gravitational lensing signatures. This will be the first program targeting a purely strong lensing selected cluster sample, enabling new comparisons between the ICM properties and scaling relations of strong lensing and mass/ICM selected cluster samples. Chandra imaging, combined with high precision strong lens models, ensures powerful constraints on the distribution and state of matter in the cluster cores. This represents a novel angle from which we can address the role played by baryonic physics -- the infamous ``gastrophysics''-- in shaping the cores of massive clusters, and opens up an exciting new galaxy cluster discovery space with Chandra.

Use of mRNA expression signatures to discover small molecule inhibitors of skeletal muscle atrophy

PubMed Central

Adams, Christopher M.; Ebert, Scott M.; Dyle, Michael C.

2017-01-01

Purpose of review Here, we discuss a recently developed experimental strategy for discovering small molecules with potential to prevent and treat skeletal muscle atrophy. Recent findings Muscle atrophy involves and requires widespread changes in skeletal muscle gene expression, which generate complex but measurable patterns of positive and negative changes in skeletal muscle mRNA levels (a.k.a. mRNA expression signatures of muscle atrophy). Many bioactive small molecules generate their own characteristic mRNA expression signatures, and by identifying small molecules whose signatures approximate mirror images of muscle atrophy signatures, one may identify small molecules with potential to prevent and/or reverse muscle atrophy. Unlike a conventional drug discovery approach, this strategy does not rely on a predefined molecular target but rather exploits the complexity of muscle atrophy to identify small molecules that counter the entire spectrum of pathological changes in atrophic muscle. We discuss how this strategy has been used to identify two natural compounds, ursolic acid and tomatidine, that reduce muscle atrophy and improve skeletal muscle function. Summary Discovery strategies based on mRNA expression signatures can elucidate new approaches for preserving and restoring muscle mass and function. PMID:25807353

Use of mRNA expression signatures to discover small molecule inhibitors of skeletal muscle atrophy.

PubMed

Adams, Christopher M; Ebert, Scott M; Dyle, Michael C

2015-05-01

Here, we discuss a recently developed experimental strategy for discovering small molecules with potential to prevent and treat skeletal muscle atrophy. Muscle atrophy involves and requires widespread changes in skeletal muscle gene expression, which generate complex but measurable patterns of positive and negative changes in skeletal muscle mRNA levels (a.k.a. mRNA expression signatures of muscle atrophy). Many bioactive small molecules generate their own characteristic mRNA expression signatures, and by identifying small molecules whose signatures approximate mirror images of muscle atrophy signatures, one may identify small molecules with potential to prevent and/or reverse muscle atrophy. Unlike a conventional drug discovery approach, this strategy does not rely on a predefined molecular target but rather exploits the complexity of muscle atrophy to identify small molecules that counter the entire spectrum of pathological changes in atrophic muscle. We discuss how this strategy has been used to identify two natural compounds, ursolic acid and tomatidine, that reduce muscle atrophy and improve skeletal muscle function. Discovery strategies based on mRNA expression signatures can elucidate new approaches for preserving and restoring muscle mass and function.

Signatures of Extended Storage of Used Nuclear Fuel in Casks

DOE Office of Scientific and Technical Information (OSTI.GOV)

Rauch, Eric Benton

2016-09-28

As the amount of used nuclear fuel continues to grow, more and more used nuclear fuel will be transferred to storage casks. A consolidated storage facility is currently in the planning stages for storing these casks, where at least 10,000 MTHM of fuel will be stored. This site will have potentially thousands of casks once it is operational. A facility this large presents new safeguards and nuclear material accounting concerns. A new signature based on the distribution of neutron sources and multiplication within casks was part of the Department of Energy Office of Nuclear Energy’s Material Protection, Account and Controlmore » Technologies (MPACT) campaign. Under this project we looked at fingerprinting each cask's neutron signature. Each cask has a unique set of fuel, with a unique spread of initial enrichment, burnup, cooling time, and power history. The unique set of fuel creates a unique signature of neutron intensity based on the arrangement of the assemblies. The unique arrangement of neutron sources and multiplication produces a reliable and unique identification of the cask that has been shown to be relatively constant over long time periods. The work presented here could be used to restore from a loss of continuity of knowledge at the storage site. This presentation will show the steps used to simulate and form this signature from the start of the effort through its conclusion in September 2016.« less

The impact of genetics on future drug discovery in schizophrenia.

PubMed

Matsumoto, Mitsuyuki; Walton, Noah M; Yamada, Hiroshi; Kondo, Yuji; Marek, Gerard J; Tajinda, Katsunori

2017-07-01

Failures of investigational new drugs (INDs) for schizophrenia have left huge unmet medical needs for patients. Given the recent lackluster results, it is imperative that new drug discovery approaches (and resultant drug candidates) target pathophysiological alterations that are shared in specific, stratified patient populations that are selected based on pre-identified biological signatures. One path to implementing this paradigm is achievable by leveraging recent advances in genetic information and technologies. Genome-wide exome sequencing and meta-analysis of single nucleotide polymorphism (SNP)-based association studies have already revealed rare deleterious variants and SNPs in patient populations. Areas covered: Herein, the authors review the impact that genetics have on the future of schizophrenia drug discovery. The high polygenicity of schizophrenia strongly indicates that this disease is biologically heterogeneous so the identification of unique subgroups (by patient stratification) is becoming increasingly necessary for future investigational new drugs. Expert opinion: The authors propose a pathophysiology-based stratification of genetically-defined subgroups that share deficits in particular biological pathways. Existing tools, including lower-cost genomic sequencing and advanced gene-editing technology render this strategy ever more feasible. Genetically complex psychiatric disorders such as schizophrenia may also benefit from synergistic research with simpler monogenic disorders that share perturbations in similar biological pathways.

21 CFR 11.100 - General requirements.

Code of Federal Regulations, 2010 CFR

2010-04-01

... RECORDS; ELECTRONIC SIGNATURES Electronic Signatures § 11.100 General requirements. (a) Each electronic signature shall be unique to one individual and shall not be reused by, or reassigned to, anyone else. (b... signature, or any element of such electronic signature, the organization shall verify the identity of the...

Transcriptome of interstitial cells of Cajal reveals unique and selective gene signatures

PubMed Central

Park, Paul J.; Fuchs, Robert; Wei, Lai; Jorgensen, Brian G.; Redelman, Doug; Ward, Sean M.; Sanders, Kenton M.

2017-01-01

Transcriptome-scale data can reveal essential clues into understanding the underlying molecular mechanisms behind specific cellular functions and biological processes. Transcriptomics is a continually growing field of research utilized in biomarker discovery. The transcriptomic profile of interstitial cells of Cajal (ICC), which serve as slow-wave electrical pacemakers for gastrointestinal (GI) smooth muscle, has yet to be uncovered. Using copGFP-labeled ICC mice and flow cytometry, we isolated ICC populations from the murine small intestine and colon and obtained their transcriptomes. In analyzing the transcriptome, we identified a unique set of ICC-restricted markers including transcription factors, epigenetic enzymes/regulators, growth factors, receptors, protein kinases/phosphatases, and ion channels/transporters. This analysis provides new and unique insights into the cellular and biological functions of ICC in GI physiology. Additionally, we constructed an interactive ICC genome browser (http://med.unr.edu/physio/transcriptome) based on the UCSC genome database. To our knowledge, this is the first online resource that provides a comprehensive library of all known genetic transcripts expressed in primary ICC. Our genome browser offers a new perspective into the alternative expression of genes in ICC and provides a valuable reference for future functional studies. PMID:28426719

A New Omics Data Resource of Pleurocybella porrigens for Gene Discovery

PubMed Central

Dohra, Hideo; Someya, Takumi; Takano, Tomoyuki; Harada, Kiyonori; Omae, Saori; Hirai, Hirofumi; Yano, Kentaro; Kawagishi, Hirokazu

2013-01-01

Background Pleurocybella porrigens is a mushroom-forming fungus, which has been consumed as a traditional food in Japan. In 2004, 55 people were poisoned by eating the mushroom and 17 people among them died of acute encephalopathy. Since then, the Japanese government has been alerting Japanese people to take precautions against eating the P . porrigens mushroom. Unfortunately, despite efforts, the molecular mechanism of the encephalopathy remains elusive. The genome and transcriptome sequence data of P . porrigens and the related species, however, are not stored in the public database. To gain the omics data in P . porrigens , we sequenced genome and transcriptome of its fruiting bodies and mycelia by next generation sequencing. Methodology/Principal Findings Short read sequences of genomic DNAs and mRNAs in P . porrigens were generated by Illumina Genome Analyzer. Genome short reads were de novo assembled into scaffolds using Velvet. Comparisons of genome signatures among Agaricales showed that P . porrigens has a unique genome signature. Transcriptome sequences were assembled into contigs (unigenes). Biological functions of unigenes were predicted by Gene Ontology and KEGG pathway analyses. The majority of unigenes would be novel genes without significant counterparts in the public omics databases. Conclusions Functional analyses of unigenes present the existence of numerous novel genes in the basidiomycetes division. The results mean that the omics information such as genome, transcriptome and metabolome in basidiomycetes is short in the current databases. The large-scale omics information on P . porrigens , provided from this research, will give a new data resource for gene discovery in basidiomycetes. PMID:23936076

Development of Transcriptomics-based Biomarkers for Selected Endocrine Disrupting Chemicals in Zebrafish (Danio rerio)

EPA Science Inventory

Genome-wide transcriptional profiling by microarrays provides a powerful platform for gene expression-based biomarker discovery. After their wide acceptance in human disease diagnosis, prognosis, and drug discovery, these gene signatures are increasingly being adopted for environ...

Development of transcriptomics-based biomarkers for selected endocrine disrupting chemicals in zebrafish (Danio rerio)

EPA Science Inventory

Genome-wide transcriptional profiling by microarrays provides a powerful platform for gene expression-based biomarker discovery. After their wide acceptance in human disease diagnosis, prognosis, and drug discovery, these gene signatures are increasingly being adopted for environ...

The Laccaria and Tuber Genomes Reveal Unique Signatures of Mycorrhizal Symbiosis Evolution (2010 JGI User Meeting)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Martin, Francis

Francis Martin from the French National Institute for Agricultural Research (INRA) talks on how "The Laccaria and Tuber genomes reveal unique signatures of mycorrhizal symbiosis evolution" on March 24, 2010 at the 5th Annual DOE JGI User Meeting

A Resource for Discovering Specific and Universal Biomarkers for Distributed Stem Cells

PubMed Central

Noh, Minsoo; Smith, Janet L.; Huh, Yang Hoon; Sherley, James L.

2011-01-01

Specific and universal biomarkers for distributed stem cells (DSCs) have been elusive. A major barrier to discovery of such ideal DSC biomarkers is difficulty in obtaining DSCs in sufficient quantity and purity. To solve this problem, we used cell lines genetically engineered for conditional asymmetric self-renewal, the defining DSC property. In gene microarray analyses, we identified 85 genes whose expression is tightly asymmetric self-renewal associated (ASRA). The ASRA gene signature prescribed DSCs to undergo asymmetric self-renewal to a greater extent than committed progenitor cells, embryonic stem cells, or induced pluripotent stem cells. This delineation has several significant implications. These include: 1) providing experimental evidence that DSCs in vivo undergo asymmetric self-renewal as individual cells; 2) providing an explanation why earlier attempts to define a common gene expression signature for DSCs were unsuccessful; and 3) predicting that some ASRA proteins may be ideal biomarkers for DSCs. Indeed, two ASRA proteins, CXCR6 and BTG2, and two other related self-renewal pattern associated (SRPA) proteins identified in this gene resource, LGR5 and H2A.Z, display unique asymmetric patterns of expression that have a high potential for universal and specific DSC identification. PMID:21818293

Delineation of metabolic gene clusters in plant genomes by chromatin signatures

PubMed Central

Yu, Nan; Nützmann, Hans-Wilhelm; MacDonald, James T.; Moore, Ben; Field, Ben; Berriri, Souha; Trick, Martin; Rosser, Susan J.; Kumar, S. Vinod; Freemont, Paul S.; Osbourn, Anne

2016-01-01

Plants are a tremendous source of diverse chemicals, including many natural product-derived drugs. It has recently become apparent that the genes for the biosynthesis of numerous different types of plant natural products are organized as metabolic gene clusters, thereby unveiling a highly unusual form of plant genome architecture and offering novel avenues for discovery and exploitation of plant specialized metabolism. Here we show that these clustered pathways are characterized by distinct chromatin signatures of histone 3 lysine trimethylation (H3K27me3) and histone 2 variant H2A.Z, associated with cluster repression and activation, respectively, and represent discrete windows of co-regulation in the genome. We further demonstrate that knowledge of these chromatin signatures along with chromatin mutants can be used to mine genomes for cluster discovery. The roles of H3K27me3 and H2A.Z in repression and activation of single genes in plants are well known. However, our discovery of highly localized operon-like co-regulated regions of chromatin modification is unprecedented in plants. Our findings raise intriguing parallels with groups of physically linked multi-gene complexes in animals and with clustered pathways for specialized metabolism in filamentous fungi. PMID:26895889

Sulforaphane reduces hepatic glucose production and improves glucose control in patients with type 2 diabetes

USDA-ARS?s Scientific Manuscript database

A potentially useful approach for drug discovery is to connect gene expression profiles of disease-affected tissues ("disease signatures") to drug signatures, but it remains to be shown whether it can be used to identify clinically relevant treatment options. We analyzed coexpression networks and ge...

SR2067 reveals a unique kinetic and structural signature for PPARγ partial agonism

DOE PAGES

van Marrewijk, Laura M.; Polyak, Steven W.; Hijnen, Marcel; ...

2015-11-18

Here, synthetic full agonists of PPARγ have been prescribed for the treatment of diabetes due to their ability to regulate glucose homeostasis and insulin sensitization. While the use of full agonists of PPARγ has been hampered due to severe side effects, partial agonists have shown promise due to their decreased incidence of such side effects in preclinical models. No kinetic information has been forthcoming in regard to the mechanism of full versus partial agonism of PPARγ to date. In this paper, we describe the discovery of a partial agonist, SR2067. A co-crystal structure obtained at 2.2 Å resolution demonstrates thatmore » interactions with the β-sheet are driven exclusively via hydrophobic interactions mediated through a naphthalene group, an observation that is unique from other partial agonists. Finally, surface plasmon resonance revealed that SR2067 binds to the receptor with higher affinity (K D = 513 nM) as compared to that of full agonist rosiglitazone, yet it has a much slower off rate compared to that of rosiglitazone.« less

Sequencing Needs for Viral Diagnostics

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gardner, S N; Lam, M; Mulakken, N J

2004-01-26

We built a system to guide decisions regarding the amount of genomic sequencing required to develop diagnostic DNA signatures, which are short sequences that are sufficient to uniquely identify a viral species. We used our existing DNA diagnostic signature prediction pipeline, which selects regions of a target species genome that are conserved among strains of the target (for reliability, to prevent false negatives) and unique relative to other species (for specificity, to avoid false positives). We performed simulations, based on existing sequence data, to assess the number of genome sequences of a target species and of close phylogenetic relatives (''nearmore » neighbors'') that are required to predict diagnostic signature regions that are conserved among strains of the target species and unique relative to other bacterial and viral species. For DNA viruses such as variola (smallpox), three target genomes provide sufficient guidance for selecting species-wide signatures. Three near neighbor genomes are critical for species specificity. In contrast, most RNA viruses require four target genomes and no near neighbor genomes, since lack of conservation among strains is more limiting than uniqueness. SARS and Ebola Zaire are exceptional, as additional target genomes currently do not improve predictions, but near neighbor sequences are urgently needed. Our results also indicate that double stranded DNA viruses are more conserved among strains than are RNA viruses, since in most cases there was at least one conserved signature candidate for the DNA viruses and zero conserved signature candidates for the RNA viruses.« less

Lesson 5: Defining Valid Electronic Signatures

EPA Pesticide Factsheets

A valid electronic signature on an electronic document is one that is created with an electronic signature device that is uniquely entitled to a signatory, not compromised, and used by a signatory who is authorized to sign the electronic document.

A luminous X-ray outburst from an intermediate-mass black hole in an off-centre star cluster

NASA Astrophysics Data System (ADS)

Lin, Dacheng; Strader, Jay; Carrasco, Eleazar R.; Page, Dany; Romanowsky, Aaron J.; Homan, Jeroen; Irwin, Jimmy A.; Remillard, Ronald A.; Godet, Olivier; Webb, Natalie A.; Baumgardt, Holger; Wijnands, Rudy; Barret, Didier; Duc, Pierre-Alain; Brodie, Jean P.; Gwyn, Stephen D. J.

2018-06-01

A unique signature for the presence of massive black holes in very dense stellar regions is occasional giant-amplitude outbursts of multi-wavelength radiation from tidal disruption and subsequent accretion of stars that make a close approach to the black holes1. Previous strong tidal disruption event (TDE) candidates were all associated with the centres of largely isolated galaxies2-6. Here, we report the discovery of a luminous X-ray outburst from a massive star cluster at a projected distance of 12.5 kpc from the centre of a large lenticular galaxy. The luminosity peaked at 1043 erg s-1 and decayed systematically over 10 years, approximately following a trend that supports the identification of the event as a TDE. The X-ray spectra were all very soft, with emission confined to be ≲3.0 keV, and could be described with a standard thermal disk. The disk cooled significantly as the luminosity decreased—a key thermal-state signature often observed in accreting stellar-mass black holes. This thermal-state signature, coupled with very high luminosities, ultrasoft X-ray spectra and the characteristic power-law evolution of the light curve, provides strong evidence that the source contains an intermediate-mass black hole with a mass tens of thousand times that of the solar mass. This event demonstrates that one of the most effective means of detecting intermediate-mass black holes is through X-ray flares from TDEs in star clusters.

Data-Driven Process Discovery: A Discrete Time Algebra for Relational Signal Analysis

DTIC Science & Technology

1996-12-01

would also like to thank Dr. Mark Oxley for his assistance in developing this abstract algebra and the mathematical notation found herein. Lastly, I... Mathematical Result.. 4-13 4.4. Demostration of Coefficient Signature Additon ........................ 4-14 4.5. Multivariate Relational Discovery...spaces with the recognition of cues in a specific space" [21]. Up to now, most of the Artificial Intelligence (Al) ’discovery’ work has emphasized one

Live Cell in Vitro and in Vivo Imaging Applications: Accelerating Drug Discovery

PubMed Central

Isherwood, Beverley; Timpson, Paul; McGhee, Ewan J; Anderson, Kurt I; Canel, Marta; Serrels, Alan; Brunton, Valerie G; Carragher, Neil O

2011-01-01

Dynamic regulation of specific molecular processes and cellular phenotypes in live cell systems reveal unique insights into cell fate and drug pharmacology that are not gained from traditional fixed endpoint assays. Recent advances in microscopic imaging platform technology combined with the development of novel optical biosensors and sophisticated image analysis solutions have increased the scope of live cell imaging applications in drug discovery. We highlight recent literature examples where live cell imaging has uncovered novel insight into biological mechanism or drug mode-of-action. We survey distinct types of optical biosensors and associated analytical methods for monitoring molecular dynamics, in vitro and in vivo. We describe the recent expansion of live cell imaging into automated target validation and drug screening activities through the development of dedicated brightfield and fluorescence kinetic imaging platforms. We provide specific examples of how temporal profiling of phenotypic response signatures using such kinetic imaging platforms can increase the value of in vitro high-content screening. Finally, we offer a prospective view of how further application and development of live cell imaging technology and reagents can accelerate preclinical lead optimization cycles and enhance the in vitro to in vivo translation of drug candidates. PMID:24310493

Determination of burn patient outcome by large-scale quantitative discovery proteomics

PubMed Central

Finnerty, Celeste C.; Jeschke, Marc G.; Qian, Wei-Jun; Kaushal, Amit; Xiao, Wenzhong; Liu, Tao; Gritsenko, Marina A.; Moore, Ronald J.; Camp, David G.; Moldawer, Lyle L.; Elson, Constance; Schoenfeld, David; Gamelli, Richard; Gibran, Nicole; Klein, Matthew; Arnoldo, Brett; Remick, Daniel; Smith, Richard D.; Davis, Ronald; Tompkins, Ronald G.; Herndon, David N.

2013-01-01

Objective Emerging proteomics techniques can be used to establish proteomic outcome signatures and to identify candidate biomarkers for survival following traumatic injury. We applied high-resolution liquid chromatography-mass spectrometry (LC-MS) and multiplex cytokine analysis to profile the plasma proteome of survivors and non-survivors of massive burn injury to determine the proteomic survival signature following a major burn injury. Design Proteomic discovery study. Setting Five burn hospitals across the U.S. Patients Thirty-two burn patients (16 non-survivors and 16 survivors), 19–89 years of age, were admitted within 96 h of injury to the participating hospitals with burns covering >20% of the total body surface area and required at least one surgical intervention. Interventions None. Measurements and Main Results We found differences in circulating levels of 43 proteins involved in the acute phase response, hepatic signaling, the complement cascade, inflammation, and insulin resistance. Thirty-two of the proteins identified were not previously known to play a role in the response to burn. IL-4, IL-8, GM-CSF, MCP-1, and β2-microglobulin correlated well with survival and may serve as clinical biomarkers. Conclusions These results demonstrate the utility of these techniques for establishing proteomic survival signatures and for use as a discovery tool to identify candidate biomarkers for survival. This is the first clinical application of a high-throughput, large-scale LC-MS-based quantitative plasma proteomic approach for biomarker discovery for the prediction of patient outcome following burn, trauma or critical illness. PMID:23507713

Signature-Discovery Approach for Sample Matching of a Nerve-Agent Precursor using Liquid Chromatography–Mass Spectrometry, XCMS, and Chemometrics

DOE Office of Scientific and Technical Information (OSTI.GOV)

Fraga, Carlos G.; Clowers, Brian H.; Moore, Ronald J.

2010-05-15

This report demonstrates the use of bioinformatic and chemometric tools on liquid chromatography mass spectrometry (LC-MS) data for the discovery of ultra-trace forensic signatures for sample matching of various stocks of the nerve-agent precursor known as methylphosphonic dichloride (dichlor). The use of the bioinformatic tool known as XCMS was used to comprehensively search and find candidate LC-MS peaks in a known set of dichlor samples. These candidate peaks were down selected to a group of 34 impurity peaks. Hierarchal cluster analysis and factor analysis demonstrated the potential of these 34 impurities peaks for matching samples based on their stock source.more » Only one pair of dichlor stocks was not differentiated from one another. An acceptable chemometric approach for sample matching was determined to be variance scaling and signal averaging of normalized duplicate impurity profiles prior to classification by k-nearest neighbors. Using this approach, a test set of dichlor samples were all correctly matched to their source stock. The sample preparation and LC-MS method permitted the detection of dichlor impurities presumably in the parts-per-trillion (w/w). The detection of a common impurity in all dichlor stocks that were synthesized over a 14-year period and by different manufacturers was an unexpected discovery. Our described signature-discovery approach should be useful in the development of a forensic capability to help in criminal investigations following chemical attacks.« less

Genome-wide methylomic and transcriptomic analyses identify subtype-specific epigenetic signatures commonly dysregulated in glioma stem cells and glioblastoma.

PubMed

Pangeni, Rajendra P; Zhang, Zhou; Alvarez, Angel A; Wan, Xuechao; Sastry, Namratha; Lu, Songjian; Shi, Taiping; Huang, Tianzhi; Lei, Charles X; James, C David; Kessler, John A; Brennan, Cameron W; Nakano, Ichiro; Lu, Xinghua; Hu, Bo; Zhang, Wei; Cheng, Shi-Yuan

2018-06-21

Glioma stem cells (GSCs), a subpopulation of tumor cells, contribute to tumor heterogeneity and therapy resistance. Gene expression profiling classified glioblastoma (GBM) and GSCs into four transcriptomically-defined subtypes. Here, we determined the DNA methylation signatures in transcriptomically pre-classified GSC and GBM bulk tumors subtypes. We hypothesized that these DNA methylation signatures correlate with gene expression and are uniquely associated either with only GSCs or only GBM bulk tumors. Additional methylation signatures may be commonly associated with both GSCs and GBM bulk tumors, i.e., common to non-stem-like and stem-like tumor cell populations and correlating with the clinical prognosis of glioma patients. We analyzed Illumina 450K methylation array and expression data from a panel of 23 patient-derived GSCs. We referenced these results with The Cancer Genome Atlas (TCGA) GBM datasets to generate methylomic and transcriptomic signatures for GSCs and GBM bulk tumors of each transcriptomically pre-defined tumor subtype. Survival analyses were carried out for these signature genes using publicly available datasets, including from TCGA. We report that DNA methylation signatures in proneural and mesenchymal tumor subtypes are either unique to GSCs, unique to GBM bulk tumors, or common to both. Further, dysregulated DNA methylation correlates with gene expression and clinical prognoses. Additionally, many previously identified transcriptionally-regulated markers are also dysregulated due to DNA methylation. The subtype-specific DNA methylation signatures described in this study could be useful for refining GBM sub-classification, improving prognostic accuracy, and making therapeutic decisions.

Delineation of metabolic gene clusters in plant genomes by chromatin signatures.

PubMed

Yu, Nan; Nützmann, Hans-Wilhelm; MacDonald, James T; Moore, Ben; Field, Ben; Berriri, Souha; Trick, Martin; Rosser, Susan J; Kumar, S Vinod; Freemont, Paul S; Osbourn, Anne

2016-03-18

Plants are a tremendous source of diverse chemicals, including many natural product-derived drugs. It has recently become apparent that the genes for the biosynthesis of numerous different types of plant natural products are organized as metabolic gene clusters, thereby unveiling a highly unusual form of plant genome architecture and offering novel avenues for discovery and exploitation of plant specialized metabolism. Here we show that these clustered pathways are characterized by distinct chromatin signatures of histone 3 lysine trimethylation (H3K27me3) and histone 2 variant H2A.Z, associated with cluster repression and activation, respectively, and represent discrete windows of co-regulation in the genome. We further demonstrate that knowledge of these chromatin signatures along with chromatin mutants can be used to mine genomes for cluster discovery. The roles of H3K27me3 and H2A.Z in repression and activation of single genes in plants are well known. However, our discovery of highly localized operon-like co-regulated regions of chromatin modification is unprecedented in plants. Our findings raise intriguing parallels with groups of physically linked multi-gene complexes in animals and with clustered pathways for specialized metabolism in filamentous fungi. © The Author(s) 2016. Published by Oxford University Press on behalf of Nucleic Acids Research.

An archaeal genomic signature

NASA Technical Reports Server (NTRS)

Graham, D. E.; Overbeek, R.; Olsen, G. J.; Woese, C. R.

2000-01-01

Comparisons of complete genome sequences allow the most objective and comprehensive descriptions possible of a lineage's evolution. This communication uses the completed genomes from four major euryarchaeal taxa to define a genomic signature for the Euryarchaeota and, by extension, the Archaea as a whole. The signature is defined in terms of the set of protein-encoding genes found in at least two diverse members of the euryarchaeal taxa that function uniquely within the Archaea; most signature proteins have no recognizable bacterial or eukaryal homologs. By this definition, 351 clusters of signature proteins have been identified. Functions of most proteins in this signature set are currently unknown. At least 70% of the clusters that contain proteins from all the euryarchaeal genomes also have crenarchaeal homologs. This conservative set, which appears refractory to horizontal gene transfer to the Bacteria or the Eukarya, would seem to reflect the significant innovations that were unique and fundamental to the archaeal "design fabric." Genomic protein signature analysis methods may be extended to characterize the evolution of any phylogenetically defined lineage. The complete set of protein clusters for the archaeal genomic signature is presented as supplementary material (see the PNAS web site, www.pnas.org).

RNA-Seq-based toxicogenomic assessment of fresh frozen and formalin-fixed tissues yields similar mechanistic insights.

PubMed

Auerbach, Scott S; Phadke, Dhiral P; Mav, Deepak; Holmgren, Stephanie; Gao, Yuan; Xie, Bin; Shin, Joo Heon; Shah, Ruchir R; Merrick, B Alex; Tice, Raymond R

2015-07-01

Formalin-fixed, paraffin-embedded (FFPE) pathology specimens represent a potentially vast resource for transcriptomic-based biomarker discovery. We present here a comparison of results from a whole transcriptome RNA-Seq analysis of RNA extracted from fresh frozen and FFPE livers. The samples were derived from rats exposed to aflatoxin B1 (AFB1 ) and a corresponding set of control animals. Principal components analysis indicated that samples were separated in the two groups representing presence or absence of chemical exposure, both in fresh frozen and FFPE sample types. Sixty-five percent of the differentially expressed transcripts (AFB1 vs. controls) in fresh frozen samples were also differentially expressed in FFPE samples (overlap significance: P < 0.0001). Genomic signature and gene set analysis of AFB1 differentially expressed transcript lists indicated highly similar results between fresh frozen and FFPE at the level of chemogenomic signatures (i.e., single chemical/dose/duration elicited transcriptomic signatures), mechanistic and pathology signatures, biological processes, canonical pathways and transcription factor networks. Overall, our results suggest that similar hypotheses about the biological mechanism of toxicity would be formulated from fresh frozen and FFPE samples. These results indicate that phenotypically anchored archival specimens represent a potentially informative resource for signature-based biomarker discovery and mechanistic characterization of toxicity. Copyright © 2014 John Wiley & Sons, Ltd.

Mycobacterium tuberculosis strains exhibit differential and strain-specific molecular signatures in pulmonary epithelial cells.

PubMed

Mvubu, Nontobeko Eunice; Pillay, Balakrishna; Gamieldien, Junaid; Bishai, William; Pillay, Manormoney

2016-12-01

Although pulmonary epithelial cells are integral to innate and adaptive immune responses during Mycobacterium tuberculosis infection, global transcriptomic changes in these cells remain largely unknown. Changes in gene expression induced in pulmonary epithelial cells infected with M. tuberculosis F15/LAM4/KZN, F11, F28, Beijing and Unique genotypes were investigated by RNA sequencing (RNA-Seq). The Illumina HiSeq 2000 platform generated 50 bp reads that were mapped to the human genome (Hg19) using Tophat (2.0.10). Differential gene expression induced by the different strains in infected relative to the uninfected cells was quantified and compared using Cufflinks (2.1.0) and MeV (4.0.9), respectively. Gene expression varied among the strains with the total number of genes as follows: F15/LAM4/KZN (1187), Beijing (1252), F11 (1639), F28 (870), Unique (886) and H37Rv (1179). A subset of 292 genes was commonly induced by all strains, where 52 genes were down-regulated while 240 genes were up-regulated. Differentially expressed genes were compared among the strains and the number of induced strain-specific gene signatures were as follows: F15/LAM4/KZN (138), Beijing (52), F11 (255), F28 (55), Unique (186) and H37Rv (125). Strain-specific molecular gene signatures associated with functional pathways were observed only for the Unique and H37Rv strains while certain biological functions may be associated with other strain signatures. This study demonstrated that strains of M. tuberculosis induce differential gene expression and strain-specific molecular signatures in pulmonary epithelial cells. Specific signatures induced by clinical strains of M. tuberculosis can be further explored for novel host-associated biomarkers and adjunctive immunotherapies. Copyright © 2016 Elsevier Ltd. All rights reserved.

Early Detection of NSCLC Using Stromal Markers in Peripheral Blood

DTIC Science & Technology

2017-11-01

transcriptionally altered and the alteration is tumor dependent . The specific transcriptomic signature of circulating myeloid cells may provide us unique...signature, which may be useful for early lung cancer diagnosis. The specific aims are: Aim 1. To identify a NSCLC- dependent transcriptomic signature in...circulating myeloid cells are transcriptionally altered and the alteration is tumor dependent . The specific transcriptomic signature of circulating

Cancer cell redirection biomarker discovery using a mutual information approach.

PubMed

Roche, Kimberly; Feltus, F Alex; Park, Jang Pyo; Coissieux, Marie-May; Chang, Chenyan; Chan, Vera B S; Bentires-Alj, Mohamed; Booth, Brian W

2017-01-01

Introducing tumor-derived cells into normal mammary stem cell niches at a sufficiently high ratio of normal to tumorous cells causes those tumor cells to undergo a change to normal mammary phenotype and yield normal mammary progeny. This phenomenon has been termed cancer cell redirection. We have developed an in vitro model that mimics in vivo redirection of cancer cells by the normal mammary microenvironment. Using the RNA profiling data from this cellular model, we examined high-level characteristics of the normal, redirected, and tumor transcriptomes and found the global expression profiles clearly distinguish the three expression states. To identify potential redirection biomarkers that cause the redirected state to shift toward the normal expression pattern, we used mutual information relationships between normal, redirected, and tumor cell groups. Mutual information relationship analysis reduced a dataset of over 35,000 gene expression measurements spread over 13,000 curated gene sets to a set of 20 significant molecular signatures totaling 906 unique loci. Several of these molecular signatures are hallmark drivers of the tumor state. Using differential expression as a guide, we further refined the gene set to 120 core redirection biomarker genes. The expression levels of these core biomarkers are sufficient to make the normal and redirected gene expression states indistinguishable from each other but radically different from the tumor state.

Cancer cell redirection biomarker discovery using a mutual information approach

PubMed Central

Roche, Kimberly; Feltus, F. Alex; Park, Jang Pyo; Coissieux, Marie-May; Chang, Chenyan; Chan, Vera B. S.; Bentires-Alj, Mohamed

2017-01-01

Introducing tumor-derived cells into normal mammary stem cell niches at a sufficiently high ratio of normal to tumorous cells causes those tumor cells to undergo a change to normal mammary phenotype and yield normal mammary progeny. This phenomenon has been termed cancer cell redirection. We have developed an in vitro model that mimics in vivo redirection of cancer cells by the normal mammary microenvironment. Using the RNA profiling data from this cellular model, we examined high-level characteristics of the normal, redirected, and tumor transcriptomes and found the global expression profiles clearly distinguish the three expression states. To identify potential redirection biomarkers that cause the redirected state to shift toward the normal expression pattern, we used mutual information relationships between normal, redirected, and tumor cell groups. Mutual information relationship analysis reduced a dataset of over 35,000 gene expression measurements spread over 13,000 curated gene sets to a set of 20 significant molecular signatures totaling 906 unique loci. Several of these molecular signatures are hallmark drivers of the tumor state. Using differential expression as a guide, we further refined the gene set to 120 core redirection biomarker genes. The expression levels of these core biomarkers are sufficient to make the normal and redirected gene expression states indistinguishable from each other but radically different from the tumor state. PMID:28594912

Discovery of functional elements in 12 Drosophila genomes using evolutionary signatures

PubMed Central

Stark, Alexander; Lin, Michael F.; Kheradpour, Pouya; Pedersen, Jakob S.; Parts, Leopold; Carlson, Joseph W.; Crosby, Madeline A.; Rasmussen, Matthew D.; Roy, Sushmita; Deoras, Ameya N.; Ruby, J. Graham; Brennecke, Julius; Hodges, Emily; Hinrichs, Angie S.; Caspi, Anat; Paten, Benedict; Park, Seung-Won; Han, Mira V.; Maeder, Morgan L.; Polansky, Benjamin J.; Robson, Bryanne E.; Aerts, Stein; van Helden, Jacques; Hassan, Bassem; Gilbert, Donald G.; Eastman, Deborah A.; Rice, Michael; Weir, Michael; Hahn, Matthew W.; Park, Yongkyu; Dewey, Colin N.; Pachter, Lior; Kent, W. James; Haussler, David; Lai, Eric C.; Bartel, David P.; Hannon, Gregory J.; Kaufman, Thomas C.; Eisen, Michael B.; Clark, Andrew G.; Smith, Douglas; Celniker, Susan E.; Gelbart, William M.; Kellis, Manolis

2008-01-01

Sequencing of multiple related species followed by comparative genomics analysis constitutes a powerful approach for the systematic understanding of any genome. Here, we use the genomes of 12 Drosophila species for the de novo discovery of functional elements in the fly. Each type of functional element shows characteristic patterns of change, or ‘evolutionary signatures’, dictated by its precise selective constraints. Such signatures enable recognition of new protein-coding genes and exons, spurious and incorrect gene annotations, and numerous unusual gene structures, including abundant stop-codon readthrough. Similarly, we predict non-protein-coding RNA genes and structures, and new microRNA (miRNA) genes. We provide evidence of miRNA processing and functionality from both hairpin arms and both DNA strands. We identify several classes of pre- and post-transcriptional regulatory motifs, and predict individual motif instances with high confidence. We also study how discovery power scales with the divergence and number of species compared, and we provide general guidelines for comparative studies. PMID:17994088

Phylogenetic Framework and Molecular Signatures for the Main Clades of the Phylum Actinobacteria

PubMed Central

Gao, Beile

2012-01-01

Summary: The phylum Actinobacteria harbors many important human pathogens and also provides one of the richest sources of natural products, including numerous antibiotics and other compounds of biotechnological interest. Thus, a reliable phylogeny of this large phylum and the means to accurately identify its different constituent groups are of much interest. Detailed phylogenetic and comparative analyses of >150 actinobacterial genomes reported here form the basis for achieving these objectives. In phylogenetic trees based upon 35 conserved proteins, most of the main groups of Actinobacteria as well as a number of their superageneric clades are resolved. We also describe large numbers of molecular markers consisting of conserved signature indels in protein sequences and whole proteins that are specific for either all Actinobacteria or their different clades (viz., orders, families, genera, and subgenera) at various taxonomic levels. These signatures independently support the existence of different phylogenetic clades, and based upon them, it is now possible to delimit the phylum Actinobacteria (excluding Coriobacteriia) and most of its major groups in clear molecular terms. The species distribution patterns of these markers also provide important information regarding the interrelationships among different main orders of Actinobacteria. The identified molecular markers, in addition to enabling the development of a stable and reliable phylogenetic framework for this phylum, also provide novel and powerful means for the identification of different groups of Actinobacteria in diverse environments. Genetic and biochemical studies on these Actinobacteria-specific markers should lead to the discovery of novel biochemical and/or other properties that are unique to different groups of Actinobacteria. PMID:22390973

27 CFR 73.3 - What terms must I know to understand this part?

Code of Federal Regulations, 2010 CFR

2010-04-01

... and/or actions are both unique to that individual and measurable. Digital signature. An electronic... verified. A signer creates a digital signature by using public-key encryption to transform a message digest of an electronic message. If a recipient of the digital signature has an electronic message, message...

27 CFR 73.3 - What terms must I know to understand this part?

Code of Federal Regulations, 2011 CFR

2011-04-01

... and/or actions are both unique to that individual and measurable. Digital signature. An electronic... verified. A signer creates a digital signature by using public-key encryption to transform a message digest of an electronic message. If a recipient of the digital signature has an electronic message, message...

Conventional and Non-Conventional Nuclear Material Signatures

NASA Astrophysics Data System (ADS)

Gozani, Tsahi

2009-03-01

The detection and interdiction of concealed special nuclear material (SNM) in all modes of transport is one of the most critical security issues facing the United States and the rest of the world. In principle, detection of nuclear materials is relatively easy because of their unique properties: all of them are radioactive and all emit some characteristic gamma rays. A few emit neutrons as well. These signatures are the basis for passive non-intrusive detection of nuclear materials. The low energy of the radiations necessitates additional means of detection and validation. These are provided by high-energy x-ray radiography and by active inspection based on inducing nuclear reactions in the nuclear materials. Positive confirmation that a nuclear material is present or absent can be provided by interrogation of the inspected object with penetrating probing radiation, such as neutrons and photons. The radiation induces specific reactions in the nuclear material yielding, in turn, penetrating signatures which can be detected outside the inspected object. The "conventional" signatures are first and foremost fission signatures: prompt and delayed neutrons and gamma rays. Their intensity (number per fission) and the fact that they have broad energy (non-discrete, though unique) distributions and certain temporal behaviors are key to their use. The "non- conventional" signatures are not related to the fission process but to the unique nuclear structure of each element or isotope in nature. This can be accessed through the excitation of isotopic nuclear levels (discrete and continuum) by neutron inelastic scattering or gamma resonance fluorescence. Finally there is an atomic signature, namely the high atomic number (Z>74), which obviously includes all the nuclear materials and their possible shielding. The presence of such high-Z elements can be inferred by techniques using high-energy x rays. The conventional signatures have been addressed in another article. Non-conventional signatures and some of their current or potential uses will be discussed here.

A novel prognostic six-CpG signature in glioblastomas.

PubMed

Yin, An-An; Lu, Nan; Etcheverry, Amandine; Aubry, Marc; Barnholtz-Sloan, Jill; Zhang, Lu-Hua; Mosser, Jean; Zhang, Wei; Zhang, Xiang; Liu, Yu-He; He, Ya-Long

2018-03-01

We aimed to identify a clinically useful biomarker using DNA methylation-based information to optimize individual treatment of patients with glioblastoma (GBM). A six-CpG panel was identified by incorporating genome-wide DNA methylation data and clinical information of three distinct discovery sets and was combined using a risk-score model. Different validation sets of GBMs and lower-grade gliomas and different statistical methods were implemented for prognostic evaluation. An integrative analysis of multidimensional TCGA data was performed to molecularly characterize different risk tumors. The six-CpG risk-score signature robustly predicted overall survival (OS) in all discovery and validation cohorts and in a treatment-independent manner. It also predicted progression-free survival (PFS) in available patients. The multimarker epigenetic signature was demonstrated as an independent prognosticator and had better performance than known molecular indicators such as glioma-CpG island methylator phenotype (G-CIMP) and proneural subtype. The defined risk subgroups were molecularly distinct; high-risk tumors were biologically more aggressive with concordant activation of proangiogenic signaling at multimolecular levels. Accordingly, we observed better OS benefits of bevacizumab-contained therapy to high-risk patients in independent sets, supporting its implication in guiding usage of antiangiogenic therapy. Finally, the six-CpG signature refined the risk classification based on G-CIMP and MGMT methylation status. The novel six-CpG signature is a robust and independent prognostic indicator for GBMs and is of promising value to improve personalized management. © 2018 John Wiley & Sons Ltd.

InFlo: a novel systems biology framework identifies cAMP-CREB1 axis as a key modulator of platinum resistance in ovarian cancer.

PubMed

Dimitrova, N; Nagaraj, A B; Razi, A; Singh, S; Kamalakaran, S; Banerjee, N; Joseph, P; Mankovich, A; Mittal, P; DiFeo, A; Varadan, V

2017-04-27

Characterizing the complex interplay of cellular processes in cancer would enable the discovery of key mechanisms underlying its development and progression. Published approaches to decipher driver mechanisms do not explicitly model tissue-specific changes in pathway networks and the regulatory disruptions related to genomic aberrations in cancers. We therefore developed InFlo, a novel systems biology approach for characterizing complex biological processes using a unique multidimensional framework integrating transcriptomic, genomic and/or epigenomic profiles for any given cancer sample. We show that InFlo robustly characterizes tissue-specific differences in activities of signalling networks on a genome scale using unique probabilistic models of molecular interactions on a per-sample basis. Using large-scale multi-omics cancer datasets, we show that InFlo exhibits higher sensitivity and specificity in detecting pathway networks associated with specific disease states when compared to published pathway network modelling approaches. Furthermore, InFlo's ability to infer the activity of unmeasured signalling network components was also validated using orthogonal gene expression signatures. We then evaluated multi-omics profiles of primary high-grade serous ovarian cancer tumours (N=357) to delineate mechanisms underlying resistance to frontline platinum-based chemotherapy. InFlo was the only algorithm to identify hyperactivation of the cAMP-CREB1 axis as a key mechanism associated with resistance to platinum-based therapy, a finding that we subsequently experimentally validated. We confirmed that inhibition of CREB1 phosphorylation potently sensitized resistant cells to platinum therapy and was effective in killing ovarian cancer stem cells that contribute to both platinum-resistance and tumour recurrence. Thus, we propose InFlo to be a scalable and widely applicable and robust integrative network modelling framework for the discovery of evidence-based biomarkers and therapeutic targets.

A neural signature of the unique hues

PubMed Central

Forder, Lewis; Bosten, Jenny; He, Xun; Franklin, Anna

2017-01-01

Since at least the 17th century there has been the idea that there are four simple and perceptually pure “unique” hues: red, yellow, green, and blue, and that all other hues are perceived as mixtures of these four hues. However, sustained scientific investigation has not yet provided solid evidence for a neural representation that separates the unique hues from other colors. We measured event-related potentials elicited from unique hues and the ‘intermediate’ hues in between them. We find a neural signature of the unique hues 230 ms after stimulus onset at a post-perceptual stage of visual processing. Specifically, the posterior P2 component over the parieto-occipital lobe peaked significantly earlier for the unique than for the intermediate hues (Z = −2.9, p = 0.004). Having identified a neural marker for unique hues, fundamental questions about the contribution of neural hardwiring, language and environment to the unique hues can now be addressed. PMID:28186142

Fission Signatures for Nuclear Material Detection

NASA Astrophysics Data System (ADS)

Gozani, Tsahi

2009-06-01

Detection and interdiction of nuclear materials in all forms of transport is one of the most critical security issues facing the United States and the rest of the civilized world. Naturally emitted gamma rays by these materials, while abundant and detectable when unshielded, are low in energy and readily shielded. X-ray radiography is useful in detecting the possible presence of shielding material. Positive detection of concealed nuclear materials requires methods which unequivocally detect specific attributes of the materials. These methods typically involve active interrogation by penetrating radiation of neutrons, photons or other particles. Fortunately, nuclear materials, probed by various types of radiation, yield very unique and often strong signatures. Paramount among them are the detectable fission signatures, namely prompt neutrons and gamma rays, and delayed neutrons gamma rays. Other useful signatures are the nuclear states excited by neutrons, via inelastic scattering, or photons, via nuclear resonance fluorescence and absorption. The signatures are very different in magnitude, level of specificity, ease of excitation and detection, signal to background ratios, etc. For example, delayed neutrons are very unique to the fission process, but are scarce, have low energy, and hence are easily absorbed. Delayed gamma rays are more abundant but "featureless", and have a higher background from natural sources and more importantly, from activation due to the interrogation sources. The prompt fission signatures need to be measured in the presence of the much higher levels of probing radiation. This requires taking special measures to look for the signatures, sometimes leading to a significant sensitivity loss or a complete inability to detect them. Characteristic gamma rays induced in nuclear materials reflecting their nuclear structure, while rather unique, require very high intensity of interrogation radiation and very high resolution in energy and/or time. The trade off of signatures, their means of stimulation, and methods of detection, will be reviewed.

Systematic discovery and characterization of fly microRNAs using 12 Drosophila genomes

PubMed Central

Stark, Alexander; Kheradpour, Pouya; Parts, Leopold; Brennecke, Julius; Hodges, Emily; Hannon, Gregory J.; Kellis, Manolis

2007-01-01

MicroRNAs (miRNAs) are short regulatory RNAs that inhibit target genes by complementary binding in 3′ untranslated regions (3′ UTRs). They are one of the most abundant classes of regulators, targeting a large fraction of all genes, making their comprehensive study a requirement for understanding regulation and development. Here we use 12 Drosophila genomes to define structural and evolutionary signatures of miRNA hairpins, which we use for their de novo discovery. We predict >41 novel miRNA genes, which encompass many unique families, and 28 of which are validated experimentally. We also define signals for the precise start position of mature miRNAs, which suggest corrections of previously known miRNAs, often leading to drastic changes in their predicted target spectrum. We show that miRNA discovery power scales with the number and divergence of species compared, suggesting that such approaches can be successful in human as dozens of mammalian genomes become available. Interestingly, for some miRNAs sense and anti-sense hairpins score highly and mature miRNAs from both strands can indeed be found in vivo. Similarly, miRNAs with weak 5′ end predictions show increased in vivo processing of multiple alternate 5′ ends and have fewer predicted targets. Lastly, we show that several miRNA star sequences score highly and are likely functional. For mir-10 in particular, both arms show abundant processing, and both show highly conserved target sites in Hox genes, suggesting a possible cooperation of the two arms, and their role as a master Hox regulator. PMID:17989255

Distinct Microbial Signatures Associated With Different Breast Cancer Types

PubMed Central

Banerjee, Sagarika; Tian, Tian; Wei, Zhi; Shih, Natalie; Feldman, Michael D.; Peck, Kristen N.; DeMichele, Angela M.; Alwine, James C.; Robertson, Erle S.

2018-01-01

A dysbiotic microbiome can potentially contribute to the pathogenesis of many different diseases including cancer. Breast cancer is the second leading cause of cancer death in women. Thus, we investigated the diversity of the microbiome in the four major types of breast cancer: endocrine receptor (ER) positive, triple positive, Her2 positive and triple negative breast cancers. Using a whole genome and transcriptome amplification and a pan-pathogen microarray (PathoChip) strategy, we detected unique and common viral, bacterial, fungal and parasitic signatures for each of the breast cancer types. These were validated by PCR and Sanger sequencing. Hierarchical cluster analysis of the breast cancer samples, based on their detected microbial signatures, showed distinct patterns for the triple negative and triple positive samples, while the ER positive and Her2 positive samples shared similar microbial signatures. These signatures, unique or common to the different breast cancer types, provide a new line of investigation to gain further insights into prognosis, treatment strategies and clinical outcome, as well as better understanding of the role of the micro-organisms in the development and progression of breast cancer. PMID:29867857

Graph Analytics for Signature Discovery

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hogan, Emilie A.; Johnson, John R.; Halappanavar, Mahantesh

2013-06-01

Within large amounts of seemingly unstructured data it can be diffcult to find signatures of events. In our work we transform unstructured data into a graph representation. By doing this we expose underlying structure in the data and can take advantage of existing graph analytics capabilities, as well as develop new capabilities. Currently we focus on applications in cybersecurity and communication domains. Within cybersecurity we aim to find signatures for perpetrators using the pass-the-hash attack, and in communications we look for emails or phone calls going up or down a chain of command. In both of these areas, and inmore » many others, the signature we look for is a path with certain temporal properties. In this paper we discuss our methodology for finding these temporal paths within large graphs.« less

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gardner, S; Jaing, C

The goal of this project is to develop forensic genotyping assays for select agent viruses, addressing a significant capability gap for the viral bioforensics and law enforcement community. We used a multipronged approach combining bioinformatics analysis, PCR-enriched samples, microarrays and TaqMan assays to develop high resolution and cost effective genotyping methods for strain level forensic discrimination of viruses. We have leveraged substantial experience and efficiency gained through year 1 on software development, SNP discovery, TaqMan signature design and phylogenetic signature mapping to scale up the development of forensics signatures in year 2. In this report, we have summarized the Taqmanmore » signature development for South American hemorrhagic fever viruses, tick-borne encephalitis viruses and henipaviruses, Old World Arenaviruses, filoviruses, Crimean-Congo hemorrhagic fever virus, Rift Valley fever virus and Japanese encephalitis virus.« less

Study of recreational land and open space using Skylab imagery

NASA Technical Reports Server (NTRS)

Sattinger, I. J. (Principal Investigator)

1975-01-01

The author has identified the following significant results. An analysis of the statistical uniqueness of each of the signatures of the Gratiot-Saginaw State Game Area was made by computing a matrix of probabilities of misclassification for all possible signature pairs. Within each data set, the 35 signatures were then aggregated into a smaller set of composite signatures by combining groups of signatures having high probabilities of misclassification. Computer separation of forest denisty classes was poor with multispectral scanner data collected on 5 August 1973. Signatures from the scanner data were further analyzed to determine the ranking of spectral channels for computer separation of the scene classes. Probabilities of misclassification were computed for composite signatures using four separate combinations of data source and channel selection.

Diagnostic test accuracy of a 2-transcript host RNA signature for discriminating bacterial vs viral infection in febrile children

PubMed Central

Shailes, Hannah; Eleftherohorinou, Hariklia; Hoggart, Clive J; Cebey-Lopez, Miriam; Carter, Michael J; Janes, Victoria A; Gormley, Stuart; Shimizu, Chisato; Tremoulet, Adriana H; Barendregt, Anouk M; Salas, Antonio; Kanegaye, John; Pollard, Andrew J; Faust, Saul N; Patel, Sanjay; Kuijpers, Taco; Martinon-Torres, Federico; Burns, Jane C; Coin, Lachlan JM; Levin, Michael

2018-01-01

Importance As clinical features do not reliably distinguish bacterial from viral infection, many children worldwide receive unnecessary antibiotic treatment whilst bacterial infection is missed in others. Objective To identify a blood RNA expression signature that distinguishes bacterial from viral infection in febrile children. Design Febrile children presenting to participating hospitals in UK, Spain, Netherlands and USA between 2009-2013 were prospectively recruited, comprising a discovery group and validation group. Each group was classified after microbiological investigation into definite bacterial, definite viral infection or indeterminate infection. RNA expression signatures distinguishing definite bacterial from viral infection were identified in the discovery group and diagnostic performance assessed in the validation group. Additional validation was undertaken in separate studies of children with meningococcal disease (n=24) inflammatory diseases (n=48), and on published gene expression datasets. Exposures A 2-transcript RNA expression signature distinguishing bacterial infection from viral infection was evaluated against clinical and microbiological diagnosis. Main Outcomes Definite Bacterial and viral infection was confirmed by culture or molecular detection of the pathogens. Performance of the RNA signature was evaluated in the definite bacterial and viral group, and the indeterminate group. Results The discovery cohort of 240 children (median age 19 months, 62% males) included 52 with definite bacterial infection of whom 36 (69%) required intensive care; and 92 with definite viral infection of whom 32 (35%) required intensive care. 96 children had indeterminate infection. Bioinformatic analysis of RNA expression data identified a 38-transcript signature distinguishing bacterial from viral infection. A smaller (2-transcript) signature (FAM89A and IFI44L) was identified by removing highly correlated transcripts. When this 2-transcript signature was implemented as a Disease Risk Score in the validation group (130 children, including 23 bacterial, 28 viral, 79 indeterminate; median age 17 months, 57% males), bacterial infection was identified in all 23 microbiologically-confirmed definite bacterial patients, with a sensitivity of 100% (95% confidence interval [CI], 100 - 100), and in 1 of 28 definite viral patients, with specificity of 96.4% (95% CI, 89.3 – 100). When applied to additional validation datasets from patients with meningococcal and inflammatory diseases, bacterial infection was identified with a sensitivity of 91.7% (79.2-100) and 90.0% (70.0-100) respectively, and with specificity of 96.0% (88.0-100) and 95.8% (89.6-100). A minority of children in the indeterminate group were classified as having bacterial infection (63 of 136, 46.3%), although most received antibiotic treatment (129 of 136, 94.9%). Conclusions and Relevance This study provides preliminary data regarding test accuracy of a 2-transcript host RNA signature discriminating bacterial from viral infection in febrile children. Further studies are needed in diverse groups of patients to assess accuracy and clinical utility of this test in different clinical settings. PMID:27552617

Immune signatures of protective spleen memory CD8 T cells.

PubMed

Brinza, Lilia; Djebali, Sophia; Tomkowiak, Martine; Mafille, Julien; Loiseau, Céline; Jouve, Pierre-Emmanuel; de Bernard, Simon; Buffat, Laurent; Lina, Bruno; Ottmann, Michèle; Rosa-Calatrava, Manuel; Schicklin, Stéphane; Bonnefoy, Nathalie; Lauvau, Grégoire; Grau, Morgan; Wencker, Mélanie; Arpin, Christophe; Walzer, Thierry; Leverrier, Yann; Marvel, Jacqueline

2016-11-24

Memory CD8 T lymphocyte populations are remarkably heterogeneous and differ in their ability to protect the host. In order to identify the whole range of qualities uniquely associated with protective memory cells we compared the gene expression signatures of two qualities of memory CD8 T cells sharing the same antigenic-specificity: protective (Influenza-induced, Flu-TM) and non-protective (peptide-induced, TIM) spleen memory CD8 T cells. Although Flu-TM and TIM express classical phenotypic memory markers and are polyfunctional, only Flu-TM protects against a lethal viral challenge. Protective memory CD8 T cells express a unique set of genes involved in migration and survival that correlate with their unique capacity to rapidly migrate within the infected lung parenchyma in response to influenza infection. We also enlighten a new set of poised genes expressed by protective cells that is strongly enriched in cytokines and chemokines such as Ccl1, Ccl9 and Gm-csf. CCL1 and GM-CSF genes are also poised in human memory CD8 T cells. These immune signatures are also induced by two other pathogens (vaccinia virus and Listeria monocytogenes). The immune signatures associated with immune protection were identified on circulating cells, i.e. those that are easily accessible for immuno-monitoring and could help predict vaccines efficacy.

Extraction and analysis of signatures from the Gene Expression Omnibus by the crowd

PubMed Central

Wang, Zichen; Monteiro, Caroline D.; Jagodnik, Kathleen M.; Fernandez, Nicolas F.; Gundersen, Gregory W.; Rouillard, Andrew D.; Jenkins, Sherry L.; Feldmann, Axel S.; Hu, Kevin S.; McDermott, Michael G.; Duan, Qiaonan; Clark, Neil R.; Jones, Matthew R.; Kou, Yan; Goff, Troy; Woodland, Holly; Amaral, Fabio M R.; Szeto, Gregory L.; Fuchs, Oliver; Schüssler-Fiorenza Rose, Sophia M.; Sharma, Shvetank; Schwartz, Uwe; Bausela, Xabier Bengoetxea; Szymkiewicz, Maciej; Maroulis, Vasileios; Salykin, Anton; Barra, Carolina M.; Kruth, Candice D.; Bongio, Nicholas J.; Mathur, Vaibhav; Todoric, Radmila D; Rubin, Udi E.; Malatras, Apostolos; Fulp, Carl T.; Galindo, John A.; Motiejunaite, Ruta; Jüschke, Christoph; Dishuck, Philip C.; Lahl, Katharina; Jafari, Mohieddin; Aibar, Sara; Zaravinos, Apostolos; Steenhuizen, Linda H.; Allison, Lindsey R.; Gamallo, Pablo; de Andres Segura, Fernando; Dae Devlin, Tyler; Pérez-García, Vicente; Ma'ayan, Avi

2016-01-01

Gene expression data are accumulating exponentially in public repositories. Reanalysis and integration of themed collections from these studies may provide new insights, but requires further human curation. Here we report a crowdsourcing project to annotate and reanalyse a large number of gene expression profiles from Gene Expression Omnibus (GEO). Through a massive open online course on Coursera, over 70 participants from over 25 countries identify and annotate 2,460 single-gene perturbation signatures, 839 disease versus normal signatures, and 906 drug perturbation signatures. All these signatures are unique and are manually validated for quality. Global analysis of these signatures confirms known associations and identifies novel associations between genes, diseases and drugs. The manually curated signatures are used as a training set to develop classifiers for extracting similar signatures from the entire GEO repository. We develop a web portal to serve these signatures for query, download and visualization. PMID:27667448

Extraction and analysis of signatures from the Gene Expression Omnibus by the crowd.

PubMed

Wang, Zichen; Monteiro, Caroline D; Jagodnik, Kathleen M; Fernandez, Nicolas F; Gundersen, Gregory W; Rouillard, Andrew D; Jenkins, Sherry L; Feldmann, Axel S; Hu, Kevin S; McDermott, Michael G; Duan, Qiaonan; Clark, Neil R; Jones, Matthew R; Kou, Yan; Goff, Troy; Woodland, Holly; Amaral, Fabio M R; Szeto, Gregory L; Fuchs, Oliver; Schüssler-Fiorenza Rose, Sophia M; Sharma, Shvetank; Schwartz, Uwe; Bausela, Xabier Bengoetxea; Szymkiewicz, Maciej; Maroulis, Vasileios; Salykin, Anton; Barra, Carolina M; Kruth, Candice D; Bongio, Nicholas J; Mathur, Vaibhav; Todoric, Radmila D; Rubin, Udi E; Malatras, Apostolos; Fulp, Carl T; Galindo, John A; Motiejunaite, Ruta; Jüschke, Christoph; Dishuck, Philip C; Lahl, Katharina; Jafari, Mohieddin; Aibar, Sara; Zaravinos, Apostolos; Steenhuizen, Linda H; Allison, Lindsey R; Gamallo, Pablo; de Andres Segura, Fernando; Dae Devlin, Tyler; Pérez-García, Vicente; Ma'ayan, Avi

2016-09-26

Gene expression data are accumulating exponentially in public repositories. Reanalysis and integration of themed collections from these studies may provide new insights, but requires further human curation. Here we report a crowdsourcing project to annotate and reanalyse a large number of gene expression profiles from Gene Expression Omnibus (GEO). Through a massive open online course on Coursera, over 70 participants from over 25 countries identify and annotate 2,460 single-gene perturbation signatures, 839 disease versus normal signatures, and 906 drug perturbation signatures. All these signatures are unique and are manually validated for quality. Global analysis of these signatures confirms known associations and identifies novel associations between genes, diseases and drugs. The manually curated signatures are used as a training set to develop classifiers for extracting similar signatures from the entire GEO repository. We develop a web portal to serve these signatures for query, download and visualization.

A Tale of Two Discoveries: Comparing the Usability of Summon and EBSCO Discovery Service

ERIC Educational Resources Information Center

Foster, Anita K.; MacDonald, Jean B.

2013-01-01

Web-scale discovery systems are gaining momentum among academic libraries as libraries seek a means to provide their users with a one-stop searching experience. Illinois State University's Milner Library found itself in the unique position of having access to two distinct discovery products, EBSCO Discovery Service and Serials Solutions' Summon.…

Chemicals from the Practice of Healthcare: Challenges and Unknowns Posed by Residues in the Environment

EPA Science Inventory

Medications have unique signatures - real and metaphorical fingerprints, footprints, and shadows. Signatures imparted by manufacturers use distinctive combinations of shapes, colors, and imprints. These serve as rough first tests to aid in visually identifying the types and quant...

Recent observations of negative longitudinal magnetoresistance in semimetal

NASA Astrophysics Data System (ADS)

Xu, Xi-Tong; Jia, Shuang

2016-11-01

The discovery of Dirac semimetal and Weyl semimetal has motivated a growing passion for investigating the unique magneto-transport properties in the topological materials. A Weyl semimetal can host Weyl fermions as its low-energy quasi-particle excitations, and therefore perform exotic features analogous to those in high-energy physics, such as the violation of the chiral charge conservation known as the chiral anomaly. One of the electrical transport signatures of the chiral anomaly is the Adler-Bell-Jackiw (ABJ) anomaly which presents as a negative magnetoresistance when the magnetic field and the current are parallel. Very recently, numerous experiments reported negative longitudinal magnetoresistance (NLMR) in topological materials, but the details of the measurement results are various. Here the materials and the corresponding experiment results are briefly reviewed. Besides the plausible explanation of the ABJ anomaly, some other origins of the NLMR are also discussed. Project supported by the National Basic Research Program of China (Grant Nos. 2013CB921901 and 2014CB239302).

Spectral Invariant Behavior of Zenith Radiance Around Cloud Edges Observed by ARM SWS

NASA Technical Reports Server (NTRS)

Marshak, A.; Knyazikhin, Y.; Chiu, J. C.; Wiscombe, W. J.

2009-01-01

The ARM Shortwave Spectrometer (SWS) measures zenith radiance at 418 wavelengths between 350 and 2170 nm. Because of its 1-sec sampling resolution, the SWS provides a unique capability to study the transition zone between cloudy and clear sky areas. A spectral invariant behavior is found between ratios of zenith radiance spectra during the transition from cloudy to cloud-free. This behavior suggests that the spectral signature of the transition zone is a linear mixture between the two extremes (definitely cloudy and definitely clear). The weighting function of the linear mixture is a wavelength-independent characteristic of the transition zone. It is shown that the transition zone spectrum is fully determined by this function and zenith radiance spectra of clear and cloudy regions. An important result of these discoveries is that high temporal resolution radiance measurements in the clear-to-cloud transition zone can be well approximated by lower temporal resolution measurements plus linear interpolation.

An FDA Perspective on the Regulatory Implications of Complex Signatures to Predict Response to Targeted Therapies

PubMed Central

Beaver, Julia A.; Tzou, Abraham; Blumenthal, Gideon M.; McKee, Amy E.; Kim, Geoffrey; Pazdur, Richard; Philip, Reena

2016-01-01

As technologies evolve, and diagnostics move from detection of single biomarkers toward complex signatures, an increase in the clinical use and regulatory submission of complex signatures is anticipated. However, to date, no complex signatures have been approved as companion diagnostics. In this article, we will describe the potential benefit of complex signatures and their unique regulatory challenges including analytical performance validation, complex signature simulation, and clinical performance evaluation. We also will review the potential regulatory pathways for clearance, approval, or acceptance of complex signatures by the U.S. Food and Drug Administration (FDA). These regulatory pathways include regulations applicable to in vitro diagnostic devices, including companion diagnostic devices, the potential for labeling as a complementary diagnostic, and the biomarker qualification program. PMID:27993967

Integrated omics dissection of proteome dynamics during cardiac remodeling.

PubMed

Lau, Edward; Cao, Quan; Lam, Maggie P Y; Wang, Jie; Ng, Dominic C M; Bleakley, Brian J; Lee, Jessica M; Liem, David A; Wang, Ding; Hermjakob, Henning; Ping, Peipei

2018-01-09

Transcript abundance and protein abundance show modest correlation in many biological models, but how this impacts disease signature discovery in omics experiments is rarely explored. Here we report an integrated omics approach, incorporating measurements of transcript abundance, protein abundance, and protein turnover to map the landscape of proteome remodeling in a mouse model of pathological cardiac hypertrophy. Analyzing the hypertrophy signatures that are reproducibly discovered from each omics data type across six genetic strains of mice, we find that the integration of transcript abundance, protein abundance, and protein turnover data leads to 75% gain in discovered disease gene candidates. Moreover, the inclusion of protein turnover measurements allows discovery of post-transcriptional regulations across diverse pathways, and implicates distinct disease proteins not found in steady-state transcript and protein abundance data. Our results suggest that multi-omics investigations of proteome dynamics provide important insights into disease pathogenesis in vivo.

Model identification of new heavy Z‧ bosons at ILC with polarized beams

NASA Astrophysics Data System (ADS)

Pankov, A. A.; Tsytrinov, A. V.

2017-12-01

Extra neutral gauge bosons, Z‧s, are predicted by many theoretical scenarios of physics beyond the Standard Model, and intensive searches for their signatures will be performed at present and future high energy colliders. It is quite possible that Z‧s are heavy enough to lie beyond the discovery reach expected at the CERN Large Hadron Collider LHC, in which case only indirect signatures of Z‧ exchanges may occur at future colliders, through deviations of the measured cross sections from the Standard Model predictions. We here discuss in this context the expected sensitivity to Z‧ parameters of fermion-pair production cross sections at the planned International Linear Collider (ILC), especially as regards the potential of distinguishing different Z‧ models once such deviations are observed. Specifically, we evaluate the discovery and identification reaches on Z‧ gauge bosons pertinent to the E 6, LR, ALR, and SSM classes of models at the ILC.

Discovery of a Thorne-Żytkow object candidate in the Small Magellanic Cloud

NASA Astrophysics Data System (ADS)

Levesque, Emily M.; Massey, Philip; Żytkow, Anna N.; Morrell, Nidia

2015-01-01

Thorne-Żytkow objects (TŻOs) are a theoretical class of star in which a compact neutron star is surrounded by a large, diffuse envelope. Supergiant TŻOs are predicted to be almost identical in appearance to red supergiants (RSGs), with their very red colors and cool temperatures placing them at the Hayashi limit on the H-R diagram. The only features that can be used at present to distinguish TŻOs from the general RSG population are the unusually strong heavy-element and lithium lines present in their spectra. These elements are the unique products of the stars fully convective envelope linking the photosphere with the extraordinarily hot burning region in the vicinity of the neutron star core. We have recently discovered a TŻO candidate in the Small Magellanic Cloud. It is the first star to display the distinctive chemical profile of anomalous element enhancements thought to be characteristic of TŻOs however, up-to-date models and additional observable predictions (including potential asteroseismological signatures) are required to solidify this discovery. The definitive detection of a TŻO would provide the first direct evidence for a completely new model of stellar interiors, a theoretically predicted fate for massive binary systems, and never-before-seen nucleosynthesis processes that would offer a new channel for heavy-element and lithium production in our universe.

Exploratory Spectroscopy of Magnetic Cataclysmic Variables Candidates and Other Variable Objects

DOE Office of Scientific and Technical Information (OSTI.GOV)

Oliveira, A. S.; Palhares, M. S.; Rodrigues, C. V.

2017-04-01

The increasing number of synoptic surveys made by small robotic telescopes, such as the photometric Catalina Real-Time Transient Survey (CRTS), provides a unique opportunity to discover variable sources and improves the statistical samples of such classes of objects. Our goal is the discovery of magnetic Cataclysmic Variables (mCVs). These are rare objects that probe interesting accretion scenarios controlled by the white-dwarf magnetic field. In particular, improved statistics of mCVs would help to address open questions on their formation and evolution. We performed an optical spectroscopy survey to search for signatures of magnetic accretion in 45 variable objects selected mostly from themore » CRTS. In this sample, we found 32 CVs, 22 being mCV candidates, 13 of which were previously unreported as such. If the proposed classifications are confirmed, it would represent an increase of 4% in the number of known polars and 12% in the number of known IPs. A fraction of our initial sample was classified as extragalactic sources or other types of variable stars by the inspection of the identification spectra. Despite the inherent complexity in identifying a source as an mCV, variability-based selection, followed by spectroscopic snapshot observations, has proved to be an efficient strategy for their discoveries, being a relatively inexpensive approach in terms of telescope time.« less

Thermal imaging as a biometrics approach to facial signature authentication.

PubMed

Guzman, A M; Goryawala, M; Wang, Jin; Barreto, A; Andrian, J; Rishe, N; Adjouadi, M

2013-01-01

A new thermal imaging framework with unique feature extraction and similarity measurements for face recognition is presented. The research premise is to design specialized algorithms that would extract vasculature information, create a thermal facial signature and identify the individual. The proposed algorithm is fully integrated and consolidates the critical steps of feature extraction through the use of morphological operators, registration using the Linear Image Registration Tool and matching through unique similarity measures designed for this task. The novel approach at developing a thermal signature template using four images taken at various instants of time ensured that unforeseen changes in the vasculature over time did not affect the biometric matching process as the authentication process relied only on consistent thermal features. Thirteen subjects were used for testing the developed technique on an in-house thermal imaging system. The matching using the similarity measures showed an average accuracy of 88.46% for skeletonized signatures and 90.39% for anisotropically diffused signatures. The highly accurate results obtained in the matching process clearly demonstrate the ability of the thermal infrared system to extend in application to other thermal imaging based systems. Empirical results applying this approach to an existing database of thermal images proves this assertion.

Privacy Preserved and Secured Reliable Routing Protocol for Wireless Mesh Networks.

PubMed

Meganathan, Navamani Thandava; Palanichamy, Yogesh

2015-01-01

Privacy preservation and security provision against internal attacks in wireless mesh networks (WMNs) are more demanding than in wired networks due to the open nature and mobility of certain nodes in the network. Several schemes have been proposed to preserve privacy and provide security in WMNs. To provide complete privacy protection in WMNs, the properties of unobservability, unlinkability, and anonymity are to be ensured during route discovery. These properties can be achieved by implementing group signature and ID-based encryption schemes during route discovery. Due to the characteristics of WMNs, it is more vulnerable to many network layer attacks. Hence, a strong protection is needed to avoid these attacks and this can be achieved by introducing a new Cross-Layer and Subject Logic based Dynamic Reputation (CLSL-DR) mechanism during route discovery. In this paper, we propose a new Privacy preserved and Secured Reliable Routing (PSRR) protocol for WMNs. This protocol incorporates group signature, ID-based encryption schemes, and CLSL-DR mechanism to ensure strong privacy, security, and reliability in WMNs. Simulation results prove this by showing better performance in terms of most of the chosen parameters than the existing protocols.

Discovery and Validation of Novel Expression Signature for Postcystectomy Recurrence in High-Risk Bladder Cancer

PubMed Central

Lam, Lucia L.; Ghadessi, Mercedeh; Erho, Nicholas; Vergara, Ismael A.; Alshalalfa, Mohammed; Buerki, Christine; Haddad, Zaid; Sierocinski, Thomas; Triche, Timothy J.; Skinner, Eila C.; Davicioni, Elai; Daneshmand, Siamak; Black, Peter C.

2014-01-01

Background Nearly half of muscle-invasive bladder cancer patients succumb to their disease following cystectomy. Selecting candidates for adjuvant therapy is currently based on clinical parameters with limited predictive power. This study aimed to develop and validate genomic-based signatures that can better identify patients at risk for recurrence than clinical models alone. Methods Transcriptome-wide expression profiles were generated using 1.4 million feature-arrays on archival tumors from 225 patients who underwent radical cystectomy and had muscle-invasive and/or node-positive bladder cancer. Genomic (GC) and clinical (CC) classifiers for predicting recurrence were developed on a discovery set (n = 133). Performances of GC, CC, an independent clinical nomogram (IBCNC), and genomic-clinicopathologic classifiers (G-CC, G-IBCNC) were assessed in the discovery and independent validation (n = 66) sets. GC was further validated on four external datasets (n = 341). Discrimination and prognostic abilities of classifiers were compared using area under receiver-operating characteristic curves (AUCs). All statistical tests were two-sided. Results A 15-feature GC was developed on the discovery set with area under curve (AUC) of 0.77 in the validation set. This was higher than individual clinical variables, IBCNC (AUC = 0.73), and comparable to CC (AUC = 0.78). Performance was improved upon combining GC with clinical nomograms (G-IBCNC, AUC = 0.82; G-CC, AUC = 0.86). G-CC high-risk patients had elevated recurrence probabilities (P < .001), with GC being the best predictor by multivariable analysis (P = .005). Genomic-clinicopathologic classifiers outperformed clinical nomograms by decision curve and reclassification analyses. GC performed the best in validation compared with seven prior signatures. GC markers remained prognostic across four independent datasets. Conclusions The validated genomic-based classifiers outperform clinical models for predicting postcystectomy bladder cancer recurrence. This may be used to better identify patients who need more aggressive management. PMID:25344601

Systematic CpT (ApG) depletion and CpG excess are unique genomic signatures of large DNA viruses infecting invertebrates.

PubMed

Upadhyay, Mohita; Sharma, Neha; Vivekanandan, Perumal

2014-01-01

Differences in the relative abundance of dinucleotides, if any may provide important clues on host-driven evolution of viruses. We studied dinucleotide frequencies of large DNA viruses infecting vertebrates (n = 105; viruses infecting mammals = 99; viruses infecting aves = 6; viruses infecting reptiles = 1) and invertebrates (n = 88; viruses infecting insects = 84; viruses infecting crustaceans = 4). We have identified systematic depletion of CpT(ApG) dinucleotides and over-representation of CpG dinucleotides as the unique genomic signature of large DNA viruses infecting invertebrates. Detailed investigation of this unique genomic signature suggests the existence of invertebrate host-induced pressures specifically targeting CpT(ApG) and CpG dinucleotides. The depletion of CpT dinucleotides among large DNA viruses infecting invertebrates is at least in part, explained by non-canonical DNA methylation by the infected host. Our findings highlight the role of invertebrate host-related factors in shaping virus evolution and they also provide the necessary framework for future studies on evolution, epigenetics and molecular biology of viruses infecting this group of hosts.

A novel algorithm for simplification of complex gene classifiers in cancer

PubMed Central

Wilson, Raphael A.; Teng, Ling; Bachmeyer, Karen M.; Bissonnette, Mei Lin Z.; Husain, Aliya N.; Parham, David M.; Triche, Timothy J.; Wing, Michele R.; Gastier-Foster, Julie M.; Barr, Frederic G.; Hawkins, Douglas S.; Anderson, James R.; Skapek, Stephen X.; Volchenboum, Samuel L.

2013-01-01

The clinical application of complex molecular classifiers as diagnostic or prognostic tools has been limited by the time and cost needed to apply them to patients. Using an existing fifty-gene expression signature known to separate two molecular subtypes of the pediatric cancer rhabdomyosarcoma, we show that an exhaustive iterative search algorithm can distill this complex classifier down to two or three features with equal discrimination. We validated the two-gene signatures using three separate and distinct data sets, including one that uses degraded RNA extracted from formalin-fixed, paraffin-embedded material. Finally, to demonstrate the generalizability of our algorithm, we applied it to a lung cancer data set to find minimal gene signatures that can distinguish survival. Our approach can easily be generalized and coupled to existing technical platforms to facilitate the discovery of simplified signatures that are ready for routine clinical use. PMID:23913937

A new family of magnetic stars: the Am stars

NASA Astrophysics Data System (ADS)

Blazère, A.; Neiner, C.; Petit, P.; Lignières, F.

2016-12-01

We presented the discovery of an ultra-weak field in three Am stars, β UMa, θ Leo, and Alhena, thanks to ultra-deep spectropolarimetric observations. Two of the three stars of this study shown peculiar magnetic signatures with prominent positive lobes like the one of Sirius A that are not expected in the standard theory of the Zeeman effect. Alhena, contrary to Sirius A, β UMa and θ Leo, show normal signatures. These detections of ultra-weak fields in Am stars suggest the existence of a new family of magnetic intermediate-mass stars: the Am stars. However the various shapes of the signatures required further observation to identify the physical processes at work in these stars. A preliminary explanation is based on microturbulence.

The Miami Barrel: An Innovation in Forensic Firearms Identification

ERIC Educational Resources Information Center

Fadul, Thomas G., Jr.

2009-01-01

The scientific foundation in firearm and tool mark identification is that each firearm/tool produces a signature of identification (striation/impression) that is unique to that firearm/tool, and through examining the individual striations/impressions; the signature can be positively identified to the firearm/tool that produced it. There is no set…

Noble Gas Isotopic Signatures and X-Ray and Electron Diffraction Characteristics of Tagish Lake Carbonaceous Chondrite

NASA Technical Reports Server (NTRS)

Nakamura, T.; Noguchi, T.; Zolensky, M. E.; Takaoka, N.

2001-01-01

Noble gas isotopic signatures and X-ray and electron diffraction characteristics of Tagish Lake indicate that it is a unique carbonaceous chondrite rich in saponite, Fe-Mg-Ca carbonate, primordial noble gases, and presolar grains. Additional information is contained in the original extended abstract.

Discovery of agents that eradicate leukemia stem cells using an in silico screen of public gene expression data

PubMed Central

Hassane, Duane C.; Guzman, Monica L.; Corbett, Cheryl; Li, Xiaojie; Abboud, Ramzi; Young, Fay; Liesveld, Jane L.; Carroll, Martin

2008-01-01

Increasing evidence indicates that malignant stem cells are important for the pathogenesis of acute myelogenous leukemia (AML) and represent a reservoir of cells that drive the development of AML and relapse. Therefore, new treatment regimens are necessary to prevent relapse and improve therapeutic outcomes. Previous studies have shown that the sesquiterpene lactone, parthenolide (PTL), ablates bulk, progenitor, and stem AML cells while causing no appreciable toxicity to normal hematopoietic cells. Thus, PTL must evoke cellular responses capable of mediating AML selective cell death. Given recent advances in chemical genomics such as gene expression-based high-throughput screening (GE-HTS) and the Connectivity Map, we hypothesized that the gene expression signature resulting from treatment of primary AML with PTL could be used to search for similar signatures in publicly available gene expression profiles deposited into the Gene Expression Omnibus (GEO). We therefore devised a broad in silico screen of the GEO database using the PTL gene expression signature as a template and discovered 2 new agents, celastrol and 4-hydroxy-2-nonenal, that effectively eradicate AML at the bulk, progenitor, and stem cell level. These findings suggest the use of multicenter collections of high-throughput data to facilitate discovery of leukemia drugs and drug targets. PMID:18305216

Toward reliable biomarker signatures in the age of liquid biopsies - how to standardize the small RNA-Seq workflow

PubMed Central

Buschmann, Dominik; Haberberger, Anna; Kirchner, Benedikt; Spornraft, Melanie; Riedmaier, Irmgard; Schelling, Gustav; Pfaffl, Michael W.

2016-01-01

Small RNA-Seq has emerged as a powerful tool in transcriptomics, gene expression profiling and biomarker discovery. Sequencing cell-free nucleic acids, particularly microRNA (miRNA), from liquid biopsies additionally provides exciting possibilities for molecular diagnostics, and might help establish disease-specific biomarker signatures. The complexity of the small RNA-Seq workflow, however, bears challenges and biases that researchers need to be aware of in order to generate high-quality data. Rigorous standardization and extensive validation are required to guarantee reliability, reproducibility and comparability of research findings. Hypotheses based on flawed experimental conditions can be inconsistent and even misleading. Comparable to the well-established MIQE guidelines for qPCR experiments, this work aims at establishing guidelines for experimental design and pre-analytical sample processing, standardization of library preparation and sequencing reactions, as well as facilitating data analysis. We highlight bottlenecks in small RNA-Seq experiments, point out the importance of stringent quality control and validation, and provide a primer for differential expression analysis and biomarker discovery. Following our recommendations will encourage better sequencing practice, increase experimental transparency and lead to more reproducible small RNA-Seq results. This will ultimately enhance the validity of biomarker signatures, and allow reliable and robust clinical predictions. PMID:27317696

Characterization of a Genomic Signature of Pregnancy in the Breast

PubMed Central

Belitskaya-Lévy, Ilana; Zeleniuch-Jacquotte, Anne; Russo, Jose; Russo, Irma H.; Bordás, Pal; Åhman, Janet; Afanasyeva, Yelena; Johansson, Robert; Lenner, Per; Li, Xiaochun; de Cicco, Ricardo López; Peri, Suraj; Ross, Eric; Russo, Patricia A.; Santucci-Pereira, Julia; Sheriff, Fathima S.; Slifker, Michael; Hallmans, Göran; Toniolo, Paolo; Arslan, Alan A.

2012-01-01

The objective of the current study was to comprehensively compare the genomic profiles in the breast of parous and nulliparous postmenopausal women to identify genes that permanently change their expression following pregnancy. The study was designed as a two-phase approach. In the discovery phase, we compared breast genomic profiles of 37 parous with 18 nulliparous postmenopausal women. In the validation phase, confirmation of the genomic patterns observed in the discovery phase was sought in an independent set of 30 parous and 22 nulliparous postmenopausal women. RNA was hybridized to Affymetrix HG_U133 Plus 2.0 oligonucleotide arrays containing probes to 54,675 transcripts; scanned and the images analyzed using Affymetrix GCOS software. Surrogate variable analysis, logistic regression and significance analysis for microarrays were used to identify statistically significant differences in expression of genes. The False Discovery Rate (FDR) approach was used to control for multiple comparisons. We found that 208 genes (305 probe sets) were differentially expressed between parous and nulliparous women in both discovery and validation phases of the study at a FDR of 10% and with at least a 1.25-fold change. These genes are involved in regulation of transcription, centrosome organization, RNA splicing, cell cycle control, adhesion and differentiation. The results provide persuasive evidence that full-term pregnancy induces long-term genomic changes in the breast. The genomic signature of pregnancy could be used as an intermediate marker to assess potential chemopreventive interventions with hormones mimicking the effects of pregnancy for prevention of breast cancer. PMID:21622728

cudaMap: a GPU accelerated program for gene expression connectivity mapping.

PubMed

McArt, Darragh G; Bankhead, Peter; Dunne, Philip D; Salto-Tellez, Manuel; Hamilton, Peter; Zhang, Shu-Dong

2013-10-11

Modern cancer research often involves large datasets and the use of sophisticated statistical techniques. Together these add a heavy computational load to the analysis, which is often coupled with issues surrounding data accessibility. Connectivity mapping is an advanced bioinformatic and computational technique dedicated to therapeutics discovery and drug re-purposing around differential gene expression analysis. On a normal desktop PC, it is common for the connectivity mapping task with a single gene signature to take > 2h to complete using sscMap, a popular Java application that runs on standard CPUs (Central Processing Units). Here, we describe new software, cudaMap, which has been implemented using CUDA C/C++ to harness the computational power of NVIDIA GPUs (Graphics Processing Units) to greatly reduce processing times for connectivity mapping. cudaMap can identify candidate therapeutics from the same signature in just over thirty seconds when using an NVIDIA Tesla C2050 GPU. Results from the analysis of multiple gene signatures, which would previously have taken several days, can now be obtained in as little as 10 minutes, greatly facilitating candidate therapeutics discovery with high throughput. We are able to demonstrate dramatic speed differentials between GPU assisted performance and CPU executions as the computational load increases for high accuracy evaluation of statistical significance. Emerging 'omics' technologies are constantly increasing the volume of data and information to be processed in all areas of biomedical research. Embracing the multicore functionality of GPUs represents a major avenue of local accelerated computing. cudaMap will make a strong contribution in the discovery of candidate therapeutics by enabling speedy execution of heavy duty connectivity mapping tasks, which are increasingly required in modern cancer research. cudaMap is open source and can be freely downloaded from http://purl.oclc.org/NET/cudaMap.

Beyond the scope of Free-Wilson analysis: building interpretable QSAR models with machine learning algorithms.

PubMed

Chen, Hongming; Carlsson, Lars; Eriksson, Mats; Varkonyi, Peter; Norinder, Ulf; Nilsson, Ingemar

2013-06-24

A novel methodology was developed to build Free-Wilson like local QSAR models by combining R-group signatures and the SVM algorithm. Unlike Free-Wilson analysis this method is able to make predictions for compounds with R-groups not present in a training set. Eleven public data sets were chosen as test cases for comparing the performance of our new method with several other traditional modeling strategies, including Free-Wilson analysis. Our results show that the R-group signature SVM models achieve better prediction accuracy compared with Free-Wilson analysis in general. Moreover, the predictions of R-group signature models are also comparable to the models using ECFP6 fingerprints and signatures for the whole compound. Most importantly, R-group contributions to the SVM model can be obtained by calculating the gradient for R-group signatures. For most of the studied data sets, a significant correlation with that of a corresponding Free-Wilson analysis is shown. These results suggest that the R-group contribution can be used to interpret bioactivity data and highlight that the R-group signature based SVM modeling method is as interpretable as Free-Wilson analysis. Hence the signature SVM model can be a useful modeling tool for any drug discovery project.

Sulforaphane reduces hepatic glucose production and improves glucose control in patients with type 2 diabetes.

PubMed

Axelsson, Annika S; Tubbs, Emily; Mecham, Brig; Chacko, Shaji; Nenonen, Hannah A; Tang, Yunzhao; Fahey, Jed W; Derry, Jonathan M J; Wollheim, Claes B; Wierup, Nils; Haymond, Morey W; Friend, Stephen H; Mulder, Hindrik; Rosengren, Anders H

2017-06-14

A potentially useful approach for drug discovery is to connect gene expression profiles of disease-affected tissues ("disease signatures") to drug signatures, but it remains to be shown whether it can be used to identify clinically relevant treatment options. We analyzed coexpression networks and genetic data to identify a disease signature for type 2 diabetes in liver tissue. By interrogating a library of 3800 drug signatures, we identified sulforaphane as a compound that may reverse the disease signature. Sulforaphane suppressed glucose production from hepatic cells by nuclear translocation of nuclear factor erythroid 2-related factor 2 (NRF2) and decreased expression of key enzymes in gluconeogenesis. Moreover, sulforaphane reversed the disease signature in the livers from diabetic animals and attenuated exaggerated glucose production and glucose intolerance by a magnitude similar to that of metformin. Finally, sulforaphane, provided as concentrated broccoli sprout extract, reduced fasting blood glucose and glycated hemoglobin (HbA1c) in obese patients with dysregulated type 2 diabetes. Copyright © 2017 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.

Discovery and Characterization of Novel Signatures from the Ricinus communis L. (Castor Bean) Genome

DTIC Science & Technology

2006-11-01

mortar and pestle under liquid nitrogen, using Qiagen DNeasy Plant Maxi kits according to the manufacturer’s instructions, and quantified...Former Soviet Union India Iran Indonesia Israel Japan Jordan Malaya Pakistan Philippines Saudi Arabia Sri Lanka Syria Taiwan

Glycosyltransferase Gene Expression Profiles Classify Cancer Types and Propose Prognostic Subtypes

NASA Astrophysics Data System (ADS)

Ashkani, Jahanshah; Naidoo, Kevin J.

2016-05-01

Aberrant glycosylation in tumours stem from altered glycosyltransferase (GT) gene expression but can the expression profiles of these signature genes be used to classify cancer types and lead to cancer subtype discovery? The differential structural changes to cellular glycan structures are predominantly regulated by the expression patterns of GT genes and are a hallmark of neoplastic cell metamorphoses. We found that the expression of 210 GT genes taken from 1893 cancer patient samples in The Cancer Genome Atlas (TCGA) microarray data are able to classify six cancers; breast, ovarian, glioblastoma, kidney, colon and lung. The GT gene expression profiles are used to develop cancer classifiers and propose subtypes. The subclassification of breast cancer solid tumour samples illustrates the discovery of subgroups from GT genes that match well against basal-like and HER2-enriched subtypes and correlates to clinical, mutation and survival data. This cancer type glycosyltransferase gene signature finding provides foundational evidence for the centrality of glycosylation in cancer.

Gene signature critical to cancer phenotype as a paradigm for anti-cancer drug discovery

PubMed Central

Sampson, Erik R.; McMurray, Helene R.; Hassane, Duane C.; Newman, Laurel; Salzman, Peter; Jordan, Craig T.; Land, Hartmut

2013-01-01

Malignant cell transformation commonly results in the deregulation of thousands of cellular genes, an observation that suggests a complex biological process and an inherently challenging scenario for the development of effective cancer interventions. To better define the genes/pathways essential to regulating the malignant phenotype, we recently described a novel strategy based on the cooperative nature of carcinogenesis that focuses on genes synergistically deregulated in response to cooperating oncogenic mutations. These so-called “cooperation response genes” (CRGs) are highly enriched for genes critical for the cancer phenotype, thereby suggesting their causal role in the malignant state. Here we show that CRGs play an essential role in drug-mediated anti-cancer activity and that anti-cancer agents can be identified through their ability to antagonize the CRG expression profile. These findings provide proof-of-concept for the use of the CRG signature as a novel means of drug discovery with relevance to underlying anti-cancer drug mechanisms. PMID:22964631

An Iterative Time Windowed Signature Algorithm for Time Dependent Transcription Module Discovery

PubMed Central

Meng, Jia; Gao, Shou-Jiang; Huang, Yufei

2010-01-01

An algorithm for the discovery of time varying modules using genome-wide expression data is present here. When applied to large-scale time serious data, our method is designed to discover not only the transcription modules but also their timing information, which is rarely annotated by the existing approaches. Rather than assuming commonly defined time constant transcription modules, a module is depicted as a set of genes that are co-regulated during a specific period of time, i.e., a time dependent transcription module (TDTM). A rigorous mathematical definition of TDTM is provided, which is serve as an objective function for retrieving modules. Based on the definition, an effective signature algorithm is proposed that iteratively searches the transcription modules from the time series data. The proposed method was tested on the simulated systems and applied to the human time series microarray data during Kaposi's sarcoma-associated herpesvirus (KSHV) infection. The result has been verified by Expression Analysis Systematic Explorer. PMID:21552463

Literacy Course Priorities and Signature Aspects of Nine Elementary Initial Licensure Programs

ERIC Educational Resources Information Center

Lenski, Susan; Ganske, Kathy; Chambers, Sandy; Wold, Linda; Dobler, Elizabeth; Grisham, Dana L.; Scales, Roya; Smetana, Linda; Wolsey, Thomas Devere; Yoder, Karen K.; Young, Janet

2013-01-01

The purpose of this article is to describe the first part of a three-phase study to learn what makes an effective elementary literacy initial licensure program. The first step was to identify how nine programs prioritized research-based literacy practices and to identify each program's unique features, which we called "signature aspects." Findings…

Gene Expression Signatures Based on Variability can Robustly Predict Tumor Progression and Prognosis

PubMed Central

Dinalankara, Wikum; Bravo, Héctor Corrada

2015-01-01

Gene expression signatures are commonly used to create cancer prognosis and diagnosis methods, yet only a small number of them are successfully deployed in the clinic since many fail to replicate performance on subsequent validation. A primary reason for this lack of reproducibility is the fact that these signatures attempt to model the highly variable and unstable genomic behavior of cancer. Our group recently introduced gene expression anti-profiles as a robust methodology to derive gene expression signatures based on the observation that while gene expression measurements are highly heterogeneous across tumors of a specific cancer type relative to the normal tissue, their degree of deviation from normal tissue expression in specific genes involved in tissue differentiation is a stable tumor mark that is reproducible across experiments and cancer types. Here we show that constructing gene expression signatures based on variability and the anti-profile approach yields classifiers capable of successfully distinguishing benign growths from cancerous growths based on deviation from normal expression. We then show that this same approach generates stable and reproducible signatures that predict probability of relapse and survival based on tumor gene expression. These results suggest that using the anti-profile framework for the discovery of genomic signatures is an avenue leading to the development of reproducible signatures suitable for adoption in clinical settings. PMID:26078586

Systematic CpT (ApG) Depletion and CpG Excess Are Unique Genomic Signatures of Large DNA Viruses Infecting Invertebrates

PubMed Central

Upadhyay, Mohita; Sharma, Neha; Vivekanandan, Perumal

2014-01-01

Differences in the relative abundance of dinucleotides, if any may provide important clues on host-driven evolution of viruses. We studied dinucleotide frequencies of large DNA viruses infecting vertebrates (n = 105; viruses infecting mammals = 99; viruses infecting aves = 6; viruses infecting reptiles = 1) and invertebrates (n = 88; viruses infecting insects = 84; viruses infecting crustaceans = 4). We have identified systematic depletion of CpT(ApG) dinucleotides and over-representation of CpG dinucleotides as the unique genomic signature of large DNA viruses infecting invertebrates. Detailed investigation of this unique genomic signature suggests the existence of invertebrate host-induced pressures specifically targeting CpT(ApG) and CpG dinucleotides. The depletion of CpT dinucleotides among large DNA viruses infecting invertebrates is at least in part, explained by non-canonical DNA methylation by the infected host. Our findings highlight the role of invertebrate host-related factors in shaping virus evolution and they also provide the necessary framework for future studies on evolution, epigenetics and molecular biology of viruses infecting this group of hosts. PMID:25369195

12-Chemokine Gene Signature Identifies Lymph Node-like Structures in Melanoma: Potential for Patient Selection for Immunotherapy?

NASA Astrophysics Data System (ADS)

Messina, Jane L.; Fenstermacher, David A.; Eschrich, Steven; Qu, Xiaotao; Berglund, Anders E.; Lloyd, Mark C.; Schell, Michael J.; Sondak, Vernon K.; Weber, Jeffrey S.; Mulé, James J.

2012-10-01

We have interrogated a 12-chemokine gene expression signature (GES) on genomic arrays of 14,492 distinct solid tumors and show broad distribution across different histologies. We hypothesized that this 12-chemokine GES might accurately predict a unique intratumoral immune reaction in stage IV (non-locoregional) melanoma metastases. The 12-chemokine GES predicted the presence of unique, lymph node-like structures, containing CD20+ B cell follicles with prominent areas of CD3+ T cells (both CD4+ and CD8+ subsets). CD86+, but not FoxP3+, cells were present within these unique structures as well. The direct correlation between the 12-chemokine GES score and the presence of unique, lymph nodal structures was also associated with better overall survival of the subset of melanoma patients. The use of this novel 12-chemokine GES may reveal basic information on in situ mechanisms of the anti-tumor immune response, potentially leading to improvements in the identification and selection of melanoma patients most suitable for immunotherapy.

Connection Map for Compounds (CMC): A Server for Combinatorial Drug Toxicity and Efficacy Analysis.

PubMed

Liu, Lei; Tsompana, Maria; Wang, Yong; Wu, Dingfeng; Zhu, Lixin; Zhu, Ruixin

2016-09-26

Drug discovery and development is a costly and time-consuming process with a high risk for failure resulting primarily from a drug's associated clinical safety and efficacy potential. Identifying and eliminating inapt candidate drugs as early as possible is an effective way for reducing unnecessary costs, but limited analytical tools are currently available for this purpose. Recent growth in the area of toxicogenomics and pharmacogenomics has provided with a vast amount of drug expression microarray data. Web servers such as CMap and LTMap have used this information to evaluate drug toxicity and mechanisms of action independently; however, their wider applicability has been limited by the lack of a combinatorial drug-safety type of analysis. Using available genome-wide drug transcriptional expression profiles, we developed the first web server for combinatorial evaluation of toxicity and efficacy of candidate drugs named "Connection Map for Compounds" (CMC). Using CMC, researchers can initially compare their query drug gene signatures with prebuilt gene profiles generated from two large-scale toxicogenomics databases, and subsequently perform a drug efficacy analysis for identification of known mechanisms of drug action or generation of new predictions. CMC provides a novel approach for drug repositioning and early evaluation in drug discovery with its unique combination of toxicity and efficacy analyses, expansibility of data and algorithms, and customization of reference gene profiles. CMC can be freely accessed at http://cadd.tongji.edu.cn/webserver/CMCbp.jsp .

Searching for the noninvasive biomarker Holy Grail: Are urine proteomics the answer?

USDA-ARS?s Scientific Manuscript database

Recently, biobehavioral nursing scientists have focused their attention on the search for biomarkers or biological signatures to identify patients at risk for various health problems and poor disease outcomes. In response to the national impetus for biomarker discovery, the measurement of biological...

A modern ionotropic glutamate receptor with a K(+) selectivity signature sequence.

PubMed

Janovjak, H; Sandoz, G; Isacoff, E Y

2011-01-01

Glutamate is the major excitatory neurotransmitter in the mammalian central nervous system and gates non-selective cation channels. The origins of glutamate receptors are not well understood as they differ structurally and functionally from simple bacterial ligand-gated ion channels. Here we report the discovery of an ionotropic glutamate receptor that combines the typical eukaryotic domain architecture with the 'TXVGYG' signature sequence of the selectivity filter found in K(+) channels. This receptor exhibits functional properties intermediate between bacterial and eukaryotic glutamate-gated ion channels, suggesting a link in the evolution of ionotropic glutamate receptors.

Raman spectral signatures as conformational probes of gas phase flexible molecules

NASA Astrophysics Data System (ADS)

Golan, Amir; Mayorkas, Nitzan; Rosenwaks, Salman; Bar, Ilana

2009-07-01

A novel application of ionization-loss stimulated Raman spectroscopy (ILSRS) for monitoring the spectral features of four conformers of a gas phase flexible molecule is reported. The Raman spectral signatures of four conformers of 2-phenylethylamine are well matched by the results of density functional theory calculations, showing bands uniquely identifying the structures. The measurement of spectral signatures by ILSRS in an extended spectral range, with a conventional laser source, is instrumental in facilitating the unraveling of intra- and intermolecular interactions that are significant in biological structure and activity.

Detection of Ionospheric Alfven Resonator Signatures in the Equatorial Ionosphere

NASA Technical Reports Server (NTRS)

Simoes, Fernando; Klenzing, Jeffrey; Ivanov, Stoyan; Pfaff, Robert; Freudenreich, Henry; Bilitza, Dieter; Rowland, Douglas; Bromund, Kenneth; Liebrecht, Maria Carmen; Martin, Steven;

The Human Airway Epithelial Basal Cell Transcriptome

PubMed Central

Wang, Rui; Zwick, Rachel K.; Ferris, Barbara; Witover, Bradley; Salit, Jacqueline; Crystal, Ronald G.

2011-01-01

Background The human airway epithelium consists of 4 major cell types: ciliated, secretory, columnar and basal cells. During natural turnover and in response to injury, the airway basal cells function as stem/progenitor cells for the other airway cell types. The objective of this study is to better understand human airway epithelial basal cell biology by defining the gene expression signature of this cell population. Methodology/Principal Findings Bronchial brushing was used to obtain airway epithelium from healthy nonsmokers. Microarrays were used to assess the transcriptome of basal cells purified from the airway epithelium in comparison to the transcriptome of the differentiated airway epithelium. This analysis identified the “human airway basal cell signature” as 1,161 unique genes with >5-fold higher expression level in basal cells compared to differentiated epithelium. The basal cell signature was suppressed when the basal cells differentiated into a ciliated airway epithelium in vitro. The basal cell signature displayed overlap with genes expressed in basal-like cells from other human tissues and with that of murine airway basal cells. Consistent with self-modulation as well as signaling to other airway cell types, the human airway basal cell signature was characterized by genes encoding extracellular matrix components, growth factors and growth factor receptors, including genes related to the EGF and VEGF pathways. Interestingly, while the basal cell signature overlaps that of basal-like cells of other organs, the human airway basal cell signature has features not previously associated with this cell type, including a unique pattern of genes encoding extracellular matrix components, G protein-coupled receptors, neuroactive ligands and receptors, and ion channels. Conclusion/Significance The human airway epithelial basal cell signature identified in the present study provides novel insights into the molecular phenotype and biology of the stem/progenitor cells of the human airway epithelium. PMID:21572528

Halobacterium salinarum NRC-1 PeptideAtlas: strategies for targeted proteomics

PubMed Central

Van, Phu T.; Schmid, Amy K.; King, Nichole L.; Kaur, Amardeep; Pan, Min; Whitehead, Kenia; Koide, Tie; Facciotti, Marc T.; Goo, Young-Ah; Deutsch, Eric W.; Reiss, David J.; Mallick, Parag; Baliga, Nitin S.

2009-01-01

The relatively small numbers of proteins and fewer possible posttranslational modifications in microbes provides a unique opportunity to comprehensively characterize their dynamic proteomes. We have constructed a Peptide Atlas (PA) for 62.7% of the predicted proteome of the extremely halophilic archaeon Halobacterium salinarum NRC-1 by compiling approximately 636,000 tandem mass spectra from 497 mass spectrometry runs in 88 experiments. Analysis of the PA with respect to biophysical properties of constituent peptides, functional properties of parent proteins of detected peptides, and performance of different mass spectrometry approaches has helped highlight plausible strategies for improving proteome coverage and selecting signature peptides for targeted proteomics. Notably, discovery of a significant correlation between absolute abundances of mRNAs and proteins has helped identify low abundance of proteins as the major limitation in peptide detection. Furthermore we have discovered that iTRAQ labeling for quantitative proteomic analysis introduces a significant bias in peptide detection by mass spectrometry. Therefore, despite identifying at least one proteotypic peptide for almost all proteins in the PA, a context-dependent selection of proteotypic peptides appears to be the most effective approach for targeted proteomics. PMID:18652504

"Structure and dynamics in complex chemical systems: Gaining new insights through recent advances in time-resolved spectroscopies.” ACS Division of Physical Chemistry Symposium presented at the Fall National ACS Meeting in Boston, MA, August 2015

DOE Office of Scientific and Technical Information (OSTI.GOV)

Crawford, Daniel

8-Session Symposium on STRUCTURE AND DYNAMICS IN COMPLEX CHEMICAL SYSTEMS: GAINING NEW INSIGHTS THROUGH RECENT ADVANCES IN TIME-RESOLVED SPECTROSCOPIES. The intricacy of most chemical, biochemical, and material processes and their applications are underscored by the complex nature of the environments in which they occur. Substantial challenges for building a global understanding of a heterogeneous system include (1) identifying unique signatures associated with specific structural motifs within the heterogeneous distribution, and (2) resolving the significance of each of multiple time scales involved in both small- and large-scale nuclear reorganization. This symposium focuses on the progress in our understanding of dynamics inmore » complex systems driven by recent innovations in time-resolved spectroscopies and theoretical developments. Such advancement is critical for driving discovery at the molecular level facilitating new applications. Broad areas of interest include: Structural relaxation and the impact of structure on dynamics in liquids, interfaces, biochemical systems, materials, and other heterogeneous environments.« less

The discovery and measurements of a Higgs boson.

PubMed

Gianotti, F; Virdee, T S

2015-01-13

In July 2012, the ATLAS and CMS collaborations at CERN's Large Hadron Collider announced the discovery of a Higgs-like boson, a new heavy particle at a mass more than 130 times the mass of a proton. Since then, further data have revealed its properties to be strikingly similar to those of the Standard Model Higgs boson, a particle expected from the mechanism introduced almost 50 years ago by six theoreticians including British physicists Peter Higgs from Edinburgh University and Tom Kibble from Imperial College London. The discovery is the culmination of a truly remarkable scientific journey and undoubtedly the most significant scientific discovery of the twenty-first century so far. Its experimental confirmation turned out to be a monumental task requiring the creation of an accelerator and experiments of unprecedented capability and complexity, designed to discern the signatures that correspond to the Higgs boson. Thousands of scientists and engineers, in each of the ATLAS and CMS teams, came together from all four corners of the world to make this massive discovery possible.

What can He II 304 Å tell us about transient seismic emission from solar flares?

NASA Astrophysics Data System (ADS)

Lindsey, C.; Donea, A. C.

2017-10-01

After neary 20 years since their discovery by Kosovichev and Zharkova, the mechanics of the release of seismic transients into the solar interior from some flares remain a mystery. Seismically emissive flares invariably show the signatures of intense chromosphere heating consistent with pressure variations sufficient to drive seismic transients commensurate with helioseismic observations-under certain conditions. Magnetic observations show the signatures of apparent magnetic changes, suggesting Lorentz-force transients that could likewise drive seismic transients-similarly subject to certain conditions. But, the diagnostic signatures of both of these prospective drivers are apparent over vast regions from which no significant seismic emission emanates. What distinguishes the source regions of transient seismic emission from the much vaster regions that show the signatures of both transient heating and magnetic variations but are acoustically unproductive? Observations of acoustically active flares in He II 304 Å by the Atomospheric Imaging Assembly (AIA) aboard the Solar Dynamics Observatory (SDO) offer a promising new resource with which to address this question.

The genetic architecture of normal variation in human pigmentation: an evolutionary perspective and model.

PubMed

McEvoy, Brian; Beleza, Sandra; Shriver, Mark D

2006-10-15

Skin pigmentation varies substantially across human populations in a manner largely coincident with ultraviolet radiation intensity. This observation suggests that natural selection in response to sunlight is a major force in accounting for pigmentation variability. We review recent progress in identifying the genes controlling this variation with a particular focus on the trait's evolutionary past and the potential role of testing for signatures of selection in aiding the discovery of functionally important genes. We have analyzed SNP data from the International HapMap project in 77 pigmentation candidate genes for such signatures. On the basis of these results and other similar work, we provide a tentative three-population model (West Africa, East Asia and North Europe) of the evolutionary-genetic architecture of human pigmentation. These results suggest a complex evolutionary history, with selection acting on different gene targets at different times and places in the human past. Some candidate genes may have been selected in the ancestral human population, others in the 'out of Africa' proto European-Asian population, whereas most appear to have selectively evolved solely in either Europeans or East Asians separately despite the pigmentation similarities between these two populations. Selection signatures can provide important clues to aid gene discovery. However, these should be viewed as complements, rather than replacements of, functional studies including linkage and association analyses, which can directly refine our understanding of the trait.

A data-driven, knowledge-based approach to biomarker discovery: application to circulating microRNA markers of colorectal cancer prognosis.

PubMed

Vafaee, Fatemeh; Diakos, Connie; Kirschner, Michaela B; Reid, Glen; Michael, Michael Z; Horvath, Lisa G; Alinejad-Rokny, Hamid; Cheng, Zhangkai Jason; Kuncic, Zdenka; Clarke, Stephen

2018-01-01

Recent advances in high-throughput technologies have provided an unprecedented opportunity to identify molecular markers of disease processes. This plethora of complex-omics data has simultaneously complicated the problem of extracting meaningful molecular signatures and opened up new opportunities for more sophisticated integrative and holistic approaches. In this era, effective integration of data-driven and knowledge-based approaches for biomarker identification has been recognised as key to improving the identification of high-performance biomarkers, and necessary for translational applications. Here, we have evaluated the role of circulating microRNA as a means of predicting the prognosis of patients with colorectal cancer, which is the second leading cause of cancer-related death worldwide. We have developed a multi-objective optimisation method that effectively integrates a data-driven approach with the knowledge obtained from the microRNA-mediated regulatory network to identify robust plasma microRNA signatures which are reliable in terms of predictive power as well as functional relevance. The proposed multi-objective framework has the capacity to adjust for conflicting biomarker objectives and to incorporate heterogeneous information facilitating systems approaches to biomarker discovery. We have found a prognostic signature of colorectal cancer comprising 11 circulating microRNAs. The identified signature predicts the patients' survival outcome and targets pathways underlying colorectal cancer progression. The altered expression of the identified microRNAs was confirmed in an independent public data set of plasma samples of patients in early stage vs advanced colorectal cancer. Furthermore, the generality of the proposed method was demonstrated across three publicly available miRNA data sets associated with biomarker studies in other diseases.

Metabolic Signature of Electrosurgical Liver Dissection

PubMed Central

von Schönfels, Witigo; von Kampen, Oliver; Patsenker, Eleonora; Stickel, Felix; Schniewind, Bodo; Hinz, Sebastian; Ahrens, Markus; Balschun, Katharina; Egberts, Jan-Hendrik; Richter, Klaus; Landrock, Andreas; Sipos, Bence; Will, Olga; Huebbe, Patrizia; Schreiber, Stefan; Nothnagel, Michael; Röcken, Christoph; Rimbach, Gerald; Becker, Thomas

2013-01-01

Background and Aims High frequency electrosurgery has a key role in the broadening application of liver surgery. Its molecular signature, i.e. the metabolites evolving from electrocauterization which may inhibit hepatic wound healing, have not been systematically studied. Methods Human liver samples were thus obtained during surgery before and after electrosurgical dissection and subjected to a two-stage metabolomic screening experiment (discovery sample: N = 18, replication sample: N = 20) using gas chromatography/mass spectrometry. Results In a set of 208 chemically defined metabolites, electrosurgical dissection lead to a distinct metabolic signature resulting in a separation in the first two dimensions of a principal components analysis. Six metabolites including glycolic acid, azelaic acid, 2-n-pentylfuran, dihydroactinidiolide, 2-butenal and n-pentanal were consistently increased after electrosurgery meeting the discovery (p<2.0×10−4) and the replication thresholds (p<3.5×10−3). Azelaic acid, a lipid peroxidation product from the fragmentation of abundant sn-2 linoleoyl residues, was most abundant and increased 8.1-fold after electrosurgical liver dissection (preplication = 1.6×10−4). The corresponding phospholipid hexadecyl azelaoyl glycerophosphocholine inhibited wound healing and tissue remodelling in scratch- and proliferation assays of hepatic stellate cells and cholangiocytes, and caused apoptosis dose-dependently in vitro, which may explain in part the tissue damage due to electrosurgery. Conclusion Hepatic electrosurgery generates a metabolic signature with characteristic lipid peroxidation products. Among these, azelaic acid shows a dose-dependent toxicity in liver cells and inhibits wound healing. These observations potentially pave the way for pharmacological intervention prior liver surgery to modify the metabolic response and prevent postoperative complications. PMID:24058442

A Novel mRNA Level Subtraction Method for Quick Identification of Target-Orientated Uniquely Expressed Genes Between Peanut Immature Pod and Leaf

PubMed Central

2010-01-01

Subtraction technique has been broadly applied for target gene discovery. However, most current protocols apply relative differential subtraction and result in great amount clone mixtures of unique and differentially expressed genes. This makes it more difficult to identify unique or target-orientated expressed genes. In this study, we developed a novel method for subtraction at mRNA level by integrating magnetic particle technology into driver preparation and tester–driver hybridization to facilitate uniquely expressed gene discovery between peanut immature pod and leaf through a single round subtraction. The resulting target clones were further validated through polymerase chain reaction screening using peanut immature pod and leaf cDNA libraries as templates. This study has resulted in identifying several genes expressed uniquely in immature peanut pod. These target genes can be used for future peanut functional genome and genetic engineering research. PMID:21406066

A four-gene signature predicts survival in clear-cell renal-cell carcinoma.

PubMed

Dai, Jun; Lu, Yuchao; Wang, Jinyu; Yang, Lili; Han, Yingyan; Wang, Ying; Yan, Dan; Ruan, Qiurong; Wang, Shaogang

2016-12-13

Clear-cell renal-cell carcinoma (ccRCC) is the most common pathological subtype of renal cell carcinoma (RCC), accounting for about 80% of RCC. In order to find potential prognostic biomarkers in ccRCC, we presented a four-gene signature to evaluate the prognosis of ccRCC. SurvExpress and immunohistochemical (IHC) staining of tissue microarrays were used to analyze the association between the four genes and the prognosis of ccRCC. Data from TCGA dataset revealed a prognostic prompt function of the four genes (PTEN, PIK3C2A, ITPA and BCL3). Further discovery suggested that the four-gene signature predicted survival better than any of the four genes alone. Moreover, IHC staining demonstrated a consistent result with TCGA, indicating that the signature was an independent prognostic factor of survival in ccRCC. Univariate and multivariate Cox proportional hazard regression analysis were conducted to verify the association of clinicopathological variables and the four genes' expression levels with survival. The results further testified that the risk (four-gene signature) was an independent prognostic factors of both Overall Survival (OS) and Disease-free Survival (DFS) (P<0.05). In conclusion, the four-gene signature was correlated with the survival of ccRCC, and therefore, may help to provide significant clinical implications for predicting the prognosis of patients.

Blind Quantum Signature with Blind Quantum Computation

NASA Astrophysics Data System (ADS)

Li, Wei; Shi, Ronghua; Guo, Ying

2017-04-01

Blind quantum computation allows a client without quantum abilities to interact with a quantum server to perform a unconditional secure computing protocol, while protecting client's privacy. Motivated by confidentiality of blind quantum computation, a blind quantum signature scheme is designed with laconic structure. Different from the traditional signature schemes, the signing and verifying operations are performed through measurement-based quantum computation. Inputs of blind quantum computation are securely controlled with multi-qubit entangled states. The unique signature of the transmitted message is generated by the signer without leaking information in imperfect channels. Whereas, the receiver can verify the validity of the signature using the quantum matching algorithm. The security is guaranteed by entanglement of quantum system for blind quantum computation. It provides a potential practical application for e-commerce in the cloud computing and first-generation quantum computation.

Chemodiversity of dissolved organic matter in the Amazon Basin

NASA Astrophysics Data System (ADS)

Gonsior, Michael; Valle, Juliana; Schmitt-Kopplin, Philippe; Hertkorn, Norbert; Bastviken, David; Luek, Jenna; Harir, Mourad; Bastos, Wanderley; Enrich-Prast, Alex

2016-07-01

Regions in the Amazon Basin have been associated with specific biogeochemical processes, but a detailed chemical classification of the abundant and ubiquitous dissolved organic matter (DOM), beyond specific indicator compounds and bulk measurements, has not yet been established. We sampled water from different locations in the Negro, Madeira/Jamari and Tapajós River areas to characterize the molecular DOM composition and distribution. Ultrahigh-resolution Fourier transform ion cyclotron resonance mass spectrometry (FT-ICR-MS) combined with excitation emission matrix (EEM) fluorescence spectroscopy and parallel factor analysis (PARAFAC) revealed a large proportion of ubiquitous DOM but also unique area-specific molecular signatures. Unique to the DOM of the Rio Negro area was the large abundance of high molecular weight, diverse hydrogen-deficient and highly oxidized molecular ions deviating from known lignin or tannin compositions, indicating substantial oxidative processing of these ultimately plant-derived polyphenols indicative of these black waters. In contrast, unique signatures in the Madeira/Jamari area were defined by presumably labile sulfur- and nitrogen-containing molecules in this white water river system. Waters from the Tapajós main stem did not show any substantial unique molecular signatures relative to those present in the Rio Madeira and Rio Negro, which implied a lower organic molecular complexity in this clear water tributary, even after mixing with the main stem of the Amazon River. Beside ubiquitous DOM at average H / C and O / C elemental ratios, a distinct and significant unique DOM pool prevailed in the black, white and clear water areas that were also highly correlated with EEM-PARAFAC components and define the frameworks for primary production and other aspects of aquatic life.

Textural signatures for wetland vegetation

NASA Technical Reports Server (NTRS)

Whitman, R. I.; Marcellus, K. L.

1973-01-01

This investigation indicates that unique textural signatures do exist for specific wetland communities at certain times in the growing season. When photographs with the proper resolution are obtained, the textural features can identify the spectral features of the vegetation community seen with lower resolution mapping data. The development of a matrix of optimum textural signatures is the goal of this research. Seasonal variations of spectral and textural features are particularly important when performing a vegetations analysis of fresh water marshes. This matrix will aid in flight planning, since expected seasonal variations and resolution requirements can be established prior to a given flight mission.

Nitrogen isotopic signatures in the Acapulco meteorite

NASA Technical Reports Server (NTRS)

Sturgeon, G.; Marti, K.

1991-01-01

N isotopic abundances are reported for a bulk sample of the unique meteorite Acapulco. Although the mineral chemistry indicates a high degree of recrystallization under redox conditions between those of H and E chondrites (Palme et al., 1981), the presence of two distinct N isotopic signatures shows that the carriers of these N components were not equilibrated. In stepwise pyrolysis, the larger (65 percent) N component is released mostly below 1000 C and reveals a signature of delta(N-15) = 8.9 + or - 1.2 per mil, which is within the range observed in chondrites. A second 'light' component appears above 1000 C and has a signature of delta(N-15) less than or equal to -110.5 + or - 4.0 per mil (uncorrected for spallation N-15).

GeneSigDB—a curated database of gene expression signatures

PubMed Central

Culhane, Aedín C.; Schwarzl, Thomas; Sultana, Razvan; Picard, Kermshlise C.; Picard, Shaita C.; Lu, Tim H.; Franklin, Katherine R.; French, Simon J.; Papenhausen, Gerald; Correll, Mick; Quackenbush, John

2010-01-01

The primary objective of most gene expression studies is the identification of one or more gene signatures; lists of genes whose transcriptional levels are uniquely associated with a specific biological phenotype. Whilst thousands of experimentally derived gene signatures are published, their potential value to the community is limited by their computational inaccessibility. Gene signatures are embedded in published article figures, tables or in supplementary materials, and are frequently presented using non-standard gene or probeset nomenclature. We present GeneSigDB (http://compbio.dfci.harvard.edu/genesigdb) a manually curated database of gene expression signatures. GeneSigDB release 1.0 focuses on cancer and stem cells gene signatures and was constructed from more than 850 publications from which we manually transcribed 575 gene signatures. Most gene signatures (n = 560) were successfully mapped to the genome to extract standardized lists of EnsEMBL gene identifiers. GeneSigDB provides the original gene signature, the standardized gene list and a fully traceable gene mapping history for each gene from the original transcribed data table through to the standardized list of genes. The GeneSigDB web portal is easy to search, allows users to compare their own gene list to those in the database, and download gene signatures in most common gene identifier formats. PMID:19934259

Algorithms on Flag Manifolds for Knowledge Discovery in N-way Arrays

DTIC Science & Technology

2015-11-20

that three of 18 subjects will become symptomatic after only 8 hours. Host pathway analysis of a human endotoxin gene expression data set revealed a 14...pathway analysis of a human endotoxin gene expression data set revealed a 14 pathway signature that identified symptomatic subjects within 2-3 hours post

Three plasma metabolite signatures for diagnosing high altitude pulmonary edema

NASA Astrophysics Data System (ADS)

Guo, Li; Tan, Guangguo; Liu, Ping; Li, Huijie; Tang, Lulu; Huang, Lan; Ren, Qian

2015-10-01

High-altitude pulmonary edema (HAPE) is a potentially fatal condition, occurring at altitudes greater than 3,000 m and affecting rapidly ascending, non-acclimatized healthy individuals. However, the lack of biomarkers for this disease still constitutes a bottleneck in the clinical diagnosis. Here, ultra-high performance liquid chromatography coupled with Q-TOF mass spectrometry was applied to study plasma metabolite profiling from 57 HAPE and 57 control subjects. 14 differential plasma metabolites responsible for the discrimination between the two groups from discovery set (35 HAPE subjects and 35 healthy controls) were identified. Furthermore, 3 of the 14 metabolites (C8-ceramide, sphingosine and glutamine) were selected as candidate diagnostic biomarkers for HAPE using metabolic pathway impact analysis. The feasibility of using the combination of these three biomarkers for HAPE was evaluated, where the area under the receiver operating characteristic curve (AUC) was 0.981 and 0.942 in the discovery set and the validation set (22 HAPE subjects and 22 healthy controls), respectively. Taken together, these results suggested that this composite plasma metabolite signature may be used in HAPE diagnosis, especially after further investigation and verification with larger samples.

Discovery of a z = 0.65 post-starburst BAL quasar in the DES supernova fields

DOE PAGES

Mudd, Dale; Martini, Paul; Tie, Suk Sien; ...

2017-03-23

In this paper, we present the discovery of a z = 0.65 low-ionization broad absorption line (LoBAL) quasar in a post-starburst galaxy in data from the Dark Energy Survey (DES) and spectroscopy from the Australian Dark Energy Survey (OzDES). LoBAL quasars are a minority of all BALs, and rarer still is that this object also exhibits broad Fe ii (an FeLoBAL) and Balmer absorption. This is the first BAL quasar that has signatures of recently truncated star formation, which we estimate ended about 40 Myr ago. The characteristic signatures of an FeLoBAL require high column densities, which could be explainedmore » by the emergence of a young quasar from an early, dust-enshrouded phase, or by clouds compressed by a blast wave. Finally, the age of the starburst component is comparable to estimates of the lifetime of quasars, so if we assume the quasar activity is related to the truncation of the star formation, this object is better explained by the blast wave scenario.« less

Discovery of a z = 0.65 post-starburst BAL quasar in the DES supernova fields

DOE Office of Scientific and Technical Information (OSTI.GOV)

Mudd, Dale; Martini, Paul; Tie, Suk Sien

We present the discovery of a z=0.65 low-ionization broad absorption line (LoBAL) quasar in a post-starburst galaxy in data from the Dark Energy Survey (DES) and spectroscopy from the Australian Dark Energy Survey (OzDES). LoBAL quasars are a minority of all BALs, and rarer still is that this object also exhibits broad FeII (an FeLoBAL) and Balmer absorption. This is the first BAL quasar that has signatures of recently truncated star formation, which we estimate ended about 40 Myr ago. The characteristic signatures of an FeLoBAL require high column densities, which could be explained by the emergence of a youngmore » quasar from an early, dust-enshrouded phase, or by clouds compressed by a blast wave. The age of the starburst component is comparable to estimates of the lifetime of quasars, so if we assume the quasar activity is related to the truncation of the star formation, this object is better explained by the blast wave scenario.« less

Discovery of a z = 0.65 post-starburst BAL quasar in the DES supernova fields

DOE Office of Scientific and Technical Information (OSTI.GOV)

Mudd, Dale; Martini, Paul; Tie, Suk Sien

In this paper, we present the discovery of a z = 0.65 low-ionization broad absorption line (LoBAL) quasar in a post-starburst galaxy in data from the Dark Energy Survey (DES) and spectroscopy from the Australian Dark Energy Survey (OzDES). LoBAL quasars are a minority of all BALs, and rarer still is that this object also exhibits broad Fe ii (an FeLoBAL) and Balmer absorption. This is the first BAL quasar that has signatures of recently truncated star formation, which we estimate ended about 40 Myr ago. The characteristic signatures of an FeLoBAL require high column densities, which could be explainedmore » by the emergence of a young quasar from an early, dust-enshrouded phase, or by clouds compressed by a blast wave. Finally, the age of the starburst component is comparable to estimates of the lifetime of quasars, so if we assume the quasar activity is related to the truncation of the star formation, this object is better explained by the blast wave scenario.« less

Texture analysis of radiometric signatures of new sea ice forming in Arctic leads

NASA Technical Reports Server (NTRS)

Eppler, Duane T.; Farmer, L. Dennis

1991-01-01

Analysis of 33.6-GHz, high-resolution, passive microwave images suggests that new sea ice accumulating in open leads is characterized by a unique textural signature which can be used to discriminate new ice forming in this environment from adjacent surfaces of similar radiometric temperature. Ten training areas were selected from the data set, three of which consisted entirely of first-year ice, four entirely of multilayer ice, and three of new ice in open leads in the process of freezing. A simple gradient operator was used to characterize the radiometric texture in each training region in terms of the degree to which radiometric gradients are oriented. New ice in leads has a sufficiently high proportion of well-oriented features to distinguish it uniquely from first-year ice and multiyear ice. The predominance of well-oriented features probably reflects physical processes by which new ice accumulates in open leads. Banded structures, which are evident in aerial photographs of new ice, apparently give rise to the radiometric signature observed, in which the trend of brightness temperature gradients is aligned parallel to lead trends. First-year ice and multiyear ice, which have been subjected to a more random growth and process history, lack this banded structure and therefore are characterized by signatures in which well-aligned elements are less dominant.

Used Fuel Cask Identification through Neutron Profile

DOE Office of Scientific and Technical Information (OSTI.GOV)

Rauch, Eric Benton

2015-11-20

Currently, most spent fuel is stored near reactors. An interim consolidated fuel storage facility would receive fuel from multiple sites and store it in casks on site for decades. For successful operation of such a facility there is need for a way to restore continuity of knowledge if lost as well as a method that will indicate state of fuel inside the cask. Used nuclear fuel is identifiable by its radiation emission, both gamma and neutron. Neutron emission from fission products, multiplication from remaining fissile material, and the unique distribution of both in each cask produce a unique neutron signature.more » If two signatures taken at different times do not match, either changes within the fuel content or misidentification of a cask occurred. It was found that identification of cask loadings works well through the profile of emitted neutrons in simulated real casks. Even casks with similar overall neutron emission or average counts around the circumference can be distinguished from each other by analyzing the profile. In conclusion, (1) identification of unaltered casks through neutron signature profile is viable; (2) collecting the profile provides insight to the condition and intactness of the fuel stored inside the cask; and (3) the signature profile is stable over time.« less

Resonant ultrasound spectroscopy

DOEpatents

Migliori, Albert

1991-01-01

A resonant ultrasound spectroscopy method provides a unique characterization of an object for use in distinguishing similar objects having physical differences greater than a predetermined tolerance. A resonant response spectrum is obtained for a reference object by placing excitation and detection transducers at any accessible location on the object. The spectrum is analyzed to determine the number of resonant response peaks in a predetermined frequency interval. The distribution of the resonance frequencies is then characterized in a manner effective to form a unique signature of the object. In one characterization, a small frequency interval is defined and stepped though the spectrum frequency range. Subsequent objects are similarly characterized where the characterizations serve as signatures effective to distinguish objects that differ from the reference object by more than the predetermined tolerance.

Proposal for chiral-boson search at LHC via their unique new signature

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chizhov, M. V.; Bednyakov, V. A.; Budagov, J. A.

The resonance production of new chiral spin-1 bosons and their detection through the Drell-Yan process at the CERN LHC is considered. Quantitative evaluations of various differential cross sections of the chiral-boson production are made within the CalcHEP package. The new neutral chiral bosons can be observed as a Breit-Wigner resonance peak in the invariant-dilepton-mass distribution, as usual. However, unique new signatures of the chiral bosons exist. First, there is no Jacobian peak in the lepton transverse-momentum distribution. Second, the lepton angular distribution in the Collins-Soper frame for the high on-peak invariant masses of the lepton pairs has a peculiar 'swallowtail'more » shape.« less

cudaMap: a GPU accelerated program for gene expression connectivity mapping

PubMed Central

2013-01-01

Background Modern cancer research often involves large datasets and the use of sophisticated statistical techniques. Together these add a heavy computational load to the analysis, which is often coupled with issues surrounding data accessibility. Connectivity mapping is an advanced bioinformatic and computational technique dedicated to therapeutics discovery and drug re-purposing around differential gene expression analysis. On a normal desktop PC, it is common for the connectivity mapping task with a single gene signature to take > 2h to complete using sscMap, a popular Java application that runs on standard CPUs (Central Processing Units). Here, we describe new software, cudaMap, which has been implemented using CUDA C/C++ to harness the computational power of NVIDIA GPUs (Graphics Processing Units) to greatly reduce processing times for connectivity mapping. Results cudaMap can identify candidate therapeutics from the same signature in just over thirty seconds when using an NVIDIA Tesla C2050 GPU. Results from the analysis of multiple gene signatures, which would previously have taken several days, can now be obtained in as little as 10 minutes, greatly facilitating candidate therapeutics discovery with high throughput. We are able to demonstrate dramatic speed differentials between GPU assisted performance and CPU executions as the computational load increases for high accuracy evaluation of statistical significance. Conclusion Emerging ‘omics’ technologies are constantly increasing the volume of data and information to be processed in all areas of biomedical research. Embracing the multicore functionality of GPUs represents a major avenue of local accelerated computing. cudaMap will make a strong contribution in the discovery of candidate therapeutics by enabling speedy execution of heavy duty connectivity mapping tasks, which are increasingly required in modern cancer research. cudaMap is open source and can be freely downloaded from http://purl.oclc.org/NET/cudaMap. PMID:24112435

Identification of human triple-negative breast cancer subtypes and preclinical models for selection of targeted therapies

PubMed Central

Lehmann, Brian D.; Bauer, Joshua A.; Chen, Xi; Sanders, Melinda E.; Chakravarthy, A. Bapsi; Shyr, Yu; Pietenpol, Jennifer A.

2011-01-01

Triple-negative breast cancer (TNBC) is a highly diverse group of cancers, and subtyping is necessary to better identify molecular-based therapies. In this study, we analyzed gene expression (GE) profiles from 21 breast cancer data sets and identified 587 TNBC cases. Cluster analysis identified 6 TNBC subtypes displaying unique GE and ontologies, including 2 basal-like (BL1 and BL2), an immunomodulatory (IM), a mesenchymal (M), a mesenchymal stem–like (MSL), and a luminal androgen receptor (LAR) subtype. Further, GE analysis allowed us to identify TNBC cell line models representative of these subtypes. Predicted “driver” signaling pathways were pharmacologically targeted in these cell line models as proof of concept that analysis of distinct GE signatures can inform therapy selection. BL1 and BL2 subtypes had higher expression of cell cycle and DNA damage response genes, and representative cell lines preferentially responded to cisplatin. M and MSL subtypes were enriched in GE for epithelial-mesenchymal transition, and growth factor pathways and cell models responded to NVP-BEZ235 (a PI3K/mTOR inhibitor) and dasatinib (an abl/src inhibitor). The LAR subtype includes patients with decreased relapse-free survival and was characterized by androgen receptor (AR) signaling. LAR cell lines were uniquely sensitive to bicalutamide (an AR antagonist). These data may be useful in biomarker selection, drug discovery, and clinical trial design that will enable alignment of TNBC patients to appropriate targeted therapies. PMID:21633166

A signature correlation study of ground target VHF/UHF ISAR imagery

NASA Astrophysics Data System (ADS)

Gatesman, Andrew J.; Beaudoin, Christopher J.; Giles, Robert H.; Kersey, William T.; Waldman, Jerry; Carter, Steve; Nixon, William E.

2003-09-01

VV and HH-polarized radar signatures of several ground targets were acquired in the VHF/UHF band (171-342 MHz) by using 1/35th scale models and an indoor radar range operating from 6 to 12 GHz. Data were processed into medianized radar cross sections as well as focused, ISAR imagery. Measurement validation was confirmed by comparing the radar cross section of a test object with a method of moments radar cross section prediction code. The signatures of several vehicles from three vehicle classes (tanks, trunks, and TELs) were measured and a signature cross-correlation study was performed. The VHF/UHF band is currently being exploited for its foliage penetration ability, however, the coarse image resolution which results from the relatively long radar wavelengths suggests a more challenging target recognition problem. One of the study's goals was to determine the amount of unique signature content in VHF/UHF ISAR imagery of military ground vehicles. Open-field signatures are compared with each other as well as with simplified shapes of similar size. Signatures were also acquired on one vehicle in a variety of configurations to determine the impact of monitor target variations on the signature content at these frequencies.

Glioblastoma: Vascular Habitats Detected at Preoperative Dynamic Susceptibility-weighted Contrast-enhanced Perfusion MR Imaging Predict Survival.

PubMed

Juan-Albarracín, Javier; Fuster-Garcia, Elies; Pérez-Girbés, Alexandre; Aparici-Robles, Fernando; Alberich-Bayarri, Ángel; Revert-Ventura, Antonio; Martí-Bonmatí, Luis; García-Gómez, Juan M

2018-06-01

Purpose To determine if preoperative vascular heterogeneity of glioblastoma is predictive of overall survival of patients undergoing standard-of-care treatment by using an unsupervised multiparametric perfusion-based habitat-discovery algorithm. Materials and Methods Preoperative magnetic resonance (MR) imaging including dynamic susceptibility-weighted contrast material-enhanced perfusion studies in 50 consecutive patients with glioblastoma were retrieved. Perfusion parameters of glioblastoma were analyzed and used to automatically draw four reproducible habitats that describe the tumor vascular heterogeneity: high-angiogenic and low-angiogenic regions of the enhancing tumor, potentially tumor-infiltrated peripheral edema, and vasogenic edema. Kaplan-Meier and Cox proportional hazard analyses were conducted to assess the prognostic potential of the hemodynamic tissue signature to predict patient survival. Results Cox regression analysis yielded a significant correlation between patients' survival and maximum relative cerebral blood volume (rCBV max ) and maximum relative cerebral blood flow (rCBF max ) in high-angiogenic and low-angiogenic habitats (P < .01, false discovery rate-corrected P < .05). Moreover, rCBF max in the potentially tumor-infiltrated peripheral edema habitat was also significantly correlated (P < .05, false discovery rate-corrected P < .05). Kaplan-Meier analysis demonstrated significant differences between the observed survival of populations divided according to the median of the rCBV max or rCBF max at the high-angiogenic and low-angiogenic habitats (log-rank test P < .05, false discovery rate-corrected P < .05), with an average survival increase of 230 days. Conclusion Preoperative perfusion heterogeneity contains relevant information about overall survival in patients who undergo standard-of-care treatment. The hemodynamic tissue signature method automatically describes this heterogeneity, providing a set of vascular habitats with high prognostic capabilities. © RSNA, 2018.

Novel Virtual Screening Approach for the Discovery of Human Tyrosinase Inhibitors

PubMed Central

Ai, Ni; Welsh, William J.; Santhanam, Uma; Hu, Hong; Lyga, John

2014-01-01

Tyrosinase is the key enzyme involved in the human pigmentation process, as well as the undesired browning of fruits and vegetables. Compounds inhibiting tyrosinase catalytic activity are an important class of cosmetic and dermatological agents which show high potential as depigmentation agents used for skin lightening. The multi-step protocol employed for the identification of novel tyrosinase inhibitors incorporated the Shape Signatures computational algorithm for rapid screening of chemical libraries. This algorithm converts the size and shape of a molecule, as well its surface charge distribution and other bio-relevant properties, into compact histograms (signatures) that lend themselves to rapid comparison between molecules. Shape Signatures excels at scaffold hopping across different chemical families, which enables identification of new actives whose molecular structure is distinct from other known actives. Using this approach, we identified a novel class of depigmentation agents that demonstrated promise for skin lightening product development. PMID:25426625

Novel virtual screening approach for the discovery of human tyrosinase inhibitors.

PubMed

Ai, Ni; Welsh, William J; Santhanam, Uma; Hu, Hong; Lyga, John

2014-01-01

Tyrosinase is the key enzyme involved in the human pigmentation process, as well as the undesired browning of fruits and vegetables. Compounds inhibiting tyrosinase catalytic activity are an important class of cosmetic and dermatological agents which show high potential as depigmentation agents used for skin lightening. The multi-step protocol employed for the identification of novel tyrosinase inhibitors incorporated the Shape Signatures computational algorithm for rapid screening of chemical libraries. This algorithm converts the size and shape of a molecule, as well its surface charge distribution and other bio-relevant properties, into compact histograms (signatures) that lend themselves to rapid comparison between molecules. Shape Signatures excels at scaffold hopping across different chemical families, which enables identification of new actives whose molecular structure is distinct from other known actives. Using this approach, we identified a novel class of depigmentation agents that demonstrated promise for skin lightening product development.

Comparative Evaluation of Preprocessing Freeware on Chromatography/Mass Spectrometry Data for Signature Discovery

DOE Office of Scientific and Technical Information (OSTI.GOV)

Coble, Jamie B.; Fraga, Carlos G.

2014-07-07

Preprocessing software is crucial for the discovery of chemical signatures in metabolomics, chemical forensics, and other signature-focused disciplines that involve analyzing large data sets from chemical instruments. Here, four freely available and published preprocessing tools known as metAlign, MZmine, SpectConnect, and XCMS were evaluated for impurity profiling using nominal mass GC/MS data and accurate mass LC/MS data. Both data sets were previously collected from the analysis of replicate samples from multiple stocks of a nerve-agent precursor. Each of the four tools had their parameters set for the untargeted detection of chromatographic peaks from impurities present in the stocks. The peakmore » table generated by each preprocessing tool was analyzed to determine the number of impurity components detected in all replicate samples per stock. A cumulative set of impurity components was then generated using all available peak tables and used as a reference to calculate the percent of component detections for each tool, in which 100% indicated the detection of every component. For the nominal mass GC/MS data, metAlign performed the best followed by MZmine, SpectConnect, and XCMS with detection percentages of 83, 60, 47, and 42%, respectively. For the accurate mass LC/MS data, the order was metAlign, XCMS, and MZmine with detection percentages of 80, 45, and 35%, respectively. SpectConnect did not function for the accurate mass LC/MS data. Larger detection percentages were obtained by combining the top performer with at least one of the other tools such as 96% by combining metAlign with MZmine for the GC/MS data and 93% by combining metAlign with XCMS for the LC/MS data. In terms of quantitative performance, the reported peak intensities had average absolute biases of 41, 4.4, 1.3 and 1.3% for SpectConnect, metAlign, XCMS, and MZmine, respectively, for the GC/MS data. For the LC/MS data, the average absolute biases were 22, 4.5, and 3.1% for metAlign, MZmine, and XCMS, respectively. In summary, metAlign performed the best in terms of peak discovery; however, more than one preprocessing tool should be considered to avoid missing potential chemical signatures.« less

Identifying prognostic signature in ovarian cancer using DirGenerank

PubMed Central

Wang, Jian-Yong; Chen, Ling-Ling; Zhou, Xiong-Hui

2017-01-01

Identifying the prognostic genes in cancer is essential not only for the treatment of cancer patients, but also for drug discovery. However, it's still a big challenge to select the prognostic genes that can distinguish the risk of cancer patients across various data sets because of tumor heterogeneity. In this situation, the selected genes whose expression levels are statistically related to prognostic risks may be passengers. In this paper, based on gene expression data and prognostic data of ovarian cancer patients, we used conditional mutual information to construct gene dependency network in which the nodes (genes) with more out-degrees have more chances to be the modulators of cancer prognosis. After that, we proposed DirGenerank (Generank in direct netowrk) algorithm, which concerns both the gene dependency network and genes’ correlations to prognostic risks, to identify the gene signature that can predict the prognostic risks of ovarian cancer patients. Using ovarian cancer data set from TCGA (The Cancer Genome Atlas) as training data set, 40 genes with the highest importance were selected as prognostic signature. Survival analysis of these patients divided by the prognostic signature in testing data set and four independent data sets showed the signature can distinguish the prognostic risks of cancer patients significantly. Enrichment analysis of the signature with curated cancer genes and the drugs selected by CMAP showed the genes in the signature may be drug targets for therapy. In summary, we have proposed a useful pipeline to identify prognostic genes of cancer patients. PMID:28615526

Interferon Gamma Messenger RNA Signature in Tumor Biopsies Predicts Outcomes in Patients with Non-Small-Cell Lung Carcinoma or Urothelial Cancer Treated with Durvalumab.

PubMed

Higgs, Brandon W; Morehouse, Christopher; Streicher, Katie L; Brohawn, Philip; Pilataxi, Fernanda; Gupta, Ashok; Ranade, Koustubh

2018-05-01

To identify a predictive biomarker for durvalumab, an anti-programmed death ligand 1 (PD-L1) monoclonal antibody. RNA sequencing of 97 advanced-stage non-small-cell lung carcinoma (NSCLC) biopsies from a nonrandomized phase 1b/2 clinical trial (1108/NCT01693562) were profiled to identify a predictive signature; 62 locally advanced or metastatic urothelial cancer (UC) tumors from the same study were profiled to confirm predictive utility of the signature. Thirty NSCLC patients provided pre- and posttreatment tumors for messenger RNA (mRNA) analysis. NSCLC with ≥25% tumor cells and UC with ≥25% tumor or immune cells stained for PD-L1 at any intensity were scored PD-L1 positive (PD-L1+). Kaplan-Meier and Cox proportional hazards analyses were used to adjust for gender, age, prior therapies, histology, ECOG, liver metastasis, and smoking. Tumor mutation burden (TMB) was calculated using data from The Cancer Genome Atlas (TCGA).  In the NSCLC discovery set, a four-gene interferon gamma (IFNγ)-positive (IFNγ+) signature comprising IFNγ, CD274, LAG3, and CXCL9 was associated with higher overall response rates, longer median progression-free survival, and overall survival compared with signature-low patients. IFNγ+-signature NSCLC patients had improved survival regardless of immunohistochemistry (IHC) PD-L1 status. These associations were replicated in a UC cohort. The IFNγ+ signature was induced twofold (P = 0.003) by durvalumab after 8 weeks of therapy in NSCLC patients, and baseline signature was associated with TMB but not survival in TCGA data.  The IFNγ+ mRNA signature may assist in identifying patients with improved outcomes to durvalumab, independent of PD-L1 assessed by IHC. Copyright ©2018, American Association for Cancer Research.

Discovery of a Potent Class of PI3Kα Inhibitors with Unique Binding Mode via Encoded Library Technology (ELT).

PubMed

Yang, Hongfang; Medeiros, Patricia F; Raha, Kaushik; Elkins, Patricia; Lind, Kenneth E; Lehr, Ruth; Adams, Nicholas D; Burgess, Joelle L; Schmidt, Stanley J; Knight, Steven D; Auger, Kurt R; Schaber, Michael D; Franklin, G Joseph; Ding, Yun; DeLorey, Jennifer L; Centrella, Paolo A; Mataruse, Sibongile; Skinner, Steven R; Clark, Matthew A; Cuozzo, John W; Evindar, Ghotas

2015-05-14

In the search of PI3K p110α wild type and H1047R mutant selective small molecule leads, an encoded library technology (ELT) campaign against the desired target proteins was performed which led to the discovery of a selective chemotype for PI3K isoforms from a three-cycle DNA encoded library. An X-ray crystal structure of a representative inhibitor from this chemotype demonstrated a unique binding mode in the p110α protein.

Discovery of a Potent Class of PI3Kα Inhibitors with Unique Binding Mode via Encoded Library Technology (ELT)

PubMed Central

2015-01-01

In the search of PI3K p110α wild type and H1047R mutant selective small molecule leads, an encoded library technology (ELT) campaign against the desired target proteins was performed which led to the discovery of a selective chemotype for PI3K isoforms from a three-cycle DNA encoded library. An X-ray crystal structure of a representative inhibitor from this chemotype demonstrated a unique binding mode in the p110α protein. PMID:26005528

Weekly Hydrometeorological Signatures - Characterization of Urban-Induced Streamflow and Rainfall Variability

NASA Astrophysics Data System (ADS)

Schnier, S.; Cai, X.; Sivapalan, M.

2014-12-01

About half of all humans alive today live in cities, with that number projected to grow to 70% by 2050. Because most people live in cities, urban streamflow patterns and precipitation events have a large impact on the global population. Urban environments can alter natural streamflow and precipitation patterns in a localized area. This study introduces a novel way to characterize this interference: the weekly hydrometeorological signature. Daily streamflow and precipitation data is collected from USGS gages around three climatically-different major American cities: Chicago, Los Angeles, and Charlotte. The following hypothesis is tested: a persistent weekly pattern (Monday through Sunday) exists in the hydrometeorological data which is unique to each city. All three cities appear to exhibit a persistent weekly pattern which is unique to that city for various climatological, industrial, and topographic reasons. Further study is needed; however these findings have important implications for understanding urban weather and can serve as a unique identifier, or fingerprint, for human interference to local streamflow and precipitation patterns.

Partial bisulfite conversion for unique template sequencing

PubMed Central

Kumar, Vijay; Rosenbaum, Julie; Wang, Zihua; Forcier, Talitha; Ronemus, Michael; Wigler, Michael

2018-01-01

Abstract We introduce a new protocol, mutational sequencing or muSeq, which uses sodium bisulfite to randomly deaminate unmethylated cytosines at a fixed and tunable rate. The muSeq protocol marks each initial template molecule with a unique mutation signature that is present in every copy of the template, and in every fragmented copy of a copy. In the sequenced read data, this signature is observed as a unique pattern of C-to-T or G-to-A nucleotide conversions. Clustering reads with the same conversion pattern enables accurate count and long-range assembly of initial template molecules from short-read sequence data. We explore count and low-error sequencing by profiling 135 000 restriction fragments in a PstI representation, demonstrating that muSeq improves copy number inference and significantly reduces sporadic sequencer error. We explore long-range assembly in the context of cDNA, generating contiguous transcript clusters greater than 3,000 bp in length. The muSeq assemblies reveal transcriptional diversity not observable from short-read data alone. PMID:29161423

SNP discovery in candidate adaptive genes using exon capture in a free-ranging alpine ungulate

Treesearch

Gretchen H. Roffler; Stephen J. Amish; Seth Smith; Ted Cosart; Marty Kardos; Michael K. Schwartz; Gordon Luikart

2016-01-01

Identification of genes underlying genomic signatures of natural selection is key to understanding adaptation to local conditions. We used targeted resequencing to identify SNP markers in 5321 candidate adaptive genes associated with known immunological, metabolic and growth functions in ovids and other ungulates. We selectively targeted 8161 exons in protein-coding...

From strangeness enhancement to quark-gluon plasma discovery

NASA Astrophysics Data System (ADS)

Koch, Peter; Müller, Berndt; Rafelski, Johann

2017-11-01

This is a short survey of signatures and characteristics of the quark-gluon plasma in the light of experimental results that have been obtained over the past three decades. In particular, we present an in-depth discussion of the strangeness observable, including a chronology of the experimental effort to detect QGP at CERN-SPS, BNL-RHIC, and CERN-LHC.

PYTi-NiCr Signatures in the Columbia Hills are Present in Certain Martian Meteorites

NASA Technical Reports Server (NTRS)

Clark, B. C.; Gellert, R.; Ming, D. W.; Morris, R. V.; Mittlefehldt, D. W.; Squyres, S. W.

2006-01-01

Uniquely high levels of phosphorus and titanium were observed in several samples [1-3] by the APXS x-ray fluorescence measurements as the MER Spirit rover climbed Husband Hill (Columbia Hills, Gusev crater, Mars). A careful study of many such samples and their geochemical variability has revealed additional elements in this pattern, and that the derived multi-element signature is also unambiguously manifested in several martian meteorites.

Association of Distinct Mutational Signatures With Correlates of Increased Immune Activity in Pancreatic Ductal Adenocarcinoma.

PubMed

Connor, Ashton A; Denroche, Robert E; Jang, Gun Ho; Timms, Lee; Kalimuthu, Sangeetha N; Selander, Iris; McPherson, Treasa; Wilson, Gavin W; Chan-Seng-Yue, Michelle A; Borozan, Ivan; Ferretti, Vincent; Grant, Robert C; Lungu, Ilinca M; Costello, Eithne; Greenhalf, William; Palmer, Daniel; Ghaneh, Paula; Neoptolemos, John P; Buchler, Markus; Petersen, Gloria; Thayer, Sarah; Hollingsworth, Michael A; Sherker, Alana; Durocher, Daniel; Dhani, Neesha; Hedley, David; Serra, Stefano; Pollett, Aaron; Roehrl, Michael H A; Bavi, Prashant; Bartlett, John M S; Cleary, Sean; Wilson, Julie M; Alexandrov, Ludmil B; Moore, Malcolm; Wouters, Bradly G; McPherson, John D; Notta, Faiyaz; Stein, Lincoln D; Gallinger, Steven

2017-06-01

Outcomes for patients with pancreatic ductal adenocarcinoma (PDAC) remain poor. Advances in next-generation sequencing provide a route to therapeutic approaches, and integrating DNA and RNA analysis with clinicopathologic data may be a crucial step toward personalized treatment strategies for this disease. To classify PDAC according to distinct mutational processes, and explore their clinical significance. We performed a retrospective cohort study of resected PDAC, using cases collected between 2008 and 2015 as part of the International Cancer Genome Consortium. The discovery cohort comprised 160 PDAC cases from 154 patients (148 primary; 12 metastases) that underwent tumor enrichment prior to whole-genome and RNA sequencing. The replication cohort comprised 95 primary PDAC cases that underwent whole-genome sequencing and expression microarray on bulk biospecimens. Somatic mutations accumulate from sequence-specific processes creating signatures detectable by DNA sequencing. Using nonnegative matrix factorization, we measured the contribution of each signature to carcinogenesis, and used hierarchical clustering to subtype each cohort. We examined expression of antitumor immunity genes across subtypes to uncover biomarkers predictive of response to systemic therapies. The discovery cohort was 53% male (n = 79) and had a median age of 67 (interquartile range, 58-74) years. The replication cohort was 50% male (n = 48) and had a median age of 68 (interquartile range, 60-75) years. Five predominant mutational subtypes were identified that clustered PDAC into 4 major subtypes: age related, double-strand break repair, mismatch repair, and 1 with unknown etiology (signature 8). These were replicated and validated. Signatures were faithfully propagated from primaries to matched metastases, implying their stability during carcinogenesis. Twelve of 27 (45%) double-strand break repair cases lacked germline or somatic events in canonical homologous recombination genes-BRCA1, BRCA2, or PALB2. Double-strand break repair and mismatch repair subtypes were associated with increased expression of antitumor immunity, including activation of CD8-positive T lymphocytes (GZMA and PRF1) and overexpression of regulatory molecules (cytotoxic T-lymphocyte antigen 4, programmed cell death 1, and indolamine 2,3-dioxygenase 1), corresponding to higher frequency of somatic mutations and tumor-specific neoantigens. Signature-based subtyping may guide personalized therapy of PDAC in the context of biomarker-driven prospective trials.

Signatures of mountain building: Detrital zircon U/Pb ages from northeast Tibet

USGS Publications Warehouse

Lease, Richard O.; Burbank, Douglas W.; Gehrels, George E.; Wang, Zhicai; Yuan, Daoyang

2007-01-01

Although detrital zircon has proven to be a powerful tool for determining provenance, past work has focused primarily on delimiting regional source terranes. Here we explore the limits of spatial resolution and stratigraphic sensitivity of detrital zircon in ascertaining provenance, and we demonstrate its ability to detect source changes for terranes separated by only a few tens of kilometers. For such an analysis to succeed for a given mountain, discrete intrarange source terranes must have unique U/Pb zircon age signatures and sediments eroded from the range must have well-defined depositional ages. Here we use ∼1400 single-grain U/Pb zircon ages from northeastern Tibet to identify and analyze an area that satisfies these conditions. This analysis shows that the edges of intermontane basins are stratigraphically sensitive to discrete, punctuated changes in local source terranes. By tracking eroding rock units chronologically through the stratigraphic record, this sensitivity permits the detection of the differential rock uplift and progressive erosion that began ca. 8 Ma in the Laji Shan, a 10-25-km-wide range in northeastern Tibet with a unique U/Pb age signature.

Proteomic Approaches in Biomarker Discovery: New Perspectives in Cancer Diagnostics

PubMed Central

Kocevar, Nina; Komel, Radovan

2014-01-01

Despite remarkable progress in proteomic methods, including improved detection limits and sensitivity, these methods have not yet been established in routine clinical practice. The main limitations, which prevent their integration into clinics, are high cost of equipment, the need for highly trained personnel, and last, but not least, the establishment of reliable and accurate protein biomarkers or panels of protein biomarkers for detection of neoplasms. Furthermore, the complexity and heterogeneity of most solid tumours present obstacles in the discovery of specific protein signatures, which could be used for early detection of cancers, for prediction of disease outcome, and for determining the response to specific therapies. However, cancer proteome, as the end-point of pathological processes that underlie cancer development and progression, could represent an important source for the discovery of new biomarkers and molecular targets for tailored therapies. PMID:24550697

K2 Citizen Science Discovery of a Four-Planet System in a Chain of 3:2 Resonances

NASA Astrophysics Data System (ADS)

Barentsen, Geert; Christiansen, Jessie; Crossfield, Ian; Barclay, Thomas; Lintott, Chris; Cox, Brian; Zemiro, Julia; Simmons, Brooke; Miller, Grant; NASA K2, Zooniverse, BBC, ABC

2017-06-01

We report on the discovery of a compact system of four transiting super-Earth-sized planets around a moderately bright K-type star (V=12) using data from Campaign 12 of NASA's K2 mission. Uniquely, the periods of the planets are 3.6d, 5.4d, 8.3d, and 12.8d, forming an unbroken chain of near 3:2 resonances. It is the first discovery made by citizen scientists participating in the Exoplanet Explorers project on the Zooniverse platform, and was discovered with the help of 15,000 volunteers recruited via the "Stargazing Live" show on Australia's ABC TV channel. K2's open data policy, combined with the unique format of a BBC TV production that does not shy away from including advanced scientific content, enabled the process of a genuine scientific discovery to be executed and witnessed live on air by nearly a million viewers.

The future of quantum dots in drug discovery.

PubMed

Lin, Guimiao; Yin, Feng; Yong, Ken-Tye

2014-09-01

The rapid development of drug discovery today is inseparable from the interaction of advanced particle technologies and new drug synthesis protocols. Quantum dots (QDs) are regarded as a unique class of fluorescent labels, with unique optical properties such as high brightness and long-term colloidal and optical stability; these are suitable for optical imaging, drug delivery and optical tracking, fluorescence immunoassay and other medicinal applications. More importantly, QD possesses a rich surface chemistry property that is useful for incorporating various drug molecules, targeting ligands, and additional contrast agents (e.g., MRI, PET, etc.) onto the nanoparticle surface for achieving targeted and traceable drug delivery therapy at both cellular and systemic levels. In recent times, the advancement of QD technology has promoted the use of functionalized nanocrystals for in vivo applications. Such research is paving the way for drug discovery using various bioconjugated QD formulations. In this editorial, the authors highlight the current research progress and future applications of QDs in drug discovery.

The human immune response to tuberculosis and its treatment: a view from the blood

PubMed Central

Cliff, Jacqueline M; Kaufmann, Stefan H E; McShane, Helen; van Helden, Paul; O'Garra, Anne

2015-01-01

The immune response upon infection with the pathogen Mycobacterium tuberculosis is poorly understood, hampering the discovery of new treatments and the improvements in diagnosis. In the last years, a blood transcriptional signature in tuberculosis has provided knowledge on the immune response occurring during active tuberculosis disease. This signature was absent in the majority of asymptomatic individuals who are latently infected with M. tuberculosis (referred to as latent). Using modular and pathway analyses of the complex data has shown, now in multiple studies, that the signature of active tuberculosis is dominated by overexpression of interferon-inducible genes (consisting of both type I and type II interferon signaling), myeloid genes, and inflammatory genes. There is also downregulation of genes encoding B and T-cell function. The blood signature of tuberculosis correlates with the extent of radiographic disease and is diminished upon effective treatment suggesting the possibility of new improved strategies to support diagnostic assays and methods for drug treatment monitoring. The signature suggested a previously under-appreciated role for type I interferons in development of active tuberculosis disease, and numerous mechanisms have now been uncovered to explain how type I interferon impedes the protective response to M. tuberculosis infection. PMID:25703554

CrossLink: a novel method for cross-condition classification of cancer subtypes.

PubMed

Ma, Chifeng; Sastry, Konduru S; Flore, Mario; Gehani, Salah; Al-Bozom, Issam; Feng, Yusheng; Serpedin, Erchin; Chouchane, Lotfi; Chen, Yidong; Huang, Yufei

2016-08-22

We considered the prediction of cancer classes (e.g. subtypes) using patient gene expression profiles that contain both systematic and condition-specific biases when compared with the training reference dataset. The conventional normalization-based approaches cannot guarantee that the gene signatures in the reference and prediction datasets always have the same distribution for all different conditions as the class-specific gene signatures change with the condition. Therefore, the trained classifier would work well under one condition but not under another. To address the problem of current normalization approaches, we propose a novel algorithm called CrossLink (CL). CL recognizes that there is no universal, condition-independent normalization mapping of signatures. In contrast, it exploits the fact that the signature is unique to its associated class under any condition and thus employs an unsupervised clustering algorithm to discover this unique signature. We assessed the performance of CL for cross-condition predictions of PAM50 subtypes of breast cancer by using a simulated dataset modeled after TCGA BRCA tumor samples with a cross-validation scheme, and datasets with known and unknown PAM50 classification. CL achieved prediction accuracy >73 %, highest among other methods we evaluated. We also applied the algorithm to a set of breast cancer tumors derived from Arabic population to assign a PAM50 classification to each tumor based on their gene expression profiles. A novel algorithm CrossLink for cross-condition prediction of cancer classes was proposed. In all test datasets, CL showed robust and consistent improvement in prediction performance over other state-of-the-art normalization and classification algorithms.

Unraveling signatures of biogeochemical processes and the depositional setting in the molecular composition of pore water DOM across different marine environments

NASA Astrophysics Data System (ADS)

Schmidt, Frauke; Koch, Boris P.; Goldhammer, Tobias; Elvert, Marcus; Witt, Matthias; Lin, Yu-Shih; Wendt, Jenny; Zabel, Matthias; Heuer, Verena B.; Hinrichs, Kai-Uwe

2017-06-01

Dissolved organic matter (DOM) in marine sediment pore waters derives largely from decomposition of particulate organic matter and its composition is influenced by various biogeochemical and oceanographic processes in yet undetermined ways. Here, we determine the molecular inventory of pore water DOM in marine sediments of contrasting depositional regimes with ultrahigh-resolution mass spectrometry and complementary bulk chemical analyses in order to elucidate the factors that shape DOM composition. Our sample sets from the Mediterranean, Marmara and Black Seas covered different sediment depths, ages and a range of marine environments with different (i) organic matter sources, (ii) balances of organic matter production and preservation, and (iii) geochemical conditions in sediment and water column including anoxic, sulfidic and hypersaline conditions. Pore water DOM had a higher molecular formula richness than overlying water with up to 11,295 vs. 2114 different molecular formulas in the mass range of 299-600 Da and covered a broader range of element ratios (H/C = 0.35-2.19, O/C = 0.03-1.19 vs. H/C = 0.56-2.13, O/C = 0.15-1.14). Formula richness was independent of concentrations of DOC and TOC. Near-surface pore water DOM was more similar to water column DOM than to deep pore water DOM from the same core with respect to formula richness and the molecular composition, suggesting exchange at the sediment-water interface. The DOM composition in the deeper sediments was controlled by organic matter source, selective decomposition of specific DOM fractions and early diagenetic molecule transformations. Compounds in pelagic sediment pore waters were predominantly highly unsaturated and N-bearing formulas, whereas oxygen-rich CHO-formulas and aromatic compounds were more abundant in pore water DOM from terrigenous sediments. The increase of S-bearing molecular formulas in the water column and pore waters of the Black Sea and the Mediterranean Discovery Basin was consistent with elevated HS- concentrations reflecting the incorporation of sulfur into biomolecules during early diagenesis. Sulfurization resulted in an increased average molecular mass of DOM and higher formula richness (up to 5899 formulas per sample). In sediments from the methanogenic zone in the Black Sea, the DOM pool was distinctly more reduced than overlying sediments from the sulfate-reducing zone. Bottom and pore water DOM from the Discovery Basin contained the highest abundances of aliphatic compounds in the entire dataset; a large fraction of abundant N-bearing formulas possibly represented peptide and nucleotide formulas suggesting preservation of these molecules in the life inhibiting environment of the Discovery Basin. Our unique data set provides the basis for a comprehensive understanding of the molecular signatures in pore water DOM and the turnover of sedimentary organic matter in marine sediments.

Detection of Biosignatures in Natural and Microbial Cultured Jarosites Using Laser- Desorption Fourier Transform Mass Spectrometry: Implications for Astrobiology

NASA Astrophysics Data System (ADS)

Kotler, J.; Hinman, N. W.; Yan, B.; Stoner, D. L.; Scott, J. R.

2006-12-01

The jarosite group minerals have received increasing attention since the discovery by the Mars Exploration Rover-Opportunity of jarosite on the Martian surface. The general chemical formula for jarosite is XFe3(SO4)2(OH)6 where the X represents both monovalent and divalent cations that can occupy the axial positions in the crystal structure. Commonly found ions include K+, Na+, H3O+, NH4+, and Pb2+ with reports of other large ions occupying this position in the literature. Modeling efforts have been performed to confirm that jarosite has the ability to incorporate a variety of "foreign" cations. The minerals unique ability to incorporate various large ions in its structure and its association with biological activity in terrestrial environments has lead to investigations regarding its use as an indicator of aqueous and/or biological activity. The use of laser desorption Fourier transform mass spectrometry (LD-FTMS) has revealed the presence of organic matter including the amino acid, glycine, in several jarosite samples from various worldwide locations. Iron precipitates derived from acidophilic microbial cultures were also analyzed. Using attenuated total reflectance infrared spectroscopy (ATR-IR), signals indicative of microbes or microbial exudates were weak and ambiguous. In contrast, LD-FTMS clearly detected bioorganic constituents in some desorption spots. However, the signals were sporadic and required the laser scanning/imaging capability of our laboratory built system to locate the microbial signatures in the heterogeneous samples. The ability to observe these bioorganic signatures in jarosite samples using the instrumental technique employed in this study furthers the goals of planetary geologists to determine whether signs of life (e.g., presence of biomolecules or biomolecule precursors) can be detected in the rock record of terrestrial and extraterrestrial samples.

Historeceptomic Fingerprints for Drug-Like Compounds.

PubMed

Shmelkov, Evgeny; Grigoryan, Arsen; Swetnam, James; Xin, Junyang; Tivon, Doreen; Shmelkov, Sergey V; Cardozo, Timothy

2015-01-01

Most drugs exert their beneficial and adverse effects through their combined action on several different molecular targets (polypharmacology). The true molecular fingerprint of the direct action of a drug has two components: the ensemble of all the receptors upon which a drug acts and their level of expression in organs/tissues. Conversely, the fingerprint of the adverse effects of a drug may derive from its action in bystander tissues. The ensemble of targets is almost always only partially known. Here we describe an approach improving upon and integrating both components: in silico identification of a more comprehensive ensemble of targets for any drug weighted by the expression of those receptors in relevant tissues. Our system combines more than 300,000 experimentally determined bioactivity values from the ChEMBL database and 4.2 billion molecular docking scores. We integrated these scores with gene expression data for human receptors across a panel of human tissues to produce drug-specific tissue-receptor (historeceptomics) scores. A statistical model was designed to identify significant scores, which define an improved fingerprint representing the unique activity of any drug. These multi-dimensional historeceptomic fingerprints describe, in a novel, intuitive, and easy to interpret style, the holistic, in vivo picture of the mechanism of any drug's action. Valuable applications in drug discovery and personalized medicine, including the identification of molecular signatures for drugs with polypharmacologic modes of action, detection of tissue-specific adverse effects of drugs, matching molecular signatures of a disease to drugs, target identification for bioactive compounds with unknown receptors, and hypothesis generation for drug/compound phenotypes may be enabled by this approach. The system has been deployed at drugable.org for access through a user-friendly web site.

Nature Bank and the Queensland Compound Library: unique international resources at the Eskitis Institute for Drug Discovery.

PubMed

Camp, David; Newman, Stuart; Pham, Ngoc B; Quinn, Ronald J

2014-03-01

The Eskitis Institute for Drug Discovery is home to two unique resources, Nature Bank and the Queensland Compound Library (QCL), that differentiate it from many other academic institutes pursuing chemical biology or early phase drug discovery. Nature Bank is a comprehensive collection of plants and marine invertebrates that have been subjected to a process which aligns downstream extracts and fractions with lead- and drug-like physicochemical properties. Considerable expertise in screening natural product extracts/fractions was developed at Eskitis over the last two decades. Importantly, biodiscovery activities have been conducted from the beginning in accordance with the UN Convention on Biological Diversity (CBD) to ensure compliance with all international and national legislative requirements. The QCL is a compound management and logistics facility that was established from public funds to augment previous investments in high throughput and phenotypic screening in the region. A unique intellectual property (IP) model has been developed in the case of the QCL to stimulate applied, basic and translational research in the chemical and life sciences by industry, non-profit, and academic organizations.

Microwave-Assisted Esterification: A Discovery-Based Microscale Laboratory Experiment

ERIC Educational Resources Information Center

Reilly, Maureen K.; King, Ryan P.; Wagner, Alexander J.; King, Susan M.

2014-01-01

An undergraduate organic chemistry laboratory experiment has been developed that features a discovery-based microscale Fischer esterification utilizing a microwave reactor. Students individually synthesize a unique ester from known sets of alcohols and carboxylic acids. Each student identifies the best reaction conditions given their particular…

Stable C and N isotope analysis of hair suggest undernourishment as a factor in the death of a mummified girl from late 19th century San Francisco, CA.

PubMed

Eerkens, Jelmer W; Hull, Bryna; Goodman, Jena; Evoy, Angela; Kapp, Joshua D; Hussain, Sidra; Green, Richard E

2017-01-01

The chance discovery of a 1.5-3.5 years old mummified girl presents a unique opportunity to further our understanding of health and disease among children in 19th Century San Francisco. This study focuses on carbon and nitrogen stable isotope signatures in serial samples of hair that cover the last 14 months of her life. Results suggest an initial omnivorous diet with little input from marine resources or C4 plants. Around six months before death δ15N starts a steady increase, with a noticeable acceleration just two months before she died. The magnitude of δ15N change, +1.5‰ in total, is consistent with severe undernourishment or starvation. Cemetery records from this time period in San Francisco indicate high rates of infant and child mortality, mainly due to bacterial-borne infectious diseases, about two orders of magnitude higher than today. Taken together, we hypothesize that the girl died after a prolonged battle with such an illness. Results highlight the tremendous impacts that modern sanitation and medicine have had since the 1800s on human health and lifespan in the United States.

Halobacterium salinarum NRC-1 PeptideAtlas: toward strategies for targeted proteomics and improved proteome coverage.

PubMed

Van, Phu T; Schmid, Amy K; King, Nichole L; Kaur, Amardeep; Pan, Min; Whitehead, Kenia; Koide, Tie; Facciotti, Marc T; Goo, Young Ah; Deutsch, Eric W; Reiss, David J; Mallick, Parag; Baliga, Nitin S

2008-09-01

The relatively small numbers of proteins and fewer possible post-translational modifications in microbes provide a unique opportunity to comprehensively characterize their dynamic proteomes. We have constructed a PeptideAtlas (PA) covering 62.7% of the predicted proteome of the extremely halophilic archaeon Halobacterium salinarum NRC-1 by compiling approximately 636 000 tandem mass spectra from 497 mass spectrometry runs in 88 experiments. Analysis of the PA with respect to biophysical properties of constituent peptides, functional properties of parent proteins of detected peptides, and performance of different mass spectrometry approaches has highlighted plausible strategies for improving proteome coverage and selecting signature peptides for targeted proteomics. Notably, discovery of a significant correlation between absolute abundances of mRNAs and proteins has helped identify low abundance of proteins as the major limitation in peptide detection. Furthermore, we have discovered that iTRAQ labeling for quantitative proteomic analysis introduces a significant bias in peptide detection by mass spectrometry. Therefore, despite identifying at least one proteotypic peptide for almost all proteins in the PA, a context-dependent selection of proteotypic peptides appears to be the most effective approach for targeted proteomics.

All things rhabdoid and SMARC: An enigmatic exploration with Dr. Louis P. Dehner.

PubMed

Fuller, Christine E

2016-11-01

Over the past several decades, our understanding of malignant rhabdoid tumors (MRT) and the central nervous system equivalent atypical teratoid/rhabdoid tumor (ATRT) has undergone considerable refinement, particularly in terms of genetic characterization. MRT (both renal and extra-renal) and ATRT share phenotypic similarities and a common genetic signature, that being inactivating alterations of the SWI/SNF complex component SMARCB1 (or rarely SMARCA4). Unfortunately, a wide array of tumors bears significantly overlapping phenotypic characteristics to MRT/ATRT, posing a formidable diagnostic challenge. Likewise, the list of tumors bearing SMARC-related alterations has grown at a dizzying pace, and the original assumption that SMARCB1 alterations were unique to MRT/ATRT has been essentially negated. It should come as no surprise that Dr. Louis P. Dehner, no stranger to enigmatic lesions, participated significantly in this pathologic controversy, and the circuitous journey of entity discovery and clarification. This review aims to (1) summarize our current knowledge of MRT and ATRT with an emphasis on genetic characterization, (2) present insight into so-called "composite rhabdoid tumors" (CRTs), and (3) and provide an updated account of others tumors bearing SMARC alterations. Copyright © 2016 Elsevier Inc. All rights reserved.

Biogeochemistry of microbial coal-bed methane

USGS Publications Warehouse

Strc, D.; Mastalerz, Maria; Dawson, K.; MacAlady, J.; Callaghan, A.V.; Wawrik, B.; Turich, C.; Ashby, M.

2011-01-01

Microbial methane accumulations have been discovered in multiple coal-bearing basins over the past two decades. Such discoveries were originally based on unique biogenic signatures in the stable isotopic composition of methane and carbon dioxide. Basins with microbial methane contain either low-maturity coals with predominantly microbial methane gas or uplifted coals containing older, thermogenic gas mixed with more recently produced microbial methane. Recent advances in genomics have allowed further evaluation of the source of microbial methane, through the use of high-throughput phylogenetic sequencing and fluorescent in situ hybridization, to describe the diversity and abundance of bacteria and methanogenic archaea in these subsurface formations. However, the anaerobic metabolism of the bacteria breaking coal down to methanogenic substrates, the likely rate-limiting step in biogenic gas production, is not fully understood. Coal molecules are more recalcitrant to biodegradation with increasing thermal maturity, and progress has been made in identifying some of the enzymes involved in the anaerobic degradation of these recalcitrant organic molecules using metagenomic studies and culture enrichments. In recent years, researchers have attempted lab and subsurface stimulation of the naturally slow process of methanogenic degradation of coal. Copyright ?? 2011 by Annual Reviews. All rights reserved.

Ion channel electrophysiology via integrated planar patch-clamp chip with on-demand drug exchange.

PubMed

Chen, Chang-Yu; Tu, Ting-Yuan; Jong, De-Shien; Wo, Andrew M

2011-06-01

Planar patch clamp has revolutionized characterization of ion channel behavior in drug discovery primarily via advancement in high throughput. Lab use of planar technology, however, addresses different requirements and suffers from inflexibility to enable wide range of interrogation via a single cell. This work presents integration of planar patch clamp with microfluidics, achieving multiple solution exchanges for tailor-specific measurement and allowing rapid replacement of the cell-contacting aperture. Studies via endogenously expressed ion channels in HEK 293T cells were commenced to characterize the device. Results reveal the microfluidic concentration generator produces distinct solution/drug combination/concentrations on-demand. Volume-regulated chloride channel and voltage-gated potassium channels in HEK 293T cells immersed in generated solutions under various osmolarities or drug concentrations show unique channel signature under specific condition. Excitation and blockage of ion channels in a single cell was demonstrated via serial solution exchange. Robustness of the reversible bonding and ease of glass substrate replacement were proven via repeated usage of the integrated device. The present approach reveals the capability and flexibility of integrated microfluidic planar patch-clamp system for ion channel assays. Copyright © 2011 Wiley Periodicals, Inc.

Observational signature of high spin at the Event Horizon Telescope

NASA Astrophysics Data System (ADS)

Gralla, Samuel E.; Lupsasca, Alexandru; Strominger, Andrew

2018-04-01

We analytically compute the observational appearance of an isotropically emitting point source on a circular, equatorial orbit near the horizon of a rapidly spinning black hole. The primary image moves on a vertical line segment, in contrast to the primarily horizontal motion of the spinless case. Secondary images, also on the vertical line, display a rich caustic structure. If detected, this unique signature could serve as a `smoking gun' for a high spin black hole in nature.

Digital camera with apparatus for authentication of images produced from an image file

NASA Technical Reports Server (NTRS)

Friedman, Gary L. (Inventor)

1993-01-01

A digital camera equipped with a processor for authentication of images produced from an image file taken by the digital camera is provided. The digital camera processor has embedded therein a private key unique to it, and the camera housing has a public key that is so uniquely based upon the private key that digital data encrypted with the private key by the processor may be decrypted using the public key. The digital camera processor comprises means for calculating a hash of the image file using a predetermined algorithm, and second means for encrypting the image hash with the private key, thereby producing a digital signature. The image file and the digital signature are stored in suitable recording means so they will be available together. Apparatus for authenticating at any time the image file as being free of any alteration uses the public key for decrypting the digital signature, thereby deriving a secure image hash identical to the image hash produced by the digital camera and used to produce the digital signature. The apparatus calculates from the image file an image hash using the same algorithm as before. By comparing this last image hash with the secure image hash, authenticity of the image file is determined if they match, since even one bit change in the image hash will cause the image hash to be totally different from the secure hash.

Digital Camera with Apparatus for Authentication of Images Produced from an Image File

NASA Technical Reports Server (NTRS)

Friedman, Gary L. (Inventor)

1996-01-01

A digital camera equipped with a processor for authentication of images produced from an image file taken by the digital camera is provided. The digital camera processor has embedded therein a private key unique to it, and the camera housing has a public key that is so uniquely related to the private key that digital data encrypted with the private key may be decrypted using the public key. The digital camera processor comprises means for calculating a hash of the image file using a predetermined algorithm, and second means for encrypting the image hash with the private key, thereby producing a digital signature. The image file and the digital signature are stored in suitable recording means so they will be available together. Apparatus for authenticating the image file as being free of any alteration uses the public key for decrypting the digital signature, thereby deriving a secure image hash identical to the image hash produced by the digital camera and used to produce the digital signature. The authenticating apparatus calculates from the image file an image hash using the same algorithm as before. By comparing this last image hash with the secure image hash, authenticity of the image file is determined if they match. Other techniques to address time-honored methods of deception, such as attaching false captions or inducing forced perspectives, are included.

Place recognition using batlike sonar.

PubMed

Vanderelst, Dieter; Steckel, Jan; Boen, Andre; Peremans, Herbert; Holderied, Marc W

2016-08-02

Echolocating bats have excellent spatial memory and are able to navigate to salient locations using bio-sonar. Navigating and route-following require animals to recognize places. Currently, it is mostly unknown how bats recognize places using echolocation. In this paper, we propose template based place recognition might underlie sonar-based navigation in bats. Under this hypothesis, bats recognize places by remembering their echo signature - rather than their 3D layout. Using a large body of ensonification data collected in three different habitats, we test the viability of this hypothesis assessing two critical properties of the proposed echo signatures: (1) they can be uniquely classified and (2) they vary continuously across space. Based on the results presented, we conclude that the proposed echo signatures satisfy both criteria. We discuss how these two properties of the echo signatures can support navigation and building a cognitive map.

Optical network security using unipolar Walsh code

NASA Astrophysics Data System (ADS)

Sikder, Somali; Sarkar, Madhumita; Ghosh, Shila

2018-04-01

Optical code-division multiple-access (OCDMA) is considered as a good technique to provide optical layer security. Many research works have been published to enhance optical network security by using optical signal processing. The paper, demonstrates the design of the AWG (arrayed waveguide grating) router-based optical network for spectral-amplitude-coding (SAC) OCDMA networks with Walsh Code to design a reconfigurable network codec by changing signature codes to against eavesdropping. In this paper we proposed a code reconfiguration scheme to improve the network access confidentiality changing the signature codes by cyclic rotations, for OCDMA system. Each of the OCDMA network users is assigned a unique signature code to transmit the information and at the receiving end each receiver correlates its own signature pattern a(n) with the receiving pattern s(n). The signal arriving at proper destination leads to s(n)=a(n).

Unique Biofilm Signature, Drug Susceptibility and Decreased Virulence in Drosophila through the Pseudomonas aeruginosa Two-Component System PprAB

PubMed Central

Giraud, Caroline; Bernard, Christophe S.; Calderon, Virginie; Ewald, Friederike; Plésiat, Patrick; Nguyen, Cathy; Grunwald, Didier; Attree, Ina; Jeannot, Katy; Fauvarque, Marie-Odile

2012-01-01

Bacterial biofilm is considered as a particular lifestyle helping cells to survive hostile environments triggered by a variety of signals sensed and integrated through adequate regulatory pathways. Pseudomonas aeruginosa, a Gram-negative bacterium causing severe infections in humans, forms biofilms and is a fantastic example for fine-tuning of the transition between planktonic and community lifestyles through two-component systems (TCS). Here we decipher the regulon of the P. aeruginosa response regulator PprB of the TCS PprAB. We identified genes under the control of this TCS and once this pathway is activated, analyzed and dissected at the molecular level the PprB-dependent phenotypes in various models. The TCS PprAB triggers a hyper-biofilm phenotype with a unique adhesive signature made of BapA adhesin, a Type 1 secretion system (T1SS) substrate, CupE CU fimbriae, Flp Type IVb pili and eDNA without EPS involvement. This unique signature is associated with drug hyper-susceptibility, decreased virulence in acutely infected flies and cytotoxicity toward various cell types linked to decreased Type III secretion (T3SS). Moreover, once the PprB pathway is activated, decreased virulence in orally infected flies associated with enhanced biofilm formation and dissemination defect from the intestinal lumen toward the hemolymph compartment is reported. PprB may thus represent a key bacterial adaptation checkpoint of multicellular and aggregative behavior triggering the production of a unique matrix associated with peculiar antibiotic susceptibility and attenuated virulence, a particular interesting breach for therapeutic intervention to consider in view of possible eradication of P. aeruginosa biofilm-associated infections. PMID:23209420

The spectrum of genomic signatures: from dinucleotides to chaos game representation.

PubMed

Wang, Yingwei; Hill, Kathleen; Singh, Shiva; Kari, Lila

2005-02-14

In the post genomic era, access to complete genome sequence data for numerous diverse species has opened multiple avenues for examining and comparing primary DNA sequence organization of entire genomes. Previously, the concept of a genomic signature was introduced with the observation of species-type specific Dinucleotide Relative Abundance Profiles (DRAPs); dinucleotides were identified as the subsequences with the greatest bias in representation in a majority of genomes. Herein, we demonstrate that DRAP is one particular genomic signature contained within a broader spectrum of signatures. Within this spectrum, an alternative genomic signature, Chaos Game Representation (CGR), provides a unique visualization of patterns in sequence organization. A genomic signature is associated with a particular integer order or subsequence length that represents a measure of the resolution or granularity in the analysis of primary DNA sequence organization. We quantitatively explore the organizational information provided by genomic signatures of different orders through different distance measures, including a novel Image Distance. The Image Distance and other existing distance measures are evaluated by comparing the phylogenetic trees they generate for 26 complete mitochondrial genomes from a diversity of species. The phylogenetic tree generated by the Image Distance is compatible with the known relatedness of species. Quantitative evaluation of the spectrum of genomic signatures may be used to ultimately gain insight into the determinants and biological relevance of the genome signatures.

Generation of signature databases with fast codes

NASA Astrophysics Data System (ADS)

Bradford, Robert A.; Woodling, Arthur E.; Brazzell, James S.

1990-09-01

Using the FASTSIG signature code to generate optical signature databases for the Ground-based Surveillance and Traking System (GSTS) Program has improved the efficiency of the database generation process. The goal of the current GSTS database is to provide standardized, threat representative target signatures that can easily be used for acquisition and trk studies, discrimination algorithm development, and system simulations. Large databases, with as many as eight interpolalion parameters, are required to maintain the fidelity demands of discrimination and to generalize their application to other strateg systems. As the need increases for quick availability of long wave infrared (LWIR) target signatures for an evolving design4o-threat, FASTSIG has become a database generation alternative to using the industry standard OptiCal Signatures Code (OSC). FASTSIG, developed in 1985 to meet the unique strategic systems demands imposed by the discrimination function, has the significant advantage of being a faster running signature code than the OSC, typically requiring two percent of the cpu time. It uses analytical approximations to model axisymmetric targets, with the fidelity required for discrimination analysis. Access of the signature database is accomplished through use of the waveband integration and interpolation software, INTEG and SIGNAT. This paper gives details of this procedure as well as sample interpolated signatures and also covers sample verification by comparison to the OSC, in order to establish the fidelity of the FASTSIG generated database.

American Academy of Neurology

MedlinePlus

... Found to Double Risk of Developing MS Hurley, Dan At the Bench-Alzheimer's Disease: Unique Signature in ... Today Online Restaurateur B. Smith and her husband, Dan Gasby, describe life after her diagnosis of early- ...

Dwarfs Cooler Than M: The Definition of Spectral Type L Using Discoveries form the 2-Micron All-Sky Survey (2MASS)

NASA Technical Reports Server (NTRS)

Kirkpatrick, J.; Reid, I.; Liebert, J.; Cutri, R.; Nelson, B.; Beichan, C.; Dahn, C.; Monet, D.; Gizis, J.; Skrutskie, M.

2000-01-01

Because the TiO and VO bands, which dominate the far-optical portions of late-M spectra, disappear in these cooler dwarfs, we define a new spectral class L in wich metallic oxides are replaced by metallic hydrides and neutral alkali metals as the major spectroscopic signatures.

Evolution of Shiga toxin-producing Escherichia coli O157: eight major lineages of human and cattle origin strain signature genotypes

USDA-ARS?s Scientific Manuscript database

Cattle are a major reservoir for Shiga toxin-producing Escherichia coli O157 (STEC O157) and harbor genetic subtypes that do not all associate with human disease. STEC O157 evolved from an E. coli O55:H7 progenitor, however, depauperate nucleotide polymorphism discovery from cattle and human origin...

Modelling and extraction technique for micro-doppler signature of aircraft rotor blades

NASA Astrophysics Data System (ADS)

Praveen, N.; Valarmathi, J.

2017-11-01

The process of detecting and distinguishing between different aircrafts has been a major point of interest in Defence applications. Micro-Doppler effect is one such phenomenon unique for aircrafts with different rotor dynamics and design. In this paper, we focus on deducing a mathematical model for micro-Doppler signature, of aircraft rotor blades assumed to be rotating in a plane perpendicular to the flying direction, induced on the incident radar signal. Also, we use the Wigner-Ville Distribution (WVD) to extract this signature from the radar return. This mathematical model is compared with the simulation results obtained from MATLAB, to validate the results and show the accurateness of the developed model.

New Radiation Zones on Jupiter

NASA Image and Video Library

2017-12-11

This graphic shows a new radiation zone surrounding Jupiter, located just above the atmosphere near the equator, that has been discovered by NASA's Juno mission. The new radiation zone is depicted here as a glowing blue area around the planet's middle. This radiation zone includes energetic hydrogen, oxygen and sulfur ions moving at close to the speed of light (referred to as "relativistic" speeds). It resides inside Jupiter's previously known radiation belts. The zone was identified by the mission's Jupiter Energetic Particle Detector Instrument (JEDI), enabled by Juno's unique close approach to the planet during the spacecraft's science flybys (2,100 miles or 3,400 kilometers from the cloud tops). Juno scientists believe the particles creating this region of intense radiation are derived from energetic neutral atoms -- that is, fast-moving atoms without an electric charge -- coming from the tenuous gas around Jupiter's moons Io and Europa. The neutral atoms then become ions -- atoms with an electric charge -- as their electrons are stripped away by interaction with the planet's upper atmosphere. (This discovery is discussed further in an issue of the journal Geophysical Research Letters [Kollmann et al. (2017), Geophys. Res. Lett., 44, 5259-5268].) Juno also has detected signatures of a population of high-energy, heavy ions in the inner edges of Jupiter's relativistic electron radiation belt. This radiation belt was previously understood to contain mostly electrons moving at near light speed. The signatures of the heavy ions are observed at high latitude locations within the electron belt -- a region not previously explored by spacecraft. The origin and exact species of these heavy ions is not yet understood. Juno's Stellar Reference Unit (SRU-1) star camera detects the signatures of this population as extremely high noise in images collected as part of the mission's radiation monitoring investigation. The locations where the heavy ions were detected are indicated on the graphic by two bright, glowing spots along Juno's flight path past the planet, which is shown as a white line. The invisible lines of Jupiter's magnetic field are also portrayed here for context as faint, bluish lines. https://photojournal.jpl.nasa.gov/catalog/PIA22179

Pediatric Sepsis Endotypes Among Adults With Sepsis.

PubMed

Wong, Hector R; Sweeney, Timothy E; Hart, Kimberly W; Khatri, Purvesh; Lindsell, Christopher J

2017-12-01

Recent transcriptomic studies describe two subgroups of adults with sepsis differentiated by a sepsis response signature. The implied biology and related clinical associations are comparable with recently reported pediatric sepsis endotypes, labeled "A" and "B." We classified adults with sepsis using the pediatric endotyping strategy and the sepsis response signature and determined how endotype assignment, sepsis response signature membership, and age interact with respect to mortality. Retrospective analysis of publically available transcriptomic data representing critically ill adults with sepsis from which the sepsis response signature groups were derived and validated. Multiple ICUs. Adults with sepsis. None. Transcriptomic data were conormalized into a single dataset yielding 549 unique cases with sepsis response signature assignments. Each subject was assigned to endotype A or B using the expression data for the 100 endotyping genes. There were 163 subjects (30%) assigned to endotype A and 386 to endotype B. There was a weak, positive correlation between endotype assignment and sepsis response signature membership. Mortality rates were similar between patients assigned endotype A and those assigned endotype B. A multivariable logistic regression model fit to endotype assignment, sepsis response signature membership, age, and the respective two-way interactions revealed that endotype A, sepsis response signature 1 membership, older age, and the interactions between them were associated with mortality. Subjects coassigned to endotype A, and sepsis response signature 1 had the highest mortality. Combining the pediatric endotyping strategy with sepsis response signature membership might provide complementary, age-dependent, biological, and prognostic information.

Lewy and his inclusion bodies: Discovery and rejection.

PubMed

Engelhardt, Eliasz; Gomes, Marleide da Mota

2017-01-01

Fritz Jacob Heinrich Lewy described the pathology of Paralysis agitans [Parkinson disease] and was the first to identify eosinophilic inclusion bodies in neurons of certain brain nuclei, later known as Lewy bodies, the pathological signature of the Lewy body diseases. In 1912, he published his seminal study, followed soon after by an update paper, and 10 years later, in 1923, by his voluminous book, where he exhaustively described the subject. The publication provided extensive information on the pathology of Paralysis agitans, and the entirely novel finding of eosinophilic inclusion bodies, which would become widely recognized and debated in the future. His discovery was acknowledged by important researchers who even named the structure after him. However, after his last publication on the issue, inexplicably, he never mentioned his histopathological discovery again. Despite several hypotheses, the reasons that led him to neglect (reject) the structure which he so preeminently described have remained elusive.

Circulating neutrophil transcriptome may reveal intracranial aneurysm signature

PubMed Central

Tutino, Vincent M.; Poppenberg, Kerry E.; Jiang, Kaiyu; Jarvis, James N.; Sun, Yijun; Sonig, Ashish; Siddiqui, Adnan H.; Snyder, Kenneth V.; Levy, Elad I.; Kolega, John

2018-01-01

Background Unruptured intracranial aneurysms (IAs) are typically asymptomatic and undetected except for incidental discovery on imaging. Blood-based diagnostic biomarkers could lead to improvements in IA management. This exploratory study examined circulating neutrophils to determine whether they carry RNA expression signatures of IAs. Methods Blood samples were collected from patients receiving cerebral angiography. Eleven samples were collected from patients with IAs and 11 from patients without IAs as controls. Samples from the two groups were paired based on demographics and comorbidities. RNA was extracted from isolated neutrophils and subjected to next-generation RNA sequencing to obtain differential expressions for identification of an IA-associated signature. Bioinformatics analyses, including gene set enrichment analysis and Ingenuity Pathway Analysis, were used to investigate the biological function of all differentially expressed transcripts. Results Transcriptome profiling identified 258 differentially expressed transcripts in patients with and without IAs. Expression differences were consistent with peripheral neutrophil activation. An IA-associated RNA expression signature was identified in 82 transcripts (p<0.05, fold-change ≥2). This signature was able to separate patients with and without IAs on hierarchical clustering. Furthermore, in an independent, unpaired, replication cohort of patients with IAs (n = 5) and controls (n = 5), the 82 transcripts separated 9 of 10 patients into their respective groups. Conclusion Preliminary findings show that RNA expression from circulating neutrophils carries an IA-associated signature. These findings highlight a potential to use predictive biomarkers from peripheral blood samples to identify patients with IAs. PMID:29342213

Hydrodynamics of the Dirac fluid in graphene

NASA Astrophysics Data System (ADS)

Lucas, Andrew

Recent advances in materials physics have allowed us to observe hydrodynamic electron flow in multiple materials. A uniquely interesting possibility is the emergence of a quasi-relativistic plasma of electrons and holes appearing in Dirac semimetals such as graphene. I will briefly review the unique features of the hydrodynamics of the Dirac fluid, and then discuss the theroetical signatures for the Dirac fluid, and its observation in experiment.

Challenges in Biomarker Discovery: Combining Expert Insights with Statistical Analysis of Complex Omics Data

DOE Office of Scientific and Technical Information (OSTI.GOV)

McDermott, Jason E.; Wang, Jing; Mitchell, Hugh D.

2013-01-01

The advent of high throughput technologies capable of comprehensive analysis of genes, transcripts, proteins and other significant biological molecules has provided an unprecedented opportunity for the identification of molecular markers of disease processes. However, it has simultaneously complicated the problem of extracting meaningful signatures of biological processes from these complex datasets. The process of biomarker discovery and characterization provides opportunities both for purely statistical and expert knowledge-based approaches and would benefit from improved integration of the two. Areas covered In this review we will present examples of current practices for biomarker discovery from complex omic datasets and the challenges thatmore » have been encountered. We will then present a high-level review of data-driven (statistical) and knowledge-based methods applied to biomarker discovery, highlighting some current efforts to combine the two distinct approaches. Expert opinion Effective, reproducible and objective tools for combining data-driven and knowledge-based approaches to biomarker discovery and characterization are key to future success in the biomarker field. We will describe our recommendations of possible approaches to this problem including metrics for the evaluation of biomarkers.« less

Applied metabolomics in drug discovery.

PubMed

Cuperlovic-Culf, M; Culf, A S

2016-08-01

The metabolic profile is a direct signature of phenotype and biochemical activity following any perturbation. Metabolites are small molecules present in a biological system including natural products as well as drugs and their metabolism by-products depending on the biological system studied. Metabolomics can provide activity information about possible novel drugs and drug scaffolds, indicate interesting targets for drug development and suggest binding partners of compounds. Furthermore, metabolomics can be used for the discovery of novel natural products and in drug development. Metabolomics can enhance the discovery and testing of new drugs and provide insight into the on- and off-target effects of drugs. This review focuses primarily on the application of metabolomics in the discovery of active drugs from natural products and the analysis of chemical libraries and the computational analysis of metabolic networks. Metabolomics methodology, both experimental and analytical is fast developing. At the same time, databases of compounds are ever growing with the inclusion of more molecular and spectral information. An increasing number of systems are being represented by very detailed metabolic network models. Combining these experimental and computational tools with high throughput drug testing and drug discovery techniques can provide new promising compounds and leads.

5 CFR 850.103 - Definitions.

Code of Federal Regulations, 2010 CFR

2010-01-01

... (asymmetric) cryptography is a method of creating a unique mark, known as a digital signature, on an... cryptography means a method of authentication in which a single key is used to sign and verify an electronic...

Soil Moisture: The Hydrologic Interface Between Surface and Ground Waters

NASA Technical Reports Server (NTRS)

Engman, Edwin T.

1997-01-01

A hypothesis is presented that many hydrologic processes display a unique signature that is detectable with microwave remote sensing. These signatures are in the form of the spatial and temporal distributions of surface soil moisture. The specific hydrologic processes that may be detected include groundwater recharge and discharge zones, storm runoff contributing areas, regions of potential and less than potential evapotranspiration (ET), and information about the hydrologic properties of soils. In basin and hillslope hydrology, soil moisture is the interface between surface and ground waters.

FAST TRACK COMMUNICATION Spectral signatures of the surface reconstructions of Au(110)/electrolyte interfaces

NASA Astrophysics Data System (ADS)

Smith, C. I.; Bowfield, A.; Almond, N. J.; Mansley, C. P.; Convery, J. H.; Weightman, P.

2010-10-01

It is demonstrated that the (1 × 1) structure and the (1 × 2) and (1 × 3) surface reconstructions that occur at Au(110)/electrolyte interfaces have unique optical fingerprints. The optical fingerprints are potential, pH and anion dependent and have potential for use in monitoring dynamic changes at this interface. We also observe a specific reflection anisotropy spectroscopy signature that may arise from anions adsorbed on the (1 × 1) structure of Au(110).

Implementing traceability using particle randomness-based textile printed tags

NASA Astrophysics Data System (ADS)

Agrawal, T. K.; Koehl, L.; Campagne, C.

2017-10-01

This article introduces a random particle-based traceability tag for textiles. The proposed tag not only act as a unique signature for the corresponding textile product but also possess the features such as easy to manufacture and hard to copy. It seeks applications in brand authentication and traceability in textile and clothing (T&C) supply chain. A prototype has been developed by screen printing process, in which micron-scale particles were mixed with the printing paste and printed on cotton fabrics to attain required randomness. To encode the randomness, the image of the developed tag was taken and analyzed using image processing. The randomness of the particles acts as a product key or unique signature which is required to decode the tag. Finally, washing and abrasion resistance tests were conducted to check the durability of the printed tag.

Unique Prokaryotic Consortia in Geochemically Distinct Sediments from Red Sea Atlantis II and Discovery Deep Brine Pools

PubMed Central

Siam, Rania; Mustafa, Ghada A.; Sharaf, Hazem; Moustafa, Ahmed; Ramadan, Adham R.; Antunes, Andre; Bajic, Vladimir B.; Stingl, Uli; Marsis, Nardine G. R.; Coolen, Marco J. L.; Sogin, Mitchell; Ferreira, Ari J. S.; Dorry, Hamza El

2012-01-01

The seafloor is a unique environment, which allows insights into how geochemical processes affect the diversity of biological life. Among its diverse ecosystems are deep-sea brine pools - water bodies characterized by a unique combination of extreme conditions. The ‘polyextremophiles’ that constitute the microbial assemblage of these deep hot brines have not been comprehensively studied. We report a comparative taxonomic analysis of the prokaryotic communities of the sediments directly below the Red Sea brine pools, namely, Atlantis II, Discovery, Chain Deep, and an adjacent brine-influenced site. Analyses of sediment samples and high-throughput pyrosequencing of PCR-amplified environmental 16S ribosomal RNA genes (16S rDNA) revealed that one sulfur (S)-rich Atlantis II and one nitrogen (N)-rich Discovery Deep section contained distinct microbial populations that differed from those found in the other sediment samples examined. Proteobacteria, Actinobacteria, Cyanobacteria, Deferribacteres, and Euryarchaeota were the most abundant bacterial and archaeal phyla in both the S- and N-rich sections. Relative abundance-based hierarchical clustering of the 16S rDNA pyrotags assigned to major taxonomic groups allowed us to categorize the archaeal and bacterial communities into three major and distinct groups; group I was unique to the S-rich Atlantis II section (ATII-1), group II was characteristic for the N-rich Discovery sample (DD-1), and group III reflected the composition of the remaining sediments. Many of the groups detected in the S-rich Atlantis II section are likely to play a dominant role in the cycling of methane and sulfur due to their phylogenetic affiliations with bacteria and archaea involved in anaerobic methane oxidation and sulfate reduction. PMID:22916172

CANDO and the infinite drug discovery frontier

PubMed Central

Minie, Mark; Chopra, Gaurav; Sethi, Geetika; Horst, Jeremy; White, George; Roy, Ambrish; Hatti, Kaushik; Samudrala, Ram

2014-01-01

The Computational Analysis of Novel Drug Opportunities (CANDO) platform (http://protinfo.org/cando) uses similarity of compound–proteome interaction signatures to infer homology of compound/drug behavior. We constructed interaction signatures for 3733 human ingestible compounds covering 48,278 protein structures mapping to 2030 indications based on basic science methodologies to predict and analyze protein structure, function, and interactions developed by us and others. Our signature comparison and ranking approach yielded benchmarking accuracies of 12–25% for 1439 indications with at least two approved compounds. We prospectively validated 49/82 ‘high value’ predictions from nine studies covering seven indications, with comparable or better activity to existing drugs, which serve as novel repurposed therapeutics. Our approach may be generalized to compounds beyond those approved by the FDA, and can also consider mutations in protein structures to enable personalization. Our platform provides a holistic multiscale modeling framework of complex atomic, molecular, and physiological systems with broader applications in medicine and engineering. PMID:24980786

The Lifecycle of Bayesian Network Models Developed for Multi-Source Signature Assessment of Nuclear Programs

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gastelum, Zoe N.; White, Amanda M.; Whitney, Paul D.

2013-06-04

The Multi-Source Signatures for Nuclear Programs project, part of Pacific Northwest National Laboratory’s (PNNL) Signature Discovery Initiative, seeks to computationally capture expert assessment of multi-type information such as text, sensor output, imagery, or audio/video files, to assess nuclear activities through a series of Bayesian network (BN) models. These models incorporate knowledge from a diverse range of information sources in order to help assess a country’s nuclear activities. The models span engineering topic areas, state-level indicators, and facility-specific characteristics. To illustrate the development, calibration, and use of BN models for multi-source assessment, we present a model that predicts a country’s likelihoodmore » to participate in the international nuclear nonproliferation regime. We validate this model by examining the extent to which the model assists non-experts arrive at conclusions similar to those provided by nuclear proliferation experts. We also describe the PNNL-developed software used throughout the lifecycle of the Bayesian network model development.« less

Multimessenger Signatures of Massive Black Holes in Dwarf Galaxies

NASA Astrophysics Data System (ADS)

Bellovary, Jillian; Cleary, Colleen; Tremmel, Michael; Munshi, Ferah

2018-01-01

Inspired by the recent discovery of several nearby dwarf galaxies hosting active galactic nuclei, we present results from a series of cosmological hydrodynamic simulations focusing on dwarf galaxies which host supermassive black holes (SMBHs). Cosmological simulations are a vital tool for predicting SMBH populations and merger events which will eventually be observed by LISA. Dwarf galaxies are the most numerous in the universe, so even though the occupation fraction of SMBHs in dwarfs is less than unity, their contribution to the gravitational wave background could be non-negligible. We find that electromagnetic signatures from SMBH accretion are not common among most SMBH-hosting dwarfs, but the gravitational wave signatures can be substantial. The most common mass ratio for SMBH mergers in low-mass galaxy environments is ~1:20, which is an unexplored region of gravitational waveform parameter space. We discuss the occupation fraction of SMBHs in low-mass galaxies as well as differences in field and satellite populations, providing clues to search for and characterize these elusive giants lurking in the dwarfs.

A TRPV2 interactome-based signature for prognosis in glioblastoma patients.

PubMed

Doñate-Macián, Pau; Gómez, Antonio; Dégano, Irene R; Perálvarez-Marín, Alex

2018-04-06

Proteomics aids to the discovery and expansion of protein-protein interaction networks, which are key to understand molecular mechanisms in physiology and physiopathology, but also to infer protein function in a guilt-by-association fashion. In this study we use a systematic protein-protein interaction membrane yeast two-hybrid method to expand the interactome of TRPV2, a cation channel related to nervous system development. After validation of the interactome in silico , we define a TRPV2-interactome signature combining proteomics with the available physio-pathological data in Disgenet to find interactome-disease associations, highlighting nervous system disorders and neoplasms. The TRPV2-interactome signature against available experimental data is capable of discriminating overall risk in glioblastoma multiforme prognosis, progression, recurrence, and chemotherapy resistance. Beyond the impact on glioblastoma physiopathology, this study shows that combining systematic proteomics with in silico methods and available experimental data is key to open new perspectives to define novel biomarkers for diagnosis, prognosis and therapeutics in disease.

A TRPV2 interactome-based signature for prognosis in glioblastoma patients

PubMed Central

Dégano, Irene R.; Perálvarez-Marín, Alex

2018-01-01

Proteomics aids to the discovery and expansion of protein-protein interaction networks, which are key to understand molecular mechanisms in physiology and physiopathology, but also to infer protein function in a guilt-by-association fashion. In this study we use a systematic protein-protein interaction membrane yeast two-hybrid method to expand the interactome of TRPV2, a cation channel related to nervous system development. After validation of the interactome in silico, we define a TRPV2-interactome signature combining proteomics with the available physio-pathological data in Disgenet to find interactome-disease associations, highlighting nervous system disorders and neoplasms. The TRPV2-interactome signature against available experimental data is capable of discriminating overall risk in glioblastoma multiforme prognosis, progression, recurrence, and chemotherapy resistance. Beyond the impact on glioblastoma physiopathology, this study shows that combining systematic proteomics with in silico methods and available experimental data is key to open new perspectives to define novel biomarkers for diagnosis, prognosis and therapeutics in disease. PMID:29719613

Interim Report on SNP analysis and forensic microarray probe design for South American hemorrhagic fever viruses, tick-borne encephalitis virus, henipaviruses, Old World Arenaviruses, filoviruses, Crimean-Congo hemorrhagic fever viruses, Rift Valley fever

DOE Office of Scientific and Technical Information (OSTI.GOV)

Jaing, C; Gardner, S

The goal of this project is to develop forensic genotyping assays for select agent viruses, enhancing the current capabilities for the viral bioforensics and law enforcement community. We used a multipronged approach combining bioinformatics analysis, PCR-enriched samples, microarrays and TaqMan assays to develop high resolution and cost effective genotyping methods for strain level forensic discrimination of viruses. We have leveraged substantial experience and efficiency gained through year 1 on software development, SNP discovery, TaqMan signature design and phylogenetic signature mapping to scale up the development of forensics signatures in year 2. In this report, we have summarized the whole genomemore » wide SNP analysis and microarray probe design for forensics characterization of South American hemorrhagic fever viruses, tick-borne encephalitis viruses and henipaviruses, Old World Arenaviruses, filoviruses, Crimean-Congo hemorrhagic fever virus, Rift Valley fever virus and Japanese encephalitis virus.« less

FY02 CBNP Annual Report Input: Bioinformatics Support for CBNP Research and Deployments

DOE Office of Scientific and Technical Information (OSTI.GOV)

Slezak, T; Wolinsky, M

2002-10-31

The events of FY01 dynamically reprogrammed the objectives of the CBNP bioinformatics support team, to meet rapidly-changing Homeland Defense needs and requests from other agencies for assistance: Use computational techniques to determine potential unique DNA signature candidates for microbial and viral pathogens of interest to CBNP researcher and to our collaborating partner agencies such as the Centers for Disease Control and Prevention (CDC), U.S. Department of Agriculture (USDA), Department of Defense (DOD), and Food and Drug Administration (FDA). Develop effective electronic screening measures for DNA signatures to reduce the cost and time of wet-bench screening. Build a comprehensive system formore » tracking the development and testing of DNA signatures. Build a chain-of-custody sample tracking system for field deployment of the DNA signatures as part of the BASIS project. Provide computational tools for use by CBNP Biological Foundations researchers.« less

Potential for Remotely Sensed Soil Moisture Data in Hydrologic Modeling

NASA Technical Reports Server (NTRS)

Engman, Edwin T.

1997-01-01

Many hydrologic processes display a unique signature that is detectable with microwave remote sensing. These signatures are in the form of the spatial and temporal distributions of surface soil moisture and portray the spatial heterogeneity of hydrologic processes and properties that one encounters in drainage basins. The hydrologic processes that may be detected include ground water recharge and discharge zones, storm runoff contributing areas, regions of potential and less than potential ET, and information about the hydrologic properties of soils and heterogeneity of hydrologic parameters. Microwave remote sensing has the potential to detect these signatures within a basin in the form of volumetric soil moisture measurements in the top few cm. These signatures should provide information on how and where to apply soil physical parameters in distributed and lumped parameter models and how to subdivide drainage basins into hydrologically similar sub-basins.

Container weld identification using portable laser scanners

NASA Astrophysics Data System (ADS)

Taddei, Pierluigi; Boström, Gunnar; Puig, David; Kravtchenko, Victor; Sequeira, Vítor

2015-03-01

Identification and integrity verification of sealed containers for security applications can be obtained by employing noninvasive portable optical systems. We present a portable laser range imaging system capable of identifying welds, a byproduct of a container's physical sealing, with micrometer accuracy. It is based on the assumption that each weld has a unique three-dimensional (3-D) structure which cannot be copied or forged. We process the 3-D surface to generate a normalized depth map which is invariant to mechanical alignment errors and that is used to build compact signatures representing the weld. A weld is identified by performing cross correlations of its signature against a set of known signatures. The system has been tested on realistic datasets, containing hundreds of welds, yielding no false positives or false negatives and thus showing the robustness of the system and the validity of the chosen signature.

Place recognition using batlike sonar

PubMed Central

Vanderelst, Dieter; Steckel, Jan; Boen, Andre; Peremans, Herbert; Holderied, Marc W

2016-01-01

Echolocating bats have excellent spatial memory and are able to navigate to salient locations using bio-sonar. Navigating and route-following require animals to recognize places. Currently, it is mostly unknown how bats recognize places using echolocation. In this paper, we propose template based place recognition might underlie sonar-based navigation in bats. Under this hypothesis, bats recognize places by remembering their echo signature - rather than their 3D layout. Using a large body of ensonification data collected in three different habitats, we test the viability of this hypothesis assessing two critical properties of the proposed echo signatures: (1) they can be uniquely classified and (2) they vary continuously across space. Based on the results presented, we conclude that the proposed echo signatures satisfy both criteria. We discuss how these two properties of the echo signatures can support navigation and building a cognitive map. DOI: http://dx.doi.org/10.7554/eLife.14188.001 PMID:27481189

Use of combinatorial chemistry to speed drug discovery.

PubMed

Rádl, S

1998-10-01

IBC's International Conference on Integrating Combinatorial Chemistry into the Discovery Pipeline was held September 14-15, 1998. The program started with a pre-conference workshop on High-Throughput Compound Characterization and Purification. The agenda of the main conference was divided into sessions of Synthesis, Automation and Unique Chemistries; Integrating Combinatorial Chemistry, Medicinal Chemistry and Screening; Combinatorial Chemistry Applications for Drug Discovery; and Information and Data Management. This meeting was an excellent opportunity to see how big pharma, biotech and service companies are addressing the current bottlenecks in combinatorial chemistry to speed drug discovery. (c) 1998 Prous Science. All rights reserved.

Searching for new scalar bosons via triple-top signature in cg → tS0 → tt t bar

NASA Astrophysics Data System (ADS)

Kohda, Masaya; Modak, Tanmoy; Hou, Wei-Shu

2018-01-01

The alignment phenomenon, that the 125 GeV h0 boson so resembles the Standard Model Higgs boson, can be understood in a two Higgs doublet model without discrete symmetry. New Yukawa couplings ρtt and ρtc offer new avenues to discover the extra scalar H0 and pseudoscalar A0. We propose to search for cg → tH0, tA0 followed by H0, A0 → t t bar , t c bar , where same-sign dileptons could be the harbinger, with triple-top, in the signature of three leptons plus three b-jets, as confirmation. Discovery could touch upon the origin of baryon asymmetry of the Universe.

Normalization of TAM post-receptor signaling reveals a cell invasive signature for Axl tyrosine kinase.

PubMed

Kimani, Stanley G; Kumar, Sushil; Davra, Viralkumar; Chang, Yun-Juan; Kasikara, Canan; Geng, Ke; Tsou, Wen-I; Wang, Shenyan; Hoque, Mainul; Boháč, Andrej; Lewis-Antes, Anita; De Lorenzo, Mariana S; Kotenko, Sergei V; Birge, Raymond B

2016-09-06

Tyro3, Axl, and Mertk (TAMs) are a family of three conserved receptor tyrosine kinases that have pleiotropic roles in innate immunity and homeostasis and when overexpressed in cancer cells can drive tumorigenesis. In the present study, we engineered EGFR/TAM chimeric receptors (EGFR/Tyro3, EGFR/Axl, and EGF/Mertk) with the goals to interrogate post-receptor functions of TAMs, and query whether TAMs have unique or overlapping post-receptor activation profiles. Stable expression of EGFR/TAMs in EGFR-deficient CHO cells afforded robust EGF inducible TAM receptor phosphorylation and activation of downstream signaling. Using a series of unbiased screening approaches, that include kinome-view analysis, phosphor-arrays, RNAseq/GSEA analysis, as well as cell biological and in vivo readouts, we provide evidence that each TAM has unique post-receptor signaling platforms and identify an intrinsic role for Axl that impinges on cell motility and invasion compared to Tyro3 and Mertk. These studies demonstrate that TAM show unique post-receptor signatures that impinge on distinct gene expression profiles and tumorigenic outcomes.

Partial bisulfite conversion for unique template sequencing.

PubMed

Kumar, Vijay; Rosenbaum, Julie; Wang, Zihua; Forcier, Talitha; Ronemus, Michael; Wigler, Michael; Levy, Dan

2018-01-25

We introduce a new protocol, mutational sequencing or muSeq, which uses sodium bisulfite to randomly deaminate unmethylated cytosines at a fixed and tunable rate. The muSeq protocol marks each initial template molecule with a unique mutation signature that is present in every copy of the template, and in every fragmented copy of a copy. In the sequenced read data, this signature is observed as a unique pattern of C-to-T or G-to-A nucleotide conversions. Clustering reads with the same conversion pattern enables accurate count and long-range assembly of initial template molecules from short-read sequence data. We explore count and low-error sequencing by profiling 135 000 restriction fragments in a PstI representation, demonstrating that muSeq improves copy number inference and significantly reduces sporadic sequencer error. We explore long-range assembly in the context of cDNA, generating contiguous transcript clusters greater than 3,000 bp in length. The muSeq assemblies reveal transcriptional diversity not observable from short-read data alone. © The Author(s) 2017. Published by Oxford University Press on behalf of Nucleic Acids Research.

Unique spectral signatures of the nucleic acid dye acridine orange can distinguish cell death by apoptosis and necroptosis

PubMed Central

Caprariello, Andrew V.; Henry, Tyler J.; Tsutsui, Shigeki; Chu, Tak H.; Schenk, Geert J.; Yong, V. Wee

2017-01-01

Cellular injury and death are ubiquitous features of disease, yet tools to detect them are limited and insensitive to subtle pathological changes. Acridine orange (AO), a nucleic acid dye with unique spectral properties, enables real-time measurement of RNA and DNA as proxies for cell viability during exposure to various noxious stimuli. This tool illuminates spectral signatures unique to various modes of cell death, such as cells undergoing apoptosis versus necrosis/necroptosis. This new approach also shows that cellular RNA decreases during necrotic, necroptotic, and apoptotic cell death caused by demyelinating, ischemic, and traumatic injuries, implying its involvement in a wide spectrum of tissue pathologies. Furthermore, cells with pathologically low levels of cytoplasmic RNA are detected earlier and in higher numbers than with standard markers including TdT-mediated dUTP biotin nick-end labeling and cleaved caspase 3 immunofluorescence. Our technique highlights AO-labeled cytoplasmic RNA as an important early marker of cellular injury and a sensitive indicator of various modes of cell death in a range of experimental models. PMID:28264914

Authentic Astronomical Discovery in Planetariums: Bringing Data to Domes

NASA Astrophysics Data System (ADS)

Wyatt, Ryan Jason; Subbarao, Mark; Christensen, Lars; Emmons, Ben; Hurt, Robert

2018-01-01

Planetariums offer a unique opportunity to disseminate astronomical discoveries using data visualization at all levels of complexity: the technical infrastructure to display data and a sizeable cohort of enthusiastic educators to interpret results. “Data to Dome” is an initiative the International Planetarium Society to develop our community’s capacity to integrate data in fulldome planetarium systems—including via open source software platforms such as WorldWide Telescope and OpenSpace. We are cultivating a network of planetarium professionals who integrate data into their presentations and share their content with others. Furthermore, we propose to shorten the delay between discovery and dissemination in planetariums. Currently, the “latest science” is often presented days or weeks after discoveries are announced, and we can shorten this to hours or even minutes. The Data2Dome (D2D) initiative, led by the European Southern Observatory, proposes technical infrastructure and data standards that will streamline content flow from research institutions to planetariums, offering audiences a unique opportunity to access to the latest astronomical data in near real time.

Rewinding the waves: tracking underwater signals to their source.

PubMed

Kadri, Usama; Crivelli, Davide; Parsons, Wade; Colbourne, Bruce; Ryan, Amanda

2017-10-24

Analysis of data, recorded on March 8th 2014 at the Comprehensive Nuclear-Test-Ban Treaty Organisation's hydroacoustic stations off Cape Leeuwin Western Australia, and at Diego Garcia, reveal unique pressure signatures that could be associated with objects impacting at the sea surface, such as falling meteorites, or the missing Malaysian Aeroplane MH370. To examine the recorded signatures, we carried out experiments with spheres impacting at the surface of a water tank, where we observed almost identical pressure signature structures. While the pressure structure is unique to impacting objects, the evolution of the radiated acoustic waves carries information on the source. Employing acoustic-gravity wave theory we present an analytical inverse method to retrieve the impact time and location. The solution was validated using field observations of recent earthquakes, where we were able to calculate the eruption time and location to a satisfactory degree of accuracy. Moreover, numerical validations confirm an error below 0.02% for events at relatively large distances of over 1000 km. The method can be developed to calculate other essential properties such as impact duration and geometry. Besides impacting objects and earthquakes, the method could help in identifying the location of underwater explosions and landslides.

Defining the Genomic Signature of Totipotency and Pluripotency during Early Human Development

PubMed Central

Galan, Amparo; Diaz-Gimeno, Patricia; Poo, Maria Eugenia; Valbuena, Diana; Sanchez, Eva; Ruiz, Veronica; Dopazo, Joaquin; Montaner, David; Conesa, Ana; Simon, Carlos

2013-01-01

The genetic mechanisms governing human pre-implantation embryo development and the in vitro counterparts, human embryonic stem cells (hESCs), still remain incomplete. Previous global genome studies demonstrated that totipotent blastomeres from day-3 human embryos and pluripotent inner cell masses (ICMs) from blastocysts, display unique and differing transcriptomes. Nevertheless, comparative gene expression analysis has revealed that no significant differences exist between hESCs derived from blastomeres versus those obtained from ICMs, suggesting that pluripotent hESCs involve a new developmental progression. To understand early human stages evolution, we developed an undifferentiation network signature (UNS) and applied it to a differential gene expression profile between single blastomeres from day-3 embryos, ICMs and hESCs. This allowed us to establish a unique signature composed of highly interconnected genes characteristic of totipotency (61 genes), in vivo pluripotency (20 genes), and in vitro pluripotency (107 genes), and which are also proprietary according to functional analysis. This systems biology approach has led to an improved understanding of the molecular and signaling processes governing human pre-implantation embryo development, as well as enabling us to comprehend how hESCs might adapt to in vitro culture conditions. PMID:23614026

IMAGE 100: The interactive multispectral image processing system

NASA Technical Reports Server (NTRS)

Schaller, E. S.; Towles, R. W.

1975-01-01

The need for rapid, cost-effective extraction of useful information from vast quantities of multispectral imagery available from aircraft or spacecraft has resulted in the design, implementation and application of a state-of-the-art processing system known as IMAGE 100. Operating on the general principle that all objects or materials possess unique spectral characteristics or signatures, the system uses this signature uniqueness to identify similar features in an image by simultaneously analyzing signatures in multiple frequency bands. Pseudo-colors, or themes, are assigned to features having identical spectral characteristics. These themes are displayed on a color CRT, and may be recorded on tape, film, or other media. The system was designed to incorporate key features such as interactive operation, user-oriented displays and controls, and rapid-response machine processing. Owing to these features, the user can readily control and/or modify the analysis process based on his knowledge of the input imagery. Effective use can be made of conventional photographic interpretation skills and state-of-the-art machine analysis techniques in the extraction of useful information from multispectral imagery. This approach results in highly accurate multitheme classification of imagery in seconds or minutes rather than the hours often involved in processing using other means.

Exploratory Spectroscopy of Magnetic Cataclysmic Variables Candidates and Other Variable Objects

NASA Astrophysics Data System (ADS)

Oliveira, A. S.; Rodrigues, C. V.; Cieslinski, D.; Jablonski, F. J.; Silva, K. M. G.; Almeida, L. A.; Rodríguez-Ardila, A.; Palhares, M. S.

2017-04-01

The increasing number of synoptic surveys made by small robotic telescopes, such as the photometric Catalina Real-Time Transient Survey (CRTS), provides a unique opportunity to discover variable sources and improves the statistical samples of such classes of objects. Our goal is the discovery of magnetic Cataclysmic Variables (mCVs). These are rare objects that probe interesting accretion scenarios controlled by the white-dwarf magnetic field. In particular, improved statistics of mCVs would help to address open questions on their formation and evolution. We performed an optical spectroscopy survey to search for signatures of magnetic accretion in 45 variable objects selected mostly from the CRTS. In this sample, we found 32 CVs, 22 being mCV candidates, 13 of which were previously unreported as such. If the proposed classifications are confirmed, it would represent an increase of 4% in the number of known polars and 12% in the number of known IPs. A fraction of our initial sample was classified as extragalactic sources or other types of variable stars by the inspection of the identification spectra. Despite the inherent complexity in identifying a source as an mCV, variability-based selection, followed by spectroscopic snapshot observations, has proved to be an efficient strategy for their discoveries, being a relatively inexpensive approach in terms of telescope time. Based on observations obtained at the Observatório do Pico dos Dias/LNA, and at the Southern Astrophysical Research (SOAR) telescope, which is a joint project of the Ministério da Ciência, Tecnologia, e Inovação (MCTI) da República Federativa do Brasil, the U.S. National Optical Astronomy Observatory (NOAO), the University of North Carolina at Chapel Hill (UNC), and Michigan State University (MSU).

Physics of Boundaries and their Interactions in Space Plasmas

NASA Technical Reports Server (NTRS)

Omidi, Nojan; Karimabadi, Homayoun; Krauss-Varban, Dietmar

1998-01-01

This final report describes a brief summary of our accomplishments during the complete contract period. Traditionally, due to computational limitations, it has been impossible to obtain a global view of the magnetosphere on ion time and spatial scales. As a result, kinetic simulations have concentrated on the local structure of different magnetospheric discontinuities and boundaries. However, due to the emergence of low cost desktop superconductors, as well as by taking full advantage of latest advances in data mining and visualization technology, we were able to bypass our planned (proposed) regional simulations and proceed to large-scale 3-D and 2-D global hybrid simulations of the magnetosphere. As a result, although we are only finishing the second year of the proposed activity, much of the original scientific objectives have been surpassed and new avenues of investigation have been opened. Such simulations have led us to possible explanations of some long-standing issues in magnetospheric physics. They have also enabled us to make a number of important discoveries/predictions, which need to be looked for in satellite data. Examples include: (1) the finding that the bow shock can become unstable to the Kelvin-Helmholtz (KH;) (2) the discovery of a mechanism for intermittent reconnection due to ion physics which may be relevant to the explanation of the recurrence rate of flux transfer events (FTEs;) and (3) the finding that the current sheet in the near-Earth magnetotail region can become unstable to KH with detectable, unique ionospheric signatures. Further, we demonstrated a viable mechanism for the onset of reconnection at the magnetopause, examined the detailed structure of the boundary layer incorporating curvature effects, and provided an explanation for the large core fields observed within FTEs as well as flux ropes in the magnetotail.

Physics of Boundaries and their Interactions in Space Plasmas

NASA Technical Reports Server (NTRS)

Omidi, Nojan; Karimabadi, Homayoun; Krauss-Varban, Dietmar

1998-01-01

This final report describes a brief summary of our accomplishments during the complete contract period. Traditionally, due to computational limitations, it has been impossible to obtain a global view of the magnetosphere on ion time and spatial scales. As a result, kinetic-simulations have concentrated on the local structure of different magnetospheric discontinuities and boundaries. However, due to the emergence of low cost supercomputers, as well as by taking full advantage of latest advances in data mining and visualization technology, we were able to bypass our planned (proposed) regional simulations and proceed to large-scale 3-D and 2-D global hybrid simulations of the magnetosphere. As a result, although we are only finishing the second year of the proposed activity, much of the original scientific objectives have been surpassed and new avenues of investigation have been opened. Such simulations have led us to possible explanations of some long-standing issues in magnetospheric physics. They have also enables us to make a number of important discoveries predictions, which need to be looked for in satellite data. Examples include the finding that the bow shock can become unstable to the Kelvin-Helmholtz (KH), (2) the discovery of a mechanism for intermittent reconnection due to ion physics which may be relevant to the explanation of the recurrence rate of flux transfer events (FTEs), and (3) this finding that the current sheet in the near-Earth magnetotail region can become unstable to KH with detectable, unique ionospheric signatures. Further, we demonstrated a viable mechanism for the onset of reconnection at the magnetopause, examined the detailed structure of the boundary layer incorporating curvature effects, and provided an explanation for the large core fields observed within FTEs as well as flux ropes in the magnetotail.

A Stepwise Integrated Approach to Personalized Risk Predictions in Stage III Colorectal Cancer.

PubMed

Salvucci, Manuela; Würstle, Maximilian L; Morgan, Clare; Curry, Sarah; Cremona, Mattia; Lindner, Andreas U; Bacon, Orna; Resler, Alexa J; Murphy, Áine C; O'Byrne, Robert; Flanagan, Lorna; Dasgupta, Sonali; Rice, Nadege; Pilati, Camilla; Zink, Elisabeth; Schöller, Lisa M; Toomey, Sinead; Lawler, Mark; Johnston, Patrick G; Wilson, Richard; Camilleri-Broët, Sophie; Salto-Tellez, Manuel; McNamara, Deborah A; Kay, Elaine W; Laurent-Puig, Pierre; Van Schaeybroeck, Sandra; Hennessy, Bryan T; Longley, Daniel B; Rehm, Markus; Prehn, Jochen H M

2017-03-01

Purpose: Apoptosis is essential for chemotherapy responses. In this discovery and validation study, we evaluated the suitability of a mathematical model of apoptosis execution (APOPTO-CELL) as a stand-alone signature and as a constituent of further refined prognostic stratification tools. Experimental Design: Apoptosis competency of primary tumor samples from patients with stage III colorectal cancer ( n = 120) was calculated by APOPTO-CELL from measured protein concentrations of Procaspase-3, Procaspase-9, SMAC, and XIAP. An enriched APOPTO-CELL signature (APOPTO-CELL-PC3) was synthesized to capture apoptosome-independent effects of Caspase-3. Furthermore, a machine learning Random Forest approach was applied to APOPTO-CELL-PC3 and available molecular and clinicopathologic data to identify a further enhanced signature. Association of the signature with prognosis was evaluated in an independent colon adenocarcinoma cohort (TCGA COAD, n = 136). Results: We identified 3 prognostic biomarkers ( P = 0.04, P = 0.006, and P = 0.0004 for APOPTO-CELL, APOPTO-CELL-PC3, and Random Forest signatures, respectively) with increasing stratification accuracy for patients with stage III colorectal cancer.The APOPTO-CELL-PC3 signature ranked highest among all features. The prognostic value of the signatures was independently validated in stage III TCGA COAD patients ( P = 0.01, P = 0.04, and P = 0.02 for APOPTO-CELL, APOPTO-CELL-PC3, and Random Forest signatures, respectively). The signatures provided further stratification for patients with CMS1-3 molecular subtype. Conclusions: The integration of a systems-biology-based biomarker for apoptosis competency with machine learning approaches is an appealing and innovative strategy toward refined patient stratification. The prognostic value of apoptosis competency is independent of other available clinicopathologic and molecular factors, with tangible potential of being introduced in the clinical management of patients with stage III colorectal cancer. Clin Cancer Res; 23(5); 1200-12. ©2016 AACR . ©2016 American Association for Cancer Research.

Fatty acid signatures of stomach oil and adipose tissue of northern fulmars (Fulmarus glacialis) in Alaska: Implications for diet analysis of Procellariiform birds

USGS Publications Warehouse

Wang, S.W.; Iverson, S.J.; Springer, A.M.; Hatch, Shyla A.

2007-01-01

Procellariiforms are unique among seabirds in storing dietary lipids in both adipose tissue and stomach oil. Thus, both lipid sources are potentially useful for trophic studies using fatty acid (FA) signatures. However, little is known about the relationship between FA signatures in stomach oil and adipose tissue of individuals or whether these signatures provide similar information about diet and physiology. We compared the FA composition of stomach oil and adipose tissue biopsies of individual northern fulmars (N = 101) breeding at three major colonies in Alaska. Fatty acid signatures differed significantly between the two lipid sources, reflecting differences in dietary time scales, metabolic processing, or both. However, these signatures exhibited a relatively consistent relationship between individuals, such that the two lipid sources provided a similar ability to distinguish foraging differences among individuals and colonies. Our results, including the exclusive presence of dietary wax esters in stomach oil but not adipose tissue, are consistent with the notion that stomach oil FA signatures represent lipids retained from prey consumed during recent foraging and reflect little metabolic processing, whereas adipose tissue FA signatures represent a longer-term integration of dietary intake. Our study illustrates the potential for elucidating short- versus longer-term diet information in Procellariiform birds using different lipid sources. ?? 2007 Springer-Verlag.

Comparative Oncogenomics for Peripheral Nerve Sheath Cancer Gene Discovery

DTIC Science & Technology

2015-06-01

neurofibromas and MPNSTs, establish gene signatures defining distinct tumor subtypes and functionally test the role of selected driver mutations ...allografted tumor cells, and a variety of in vitro functional assays. We will validate the relevance of these mutated mouse genes in human neurofibromas...and MPNSTs by determining whether these same genes are mutated in human tumors. 15. SUBJECT TERMS Nothing listed 16. SECURITY CLASSIFICATION OF: 17

Development of high resolution target monitor.

DOT National Transportation Integrated Search

2008-01-01

The proposed High-resolution Target Movement Monitor uses triangulation theory but in a unique way. Unlike the commercially available triangulation systems which use sensing diodes to perceive reflected laser signatures and are limited to very short ...

Sediment Fingerprinting Using Carbon and Nitrogen Stable Isotopes in the Upper Palouse Watershed, Northwestern Idaho

NASA Astrophysics Data System (ADS)

Fox, J. F.; Papanicolaou, A. T.

2003-12-01

Unwarranted soil erosion creates detrimental problems for watershed users and for habitats and human infrastructure that experience increased suspended sediment in surface water. Identification and mitigation of erosion prone uplands relies on the realization that land uses (i.e. agriculture, forest, industrial, pasture, etc.) "produce sediment differently" at the watershed scale. Quantification of sediment production from various land uses is deemed feasible by using sediment-particle fingerprinting. This technique utilizes vegetative derived carbon (C) and nitrogen (N) stable isotopes and the carbon/nitrogen (C/N) atomic ratio of sediments to identify sediment producing land uses. Past research has established differences between C and N isotopic signatures and C/N ratios for soils under forest vs. agriculture (i.e. grasses and wheat) land cover. The current research rigorously examines these distinct signatures through isotopic analysis of field soils from the Palouse River Watershed of Northwestern Idaho preceded with statistical analyses to establish soil uniqueness. In addition, stream sediments are preliminarily analyzed to identify their origin with the goal of establishing a blueprint methodology for estimating sediment source and erosion rates within the watershed. Prior to field sampling of source soils, a statistical-experimental design was established with the intent to capture spatial and temporal variations and random errors of C and N isotopic signatures and C/N ratios within the forest and agriculture land uses. Factors including, elevation, slope topography, and season, were assessed by excavating over 300 samples during 4 seasons (i.e. May 2002, August 2002, November 2002, and March 2003) and at numerous locations throughout the watershed. Atomic analyses was performed at the University of Idaho Natural Resources Stable Isotope Laboratory using a Costech 4010 Elemental Combustion System connected with a continuous flow inlet system to the Finnigan MAT Delta Plus isotope ratio mass spectrometer. The statistical analysis of variance (ANOVA) with C and N isotopic signatures and C/N ratios as three independent response variables was administered to identify the agriculture and forested uniqueness, and discriminant analysis was used to create an organic fingerprint parameter which weights the contribution of C and N isotopic signatures and C/N ratios to the land cover separation. Results indicate uniqueness of the N isotope C/N ratio for the forest and agriculture sediment sources and little distinction possible for the C isotope signature. The organic fingerprint parameter was then calculated and coupled with in-stream sediment isotopic data using a simple end-member model. Preliminary results indicate that C and N isotopic signatures and C/N ratios will serve as a useful technique in quantifying erosive source rates and understanding upland erosion processes.

Characterization of palmprints by wavelet signatures via directional context modeling.

PubMed

Zhang, Lei; Zhang, David

2004-06-01

The palmprint is one of the most reliable physiological characteristics that can be used to distinguish between individuals. Current palmprint-based systems are more user friendly, more cost effective, and require fewer data signatures than traditional fingerprint-based identification systems. The principal lines and wrinkles captured in a low-resolution palmprint image provide more than enough information to uniquely identify an individual. This paper presents a palmprint identification scheme that characterizes a palmprint using a set of statistical signatures. The palmprint is first transformed into the wavelet domain, and the directional context of each wavelet subband is defined and computed in order to collect the predominant coefficients of its principal lines and wrinkles. A set of statistical signatures, which includes gravity center, density, spatial dispersivity and energy, is then defined to characterize the palmprint with the selected directional context values. A classification and identification scheme based on these signatures is subsequently developed. This scheme exploits the features of principal lines and prominent wrinkles sufficiently and achieves satisfactory results. Compared with the line-segments-matching or interesting-points-matching based palmprint verification schemes, the proposed scheme uses a much smaller amount of data signatures. It also provides a convenient classification strategy and more accurate identification.

MicroRNA profiling of human kidney cancer subtypes.

PubMed

Petillo, David; Kort, Eric J; Anema, John; Furge, Kyle A; Yang, Ximing J; Teh, Bin Tean

2009-07-01

Although the functions of most of the identified microRNAs (miRNAs) have yet to be determined, their use as potential biomarkers has been considered in several human diseases and cancers. In order to understand their role in renal tumorigenesis, we screened the expression levels of miRNAs in four subtypes of human renal neoplasms: clear cell, papillary, and chromophobe renal cell carcinomas (RCC) as well as benign renal oncocytomas. We found a unique miRNA signature for each subtype of renal tumor. Furthermore, we identified unique patterns of miRNA expression distinguishing clear cell RCC cases with favorable vs. unfavorable outcome. Specifically, we documented the overexpression of miRs 424 and 203 in clear cell RCC relative to papillary RCC, as well as the inversion of expression of miR-203 in the benign oncocytomas (where it is underexpressed relative to normal kidney) as compared to the malignant chromophobe RCC (where it is overexpressed relative to normal kidney). Our results further suggest that overexpression of S-has-miR-32 is associated with poor outcome. While previous studies have identified unique miRNA expression pattern distinguishing tumors from different anatomical locations, here we extend this principle to demonstrate the utility of miRNA expression profiling to identify a signature unique to various tumor subtypes at a single anatomic locus.

Common patterns and disease-related signatures in tuberculosis and sarcoidosis.

PubMed

Maertzdorf, Jeroen; Weiner, January; Mollenkopf, Hans-Joachim; Bauer, Torsten; Prasse, Antje; Müller-Quernheim, Joachim; Kaufmann, Stefan H E

2012-05-15

In light of the marked global health impact of tuberculosis (TB), strong focus has been on identifying biosignatures. Gene expression profiles in blood cells identified so far are indicative of a persistent activation of the immune system and chronic inflammatory pathology in active TB. Definition of a biosignature with unique specificity for TB demands that identified profiles can differentiate diseases with similar pathology, like sarcoidosis (SARC). Here, we present a detailed comparison between pulmonary TB and SARC, including whole-blood gene expression profiling, microRNA expression, and multiplex serum analytes. Our analysis reveals that previously disclosed gene expression signatures in TB show highly similar patterns in SARC, with a common up-regulation of proinflammatory pathways and IFN signaling and close similarity to TB-related signatures. microRNA expression also presented a highly similar pattern in both diseases, whereas cytokines in the serum of TB patients revealed a slightly elevated proinflammatory pattern compared with SARC and controls. Our results indicate several differences in expression between the two diseases, with increased metabolic activity and significantly higher antimicrobial defense responses in TB. However, matrix metallopeptidase 14 was identified as the most distinctive marker of SARC. Described communalities as well as unique signatures in blood profiles of two distinct inflammatory pulmonary diseases not only have considerable implications for the design of TB biosignatures and future diagnosis, but they also provide insights into biological processes underlying chronic inflammatory disease entities of different etiology.

Transcriptional profiling of pure fibrolamellar hepatocellular carcinoma reveals an endocrine signature.

PubMed

Malouf, Gabriel G; Job, Sylvie; Paradis, Valérie; Fabre, Monique; Brugières, Laurence; Saintigny, Pierre; Vescovo, Laure; Belghiti, Jacques; Branchereau, Sophie; Faivre, Sandrine; de Reyniès, Aurélien; Raymond, Eric

2014-06-01

Fibrolamellar hepatocellular carcinoma (FLC) is a rare subtype of liver cancer occurring mostly in children and young adults. We have shown that FLC comprises two separate entities: pure (p-FLC) and mixed-FLC (m-FLC), differing in clinical presentation and course. We show that p-FLCs have a distinct gene expression signature different from that of m-FLCs, which have a signature similar to that of classical hepatocellular carcinomas. We found p-FLC profiles to be unique among 263 profiles related to diverse tumoral and nontumoral liver samples. We identified two distinct molecular subgroups of p-FLCs with different outcomes. Pathway analysis of p-FLCs revealed ERBB2 overexpression and an up-regulation of glycolysis, possibly leading to compensatory mitochondrial hyperplasia and oncocytic differentiation. Four of the sixteen genes most significantly overexpressed in p-FLCs were neuroendocrine genes: prohormone convertase 1 (PCSK1); neurotensin; delta/notch-like EGF repeat containing; and calcitonin. PCSK1 overexpression was validated by immunohistochemistry, yielding specific, diffuse staining of the protein throughout the cytoplasm, possibly corresponding to a functional form of this convertase. p-FLCs have a unique transcriptomic signature characterized by the strong expression of specific neuroendocrine genes, suggesting that these tumors may have a cellular origin different from that of HCC. Our data have implications for the use of genomic profiling for diagnosis and selection of targeted therapies in patients with p-FLC. © 2014 by the American Association for the Study of Liver Diseases.

Bottlenose dolphins can use learned vocal labels to address each other

PubMed Central

King, Stephanie L.; Janik, Vincent M.

2013-01-01

In animal communication research, vocal labeling refers to incidents in which an animal consistently uses a specific acoustic signal when presented with a specific object or class of objects. Labeling with learned signals is a foundation of human language but is notably rare in nonhuman communication systems. In natural animal systems, labeling often occurs with signals that are not influenced by learning, such as in alarm and food calling. There is a suggestion, however, that some species use learned signals to label conspecific individuals in their own communication system when mimicking individually distinctive calls. Bottlenose dolphins (Tursiops truncatus) are a promising animal for exploration in this area because they are capable of vocal production learning and can learn to use arbitrary signals to report the presence or absence of objects. Bottlenose dolphins develop their own unique identity signal, the signature whistle. This whistle encodes individual identity independently of voice features. The copying of signature whistles may therefore allow animals to label or address one another. Here, we show that wild bottlenose dolphins respond to hearing a copy of their own signature whistle by calling back. Animals did not respond to whistles that were not their own signature. This study provides compelling evidence that a dolphin’s learned identity signal is used as a label when addressing conspecifics. Bottlenose dolphins therefore appear to be unique as nonhuman mammals to use learned signals as individually specific labels for different social companions in their own natural communication system. PMID:23878217

New insights to the use of ethanol in automotive fuels: a stable isotopic tracer for fossil- and bio-fuel combustion inputs to the atmosphere.

PubMed

Giebel, Brian M; Swart, Peter K; Riemer, Daniel D

2011-08-01

Ethanol is currently receiving increased attention because of its use as a biofuel or fuel additive and because of its influence on air quality. We used stable isotopic ratio measurements of (13)C/(12)C in ethanol emitted from vehicles and a small group of tropical plants to establish ethanol's δ(13)C end-member signatures. Ethanol emitted in exhaust is distinctly different from that emitted by tropical plants and can serve as a unique stable isotopic tracer for transportation-related inputs to the atmosphere. Ethanol's unique isotopic signature in fuel is related to corn, a C4 plant and the primary source of ethanol in the U.S. We estimated a kinetic isotope effect (KIE) for ethanol's oxidative loss in the atmosphere and used previous assumptions with respect to the fractionation that may occur during wet and dry deposition. A small number of interpretive model calculations were used for source apportionment of ethanol and to understand the associated effects resulting from atmospheric removal. The models incorporated our end-member signatures and ambient measurements of ethanol, known or estimated source strengths and removal magnitudes, and estimated KIEs associated with atmospheric removal processes for ethanol. We compared transportation-related ethanol signatures to those from biogenic sources and used a set of ambient measurements to apportion each source contribution in Miami, Florida-a moderately polluted, but well ventilated urban location.

Twenty-four signature genes predict the prognosis of oral squamous cell carcinoma with high accuracy and repeatability

PubMed Central

Gao, Jianyong; Tian, Gang; Han, Xu; Zhu, Qiang

2018-01-01

Oral squamous cell carcinoma (OSCC) is the sixth most common type cancer worldwide, with poor prognosis. The present study aimed to identify gene signatures that could classify OSCC and predict prognosis in different stages. A training data set (GSE41613) and two validation data sets (GSE42743 and GSE26549) were acquired from the online Gene Expression Omnibus database. In the training data set, patients were classified based on the tumor-node-metastasis staging system, and subsequently grouped into low stage (L) or high stage (H). Signature genes between L and H stages were selected by disparity index analysis, and classification was performed by the expression of these signature genes. The established classification was compared with the L and H classification, and fivefold cross validation was used to evaluate the stability. Enrichment analysis for the signature genes was implemented by the Database for Annotation, Visualization and Integration Discovery. Two validation data sets were used to determine the precise of classification. Survival analysis was conducted followed each classification using the package ‘survival’ in R software. A set of 24 signature genes was identified based on the classification model with the Fi value of 0.47, which was used to distinguish OSCC samples in two different stages. Overall survival of patients in the H stage was higher than those in the L stage. Signature genes were primarily enriched in ‘ether lipid metabolism’ pathway and biological processes such as ‘positive regulation of adaptive immune response’ and ‘apoptotic cell clearance’. The results provided a novel 24-gene set that may be used as biomarkers to predict OSCC prognosis with high accuracy, which may be used to determine an appropriate treatment program for patients with OSCC in addition to the traditional evaluation index. PMID:29257303

Quantum oscillations in nodal line systems

NASA Astrophysics Data System (ADS)

Yang, Hui; Moessner, Roderich; Lim, Lih-King

2018-04-01

We study signatures of magnetic quantum oscillations in three-dimensional nodal line semimetals at zero temperature. The extended nature of the degenerate bands can result in a Fermi surface geometry with topological genus one, as well as a Fermi surface of electron and hole pockets encapsulating the nodal line. Moreover, the underlying two-band model to describe a nodal line is not unique, in that there are two classes of Hamiltonian with distinct band topology giving rise to the same Fermi-surface geometry. After identifying the extremal cyclotron orbits in various magnetic field directions, we study their concomitant Landau levels and resulting quantum oscillation signatures. By Landau-fan-diagram analyses, we extract the nontrivial π Berry phase signature for extremal orbits linking the nodal line.

Phylogenomic analyses and molecular signatures for the class Halobacteria and its two major clades: a proposal for division of the class Halobacteria into an emended order Halobacteriales and two new orders, Haloferacales ord. nov. and Natrialbales ord. nov., containing the novel families Haloferacaceae fam. nov. and Natrialbaceae fam. nov.

PubMed

Gupta, Radhey S; Naushad, Sohail; Baker, Sheridan

2015-03-01

The Halobacteria constitute one of the largest groups within the Archaea. The hierarchical relationship among members of this large class, which comprises a single order and a single family, has proven difficult to determine based upon 16S rRNA gene trees and morphological and physiological characteristics. This work reports detailed phylogenetic and comparative genomic studies on >100 halobacterial (haloarchaeal) genomes containing representatives from 30 genera to investigate their evolutionary relationships. In phylogenetic trees reconstructed on the basis of 32 conserved proteins, using both neighbour-joining and maximum-likelihood methods, two major clades (clades A and B) encompassing nearly two-thirds of the sequenced haloarchaeal species were strongly supported. Clades grouping the same species/genera were also supported by the 16S rRNA gene trees and trees for several individual highly conserved proteins (RpoC, EF-Tu, UvrD, GyrA, EF-2/EF-G). In parallel, our comparative analyses of protein sequences from haloarchaeal genomes have identified numerous discrete molecular markers in the form of conserved signature indels (CSI) in protein sequences and conserved signature proteins (CSPs) that are found uniquely in specific groups of haloarchaea. Thirteen CSIs in proteins involved in diverse functions and 68 CSPs that are uniquely present in all or most genome-sequenced haloarchaea provide novel molecular means for distinguishing members of the class Halobacteria from all other prokaryotes. The members of clade A are distinguished from all other haloarchaea by the unique shared presence of two CSIs in the ribose operon protein and small GTP-binding protein and eight CSPs that are found specifically in members of this clade. Likewise, four CSIs in different proteins and five other CSPs are present uniquely in members of clade B and distinguish them from all other haloarchaea. Based upon their specific clustering in phylogenetic trees for different gene/protein sequences and the unique shared presence of large numbers of molecular signatures, members of clades A and B are indicated to be distinct from all other haloarchaea because of their uniquely shared evolutionary histories. Based upon these results, it is proposed that clades A and B be recognized as two new orders, Natrialbales ord. nov. and Haloferacales ord. nov., within the class Halobacteria, containing the novel families Natrialbaceae fam. nov. and Haloferacaceae fam. nov. Other members of the class Halobacteria that are not members of these two orders will remain part of the emended order Halobacteriales in an emended family Halobacteriaceae. © 2015 IUMS.

Magnetic resonance imaging-based cerebral tissue classification reveals distinct spatiotemporal patterns of changes after stroke in non-human primates.

PubMed

Bouts, Mark J R J; Westmoreland, Susan V; de Crespigny, Alex J; Liu, Yutong; Vangel, Mark; Dijkhuizen, Rick M; Wu, Ona; D'Arceuil, Helen E

2015-12-15

Spatial and temporal changes in brain tissue after acute ischemic stroke are still poorly understood. Aims of this study were three-fold: (1) to determine unique temporal magnetic resonance imaging (MRI) patterns at the acute, subacute and chronic stages after stroke in macaques by combining quantitative T2 and diffusion MRI indices into MRI 'tissue signatures', (2) to evaluate temporal differences in these signatures between transient (n = 2) and permanent (n = 2) middle cerebral artery occlusion, and (3) to correlate histopathology findings in the chronic stroke period to the acute and subacute MRI derived tissue signatures. An improved iterative self-organizing data analysis algorithm was used to combine T2, apparent diffusion coefficient (ADC), and fractional anisotropy (FA) maps across seven successive timepoints (1, 2, 3, 24, 72, 144, 240 h) which revealed five temporal MRI signatures, that were different from the normal tissue pattern (P < 0.001). The distribution of signatures between brains with permanent and transient occlusions varied significantly between groups (P < 0.001). Qualitative comparisons with histopathology revealed that these signatures represented regions with different histopathology. Two signatures identified areas of progressive injury marked by severe necrosis and the presence of gitter cells. Another signature identified less severe but pronounced neuronal and axonal degeneration, while the other signatures depicted tissue remodeling with vascular proliferation and astrogliosis. These exploratory results demonstrate the potential of temporally and spatially combined voxel-based methods to generate tissue signatures that may correlate with distinct histopathological features. The identification of distinct ischemic MRI signatures associated with specific tissue fates may further aid in assessing and monitoring the efficacy of novel pharmaceutical treatments for stroke in a pre-clinical and clinical setting.

Burkitt lymphoma is molecularly distinct from other lymphomas

Cancer.gov

Scientists have uncovered a number of molecular signatures in Burkitt lymphoma, including unique genetic alterations that promote cell survival, that are not found in other lymphomas. These findings provide the first genetic evidence that Burkitt lymphoma

Effect of Potent γ-Secretase Modulator in Human Neurons Derived From Multiple Presenilin 1–Induced Pluripotent Stem Cell Mutant Carriers

PubMed Central

Liu, Qing; Waltz, Shannon; Woodruff, Grace; Ouyang, Joe; Israel, Mason A.; Herrera, Cheryl; Sarsoza, Floyd; Tanzi, Rudolph E.; Koo, Edward H.; Ringman, John M.; Goldstein, Lawrence S. B.; Wagner, Steven L.; Yuan, Shauna H.

2015-01-01

Importance Although considerable effort has been expended developing drug candidates for Alzheimer disease, none have yet succeeded owing to the lack of efficacy or to safety concerns. One potential shortcoming of current approaches to Alzheimer disease drug discovery and development is that they rely primarily on transformed cell lines and animal models that substantially overexpress wild-type or mutant proteins. It is possible that drug development failures thus far are caused in part by the limits of these approaches, which do not accurately reveal how drug candidates will behave in naive human neuronal cells. Objective To analyze purified neurons derived from human induced pluripotent stem cells from patients carrying 3 different presenilin 1 (PS1) mutations and nondemented control individuals in the absence of any overexpression. We tested the efficacy of γ-secretase inhibitor and γ-secretase modulator (GSM) in neurons derived from both normal control and 3 PS1 mutations (A246E, H163R, and M146L). Design, Setting, and Participants Adult human skin biopsies were obtained from volunteers at the Alzheimer Disease Research Center, University of California, San Diego. Cell cultures were treated with γ-secretase inhibitor or GSM. Comparisons of total β-amyloid (Aβ) and Aβ peptides 38, 40, and 42 in the media were made between vehicle- vs drug-treated cultures. Main Outcomes and Measures Soluble Aβ levels in the media were measured by enzyme-linked immunosorbent assay. Results As predicted, mutant PS1 neurons exhibited an elevated Aβ42:Aβ40 ratio (P <.05) at the basal state as compared with the nondemented control neurons. Treatment with a potent non–nonsteroidal anti-inflammatory druglike GSM revealed a new biomarker signature that differs from all previous cell types and animals tested. This new signature was the same in both the mutant and control neurons and consisted of a reduction in Aβ42, Aβ40, and Aβ38 and in the Aβ42:Aβ40 ratio, with no change in the total Aβ levels. Conclusions and Relevance This biomarker discrepancy is likely due to overexpression of amyloid precursor protein in the transformed cellular models. Our results suggest that biomarker signatures obtained with such models are misleading and that human neurons derived from human induced pluripotent stem cells provide a unique signature that will more accurately reflect drug response in human patients and in cerebrospinal fluid biomarker changes observed during GSM treatment. PMID:25285942

Integrative ChIP-seq/Microarray Analysis Identifies a CTNNB1 Target Signature Enriched in Intestinal Stem Cells and Colon Cancer

PubMed Central

Watanabe, Kazuhide; Biesinger, Jacob; Salmans, Michael L.; Roberts, Brian S.; Arthur, William T.; Cleary, Michele; Andersen, Bogi; Xie, Xiaohui; Dai, Xing

2014-01-01

Background Deregulation of canonical Wnt/CTNNB1 (beta-catenin) pathway is one of the earliest events in the pathogenesis of colon cancer. Mutations in APC or CTNNB1 are highly frequent in colon cancer and cause aberrant stabilization of CTNNB1, which activates the transcription of Wnt target genes by binding to chromatin via the TCF/LEF transcription factors. Here we report an integrative analysis of genome-wide chromatin occupancy of CTNNB1 by chromatin immunoprecipitation coupled with high-throughput sequencing (ChIP-seq) and gene expression profiling by microarray analysis upon RNAi-mediated knockdown of CTNNB1 in colon cancer cells. Results We observed 3629 CTNNB1 binding peaks across the genome and a significant correlation between CTNNB1 binding and knockdown-induced gene expression change. Our integrative analysis led to the discovery of a direct Wnt target signature composed of 162 genes. Gene ontology analysis of this signature revealed a significant enrichment of Wnt pathway genes, suggesting multiple feedback regulations of the pathway. We provide evidence that this gene signature partially overlaps with the Lgr5+ intestinal stem cell signature, and is significantly enriched in normal intestinal stem cells as well as in clinical colorectal cancer samples. Interestingly, while the expression of the CTNNB1 target gene set does not correlate with survival, elevated expression of negative feedback regulators within the signature predicts better prognosis. Conclusion Our data provide a genome-wide view of chromatin occupancy and gene regulation of Wnt/CTNNB1 signaling in colon cancer cells. PMID:24651522

Integrative ChIP-seq/microarray analysis identifies a CTNNB1 target signature enriched in intestinal stem cells and colon cancer.

PubMed

Watanabe, Kazuhide; Biesinger, Jacob; Salmans, Michael L; Roberts, Brian S; Arthur, William T; Cleary, Michele; Andersen, Bogi; Xie, Xiaohui; Dai, Xing

2014-01-01

Deregulation of canonical Wnt/CTNNB1 (beta-catenin) pathway is one of the earliest events in the pathogenesis of colon cancer. Mutations in APC or CTNNB1 are highly frequent in colon cancer and cause aberrant stabilization of CTNNB1, which activates the transcription of Wnt target genes by binding to chromatin via the TCF/LEF transcription factors. Here we report an integrative analysis of genome-wide chromatin occupancy of CTNNB1 by chromatin immunoprecipitation coupled with high-throughput sequencing (ChIP-seq) and gene expression profiling by microarray analysis upon RNAi-mediated knockdown of CTNNB1 in colon cancer cells. We observed 3629 CTNNB1 binding peaks across the genome and a significant correlation between CTNNB1 binding and knockdown-induced gene expression change. Our integrative analysis led to the discovery of a direct Wnt target signature composed of 162 genes. Gene ontology analysis of this signature revealed a significant enrichment of Wnt pathway genes, suggesting multiple feedback regulations of the pathway. We provide evidence that this gene signature partially overlaps with the Lgr5+ intestinal stem cell signature, and is significantly enriched in normal intestinal stem cells as well as in clinical colorectal cancer samples. Interestingly, while the expression of the CTNNB1 target gene set does not correlate with survival, elevated expression of negative feedback regulators within the signature predicts better prognosis. Our data provide a genome-wide view of chromatin occupancy and gene regulation of Wnt/CTNNB1 signaling in colon cancer cells.

Radiomic signature of infiltration in peritumoral edema predicts subsequent recurrence in glioblastoma: implications for personalized radiotherapy planning.

PubMed

Rathore, Saima; Akbari, Hamed; Doshi, Jimit; Shukla, Gaurav; Rozycki, Martin; Bilello, Michel; Lustig, Robert; Davatzikos, Christos

2018-04-01

Standard surgical resection of glioblastoma, mainly guided by the enhancement on postcontrast T1-weighted magnetic resonance imaging (MRI), disregards infiltrating tumor within the peritumoral edema region (ED). Subsequent radiotherapy typically delivers uniform radiation to peritumoral FLAIR-hyperintense regions, without attempting to target areas likely to be infiltrated more heavily. Noninvasive in vivo delineation of the areas of tumor infiltration and prediction of early recurrence in peritumoral ED could assist in targeted intensification of local therapies, thereby potentially delaying recurrence and prolonging survival. This paper presents a method for estimating peritumoral edema infiltration using radiomic signatures determined via machine learning methods, and tests it on 90 patients with de novo glioblastoma. The generalizability of the proposed predictive model was evaluated via cross-validation in a discovery cohort ([Formula: see text]) and was subsequently evaluated in a replication cohort ([Formula: see text]). Spatial maps representing the likelihood of tumor infiltration and future early recurrence were compared with regions of recurrence on postresection follow-up studies with pathology confirmation. The cross-validated accuracy of our predictive infiltration model on the discovery and replication cohorts was 87.51% (odds ratio = 10.22, sensitivity = 80.65, and specificity = 87.63) and 89.54% (odds ratio = 13.66, sensitivity = 97.06, and specificity = 76.73), respectively. The radiomic signature of the recurrent tumor region revealed higher vascularity and cellularity when compared with the nonrecurrent region. The proposed model shows evidence that multiparametric pattern analysis from clinical MRI sequences can assist in in vivo estimation of the spatial extent and pattern of tumor recurrence in peritumoral edema, which may guide supratotal resection and/or intensification of postoperative radiation therapy.

Raman Spectral Signatures as Conformational Probes of Biomolecules

NASA Astrophysics Data System (ADS)

Golan, Amir; Mayorkas, Nitzan; Rosenwaks, Salman; Bar, Ilana

2009-06-01

A first application of ionization-loss stimulated Raman spectroscopy (ILSRS) for monitoring the spectral features of four conformers of a gas phase neurotransmitter (2-phenylethylamine) is reported. The Raman spectra of the conformers show bands that uniquely identify the conformational structure of the molecule and are well matched by density functional theory calculations. The measurement of spectral signatures by ILSRS in an extended spectral range, with a relatively convenient laser source, is extremely important, allowing enhanced accessibility to intra- and inter-molecular forces, which are significant in biological structure and activity.

Raman Spectral Signatures as Conformational Probes of Biomolecules

NASA Astrophysics Data System (ADS)

Bar, Ilana; Golan, Amir; Mayorkas, Nitzan; Rosenwaks, Salman

2009-03-01

A first application of ionization-loss stimulated Raman spectroscopy (ILSRS) monitoring the spectral features of four conformers of a gas phase neurotransmitter (2-phenylethylamine) is reported. The Raman spectra of the conformers show bands that uniquely identify the conformational structure of the molecule and are well matched by density functional theory calculations. The measurement of spectral signatures by ILSRS in an extended spectral range, with a relatively convenient laser source, is extremely important, allowing enhanced accessibility to intra- and inter-molecular forces, which are significant in biological structure and activity.

Stray field signatures of Néel textured skyrmions in Ir/Fe/Co/Pt multilayer films

NASA Astrophysics Data System (ADS)

Yagil, A.; Almoalem, A.; Soumyanarayanan, Anjan; Tan, Anthony K. C.; Raju, M.; Panagopoulos, C.; Auslaender, O. M.

2018-05-01

Skyrmions are nanoscale spin configurations with topological properties that hold great promise for spintronic devices. Here, we establish their Néel texture, helicity, and size in Ir/Fe/Co/Pt multilayer films by constructing a multipole expansion to model their stray field signatures and applying it to magnetic force microscopy images. Furthermore, the demonstrated sensitivity to inhomogeneity in skyrmion properties, coupled with a unique capability to estimate the pinning force governing dynamics, portend broad applicability in the burgeoning field of topological spin textures.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Rauch, Eric Benton

This report serves as a comprehensive overview of the Extended Storage of Used Nuclear Fuel work performed for the Material Protection, Accounting and Control Technologies campaign under the Department of Energy Office of Nuclear Energy. This paper describes a signature based on the source and fissile material distribution found within a population of used fuel assemblies combined with the neutron absorbers found within cask design that is unique to a specific cask with its specific arrangement of fuel. The paper describes all the steps used in producing and analyzing this signature from the beginning to the project end.

Note: Model identification and analysis of bivalent analyte surface plasmon resonance data.

PubMed

Tiwari, Purushottam Babu; Üren, Aykut; He, Jin; Darici, Yesim; Wang, Xuewen

2015-10-01

Surface plasmon resonance (SPR) is a widely used, affinity based, label-free biophysical technique to investigate biomolecular interactions. The extraction of rate constants requires accurate identification of the particular binding model. The bivalent analyte model involves coupled non-linear differential equations. No clear procedure to identify the bivalent analyte mechanism has been established. In this report, we propose a unique signature for the bivalent analyte model. This signature can be used to distinguish the bivalent analyte model from other biphasic models. The proposed method is demonstrated using experimentally measured SPR sensorgrams.

Gravitational Wave Signatures of Crystalline Color Superconductors

NASA Astrophysics Data System (ADS)

Lin, Lap-Ming

Deconfined quark matter may exist in a crystalline color-superconducing phase in the interiors of compact stars. One of the special properties of this exotic phase of matter is that it is extremely rigid and the corresponding shear modulus can be up to 1000 times larger than that of the neutron-star crust. In this paper, we review how the extreme rigidity of this crystalline phase of quark matter can lead to unique gravitational-wave signatures that may be detectable by the current or the next-generation gravitational-wave detectors.

Hypermutation and unique mutational signatures of occupational cholangiocarcinoma in printing workers exposed to haloalkanes.

PubMed

Mimaki, Sachiyo; Totsuka, Yukari; Suzuki, Yutaka; Nakai, Chikako; Goto, Masanori; Kojima, Motohiro; Arakawa, Hirofumi; Takemura, Shigekazu; Tanaka, Shogo; Marubashi, Shigeru; Kinoshita, Masahiko; Matsuda, Tomonari; Shibata, Tatsuhiro; Nakagama, Hitoshi; Ochiai, Atsushi; Kubo, Shoji; Nakamori, Shoji; Esumi, Hiroyasu; Tsuchihara, Katsuya

2016-08-01

Cholangiocarcinoma is a relatively rare cancer, but its incidence is increasing worldwide. Although several risk factors have been suggested, the etiology and pathogenesis of the majority of cholangiocarcinomas remain unclear. Recently, a high incidence of early-onset cholangiocarcinoma was reported among the workers of a printing company in Osaka, Japan. These workers underwent high exposure to organic solvents, mainly haloalkanes such as 1,2-dichloropropane (1,2-DCP) and/or dichloromethane. We performed whole-exome analysis on four cases of cholangiocarcinoma among the printing workers. An average of 44.8 somatic mutations was detected per Mb in the genome of the printing workers' cholangiocarcinoma tissues, approximately 30-fold higher than that found in control common cholangiocarcinoma tissues. Furthermore, C:G-to-T:A transitions with substantial strand bias as well as unique trinucleotide mutational changes of GpCpY to GpTpY and NpCpY to NpTpY or NpApY were predominant in all of the printing workers' cholangiocarcinoma genomes. These results were consistent with the epidemiological observation that they had been exposed to high concentrations of chemical compounds. Whole-genome analysis of Salmonella typhimurium strain TA100 exposed to 1,2-DCP revealed a partial recapitulation of the mutational signature in the printing workers' cholangiocarcinoma. Although our results provide mutational signatures unique to occupational cholangiocarcinoma, the underlying mechanisms of the disease should be further investigated by using appropriate model systems and by comparison with genomic data from other cancers. © The Author 2016. Published by Oxford University Press.

The opportunities of mining historical and collective data in drug discovery.

PubMed

Wassermann, Anne Mai; Lounkine, Eugen; Davies, John W; Glick, Meir; Camargo, L Miguel

2015-04-01

Vast amounts of bioactivity data have been generated for small molecules across public and corporate domains. Biological signatures, either derived from systematic profiling efforts or from existing historical assay data, have been successfully employed for small molecule mechanism-of-action elucidation, drug repositioning, hit expansion and screening subset design. This article reviews different types of biological descriptors and applications, and we demonstrate how biological data can outlive the original purpose or project for which it was generated. By comparing 150 HTS campaigns run at Novartis over the past decade on the basis of their active and inactive chemical matter, we highlight the opportunities and challenges associated with cross-project learning in drug discovery. Copyright © 2014 Elsevier Ltd. All rights reserved.

STS-39 Space Shuttle mission report

NASA Technical Reports Server (NTRS)

Fricke, Robert W.

1991-01-01

The STS-39 Space Shuttle Program Mission Report contains a summary of the vehicle subsystem operations during the fortieth flight of the Space Shuttle and the twelfth flight of the Orbiter Vehicle Discovery (OV-103). In addition to the Discovery vehicle, the flight vehicle consisted of the following: an External Tank (ET) (designated as ET-46 (LWT-39); three Space Shuttle main engines (SSME's) (serial numbers 2026, 2030, and 2029 in positions 1, 2, and 3, respectively); and two Solid Rocket Boosters (SRB's) designated as BI-043. The primary objective of this flight was to successfully perform the planned operations of the Infrared Background Signature Survey (IBSS), Air Force Payload (AFP)-675, Space Test Payload (STP)-1, and the Multipurpose Experiment Canister (MPEC) payloads.

STS-39 Space Shuttle mission report

NASA Astrophysics Data System (ADS)

Fricke, Robert W.

1991-06-01

The STS-39 Space Shuttle Program Mission Report contains a summary of the vehicle subsystem operations during the fortieth flight of the Space Shuttle and the twelfth flight of the Orbiter Vehicle Discovery (OV-103). In addition to the Discovery vehicle, the flight vehicle consisted of the following: an External Tank (ET) (designated as ET-46 (LWT-39); three Space Shuttle main engines (SSME's) (serial numbers 2026, 2030, and 2029 in positions 1, 2, and 3, respectively); and two Solid Rocket Boosters (SRB's) designated as BI-043. The primary objective of this flight was to successfully perform the planned operations of the Infrared Background Signature Survey (IBSS), Air Force Payload (AFP)-675, Space Test Payload (STP)-1, and the Multipurpose Experiment Canister (MPEC) payloads.

Systematic computation with functional gene-sets among leukemic and hematopoietic stem cells reveals a favorable prognostic signature for acute myeloid leukemia.

PubMed

Yang, Xinan Holly; Li, Meiyi; Wang, Bin; Zhu, Wanqi; Desgardin, Aurelie; Onel, Kenan; de Jong, Jill; Chen, Jianjun; Chen, Luonan; Cunningham, John M

2015-03-24

Genes that regulate stem cell function are suspected to exert adverse effects on prognosis in malignancy. However, diverse cancer stem cell signatures are difficult for physicians to interpret and apply clinically. To connect the transcriptome and stem cell biology, with potential clinical applications, we propose a novel computational "gene-to-function, snapshot-to-dynamics, and biology-to-clinic" framework to uncover core functional gene-sets signatures. This framework incorporates three function-centric gene-set analysis strategies: a meta-analysis of both microarray and RNA-seq data, novel dynamic network mechanism (DNM) identification, and a personalized prognostic indicator analysis. This work uses complex disease acute myeloid leukemia (AML) as a research platform. We introduced an adjustable "soft threshold" to a functional gene-set algorithm and found that two different analysis methods identified distinct gene-set signatures from the same samples. We identified a 30-gene cluster that characterizes leukemic stem cell (LSC)-depleted cells and a 25-gene cluster that characterizes LSC-enriched cells in parallel; both mark favorable-prognosis in AML. Genes within each signature significantly share common biological processes and/or molecular functions (empirical p = 6e-5 and 0.03 respectively). The 25-gene signature reflects the abnormal development of stem cells in AML, such as AURKA over-expression. We subsequently determined that the clinical relevance of both signatures is independent of known clinical risk classifications in 214 patients with cytogenetically normal AML. We successfully validated the prognosis of both signatures in two independent cohorts of 91 and 242 patients respectively (log-rank p < 0.0015 and 0.05; empirical p < 0.015 and 0.08). The proposed algorithms and computational framework will harness systems biology research because they efficiently translate gene-sets (rather than single genes) into biological discoveries about AML and other complex diseases.

Symbolic Metal Bit and Saddlebag Fastenings in a Middle Bronze Age Donkey Burial

PubMed Central

Bar-Oz, Guy; Nahshoni, Pirhiya; Motro, Hadas; Oren, Eliezer D.

2013-01-01

Here we report the unprecedented discovery of the skeleton of a ritually interred donkey with a metal horse bit in association with its teeth and saddlebag fastenings on its back. This discovery in the Middle Bronze Age III sacred precinct (1700/1650-1550 BCE) at Tel Haror, Israel, presents a unique combination of evidence for the early employment of equid harnessing equipment, both for chariot bridling (horse bit) and pack animals (saddlebags). The ritually deposited donkey with its unique accoutrements advances our understanding of the broad social and religious significance of equids in the Levantine Bronze Age, previously known mainly from textual and iconographical sources. PMID:23484046

Spatial and temporal diet segregation in northern fulmars Fulmarus glacialis breeding in Alaska: Insights from fatty acid signatures

USGS Publications Warehouse

Wang, S.W.; Iverson, S.J.; Springer, A.M.; Hatch, Shyla A.

2009-01-01

Northern fulmars Fulmarus glacialis in the North Pacific Ocean are opportunistic, generalist predators, yet their diets are poorly described; thus, relationships of fulmars to supporting food webs, their utility as indicators of variability in forage fish abundances, and their sensitivity to ecosystem change are not known. We employed fatty acid (FA) signature analysis of adipose tissue from adults (n = 235) and chicks (n = 33) to compare spatial, temporal, and age-related variation in diets of fulmars breeding at 3 colonies in Alaska. FA signatures of adult fulmars differed between colonies within years, and between seasons at individual colonies. Seasonal and spatial differences in signatures were greater than interannual differences at all colonies. Differences in FA signatures reflect differences in diets, probably because the breeding colonies are located in distinct ecoregions which create unique habitats for prey assemblages, and because interannual variation in the physical environment affects the availability of forage species. Differences between FA signatures of adults and chicks in 2003 and 2004 suggest that adults fed chicks different prey than they consumed themselves. Alternatively, if adults relied on the same prey as those fed to chicks, the differences in signatures could have resulted from partial digestion of prey items by adults before chicks were fed, or direct metabolism of FAs by chicks for tissue synthesis before FAs could be deposited into adipose tissue. ?? Inter-Research 2009.

Discovery Bottles: A Unique Inexpensive Tool for the K-2 Science Classroom

ERIC Educational Resources Information Center

Watson, Sandy

2008-01-01

Discover discovery bottles! These wide-mouth plastic containers of any size filled with objects of different kinds can be terrific tools for science explorations and a great way to cultivate science minds in a K-2 science classroom. In addition, the author has found them to be a useful, inexpensive, and engaging way to help students develop skills…

Molecular property diagnostic suite (MPDS): Development of disease-specific open source web portals for drug discovery.

PubMed

Nagamani, S; Gaur, A S; Tanneeru, K; Muneeswaran, G; Madugula, S S; Consortium, Mpds; Druzhilovskiy, D; Poroikov, V V; Sastry, G N

2017-11-01

Molecular property diagnostic suite (MPDS) is a Galaxy-based open source drug discovery and development platform. MPDS web portals are designed for several diseases, such as tuberculosis, diabetes mellitus, and other metabolic disorders, specifically aimed to evaluate and estimate the drug-likeness of a given molecule. MPDS consists of three modules, namely data libraries, data processing, and data analysis tools which are configured and interconnected to assist drug discovery for specific diseases. The data library module encompasses vast information on chemical space, wherein the MPDS compound library comprises 110.31 million unique molecules generated from public domain databases. Every molecule is assigned with a unique ID and card, which provides complete information for the molecule. Some of the modules in the MPDS are specific to the diseases, while others are non-specific. Importantly, a suitably altered protocol can be effectively generated for another disease-specific MPDS web portal by modifying some of the modules. Thus, the MPDS suite of web portals shows great promise to emerge as disease-specific portals of great value, integrating chemoinformatics, bioinformatics, molecular modelling, and structure- and analogue-based drug discovery approaches.

Ontology for Transforming Geo-Spatial Data for Discovery and Integration of Scientific Data

NASA Astrophysics Data System (ADS)

Nguyen, L.; Chee, T.; Minnis, P.

2013-12-01

Discovery and access to geo-spatial scientific data across heterogeneous repositories and multi-discipline datasets can present challenges for scientist. We propose to build a workflow for transforming geo-spatial datasets into semantic environment by using relationships to describe the resource using OWL Web Ontology, RDF, and a proposed geo-spatial vocabulary. We will present methods for transforming traditional scientific dataset, use of a semantic repository, and querying using SPARQL to integrate and access datasets. This unique repository will enable discovery of scientific data by geospatial bound or other criteria.

Drug discovery in an academic setting: playing to the strengths.

PubMed

Huryn, Donna M

2013-03-14

Drug discovery and medicinal chemistry initiatives in academia provide an opportunity to create a unique environment that is distinct from the traditional industrial model. Two characteristics of a university setting that are not usually associated with pharma are the ability to pursue high-risk projects and a depth of expertise, infrastructure, and capabilities in focused areas. Encouraging, supporting, and fostering drug discovery efforts that take advantage of these and other distinguishing characteristics of an academic setting can lead to novel and innovative therapies that might not be discovered otherwise.

Molecular signatures that are distinctive characteristics of the vertebrates and chordates and supporting a grouping of vertebrates with the tunicates.

PubMed

Gupta, Radhey S

2016-01-01

Members of the phylum Chordata and the subphylum Vertebrata are presently distinguished solely on the basis of morphological characteristics. The relationship of the vertebrates to the two non-vertebrate chordate subphyla is also a subject of debate. Analyses of protein sequences have identified multiple conserved signature indels (CSIs) that are specific for Chordata or for Vertebrata. Five CSIs in 4 important proteins are specific for the Vertebrata, whereas two other CSIs are uniquely found in all sequenced chordate species including Ciona intestinalis and Oikapleura dioica (Tunicates) as well as Branchiostoma floridae (Cephalochordates). The shared presence of these molecular signatures by all vertebrates/chordate species, but in no other animal taxa, strongly indicates that the genetic changes represented by the identified CSIs diagnose monophyletic groups. Two other discovered CSIs are uniquely shared by different vertebrate species and by either one (Ciona intestinalis) or both tunicate (Ciona and Oikapleura) species, but they are not found in Branchiostoma or other animal species. Specific presence of these CSIs in different vertebrates and either one or both tunicate species provides strong independent evidence that the vertebrate species are more closely related to the urochordates (tunicates) than to the cephalochordates. Copyright © 2015 Elsevier Inc. All rights reserved.

Solar Wind Plasma Interaction with Asteroid 16 Psyche: Implication for Formation Theories

NASA Astrophysics Data System (ADS)

Fatemi, Shahab; Poppe, Andrew R.

2018-01-01

The asteroid 16 Psyche is a primitive metal-rich asteroid that has not yet been visited by spacecraft. Based on remote observations, Psyche is most likely composed of iron and nickel metal; however, the history of its formation and solidification is still unknown. If Psyche is a remnant core of a differentiated planetesimal exposed by collisions, it opens a unique window toward understanding the cores of the terrestrial bodies, including the Earth and Mercury. If not, it is perhaps a reaccreted rubble pile that has never melted. In the former case, Psyche may have a remanent, dipolar magnetic field; in the latter case, Psyche may have no intrinsic field, but nevertheless would be a conductive object in the solar wind. We use Advanced Modeling Infrastructure in Space Simulation (AMITIS), a three-dimensional GPU-based hybrid model of plasma that self-consistently couples the interior electromagnetic response of Psyche (i.e., magnetic diffusion) to its ambient plasma environment in order to quantify the different interactions under these two cases. The model results provide estimates for the electromagnetic environment of Psyche, showing that the magnetized case and the conductive case present very different signatures in the solar wind. These results have implications for an accurate interpretation of magnetic field observations by NASA's Discovery mission (Psyche mission) to the asteroid 16 Psyche.

The γ Dor stars as revealed by Kepler: A key to reveal deep-layer rotation in A and F stars

NASA Astrophysics Data System (ADS)

Salmon, S. J. A. J.; Ouazzani, R.-M.; Antoci, V.; Bedding, T. R.; Murphy, S. J.

2017-09-01

The γ Dor pulsating stars present high-order gravity modes, which make them important targets in the intermediate-and low-mass main-sequence region of the Hertzsprung-Russell diagram. Whilst we have only access to rotation in the envelope of the Sun, the g modes of γ Dor stars can in principle deliver us constraints on the inner layers. With the puzzling discovery of unexpectedly low rotation rates in the core of red giants, the γ Dor stars appear now as unique targets to explore internal angular momentum transport in the progenitors of red giants. Yet, the γ Dor pulsations remain hard to detect from the ground for their periods are close to 1 day. While the CoRoT space mission first revealed intriguing frequency spectra, the almost uninterrupted 4-year photometry from the Kepler mission eventually shed a new light on them. It revealed regularities in the spectra, expected to bear signature of physical processes, including rotation, in the shear layers close to the convective core. We present here the first results of our effort to derive exploitable seismic diagnosis for mid- to fast rotators among γ Dor stars. We confirm their potential to explore the rotation history of this early phase of stellar evolution.

Self-Assembled Resonance Energy Transfer Keys for Secure Communication over Classical Channels.

PubMed

Nellore, Vishwa; Xi, Sam; Dwyer, Chris

2015-12-22

Modern authentication and communication protocols increasingly use physical keys in lieu of conventional software-based keys for security. This shift is primarily driven by the ability to derive a unique, unforgeable signature from a physical key. The sole demonstration of an unforgeable key, thus far, has been through quantum key distribution, which suffers from limited communication distances and expensive infrastructure requirements. Here, we show a method for creating unclonable keys by molecular self-assembly of resonance energy transfer (RET) devices. It is infeasible to clone the RET-key due to the inability to characterize the key using current technology, the large number of input-output combinations per key, and the variation of the key's response with time. However, the manufacturer can produce multiple identical devices, which enables inexpensive, secure authentication and communication over classical channels, and thus any distance. Through a detailed experimental survey of the nanoscale keys, we demonstrate that legitimate users are successfully authenticated 99.48% of the time and the false-positives are only 0.39%, over two attempts. We estimate that a legitimate user would have a computational advantage of more than 10(340) years over an attacker. Our method enables the discovery of physical key based multiparty authentication and communication schemes that are both practical and possess unprecedented security.

Microbial Lifestyle and Genome Signatures

PubMed Central

Dutta, Chitra; Paul, Sandip

2012-01-01

Microbes are known for their unique ability to adapt to varying lifestyle and environment, even to the extreme or adverse ones. The genomic architecture of a microbe may bear the signatures not only of its phylogenetic position, but also of the kind of lifestyle to which it is adapted. The present review aims to provide an account of the specific genome signatures observed in microbes acclimatized to distinct lifestyles or ecological niches. Niche-specific signatures identified at different levels of microbial genome organization like base composition, GC-skew, purine-pyrimidine ratio, dinucleotide abundance, codon bias, oligonucleotide composition etc. have been discussed. Among the specific cases highlighted in the review are the phenomena of genome shrinkage in obligatory host-restricted microbes, genome expansion in strictly intra-amoebal pathogens, strand-specific codon usage in intracellular species, acquisition of genome islands in pathogenic or symbiotic organisms, discriminatory genomic traits of marine microbes with distinct trophic strategies, and conspicuous sequence features of certain extremophiles like those adapted to high temperature or high salinity. PMID:23024607

Observational Signatures of Magnetic Reconnection in the Extended Corona

NASA Technical Reports Server (NTRS)

Savage, Sabrina; West, Matthew J.; Seaton, Daniel B.; Kobelski, Adam

2016-01-01

Observational signatures of reconnection have been studied extensively in the lower corona for decades, successfully providing insight into energy release mechanisms in the region above post-flare arcade loops and below 1.5 solar radii. During large eruptive events, however, energy release continues to occur well beyond the presence of reconnection signatures at these low heights. Supra-Arcade Downflows (SADs) and Supra-Arcade Downflowing Loops (SADLs) are particularly useful measures of continual reconnection in the corona as they may indicate the presence and path of retracting post-reconnection loops. SADs and SADLs have been faintly observed up to 18 hours beyond the passage of coronas mass ejections through the SOHO/LASCO field of view, but a recent event from 2014 October 14 associated with giant arches provides very clear observations of these downflows for days after the initial eruption. We report on this unique event and compare these findings with observational signatures of magnetic reconnection in the extended corona for more typical eruptions.

Observational Signatures of Magnetic Reconnection in the Extended Corona

NASA Technical Reports Server (NTRS)

Savage, Sabrina; West, Matthew J.; Seaton, Danial B.; Kobelski, Adam

2016-01-01

Observational signatures of reconnection have been studied extensively in the lower corona for decades, successfully providing insight into energy release mechanisms in the region above post-flare arcade loops and below 1.5 solar radii. During large eruptive events, however, energy release continues to occur well beyond the presence of reconnection signatures at these low heights. Supra-Arcade Downflows (SADs) and Supra-Arcade Downflowing Loops (SADLs) are particularly useful measures of continual reconnection in the corona as they may indicate the presence and path of retracting post-reconnection loops. SADs and SADLs have been faintly observed up to 18 hours beyond the passage of corona mass ejections through the SOHO/LASCO field of view, but a recent event from 2014 October 14 associated with giant arches provides very clear observations of these downflows for days after the initial eruption. We report on this unique event and compare these findings with observational signatures of magnetic reconnection in the extended corona for more typical eruptions.

Observational Signatures of Magnetic Reconnection in the Extended Corona

NASA Technical Reports Server (NTRS)

Savage, Sabrina; West, Matthew J.; Seaton, Daniel B.; Kobelski, Adam

2017-01-01

Observational signatures of reconnection have been studied extensively in the lower corona for decades, successfully providing insight into energy release mechanisms in the region above post-flare arcade loops and below 1.5 solar radii. During large eruptive events, however, energy release continues to occur well beyond the presence of reconnection signatures at these low heights. Supra-Arcade Downflows (SADs) and Supra-Arcade Downflowing Loops (SADLs) are particularly useful measures of continual reconnection in the corona as they may indicate the presence and path of retracting post-reconnection loops. SADs and SADLs have been faintly observed up to 18 hours beyond the passage of corona mass ejections through the SOHO/LASCO field of view, but a recent event from 2014 October 14 associated with giant arches provides very clear observations of these downflows for days after the initial eruption. We report on this unique event and compare these findings with observational signatures of magnetic reconnection in the extended corona for more typical eruptions.

Isotopic signatures and distribution of nitrogen and trapped and radiogenic xenon in the Acapulco and FRO90011 meteorites

NASA Technical Reports Server (NTRS)

Kim, Y.; Marti, K.

1993-01-01

Acapulco metal and silicate show distinct N isotopic signatures. Trapped heavy noble gases are carried by 'magnetic' opx and radiogenic Xe-129 excesses are observed in phosphate and in minor surficial phases on metal grains. N and Xe isotopic signatures in FRO90011 do not agree with those observed in Acapulco. The Acapulco meteorite is unique in having achondritic texture and chondritic composition. Its mineralogical study shows the record of high temperature (1100 C) recrystallization. However, this meteorite shows abundances of volatile elements close to the levels observed in carbonaceous chondrites and concentrations of heavy noble gases comparable to those observed in type 4 ordinary chondrites, not expected for a presumed highly equilibrated object. Nitrogen measurements in bulk Acapulco revealed two different isotopic signatures, in apparent conflict with evidence for a high degree of recrystallization. N and Xe were studied in separated mineral phases to search for the carriers in order to better understand the formation and thermal history of the Acapulco parent body.

Standing Out From the Crowd: New Fish Recruits Have Unique δ15N Signatures in a Heavily Polluted Intermittently Open Estuary.

NASA Astrophysics Data System (ADS)

Hadwen, W. L.; Arthington, A. H.

2005-05-01

Intermittently open estuaries (IOEs) are the dominant coastal ecosystems of the Australian coastline. Conditions in IOEs range from freshwater when closed, to marine when open to the ocean, during which time marine fish often migrate into these systems. Many IOEs are facing increasing pressure from coastal development and ongoing nutrient inputs from industrial and urban sources have been shown to increase the δ15N isotope signatures of biota in receiving waters. In this study, we examined the food web structure of Tallows Creek, a relatively small IOE in northern NSW, Australia, which receives ongoing sewage treatment plant inputs. We first sampled Tallows Creek when it was closed to the ocean and found that all components of the food web had enriched δ15N signatures relative to biota sampled from a relatively undisturbed neighbouring system. However, samples collected immediately following an entrance opening event revealed some individuals of highly mobile taxa with δ15N signatures more typical of unpolluted estuaries. We suggest that these isotopically light individuals were recent migrants into Tallows Creek and that δ15N signatures can act as a guide to the importance of heavily polluted systems as nursery grounds for mobile taxa, owing to the distinction between resident and migrant signatures.

MAOA gene hypomethylation in panic disorder—reversibility of an epigenetic risk pattern by psychotherapy

PubMed Central

Ziegler, C; Richter, J; Mahr, M; Gajewska, A; Schiele, M A; Gehrmann, A; Schmidt, B; Lesch, K-P; Lang, T; Helbig-Lang, S; Pauli, P; Kircher, T; Reif, A; Rief, W; Vossbeck-Elsebusch, A N; Arolt, V; Wittchen, H-U; Hamm, A O; Deckert, J; Domschke, K

2016-01-01

Epigenetic signatures such as methylation of the monoamine oxidase A (MAOA) gene have been found to be altered in panic disorder (PD). Hypothesizing temporal plasticity of epigenetic processes as a mechanism of successful fear extinction, the present psychotherapy-epigenetic study for we believe the first time investigated MAOA methylation changes during the course of exposure-based cognitive behavioral therapy (CBT) in PD. MAOA methylation was compared between N=28 female Caucasian PD patients (discovery sample) and N=28 age- and sex-matched healthy controls via direct sequencing of sodium bisulfite-treated DNA extracted from blood cells. MAOA methylation was furthermore analyzed at baseline (T0) and after a 6-week CBT (T1) in the discovery sample parallelized by a waiting time in healthy controls, as well as in an independent sample of female PD patients (N=20). Patients exhibited lower MAOA methylation than healthy controls (P<0.001), and baseline PD severity correlated negatively with MAOA methylation (P=0.01). In the discovery sample, MAOA methylation increased up to the level of healthy controls along with CBT response (number of panic attacks; T0–T1: +3.37±2.17%), while non-responders further decreased in methylation (−2.00±1.28% P=0.001). In the replication sample, increases in MAOA methylation correlated with agoraphobic symptom reduction after CBT (P=0.02–0.03). The present results support previous evidence for MAOA hypomethylation as a PD risk marker and suggest reversibility of MAOA hypomethylation as a potential epigenetic correlate of response to CBT. The emerging notion of epigenetic signatures as a mechanism of action of psychotherapeutic interventions may promote epigenetic patterns as biomarkers of lasting extinction effects. PMID:27045843

MAOA gene hypomethylation in panic disorder-reversibility of an epigenetic risk pattern by psychotherapy.

PubMed

Ziegler, C; Richter, J; Mahr, M; Gajewska, A; Schiele, M A; Gehrmann, A; Schmidt, B; Lesch, K-P; Lang, T; Helbig-Lang, S; Pauli, P; Kircher, T; Reif, A; Rief, W; Vossbeck-Elsebusch, A N; Arolt, V; Wittchen, H-U; Hamm, A O; Deckert, J; Domschke, K

2016-04-05

Epigenetic signatures such as methylation of the monoamine oxidase A (MAOA) gene have been found to be altered in panic disorder (PD). Hypothesizing temporal plasticity of epigenetic processes as a mechanism of successful fear extinction, the present psychotherapy-epigenetic study for we believe the first time investigated MAOA methylation changes during the course of exposure-based cognitive behavioral therapy (CBT) in PD. MAOA methylation was compared between N=28 female Caucasian PD patients (discovery sample) and N=28 age- and sex-matched healthy controls via direct sequencing of sodium bisulfite-treated DNA extracted from blood cells. MAOA methylation was furthermore analyzed at baseline (T0) and after a 6-week CBT (T1) in the discovery sample parallelized by a waiting time in healthy controls, as well as in an independent sample of female PD patients (N=20). Patients exhibited lower MAOA methylation than healthy controls (P<0.001), and baseline PD severity correlated negatively with MAOA methylation (P=0.01). In the discovery sample, MAOA methylation increased up to the level of healthy controls along with CBT response (number of panic attacks; T0-T1: +3.37±2.17%), while non-responders further decreased in methylation (-2.00±1.28%; P=0.001). In the replication sample, increases in MAOA methylation correlated with agoraphobic symptom reduction after CBT (P=0.02-0.03). The present results support previous evidence for MAOA hypomethylation as a PD risk marker and suggest reversibility of MAOA hypomethylation as a potential epigenetic correlate of response to CBT. The emerging notion of epigenetic signatures as a mechanism of action of psychotherapeutic interventions may promote epigenetic patterns as biomarkers of lasting extinction effects.

L1000CDS2: LINCS L1000 characteristic direction signatures search engine.

PubMed

Duan, Qiaonan; Reid, St Patrick; Clark, Neil R; Wang, Zichen; Fernandez, Nicolas F; Rouillard, Andrew D; Readhead, Ben; Tritsch, Sarah R; Hodos, Rachel; Hafner, Marc; Niepel, Mario; Sorger, Peter K; Dudley, Joel T; Bavari, Sina; Panchal, Rekha G; Ma'ayan, Avi

2016-01-01

The library of integrated network-based cellular signatures (LINCS) L1000 data set currently comprises of over a million gene expression profiles of chemically perturbed human cell lines. Through unique several intrinsic and extrinsic benchmarking schemes, we demonstrate that processing the L1000 data with the characteristic direction (CD) method significantly improves signal to noise compared with the MODZ method currently used to compute L1000 signatures. The CD processed L1000 signatures are served through a state-of-the-art web-based search engine application called L1000CDS 2 . The L1000CDS 2 search engine provides prioritization of thousands of small-molecule signatures, and their pairwise combinations, predicted to either mimic or reverse an input gene expression signature using two methods. The L1000CDS 2 search engine also predicts drug targets for all the small molecules profiled by the L1000 assay that we processed. Targets are predicted by computing the cosine similarity between the L1000 small-molecule signatures and a large collection of signatures extracted from the gene expression omnibus (GEO) for single-gene perturbations in mammalian cells. We applied L1000CDS 2 to prioritize small molecules that are predicted to reverse expression in 670 disease signatures also extracted from GEO, and prioritized small molecules that can mimic expression of 22 endogenous ligand signatures profiled by the L1000 assay. As a case study, to further demonstrate the utility of L1000CDS 2 , we collected expression signatures from human cells infected with Ebola virus at 30, 60 and 120 min. Querying these signatures with L1000CDS 2 we identified kenpaullone, a GSK3B/CDK2 inhibitor that we show, in subsequent experiments, has a dose-dependent efficacy in inhibiting Ebola infection in vitro without causing cellular toxicity in human cell lines. In summary, the L1000CDS 2 tool can be applied in many biological and biomedical settings, while improving the extraction of knowledge from the LINCS L1000 resource.

Gene Signature in Sessile Serrated Polyps Identifies Colon Cancer Subtype

PubMed Central

Kanth, Priyanka; Bronner, Mary P.; Boucher, Kenneth M.; Burt, Randall W.; Neklason, Deborah W.; Hagedorn, Curt H.; Delker, Don A.

2016-01-01

Sessile serrated colon adenoma/polyps (SSA/Ps) are found during routine screening colonoscopy and may account for 20–30% of colon cancers. However, differentiating SSA/Ps from hyperplastic polyps (HP) with little risk of cancer is challenging and complementary molecular markers are needed. Additionally, the molecular mechanisms of colon cancer development from SSA/Ps are poorly understood. RNA sequencing was performed on 21 SSA/Ps, 10 HPs, 10 adenomas, 21 uninvolved colon and 20 control colon specimens. Differential expression and leave-one-out cross validation methods were used to define a unique gene signature of SSA/Ps. Our SSA/P gene signature was evaluated in colon cancer RNA-Seq data from The Cancer Genome Atlas (TCGA) to identify a subtype of colon cancers that may develop from SSA/Ps. A total of 1422 differentially expressed genes were found in SSA/Ps relative to controls. Serrated polyposis syndrome (n=12) and sporadic SSA/Ps (n=9) exhibited almost complete (96%) gene overlap. A 51-gene panel in SSA/P showed similar expression in a subset of TCGA colon cancers with high microsatellite instability (MSI-H). A smaller seven-gene panel showed high sensitivity and specificity in identifying BRAF mutant, CpG island methylator phenotype high (CIMP-H) and MLH1 silenced colon cancers. We describe a unique gene signature in SSA/Ps that identifies a subset of colon cancers likely to develop through the serrated pathway. These gene panels may be utilized for improved differentiation of SSA/Ps from HPs and provide insights into novel molecular pathways altered in colon cancer arising from the serrated pathway. PMID:27026680

From Extrasolar Planets to Exo-Earths

NASA Astrophysics Data System (ADS)

Fischer, Debra

2018-06-01

The ancient Greeks debated whether the Earth was unique, or innumerable worlds existed around other Suns. Twenty five years ago, technology and human ingenuity enabled the discovery of the first extrasolar planet candidates. The architectures of these first systems, with gas giant planets in star-skirting orbits, were unexpected and again raised an echo of that ancient question: is the Earth typical or unique? We are interested in this seemingly anthropocentric question because with all of our searching and discoveries, Earth is the only place where life has been found. It is the question of whether life exists elsewhere that energizes the search for exoplanets. The trajectory of this field has been stunning. After a steady stream of detections with the radial velocity method, a burst of discovery was made possible with the NASA Kepler mission. While thousands of smaller planets have now been found, true Earth analogs have eluded robust detection. However, we are sharpening the knives of our technology and without a doubt we now stand at the threshold of detecting hundreds of Earth analogs. Using Gaia, TESS, WFIRST, JWST and new ground-based spectrographs, we will learn the names and addresses of the worlds that orbit nearby stars and we will be ready to probe their atmospheres. We will finally resolve the ancient question of whether life is unique or common.

The sRNAome mining revealed existence of unique signature small RNAs derived from 5.8SrRNA from Piper nigrum and other plant lineages.

PubMed

Asha, Srinivasan; Soniya, E V

2017-02-01

Small RNAs derived from ribosomal RNAs (srRNAs) are rarely explored in the high-throughput data of plant systems. Here, we analyzed srRNAs from the deep-sequenced small RNA libraries of Piper nigrum, a unique magnoliid plant. The 5' end of the putative long form of 5.8S rRNA (5.8S L rRNA) was identified as the site for biogenesis of highly abundant srRNAs that are unique among the Piperaceae family of plants. A subsequent comparative analysis of the ninety-seven sRNAomes of diverse plants successfully uncovered the abundant existence and precise cleavage of unique rRF signature small RNAs upstream of a novel 5' consensus sequence of the 5.8S rRNA. The major cleavage process mapped identically among the different tissues of the same plant. The differential expression and cleavage of 5'5.8S srRNAs in Phytophthora capsici infected P. nigrum tissues indicated the critical biological functions of these srRNAs during stress response. The non-canonical short hairpin precursor structure, the association with Argonaute proteins, and the potential targets of 5'5.8S srRNAs reinforced their regulatory role in the RNAi pathway in plants. In addition, this novel lineage specific small RNAs may have tremendous biological potential in the taxonomic profiling of plants.

The sRNAome mining revealed existence of unique signature small RNAs derived from 5.8SrRNA from Piper nigrum and other plant lineages

PubMed Central

Asha, Srinivasan; Soniya, E. V.

2017-01-01

Small RNAs derived from ribosomal RNAs (srRNAs) are rarely explored in the high-throughput data of plant systems. Here, we analyzed srRNAs from the deep-sequenced small RNA libraries of Piper nigrum, a unique magnoliid plant. The 5′ end of the putative long form of 5.8S rRNA (5.8SLrRNA) was identified as the site for biogenesis of highly abundant srRNAs that are unique among the Piperaceae family of plants. A subsequent comparative analysis of the ninety-seven sRNAomes of diverse plants successfully uncovered the abundant existence and precise cleavage of unique rRF signature small RNAs upstream of a novel 5′ consensus sequence of the 5.8S rRNA. The major cleavage process mapped identically among the different tissues of the same plant. The differential expression and cleavage of 5′5.8S srRNAs in Phytophthora capsici infected P. nigrum tissues indicated the critical biological functions of these srRNAs during stress response. The non-canonical short hairpin precursor structure, the association with Argonaute proteins, and the potential targets of 5′5.8S srRNAs reinforced their regulatory role in the RNAi pathway in plants. In addition, this novel lineage specific small RNAs may have tremendous biological potential in the taxonomic profiling of plants. PMID:28145468

Composition of Meridiani Hematite-rich Spherules: A Mass-Balance Mixing-Model Approach

NASA Technical Reports Server (NTRS)

jOLLIFF, b. l.

2005-01-01

One of the great surprises of the Mars Exploration Rovers (MER) mission is the discovery at Meridiani Planum that the surface hematite signature observed from orbit is attributable largely to a surface enrichment of hematite-rich spherules, thought to be concretions, that have weathered out of rocks similar to the underlying sulfate-rich rock formation [1]. A strong hematite signature has been observed by the Mini-TES [2] and by in-situ measurements of spherule-rich targets by the Mossbauer spectrometer (MB) [3] and the alpha-particle X-ray spectrometer (APXS) [4]. The Mini-TES derived spectrum of spherule-rich targets on the plains is consistent with nearly pure coarse-grained hematite, with perhaps as little as 5-10 areal % of other components [2]. The occurrence and abundance of the spherules as the bearer of the widespread hematite signature observed by MGS TES over much of Meridiani Planum is significant for global remote sensing, and their occurrence as concretions in the outcrop lithology is significant for the diagenetic history and role of water in the formation of the sedimentary rock formation [5].

Orphan diseases: state of the drug discovery art.

PubMed

Volmar, Claude-Henry; Wahlestedt, Claes; Brothers, Shaun P

2017-06-01

Since 1983 more than 300 drugs have been developed and approved for orphan diseases. However, considering the development of novel diagnosis tools, the number of rare diseases vastly outpaces therapeutic discovery. Academic centers and nonprofit institutes are now at the forefront of rare disease R&D, partnering with pharmaceutical companies when academic researchers discover novel drugs or targets for specific diseases, thus reducing the failure risk and cost for pharmaceutical companies. Considerable progress has occurred in the art of orphan drug discovery, and a symbiotic relationship now exists between pharmaceutical industry, academia, and philanthropists that provides a useful framework for orphan disease therapeutic discovery. Here, the current state-of-the-art of drug discovery for orphan diseases is reviewed. Current technological approaches and challenges for drug discovery are considered, some of which can present somewhat unique challenges and opportunities in orphan diseases, including the potential for personalized medicine, gene therapy, and phenotypic screening.

Probing light sterile neutrino signatures at reactor and Spallation Neutron Source neutrino experiments

NASA Astrophysics Data System (ADS)

Kosmas, T. S.; Papoulias, D. K.; Tórtola, M.; Valle, J. W. F.

2017-09-01

We investigate the impact of a fourth sterile neutrino at reactor and Spallation Neutron Source neutrino detectors. Specifically, we explore the discovery potential of the TEXONO and COHERENT experiments to subleading sterile neutrino effects through the measurement of the coherent elastic neutrino-nucleus scattering event rate. Our dedicated χ2-sensitivity analysis employs realistic nuclear structure calculations adequate for high purity sub-keV threshold Germanium detectors.

FHIR Healthcare Directories: Adopting Shared Interfaces to Achieve Interoperable Medical Device Data Integration.

PubMed

Tyndall, Timothy; Tyndall, Ayami

2018-01-01

Healthcare directories are vital for interoperability among healthcare providers, researchers and patients. Past efforts at directory services have not provided the tools to allow integration of the diverse data sources. Many are overly strict, incompatible with legacy databases, and do not provide Data Provenance. A more architecture-independent system is needed to enable secure, GDPR-compatible (8) service discovery across organizational boundaries. We review our development of a portable Data Provenance Toolkit supporting provenance within Health Information Exchange (HIE) systems. The Toolkit has been integrated with client software and successfully leveraged in clinical data integration. The Toolkit validates provenance stored in a Blockchain or Directory record and creates provenance signatures, providing standardized provenance that moves with the data. This healthcare directory suite implements discovery of healthcare data by HIE and EHR systems via FHIR. Shortcomings of past directory efforts include the ability to map complex datasets and enabling interoperability via exchange endpoint discovery. By delivering data without dictating how it is stored we improve exchange and facilitate discovery on a multi-national level through open source, fully interoperable tools. With the development of Data Provenance resources we enhance exchange and improve security and usability throughout the health data continuum.

Fatty acid methyl ester (FAME) technology for monitoring biological foaming in activated sludge: full scale plant verification.

PubMed

Lee, J W; Cha, D K; Kim, I; Son, A; Ahn, K H

2008-02-01

Fatty acid methyl ester (FAME) technology was evaluated as a monitoring tool for quantification of Gordonia amarae in activated sludge systems. The fatty acid, 19:1 alcohol, which was identified as a unique fatty acid in G. amarae was not only confirmed to be present in foaming plant samples, but the quantity of the signature peak correlated closely with the degree of foaming. Foaming potential experiment provided a range of critical foaming levels that corresponded to G. amarae population. This range of critical Gordonia levels was correlated to the threshold signature FAME amount. Six full-scale wastewater treatment plants were selected based on a survey to participate in our full-scale study to evaluate the potential application of the FAME technique as the Gordonia monitoring tool. Greater amounts of signature FAME were extracted from the mixed liquor samples obtained from treatment plants experiencing Gordonia foaming problems. The amounts of signature FAME correlated well with the conventional filamentous counting technique. These results demonstrated that the relative abundance of the signature FAMEs can be used to quantitatively monitor the abundance of foam-causing microorganism in activated sludge.

Identification of Single- and Multiple-Class Specific Signature Genes from Gene Expression Profiles by Group Marker Index

PubMed Central

Tsai, Yu-Shuen; Aguan, Kripamoy; Pal, Nikhil R.; Chung, I-Fang

2011-01-01

Informative genes from microarray data can be used to construct prediction model and investigate biological mechanisms. Differentially expressed genes, the main targets of most gene selection methods, can be classified as single- and multiple-class specific signature genes. Here, we present a novel gene selection algorithm based on a Group Marker Index (GMI), which is intuitive, of low-computational complexity, and efficient in identification of both types of genes. Most gene selection methods identify only single-class specific signature genes and cannot identify multiple-class specific signature genes easily. Our algorithm can detect de novo certain conditions of multiple-class specificity of a gene and makes use of a novel non-parametric indicator to assess the discrimination ability between classes. Our method is effective even when the sample size is small as well as when the class sizes are significantly different. To compare the effectiveness and robustness we formulate an intuitive template-based method and use four well-known datasets. We demonstrate that our algorithm outperforms the template-based method in difficult cases with unbalanced distribution. Moreover, the multiple-class specific genes are good biomarkers and play important roles in biological pathways. Our literature survey supports that the proposed method identifies unique multiple-class specific marker genes (not reported earlier to be related to cancer) in the Central Nervous System data. It also discovers unique biomarkers indicating the intrinsic difference between subtypes of lung cancer. We also associate the pathway information with the multiple-class specific signature genes and cross-reference to published studies. We find that the identified genes participate in the pathways directly involved in cancer development in leukemia data. Our method gives a promising way to find genes that can involve in pathways of multiple diseases and hence opens up the possibility of using an existing drug on other diseases as well as designing a single drug for multiple diseases. PMID:21909426

Mapping Hydrated Materials with MER Pancam and MSL Mastcam: Results from Gusev Crater and Meridiani Planum, and Plans for Gale Crater

NASA Astrophysics Data System (ADS)

Rice, M. S.; Bell, J. F.

2011-12-01

We have developed a "hydration signature" for mapping H2O- and/or OH-bearing materials at Mars landing sites using multispectral visible to near-infrared (Vis-NIR) observations from the Mars Exploration Rover (MER) Panoramic Camera (Pancam). Pancam's 13 narrowband geology filters cover 11 unique wavelengths in the visible and near infrared (434 to 1009 nm). The hydration signature is based on a strongly negative slope from 934 to 1009 nm that characterizes the spectra of hydrated silica-rich rocks and soils observed by MER Spirit; this feature is likely due to the 2ν1 + ν3 H2O combination band and/or the 3vOH overtone centered near ~1000 nm, whose positions vary slightly depending on bonding to nearest-neighbor atoms. Here we present the ways we have used this hydration signature, in combination with observations of morphology and texture, to remotely identify candidate hydrated materials in Pancam observations. At Gusev Crater, we find that the hydration signature is widespread along Spirit's traverse in the Columbia Hills, which adds to the growing body of evidence that aqueous alteration has played a significant role in the complex geologic history of this site. At Meridiani Planum, the hydration signature is associated with a specific stratigraphic layer ("Smith") exposed within the walls of Victoria Crater. We also discuss limitations to the use of the hydration signature, which can give false detections under specific viewing geometries. This hydration signature can similarly be used to map hydrated materials at the Mars Science Laboratory (MSL) landing site, Gale Crater. The MSL Mast Camera (Mastcam) is a two-instrument suite of fixed-focal length (FFL) cameras, one with a 15-degree field of view (FOV) and the other with a 5.1-degree FOV. Mastcam's narrowband filters cover 9 unique wavelengths in the visible and near-infrared (band centers near 440, 525, 675, 750, 800, 865, 905, 935, and 1035 nm), and are distributed between the two FFL cameras. Full-filter multispectral observations of the region of overlap between the two cameras can be used for our hydration signature mapping. Mastcam's longest-wavelength filter should be able to detect hydrated and/or hydroxylated minerals with strong absorptions between ~990 and ~1080 nm; because of the width of this IR filter, Mastcam will be sensitive to more H2O and/or OH-bearing species than Pancam. Here we summarize the minerals Mastcam should be able to detect if present at Gale Crater, and our plans for hydration signature mapping with MSL.

Integrated optical tamper sensor with planar waveguide

DOEpatents

Carson, Richard F.; Casalnuovo, Stephen A.

1993-01-01

A monolithic optical tamper sensor, comprising an optical emitter and detector, connected by an optical waveguide and placed into the critical entry plane of an enclosed sensitive region, the tamper sensor having a myriad of scraps of a material optically absorbent at the wavelength of interest, such that when the absorbent material is in place on the waveguide, an unique optical signature can be recorded, but when entry is attempted into the enclosed sensitive region, the scraps of absorbent material will be displaced and the optical/electrical signature of the tamper sensor will change and that change can be recorded.

Integrated optical tamper sensor with planar waveguide

DOEpatents

Carson, R.F.; Casalnuovo, S.A.

1993-01-05

A monolithic optical tamper sensor, comprising an optical emitter and detector, connected by an optical waveguide and placed into the critical entry plane of an enclosed sensitive region, the tamper sensor having a myriad of scraps of a material optically absorbent at the wavelength of interest, such that when the absorbent material is in place on the waveguide, an unique optical signature can be recorded, but when entry is attempted into the enclosed sensitive region, the scraps of absorbent material will be displaced and the optical/electrical signature of the tamper sensor will change and that change can be recorded.

Microwave-induced direct spin-flip transitions in mesoscopic Pd/Co heterojunctions

NASA Astrophysics Data System (ADS)

Pietsch, Torsten; Egle, Stefan; Keller, Martin; Fridtjof-Pernau, Hans; Strigl, Florian; Scheer, Elke

2016-09-01

We experimentally investigate the effect of resonant microwave absorption on the magneto-conductance of tunable Co/Pd point contacts. At the interface a non-equilibrium spin accumulation is created via microwave absorption and can be probed via point contact spectroscopy. We interpret the results as a signature of direct spin-flip excitations in Zeeman-split spin-subbands within the Pd normal metal part of the junction. The inverse effect, which is associated with the emission of a microwave photon in a ferromagnet/normal metal point contact, can also be detected via its unique signature in transport spectroscopy.

Polarized x-ray emission from magnetized neutron stars: signature of strong-field vacuum polarization.

PubMed

Lai, Dong; Ho, Wynn C G

2003-08-15

In the atmospheric plasma of a strongly magnetized neutron star, vacuum polarization can induce a Mikheyev-Smirnov-Wolfenstein type resonance across which an x-ray photon may (depending on its energy) convert from one mode into the other, with significant changes in opacities and polarizations. We show that this vacuum resonance effect gives rise to a unique energy-dependent polarization signature in the surface emission from neutron stars. The detection of polarized x rays from neutron stars can provide a direct probe of strong-field quantum electrodynamics and constrain the neutron star magnetic field and geometry.

Polarized X-Ray Emission from Magnetized Neutron Stars: Signature of Strong-Field Vacuum Polarization

NASA Astrophysics Data System (ADS)

Lai, Dong; Ho, Wynn C.

2003-08-01

In the atmospheric plasma of a strongly magnetized neutron star, vacuum polarization can induce a Mikheyev-Smirnov-Wolfenstein type resonance across which an x-ray photon may (depending on its energy) convert from one mode into the other, with significant changes in opacities and polarizations. We show that this vacuum resonance effect gives rise to a unique energy-dependent polarization signature in the surface emission from neutron stars. The detection of polarized x rays from neutron stars can provide a direct probe of strong-field quantum electrodynamics and constrain the neutron star magnetic field and geometry.

The destination defines the journey: an examination of the kinematics of hand-to-mouth movements

PubMed Central

Gonzalez, Claudia L. R.

2016-01-01

Long-train electrical stimulation of the motor and premotor cortices of nonhuman primates can produce either hand-to-mouth or grasp-to-inspect movements, depending on the precise location of stimulation. Furthermore, single-neuron recording studies identify discrete neuronal populations in the inferior parietal and ventral premotor cortices that respond uniquely to either grasp-to-eat or grasp-to-place movements, despite their identical mechanistic requirements. These studies demonstrate that the macaque motor cortex is organized around producing functional, goal-oriented movements, rather than simply fulfilling muscular prerequisites of action. In humans, right-handed hand-to-mouth movements have a unique kinematic signature; smaller maximum grip apertures are produced when grasping to eat than when grasping to place identical targets. This is evidence that the motor cortex in humans is also organized around producing functional movements. However, in both macaques and humans, grasp-to-eat/hand-to-mouth movements have always been elicited using edible targets and have (necessarily) been paired with mouth movement. It is therefore unknown whether the kinematic distinction is a natural result of grasping food and/or is simply attributable to concurrent opening of the mouth while grasping. In experiment 1, we used goal-differentiated grasping tasks, directed toward edible and inedible targets, to show that the unique kinematic signature is present even with inedible targets. In experiment 2, we used the same goal-differentiated grasping tasks, either coupled with or divorced from an open-mouth movement, to show that the signature is not attributable merely to a planned opening of the mouth during the grasp. These results are discussed in relation to the role of hand-to-mouth movements in human development, independently of grasp-to-eat behavior. PMID:27512020

A History and Informal Assessment of the "Slacker Astronomy" Podcast

ERIC Educational Resources Information Center

Price, Aaron; Gay, Pamela; Searle, Travis; Brissenden, Gina

2007-01-01

"Slacker Astronomy" is a weekly podcast that covers a recent astronomical news event or discovery. The show has a unique style consisting of irreverent, over-the-top humor combined with a healthy dose of hard science. According to our demographic analysis, the combination of this style and the unique podcasting distribution mechanism allows the…

Phylogenomic analysis of proteins that are distinctive of Archaea and its main subgroups and the origin of methanogenesis

PubMed Central

Gao, Beile; Gupta, Radhey S

2007-01-01

Background The Archaea are highly diverse in terms of their physiology, metabolism and ecology. Presently, very few molecular characteristics are known that are uniquely shared by either all archaea or the different main groups within archaea. The evolutionary relationships among different groups within the Euryarchaeota branch are also not clearly understood. Results We have carried out comprehensive analyses on each open reading frame (ORFs) in the genomes of 11 archaea (3 Crenarchaeota – Aeropyrum pernix, Pyrobaculum aerophilum and Sulfolobus acidocaldarius; 8 Euryarchaeota – Pyrococcus abyssi, Methanococcus maripaludis, Methanopyrus kandleri, Methanococcoides burtonii, Halobacterium sp. NCR-1, Haloquadratum walsbyi, Thermoplasma acidophilum and Picrophilus torridus) to search for proteins that are unique to either all Archaea or for its main subgroups. These studies have identified 1448 proteins or ORFs that are distinctive characteristics of Archaea and its various subgroups and whose homologues are not found in other organisms. Six of these proteins are unique to all Archaea, 10 others are only missing in Nanoarchaeum equitans and a large number of other proteins are specific for various main groups within the Archaea (e.g. Crenarchaeota, Euryarchaeota, Sulfolobales and Desulfurococcales, Halobacteriales, Thermococci, Thermoplasmata, all methanogenic archaea or particular groups of methanogens). Of particular importance is the observation that 31 proteins are uniquely present in virtually all methanogens (including M. kandleri) and 10 additional proteins are only found in different methanogens as well as A. fulgidus. In contrast, no protein was exclusively shared by various methanogen and any of the Halobacteriales or Thermoplasmatales. These results strongly indicate that all methanogenic archaea form a monophyletic group exclusive of other archaea and that this lineage likely evolved from Archaeoglobus. In addition, 15 proteins that are uniquely shared by M. kandleri and Methanobacteriales suggest a close evolutionary relationship between them. In contrast to the phylogenomics studies, a monophyletic grouping of archaea is not supported by phylogenetic analyses based on protein sequences. Conclusion The identified archaea-specific proteins provide novel molecular markers or signature proteins that are distinctive characteristics of Archaea and all of its major subgroups. The species distributions of these proteins provide novel insights into the evolutionary relationships among different groups within Archaea, particularly regarding the origin of methanogenesis. Most of these proteins are of unknown function and further studies should lead to discovery of novel biochemical and physiological characteristics that are unique to either all archaea or its different subgroups. PMID:17394648

Usage monitoring of electrical devices in a smart home.

PubMed

Rahimi, Saba; Chan, Adrian D C; Goubran, Rafik A

2011-01-01

Profiling the usage of electrical devices within a smart home can be used as a method for determining an occupant's activities of daily living. A nonintrusive load monitoring system monitors the electrical consumption at a single electrical source (e.g., main electric utility service entry) and the operating schedules of individual devices are determined by disaggregating the composite electrical consumption waveforms. An electrical device's load signature plays a key role in nonintrusive load monitoring systems. A load signature is the unique electrical behaviour of an individual device when it is in operation. This paper proposes a feature-based model, using the real power and reactive power as features for describing the load signatures of individual devices. Experimental results for single device recognition for 7 devices show that the proposed approach can achieve 100% classification accuracy with discriminant analysis using Mahalanobis distances.

Rational Design of Novel Allosteric Dihydrofolate Reductase Inhibitors Showing Antibacterial Effects on Drug-Resistant Escherichia coli Escape Variants.

PubMed

Srinivasan, Bharath; Rodrigues, João V; Tonddast-Navaei, Sam; Shakhnovich, Eugene; Skolnick, Jeffrey

2017-07-21

In drug discovery, systematic variations of substituents on a common scaffold and bioisosteric replacements are often used to generate diversity and obtain molecules with better biological effects. However, this could saturate the small-molecule diversity pool resulting in drug resistance. On the other hand, conventional drug discovery relies on targeting known pockets on protein surfaces leading to drug resistance by mutations of critical pocket residues. Here, we present a two-pronged strategy of designing novel drugs that target unique pockets on a protein's surface to overcome the above problems. Dihydrofolate reductase, DHFR, is a critical enzyme involved in thymidine and purine nucleotide biosynthesis. Several classes of compounds that are structural analogues of the substrate dihydrofolate have been explored for their antifolate activity. Here, we describe 10 novel small-molecule inhibitors of Escherichia coli DHFR, EcDHFR, belonging to the stilbenoid, deoxybenzoin, and chalcone family of compounds discovered by a combination of pocket-based virtual ligand screening and systematic scaffold hopping. These inhibitors show a unique uncompetitive or noncompetitive inhibition mechanism, distinct from those reported for all known inhibitors of DHFR, indicative of binding to a unique pocket distinct from either substrate or cofactor-binding pockets. Furthermore, we demonstrate that rescue mutants of EcDHFR, with reduced affinity to all known classes of DHFR inhibitors, are inhibited at the same concentration as the wild-type. These compounds also exhibit antibacterial activity against E. coli harboring the drug-resistant variant of DHFR. This discovery is the first report on a novel class of inhibitors targeting a unique pocket on EcDHFR.

Joint analysis of multiple high-dimensional data types using sparse matrix approximations of rank-1 with applications to ovarian and liver cancer.

PubMed

Okimoto, Gordon; Zeinalzadeh, Ashkan; Wenska, Tom; Loomis, Michael; Nation, James B; Fabre, Tiphaine; Tiirikainen, Maarit; Hernandez, Brenda; Chan, Owen; Wong, Linda; Kwee, Sandi

2016-01-01

Technological advances enable the cost-effective acquisition of Multi-Modal Data Sets (MMDS) composed of measurements for multiple, high-dimensional data types obtained from a common set of bio-samples. The joint analysis of the data matrices associated with the different data types of a MMDS should provide a more focused view of the biology underlying complex diseases such as cancer that would not be apparent from the analysis of a single data type alone. As multi-modal data rapidly accumulate in research laboratories and public databases such as The Cancer Genome Atlas (TCGA), the translation of such data into clinically actionable knowledge has been slowed by the lack of computational tools capable of analyzing MMDSs. Here, we describe the Joint Analysis of Many Matrices by ITeration (JAMMIT) algorithm that jointly analyzes the data matrices of a MMDS using sparse matrix approximations of rank-1. The JAMMIT algorithm jointly approximates an arbitrary number of data matrices by rank-1 outer-products composed of "sparse" left-singular vectors (eigen-arrays) that are unique to each matrix and a right-singular vector (eigen-signal) that is common to all the matrices. The non-zero coefficients of the eigen-arrays identify small subsets of variables for each data type (i.e., signatures) that in aggregate, or individually, best explain a dominant eigen-signal defined on the columns of the data matrices. The approximation is specified by a single "sparsity" parameter that is selected based on false discovery rate estimated by permutation testing. Multiple signals of interest in a given MDDS are sequentially detected and modeled by iterating JAMMIT on "residual" data matrices that result from a given sparse approximation. We show that JAMMIT outperforms other joint analysis algorithms in the detection of multiple signatures embedded in simulated MDDS. On real multimodal data for ovarian and liver cancer we show that JAMMIT identified multi-modal signatures that were clinically informative and enriched for cancer-related biology. Sparse matrix approximations of rank-1 provide a simple yet effective means of jointly reducing multiple, big data types to a small subset of variables that characterize important clinical and/or biological attributes of the bio-samples from which the data were acquired.

Polarimetry of Solar System Objects: Observations vs. Models

NASA Astrophysics Data System (ADS)

Yanamandra-Fisher, P. A.

2014-04-01

The overarching goals for the remote sensing and robotic exploration of planetary systems are: (1) understanding the formation of planetary systems and their diversity; and (2) search for habitability. Since all objects have unique polarimetric signatures inclusion of spectrophotopolarimetry as a complementary approach to standard techniques of imaging and spectroscopy, provides insight into the scattering properties of the planetary media. Specifically, linear and circular polarimetric signatures of the object arise from different physical processes and their study proves essential to the characterization of the object. Linear polarization of reflected light by various solar system objects provides insight into the scattering characteristics of atmospheric aerosols and hazes? and surficial properties of atmosphereless bodies. Many optically active materials are anisotropic and so their scattering properties differ with the object's principal axes (such as dichroic or birefringent materials) and are crystalline in structure instead of amorphous, (eg., the presence of olivines and silicates in cometary dust and circumstellar disks? Titan, etc.). Ices (water and other species) are abundant in the system indicated in their near - infrared spectra. Gas giants form outside the frost line (where ices condense), and their satellites and ring systems exhibit signature of water ice? clathrates, nonices (Si, C, Fe) in their NIR spectra and spectral dependence of linear polarization. Additionally, spectral dependence of polarization is important to separate the macroscopic (bulk) properties of the scattering medium from the microscopic (particulate) properties of the scattering medium. Circular polarization, on the other hand, is indicative of magnetic fields and biologically active molecules, necessary for habitability. These applications suffer from lack of detailed observations, instrumentation, dedicated missions and numericalretrieval methods. With recent discoveries and results of main belt comets, asteroids with ring system, lunar studies, planned exploration of planetary satellites that may harbour sub-surface oceans, there is increasing need to include polarimetric (linear, circular and differential) as an integral observing mode of instruments and facilities. For laboratory measurements, there is a need to identify simulants that mimic the polarimetric behaviour of solar system small bodies and measure their polarimetric behavior as function of various physical process they are subject to and have undergone radiation changes of their surfaces. Therefore, inclusion of polarimetric remote sensing and development of spectropolarimeters for groundbased facilities and instruments on space missions is needed, with similar maturation of vector radiative transfer models and related laboratory measurements.

Modeling & Informatics at Vertex Pharmaceuticals Incorporated: our philosophy for sustained impact

NASA Astrophysics Data System (ADS)

McGaughey, Georgia; Patrick Walters, W.

2017-03-01

Molecular modelers and informaticians have the unique opportunity to integrate cross-functional data using a myriad of tools, methods and visuals to generate information. Using their drug discovery expertise, information is transformed to knowledge that impacts drug discovery. These insights are often times formulated locally and then applied more broadly, which influence the discovery of new medicines. This is particularly true in an organization where the members are exposed to projects throughout an organization, such as in the case of the global Modeling & Informatics group at Vertex Pharmaceuticals. From its inception, Vertex has been a leader in the development and use of computational methods for drug discovery. In this paper, we describe the Modeling & Informatics group at Vertex and the underlying philosophy, which has driven this team to sustain impact on the discovery of first-in-class transformative medicines.

Vertex Space Analysis for Model-Based Target Recognition.

DTIC Science & Technology

1996-08-01

performed in our unique invariant representation, Vertex Space, that reduces both the dimensionality and size of the required search space. Vertex Space ... mapping results in a reduced representation that serves as a characteristic target signature which is invariant to four of the six viewing geometry

49 CFR 213.369 - Inspection records.

Code of Federal Regulations, 2010 CFR

2010-10-01

... transfer records through electronic transmission, storage, and retrieval provided that— (1) The electronic... security such as recognition of an electronic signature, or other means, which uniquely identify the initiating person as the author of that record. No two persons shall have the same electronic identity; (2...

Close up detail of the underside of the Orbiter Discovery ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

Close up detail of the underside of the Orbiter Discovery in the Vehicle Assembly Building at NASA's Kennedy Space Center. This view is from underneath the aft section looking forward. It is a close-up view of the High-temperature Reusable Surface Insulation tiles showing the wear patterns from the heat of reentry, consequential replacement of worn and damaged tiles. The wear and replacement patters are unique to each Orbiter which can serve as their particular "fingerprint". - Space Transportation System, Orbiter Discovery (OV-103), Lyndon B. Johnson Space Center, 2101 NASA Parkway, Houston, Harris County, TX

Prognostic Power of a Tumor Differentiation Gene Signature for Bladder Urothelial Carcinomas.

PubMed

Mo, Qianxing; Nikolos, Fotis; Chen, Fengju; Tramel, Zoe; Lee, Yu-Cheng; Hayashi, Kazukuni; Xiao, Jing; Shen, Jianjun; Chan, Keith Syson

2018-05-01

Muscle-invasive bladder cancers (MIBCs) cause approximately 150 000 deaths per year worldwide. Survival for MIBC patients is heterogeneous, with no clinically validated molecular markers that predict clinical outcome. Non-MIBCs (NMIBCs) generally have favorable outcome; however, a portion progress to MIBC. Hence, development of a prognostic tool that can guide decision-making is crucial for improving clinical management of bladder urothelial carcinomas. Tumor grade is defined by pathologic evaluation of tumor cell differentiation, and it often associates with clinical outcome. The current study extrapolates this conventional wisdom and combines it with molecular profiling. We developed an 18-gene signature that molecularly defines urothelial cellular differentiation, thus classifying MIBCs and NMIBCs into two subgroups: basal and differentiated. We evaluated the prognostic capability of this "tumor differentiation signature" and three other existing gene signatures including the The Cancer Genome Atlas (TCGA; 2707 genes), MD Anderson Cancer Center (MDA; 2252 genes/2697 probes), and University of North Carolina at Chapel Hill (UNC; 47 genes) using five gene expression data sets derived from MIBC and NMIBC patients. All statistical tests were two-sided. The tumor differentiation signature demonstrated consistency and statistical robustness toward stratifying MIBC patients into different overall survival outcomes (TCGA cohort 1, P = .03; MDA discovery, P = .009; MDA validation, P = .01), while the other signatures were not as consistent. In addition, we analyzed the progression (Ta/T1 progressing to ≥T2) probability of NMIBCs. NMIBC patients with a basal tumor differentiation signature associated with worse progression outcome (P = .008). Gene functional term enrichment and gene set enrichment analyses revealed that genes involved in the biologic process of immune response and inflammatory response are among the most elevated within basal bladder cancers, implicating them as candidates for immune checkpoint therapies. These results provide definitive evidence that a biology-prioritizing clustering methodology generates meaningful insights into patient stratification and reveals targetable molecular pathways to impact future therapeutic approach.

Unique disease heritage of the Dutch-German Mennonite population.

PubMed

Orton, Noelle C; Innes, A Micheil; Chudley, Albert E; Bech-Hansen, N Torben

2008-04-15

The Dutch-German Mennonites are a religious isolate with foundational roots in the 16th century. A tradition of endogamy, large families, detailed genealogical records, and a unique disease history all contribute to making this a valuable population for genetic studies. Such studies in the Dutch-German Mennonite population have already contributed to the identification of the causative genes in several conditions such as the incomplete form of X-linked congenital stationary night blindness (CSNB2; previously iCSNB) and hypophosphatasia (HOPS), as well as the discovery of founder mutations within established disease genes (MYBPC1, CYP17alpha). The Dutch-German Mennonite population provides a strong resource for gene discovery and could lead to the identification of additional disease genes with relevance to the general population. In addition, further research developments should enhance delivery of clinical genetic services to this unique community. In the current review we discuss 31 genetic conditions, including 17 with identified gene mutations, within the Dutch-German Mennonite population. Copyright 2008 Wiley-Liss, Inc.

Session Initiation Protocol Network Encryption Device Plain Text Domain Discovery Service

DTIC Science & Technology

2007-12-07

MONITOR’S REPORT NUMBER(S) 12. DISTRIBUTION / AVAILABILITY STATEMENT 13. SUPPLEMENTARY NOTES 14. ABSTRACT 15. SUBJECT TERMS 16. SECURITY CLASSIFICATION OF: a...such as the TACLANE, have developed unique discovery methods to establish Plain Text Domain (PTD) Security Associations (SA). All of these techniques...can include network and host Internet Protocol (IP) addresses, Information System Security Office (ISSO) point of contact information and PTD status

Modern Natural Products Drug Discovery and its Relevance to Biodiversity Conservation†

PubMed Central

Kingston, David G. I.

2010-01-01

Natural products continue to provide a diverse and unique source of bioactive lead compounds for drug discovery, but maintaining their continued eminence as source compounds is challenging in the face of the changing face of the pharmaceutical industry and the changing nature of biodiversity prospecting brought about by the Convention of Biodiversity. This review provides an overview of some of these challenges, and suggests ways in which they can be addressed so that natural products research can remain a viable and productive route to drug discovery. Results from International Cooperative Biodiversity Groups (ICBGs) working in Madagascar, Panama, and Suriname are used as examples of what can be achieved when biodiversity conservation is linked to drug discovery. PMID:21138324

Marinopyrroles: Unique Drug Discoveries Based on Marine Natural Products.

PubMed

Li, Rongshi

2016-01-01

Natural products provide a successful supply of new chemical entities (NCEs) for drug discovery to treat human diseases. Approximately half of the NCEs are based on natural products and their derivatives. Notably, marine natural products, a largely untapped resource, have contributed to drug discovery and development with eight drugs or cosmeceuticals approved by the U.S. Food and Drug Administration and European Medicines Agency, and ten candidates undergoing clinical trials. Collaborative efforts from drug developers, biologists, organic, medicinal, and natural product chemists have elevated drug discoveries to new levels. These efforts are expected to continue to improve the efficiency of natural product-based drugs. Marinopyrroles are examined here as a case study for potential anticancer and antibiotic agents. © 2015 Wiley Periodicals, Inc.

Recent Progress on GRBs with Swift

NASA Technical Reports Server (NTRS)

Gehrels, N.; Cannizzo, J. K.

2010-01-01

We are in an exciting period of discovery for gamma-ray bursts. The Swift observatory is detecting 100 bursts per year, providing arcsecond localizations and sensitive observations of the prompt and afterglow emission. In addition, rapid-response telescopes on the ground have new capabilities to study optical emission during the prompt phase and spectral signatures of the host galaxies. The combined data set is enabling great advances in our understanding of GRBs including afterglow physics, short burst origin, and supernova physics.

Toward an automated signature recognition toolkit for mission operations

NASA Technical Reports Server (NTRS)

Cleghorn, T.; Laird, P; Perrine, L.; Culbert, C.; Macha, M.; Saul, R.; Hammen, D.; Moebes, T.; Shelton, R.

1994-01-01

Signature recognition is the problem of identifying an event or events from its time series. The generic problem has numerous applications to science and engineering. At NASA's Johnson Space Center, for example, mission control personnel, using electronic displays and strip chart recorders, monitor telemetry data from three-phase electrical buses on the Space Shuttle and maintain records of device activation and deactivation. Since few electrical devices have sensors to indicate their actual status, changes of state are inferred from characteristic current and voltage fluctuations. Controllers recognize these events both by examining the waveform signatures and by listening to audio channels between ground and crew. Recently the authors have developed a prototype system that identifies major electrical events from the telemetry and displays them on a workstation. Eventually the system will be able to identify accurately the signatures of over fifty distinct events in real time, while contending with noise, intermittent loss of signal, overlapping events, and other complications. This system is just one of many possible signature recognition applications in Mission Control. While much of the technology underlying these applications is the same, each application has unique data characteristics, and every control position has its own interface and performance requirements. There is a need, therefore, for CASE tools that can reduce the time to implement a running signature recognition application from months to weeks or days. This paper describes our work to date and our future plans.

Toward an automated signature recognition toolkit for mission operations

NASA Astrophysics Data System (ADS)

Cleghorn, T.; Laird, P.; Perrine, L.; Culbert, C.; Macha, M.; Saul, R.; Hammen, D.; Moebes, T.; Shelton, R.

1994-10-01

Signature recognition is the problem of identifying an event or events from its time series. The generic problem has numerous applications to science and engineering. At NASA's Johnson Space Center, for example, mission control personnel, using electronic displays and strip chart recorders, monitor telemetry data from three-phase electrical buses on the Space Shuttle and maintain records of device activation and deactivation. Since few electrical devices have sensors to indicate their actual status, changes of state are inferred from characteristic current and voltage fluctuations. Controllers recognize these events both by examining the waveform signatures and by listening to audio channels between ground and crew. Recently the authors have developed a prototype system that identifies major electrical events from the telemetry and displays them on a workstation. Eventually the system will be able to identify accurately the signatures of over fifty distinct events in real time, while contending with noise, intermittent loss of signal, overlapping events, and other complications. This system is just one of many possible signature recognition applications in Mission Control. While much of the technology underlying these applications is the same, each application has unique data characteristics, and every control position has its own interface and performance requirements. There is a need, therefore, for CASE tools that can reduce the time to implement a running signature recognition application from months to weeks or days. This paper describes our work to date and our future plans.

Discovery stories in the science classroom

NASA Astrophysics Data System (ADS)

Arya, Diana Jaleh

School science has been criticized for its lack of emphasis on the tentative, dynamic nature of science as a process of learning more about our world. This criticism is the guiding force for this present body of work, which focuses on the question: what are the educational benefits for middle school students of reading texts that highlight the process of science in the form of a discovery narrative? This dissertation traces my journey through a review of theoretical perspectives of narrative, an analysis of first-hand accounts of scientific discovery, the complex process of developing age-appropriate, cohesive and engaging science texts for middle school students, and a comparison study (N=209) that seeks to determine the unique benefits of the scientific discovery narrative for the interest in and retained understanding of conceptual information presented in middle school science texts. A total of 209 middle school participants in nine different classrooms from two different schools participated in the experimental study. Each subject read two science texts that differed in topic (the qualities of and uses for radioactive elements and the use of telescopic technology to see planets in space) and genre (the discovery narrative and the "conceptually known exposition" comparison text). The differences between the SDN and CKE versions for each topic were equivalent in all possible ways (initial introduction, overall conceptual accuracy, elements of human interest, coherence and readability level), save for the unique components of the discovery narrative (i.e., love for their work, acknowledgement of the known, identification of the unknown and the explorative or experimental process to discovery). Participants generally chose the discovery narrative version as the more interesting of the two texts. Additional findings from the experimental study suggest that science texts in the form of SDNs elicit greater long-term retention of key conceptual information, especially when the readers have little prior knowledge of a given topic. Further, ethnic minority groups of lower socio-economic level (i.e., Latin and African-American origins) demonstrated an even greater benefit from the SDN texts, suggesting that a scientist's story of discovery can help to close the gap in academic performance in science.

Secreted primary human malignant mesothelioma exosome signature reflects oncogenic cargo

PubMed Central

Greening, David W.; Ji, Hong; Chen, Maoshan; Robinson, Bruce W. S.; Dick, Ian M.; Creaney, Jenette; Simpson, Richard J.

2016-01-01

Malignant mesothelioma (MM) is a highly-aggressive heterogeneous malignancy, typically diagnosed at advanced stage. An important area of mesothelioma biology and progression is understanding intercellular communication and the contribution of the secretome. Exosomes are secreted extracellular vesicles shown to shuttle cellular cargo and direct intercellular communication in the tumour microenvironment, facilitate immunoregulation and metastasis. In this study, quantitative proteomics was used to investigate MM-derived exosomes from distinct human models and identify select cargo protein networks associated with angiogenesis, metastasis, and immunoregulation. Utilising bioinformatics pathway/network analyses, and correlation with previous studies on tumour exosomes, we defined a select mesothelioma exosomal signature (mEXOS, 570 proteins) enriched in tumour antigens and various cancer-specific signalling (HPGD/ENO1/OSMR) and secreted modulators (FN1/ITLN1/MAMDC2/PDGFD/GBP1). Notably, such circulating cargo offers unique insights into mesothelioma progression and tumour microenvironment reprogramming. Functionally, we demonstrate that oncogenic exosomes facilitate the migratory capacity of fibroblast/endothelial cells, supporting the systematic model of MM progression associated with vascular remodelling and angiogenesis. We provide biophysical and proteomic characterisation of exosomes, define a unique oncogenic signature (mEXOS), and demonstrate the regulatory capacity of exosomes in cell migration/tube formation assays. These findings contribute to understanding tumour-stromal crosstalk in the context of MM, and potential new diagnostic and therapeutic extracellular targets. PMID:27605433

Cross-modal signatures in maternal speech and singing

PubMed Central

Trehub, Sandra E.; Plantinga, Judy; Brcic, Jelena; Nowicki, Magda

2013-01-01

We explored the possibility of a unique cross-modal signature in maternal speech and singing that enables adults and infants to link unfamiliar speaking or singing voices with subsequently viewed silent videos of the talkers or singers. In Experiment 1, adults listened to 30-s excerpts of speech followed by successively presented 7-s silent video clips, one from the previously heard speaker (different speech content) and the other from a different speaker. They successfully identified the previously heard speaker. In Experiment 2, adults heard comparable excerpts of singing followed by silent video clips from the previously heard singer (different song) and another singer. They failed to identify the previously heard singer. In Experiment 3, the videos of talkers and singers were blurred to obscure mouth movements. Adults successfully identified the talkers and they also identified the singers from videos of different portions of the song previously heard. In Experiment 4, 6− to 8-month-old infants listened to 30-s excerpts of the same maternal speech or singing followed by exposure to the silent videos on alternating trials. They looked longer at the silent videos of previously heard talkers and singers. The findings confirm the individuality of maternal speech and singing performance as well as adults' and infants' ability to discern the unique cross-modal signatures. The cues that enable cross-modal matching of talker and singer identity remain to be determined. PMID:24198805

Cross-modal signatures in maternal speech and singing.

PubMed

Trehub, Sandra E; Plantinga, Judy; Brcic, Jelena; Nowicki, Magda

2013-01-01

We explored the possibility of a unique cross-modal signature in maternal speech and singing that enables adults and infants to link unfamiliar speaking or singing voices with subsequently viewed silent videos of the talkers or singers. In Experiment 1, adults listened to 30-s excerpts of speech followed by successively presented 7-s silent video clips, one from the previously heard speaker (different speech content) and the other from a different speaker. They successfully identified the previously heard speaker. In Experiment 2, adults heard comparable excerpts of singing followed by silent video clips from the previously heard singer (different song) and another singer. They failed to identify the previously heard singer. In Experiment 3, the videos of talkers and singers were blurred to obscure mouth movements. Adults successfully identified the talkers and they also identified the singers from videos of different portions of the song previously heard. In Experiment 4, 6- to 8-month-old infants listened to 30-s excerpts of the same maternal speech or singing followed by exposure to the silent videos on alternating trials. They looked longer at the silent videos of previously heard talkers and singers. The findings confirm the individuality of maternal speech and singing performance as well as adults' and infants' ability to discern the unique cross-modal signatures. The cues that enable cross-modal matching of talker and singer identity remain to be determined.

Neutrino masses, scale-dependent growth, and redshift-space distortions

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hernández, Oscar F., E-mail: oscarh@physics.mcgill.ca

2017-06-01

Massive neutrinos leave a unique signature in the large scale clustering of matter. We investigate the wavenumber dependence of the growth factor arising from neutrino masses and use a Fisher analysis to determine the aspects of a galaxy survey needed to measure this scale dependence.

Biochemical Activities of 320 ToxCast Chemicals Evaluated Across 239 Functional Targets

EPA Science Inventory

EPA’s ToxCast research program is profiling chemical bioactivity in order to generate predictive signatures of toxicity. The present study evaluated 320 chemicals across 239 biochemical assays. ToxCast phase I chemicals include 309 unique structures, most of which are pesticide ...

L1000CDS2: LINCS L1000 characteristic direction signatures search engine

PubMed Central

Duan, Qiaonan; Reid, St Patrick; Clark, Neil R; Wang, Zichen; Fernandez, Nicolas F; Rouillard, Andrew D; Readhead, Ben; Tritsch, Sarah R; Hodos, Rachel; Hafner, Marc; Niepel, Mario; Sorger, Peter K; Dudley, Joel T; Bavari, Sina; Panchal, Rekha G; Ma’ayan, Avi

2016-01-01

The library of integrated network-based cellular signatures (LINCS) L1000 data set currently comprises of over a million gene expression profiles of chemically perturbed human cell lines. Through unique several intrinsic and extrinsic benchmarking schemes, we demonstrate that processing the L1000 data with the characteristic direction (CD) method significantly improves signal to noise compared with the MODZ method currently used to compute L1000 signatures. The CD processed L1000 signatures are served through a state-of-the-art web-based search engine application called L1000CDS2. The L1000CDS2 search engine provides prioritization of thousands of small-molecule signatures, and their pairwise combinations, predicted to either mimic or reverse an input gene expression signature using two methods. The L1000CDS2 search engine also predicts drug targets for all the small molecules profiled by the L1000 assay that we processed. Targets are predicted by computing the cosine similarity between the L1000 small-molecule signatures and a large collection of signatures extracted from the gene expression omnibus (GEO) for single-gene perturbations in mammalian cells. We applied L1000CDS2 to prioritize small molecules that are predicted to reverse expression in 670 disease signatures also extracted from GEO, and prioritized small molecules that can mimic expression of 22 endogenous ligand signatures profiled by the L1000 assay. As a case study, to further demonstrate the utility of L1000CDS2, we collected expression signatures from human cells infected with Ebola virus at 30, 60 and 120 min. Querying these signatures with L1000CDS2 we identified kenpaullone, a GSK3B/CDK2 inhibitor that we show, in subsequent experiments, has a dose-dependent efficacy in inhibiting Ebola infection in vitro without causing cellular toxicity in human cell lines. In summary, the L1000CDS2 tool can be applied in many biological and biomedical settings, while improving the extraction of knowledge from the LINCS L1000 resource. PMID:28413689

Gamma watermarking

DOEpatents

Ishikawa, Muriel Y.; Wood, Lowell L.; Lougheed, Ronald W.; Moody, Kenton J.; Wang, Tzu-Fang

2004-05-25

A covert, gamma-ray "signature" is used as a "watermark" for property identification. This new watermarking technology is based on a unique steganographic or "hidden writing" digital signature, implemented in tiny quantities of gamma-ray-emitting radioisotopic material combinations, generally covertly emplaced on or within an object. This digital signature may be readily recovered at distant future times, by placing a sensitive, high energy-resolution gamma-ray detecting instrument reasonably precisely over the location of the watermark, which location may be known only to the object's owner; however, the signature is concealed from all ordinary detection means because its exceedingly low level of activity is obscured by the natural radiation background (including the gamma radiation naturally emanating from the object itself, from cosmic radiation and material surroundings, from human bodies, etc.). The "watermark" is used in object-tagging for establishing object identity, history or ownership. It thus may serve as an aid to law enforcement officials in identifying stolen property and prosecuting theft thereof. Highly effective, potentially very low cost identification-on demand of items of most all types is thus made possible.

β-Cell Autophagy in Diabetes Pathogenesis.

PubMed

Marasco, Michelle R; Linnemann, Amelia K

2018-05-01

Nearly 100 years have passed since Frederick Banting and Charles Best first discovered and purified insulin. Their discovery and subsequent improvements revolutionized the treatment of diabetes, and the field continues to move at an ever-faster pace with respect to unique treatments for both type 1 and type 2 diabetes. Despite these advances, we still do not fully understand how apoptosis of the insulin-producing β-cells is triggered, presenting a challenge in the development of preventative measures. In recent years, the process of autophagy has generated substantial interest in this realm due to discoveries highlighting its clear role in the maintenance of cellular homeostasis. As a result, the number of studies focused on islet and β-cell autophagy has increased substantially in recent years. In this review, we will discuss what is currently known regarding the role of β-cell autophagy in type 1 and type 2 diabetes pathogenesis, with an emphasis on new and exciting developments over the past 5 years. Further, we will discuss how these discoveries might be translated into unique treatments in the coming years.

A gene-signature progression approach to identifying candidate small-molecule cancer therapeutics with connectivity mapping.

PubMed

Wen, Qing; Kim, Chang-Sik; Hamilton, Peter W; Zhang, Shu-Dong

2016-05-11

Gene expression connectivity mapping has gained much popularity recently with a number of successful applications in biomedical research testifying its utility and promise. Previously methodological research in connectivity mapping mainly focused on two of the key components in the framework, namely, the reference gene expression profiles and the connectivity mapping algorithms. The other key component in this framework, the query gene signature, has been left to users to construct without much consensus on how this should be done, albeit it has been an issue most relevant to end users. As a key input to the connectivity mapping process, gene signature is crucially important in returning biologically meaningful and relevant results. This paper intends to formulate a standardized procedure for constructing high quality gene signatures from a user's perspective. We describe a two-stage process for making quality gene signatures using gene expression data as initial inputs. First, a differential gene expression analysis comparing two distinct biological states; only the genes that have passed stringent statistical criteria are considered in the second stage of the process, which involves ranking genes based on statistical as well as biological significance. We introduce a "gene signature progression" method as a standard procedure in connectivity mapping. Starting from the highest ranked gene, we progressively determine the minimum length of the gene signature that allows connections to the reference profiles (drugs) being established with a preset target false discovery rate. We use a lung cancer dataset and a breast cancer dataset as two case studies to demonstrate how this standardized procedure works, and we show that highly relevant and interesting biological connections are returned. Of particular note is gefitinib, identified as among the candidate therapeutics in our lung cancer case study. Our gene signature was based on gene expression data from Taiwan female non-smoker lung cancer patients, while there is evidence from independent studies that gefitinib is highly effective in treating women, non-smoker or former light smoker, advanced non-small cell lung cancer patients of Asian origin. In summary, we introduced a gene signature progression method into connectivity mapping, which enables a standardized procedure for constructing high quality gene signatures. This progression method is particularly useful when the number of differentially expressed genes identified is large, and when there is a need to prioritize them to be included in the query signature. The results from two case studies demonstrate that the approach we have developed is capable of obtaining pertinent candidate drugs with high precision.

Collision or convergence?: beliefs and politics in neuroscience discovery, ethics, and intervention.

PubMed

Paylor, Ben; Longstaff, Holly; Rossi, Fabio; Illes, Judy

2014-08-01

Discovery and interventions for neurological disorders have a unique capacity to galvanize public opinion over issues of access, human rights, decision making, and the definition of disease. Here we highlight five cases where beliefs and politics prevailed over evidence and ethics. We examine lessons from them about the communication of risk and the power of public influence on science, society, and policy. Copyright © 2014 Elsevier Ltd. All rights reserved.

A system identification technique based on the random decrement signatures. Part 2: Experimental results

NASA Technical Reports Server (NTRS)

Bedewi, Nabih E.; Yang, Jackson C. S.

1987-01-01

Identification of the system parameters of a randomly excited structure may be treated using a variety of statistical techniques. Of all these techniques, the Random Decrement is unique in that it provides the homogeneous component of the system response. Using this quality, a system identification technique was developed based on a least-squares fit of the signatures to estimate the mass, damping, and stiffness matrices of a linear randomly excited system. The results of an experiment conducted on an offshore platform scale model to verify the validity of the technique and to demonstrate its application in damage detection are presented.

Authentication of gold nanoparticle encoded pharmaceutical tablets using polarimetric signatures.

PubMed

Carnicer, Artur; Arteaga, Oriol; Suñé-Negre, Josep M; Javidi, Bahram

2016-10-01

The counterfeiting of pharmaceutical products represents concerns for both industry and the safety of the general public. Falsification produces losses to companies and poses health risks for patients. In order to detect fake pharmaceutical tablets, we propose producing film-coated tablets with gold nanoparticle encoding. These coated tablets contain unique polarimetric signatures. We present experiments to show that ellipsometric optical techniques, in combination with machine learning algorithms, can be used to distinguish genuine and fake samples. To the best of our knowledge, this is the first report using gold nanoparticles encoded with optical polarimetric classifiers to prevent the counterfeiting of pharmaceutical products.

Ballistic missile precession frequency extraction based on the Viterbi & Kalman algorithm

NASA Astrophysics Data System (ADS)

Wu, Longlong; Xie, Yongjie; Xu, Daping; Ren, Li

2015-12-01

Radar Micro-Doppler signatures are of great potential for target detection, classification and recognition. In the mid-course phase, warheads flying outside the atmosphere are usually accompanied by precession. Precession may induce additional frequency modulations on the returned radar signal, which can be regarded as a unique signature and provide additional information that is complementary to existing target recognition methods. The main purpose of this paper is to establish a more actual precession model of conical ballistic missile warhead and extract the precession parameters by utilizing Viterbi & Kalman algorithm, which improving the precession frequency estimation accuracy evidently , especially in low SNR.

Oil pollution signatures by remote sensing.

NASA Technical Reports Server (NTRS)

Catoe, C. E.; Mclean, J. T.

1972-01-01

Study of the possibility of developing an effective remote sensing system for oil pollution monitoring which would be capable of detecting oil films on water, mapping the areal extent of oil slicks, measuring slick thickness, and identifying the oil types. In the spectral regions considered (ultraviolet, visible, infrared, microwave, and radar), the signatures were sufficiently unique when compared to the background so that it was possible to detect and map oil slicks. Both microwave and radar techniques are capable of operating in adverse weather. Fluorescence techniques show promise in identifying oil types. A multispectral system will be required to detect oil, map its distribution, estimate film thickness, and characterize the oil pollutant.

Fungicide residue identification and discrimination using a conducting polymer electronic-nose

Treesearch

Alphus D. Wilson

2013-01-01

The identification of fungicide residues on crop foliage is necessary to make periodic pest management decisions. The determination of fungicide residue identities currently is difficult and time consuming using conventional chemical analysis methods such as gas chromatography-mass spectroscopy. Different fungicide types produce unique electronic aroma signature...

Signature Pedagogies in Outdoor Education

ERIC Educational Resources Information Center

Thomas, Glyn

2015-01-01

The new National health and physical education curriculum in Australia includes outdoor education activities as a viable way to achieve intended learning outcomes. However, most health and physical education teacher education courses do not provide a strong focus on the theories, skills and pedagogies that are unique to the effective use of…

A Contract for Excellence in Scientific Education: May I Have Your Signature Please?

ERIC Educational Resources Information Center

Tate, William F.; Malancharuvil-Berkes, Elizabeth

2006-01-01

Recent advances in biology and digital technology represent unique opportunities for teacher educators to rethink the programmatic experiences of prospective secondary science and mathematics teachers. This article discusses the importance of teacher education programs that connect mathematics and science where appropriate, recognize the…

Viruses as groundwater tracers: using ecohydrology to characterize short travel times in aquifers

USDA-ARS?s Scientific Manuscript database

Viruses are attractive tracers of short (<3 yr) travel times in aquifers because they have unique genetic signatures, are detectable in trace quantities, and are mobile and stable in groundwater. Virus “snaphots” result from infection and disappearance over time as a community develops resistance. T...

Physical unclonable functions: A primer

DOE PAGES

Bauer, Todd; Hamlet, Jason

2014-11-01

Physical unclonable functions (PUFs) make use of the measurable intrinsic randomness of physical systems to establish signatures for those systems. Thus, PUFs provide a means to generate unique keys that don't need to be stored in nonvolatile memory, and they offer exciting opportunities for new authentication and supply chain security technologies.

Discovery of a Possible Symbiotic Binary in the Large Magellanic Cloud

NASA Astrophysics Data System (ADS)

Mathew, Blesson; Reid, Warren A.; Mennickent, R. E.; Banerjee, D. P. K.

2017-12-01

We report the discovery of a possible symbiotic star, in the Large Magellanic Cloud (LMC). The object under consideration here, designated as RP 870, was detected during the course of a comprehensive H$\\alpha$ survey of the LMC by Reid & Parker (2012). The spectrum of RP 870 showed high ionization emission lines of He I, He II and [O III] and molecular absorption bands of TiO $\\lambda$$\\lambda$6180, 7100. The collective signatures of a hot component (high excitation/ionization lines) and of a cool component (TiO molecular bands) are seen in RP 870, from which we propose it as a symbiotic star. Since known symbiotic systems are rare in the LMC, possibly less than a dozen are known, we thought the present detection to be interesting enough to be reported.

Echoes of the electroweak phase transition: discovering a second Higgs doublet through A0→ZH0.

PubMed

Dorsch, G C; Huber, S J; Mimasu, K; No, J M

2014-11-21

The existence of a second Higgs doublet in nature could lead to a cosmological first-order electroweak phase transition and explain the origin of the matter-antimatter asymmetry in the Universe. We obtain the spectrum and properties of the new scalars H0, A0, and H(±) that signal such a phase transition and show that the observation of the decay A0→ZH0 at LHC would be a "smoking gun" signature of these scenarios. We analyze the LHC search prospects for this decay in the ℓℓbb and ℓℓW(+)W(-) final states, arguing that current data may be sensitive to this signature in the former channel as well as there being great potential for a discovery in either channel at the very early stages of the 14 TeV run.

Discovery of an unconventional charge density wave at the surface of K 0.9Mo 6O 17

DOE PAGES

Mou, Daixiang; Sapkota, Aashish; Kung, H. -H.; ...

2016-05-13

In this study, we use angle resolved photoemission spectroscopy, Raman spectroscopy, low energy electron diffraction, and x-ray scattering to reveal an unusual electronically mediated charge density wave (CDW) in K 0.9Mo 6O 17. Not only does K 0.9Mo 6O 17 lack signatures of electron-phonon coupling, but it also hosts an extraordinary surface CDW, with T S_CDW = 220 K nearly twice that of the bulk CDW, T B_CDW = 115 K. While the bulk CDW has a BCS-like gap of 12 meV, the surface gap is 10 times larger and well in the strong coupling regime. Strong coupling behavior combinedmore » with the absence of signatures of strong electron-phonon coupling indicates that the CDW is likely mediated by electronic interactions enhanced by low dimensionality.« less

Can Untargeted Metabolomics Be Utilized in Drug Discovery/Development?

PubMed

Caldwell, Gary W; Leo, Gregory C

2017-01-01

Untargeted metabolomics is a promising approach for reducing the significant attrition rate for discovering and developing drugs in the pharmaceutical industry. This review aims to highlight the practical decision-making value of untargeted metabolomics for the advancement of drug candidates in drug discovery/development including potentially identifying and validating novel therapeutic targets, creating alternative screening paradigms, facilitating the selection of specific and translational metabolite biomarkers, identifying metabolite signatures for the drug efficacy mechanism of action, and understanding potential drug-induced toxicity. The review provides an overview of the pharmaceutical process workflow to discover and develop new small molecule drugs followed by the metabolomics process workflow that is involved in conducting metabolomics studies. The pros and cons of the major components of the pharmaceutical and metabolomics workflows are reviewed and discussed. Finally, selected untargeted metabolomics literature examples, from primarily 2010 to 2016, are used to illustrate why, how, and where untargeted metabolomics can be integrated into the drug discovery/preclinical drug development process. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Laboratory Directed Research and Development Annual Report for 2009

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hughes, Pamela J.

This report documents progress made on all LDRD-funded projects during fiscal year 2009. As a US Department of Energy (DOE) Office of Science (SC) national laboratory, Pacific Northwest National Laboratory (PNNL) has an enduring mission to bring molecular and environmental sciences and engineering strengths to bear on DOE missions and national needs. Their vision is to be recognized worldwide and valued nationally for leadership in accelerating the discovery and deployment of solutions to challenges in energy, national security, and the environment. To achieve this mission and vision, they provide distinctive, world-leading science and technology in: (1) the design and scalablemore » synthesis of materials and chemicals; (2) climate change science and emissions management; (3) efficient and secure electricity management from generation to end use; and (4) signature discovery and exploitation for threat detection and reduction. PNNL leadership also extends to operating EMSL: the Environmental Molecular Sciences Laboratory, a national scientific user facility dedicated to providing itnegrated experimental and computational resources for discovery and technological innovation in the environmental molecular sciences.« less

25 Years of GenBank

MedlinePlus

... this page please turn Javascript on. Unique DNA database has helped advance scientific discoveries worldwide Since its origin 25 years ago, the database of nucleic acid sequences known as GenBank has ...

Evaluation of Signature Erosion in Ebola Virus Due to Genomic Drift and Its Impact on the Performance of Diagnostic Assays

PubMed Central

Sozhamannan, Shanmuga; Holland, Mitchell Y.; Hall, Adrienne T.; Negrón, Daniel A.; Ivancich, Mychal; Koehler, Jeffrey W.; Minogue, Timothy D.; Campbell, Catherine E.; Berger, Walter J.; Christopher, George W.; Goodwin, Bruce G.; Smith, Michael A.

2015-01-01

Genome sequence analyses of the 2014 Ebola Virus (EBOV) isolates revealed a potential problem with the diagnostic assays currently in use; i.e., drifting genomic profiles of the virus may affect the sensitivity or even produce false-negative results. We evaluated signature erosion in ebolavirus molecular assays using an in silico approach and found frequent potential false-negative and false-positive results. We further empirically evaluated many EBOV assays, under real time PCR conditions using EBOV Kikwit (1995) and Makona (2014) RNA templates. These results revealed differences in performance between assays but were comparable between the old and new EBOV templates. Using a whole genome approach and a novel algorithm, termed BioVelocity, we identified new signatures that are unique to each of EBOV, Sudan virus (SUDV), and Reston virus (RESTV). Interestingly, many of the current assay signatures do not fall within these regions, indicating a potential drawback in the past assay design strategies. The new signatures identified in this study may be evaluated with real-time reverse transcription PCR (rRT-PCR) assay development and validation. In addition, we discuss regulatory implications and timely availability to impact a rapidly evolving outbreak using existing but perhaps less than optimal assays versus redesign these assays for addressing genomic changes. PMID:26090727

Doppler effect on indirect detection of dark matter using dark matter only simulations

DOE PAGES

Powell, Devon; Laha, Ranjan; Ng, Kenny C. Y.; ...

2017-03-15

Indirect detection of dark matter is a major avenue for discovery. However, baryonic backgrounds are diverse enough to mimic many possible signatures of dark matter. In this work, we study the newly proposed technique of dark matter velocity spectroscopy. The nonrotating dark matter halo and the Solar motion produce a distinct longitudinal dependence of the signal which is opposite in direction to that produced by baryons. Using collisionless dark matter only simulations of Milky Way like halos, we show that this new signature is robust and holds great promise. We develop mock observations by a high energy resolution x-ray spectrometermore » on a sounding rocket, the Micro-X experiment, to our test case, the 3.5 keV line. We show that by using six different pointings, Micro-X can exclude a constant line energy over various longitudes at ≥ 3σ. As a result, the halo triaxiality is an important effect, and it will typically reduce the significance of this signal. We emphasize that this new smoking gun in motion signature of dark matter is general and is applicable to any dark matter candidate which produces a sharp photon feature in annihilation or decay.« less

Doppler effect on indirect detection of dark matter using dark matter only simulations

DOE Office of Scientific and Technical Information (OSTI.GOV)

Powell, Devon; Laha, Ranjan; Ng, Kenny C. Y.

Indirect detection of dark matter is a major avenue for discovery. However, baryonic backgrounds are diverse enough to mimic many possible signatures of dark matter. In this work, we study the newly proposed technique of dark matter velocity spectroscopy. The nonrotating dark matter halo and the Solar motion produce a distinct longitudinal dependence of the signal which is opposite in direction to that produced by baryons. Using collisionless dark matter only simulations of Milky Way like halos, we show that this new signature is robust and holds great promise. We develop mock observations by a high energy resolution x-ray spectrometermore » on a sounding rocket, the Micro-X experiment, to our test case, the 3.5 keV line. We show that by using six different pointings, Micro-X can exclude a constant line energy over various longitudes at ≥ 3σ. As a result, the halo triaxiality is an important effect, and it will typically reduce the significance of this signal. We emphasize that this new smoking gun in motion signature of dark matter is general and is applicable to any dark matter candidate which produces a sharp photon feature in annihilation or decay.« less

Targeted Sequencing for Discovery and Validation of DNA Methylation Markers of Colon Cancer Metastasis — EDRN Public Portal

Cancer.gov

Colon cancer is the second leading cause of cancer death in the United States. A key issue in treating colon cancer patients is inability to accurately predict tumors that have metastatic potential and require adjuvant chemotherapy. This project will test the model that tumor metastases arise from intra-tumor heterogeneity generated by DNA methylation events, and that detecting these events can provide a predictve signature of tumors with poor outcome

Molecular subgroups of medulloblastoma

PubMed Central

Northcott, Paul A; Dubuc, Adrian M; Pfister, Stefan; Taylor, Michael D

2014-01-01

Recent efforts at stratifying medulloblastomas based on their molecular features have revolutionized our understanding of this morbidity. Collective efforts by multiple independent groups have subdivided medulloblastoma from a single disease into four distinct molecular subgroups characterized by disparate transcriptional signatures, mutational spectra, copy number profiles and, most importantly, clinical features. We present a summary of recent studies that have contributed to our understanding of the core medulloblastoma subgroups, focusing largely on clinically relevant discoveries that have already, and will continue to, shape research. PMID:22853794

The DataBridge: A System For Optimizing The Use Of Dark Data From The Long Tail Of Science

NASA Astrophysics Data System (ADS)

Lander, H.; Rajasekar, A.

2015-12-01

The DataBridge is a National Science Foundation funded collaborative project (OCI-1247652, OCI-1247602, OCI-1247663) designed to assist in the discovery of dark data sets from the long tail of science. The DataBridge aims to to build queryable communities of datasets using sociometric network analysis. This approach is being tested to evaluate the ability to leverage various forms of metadata to facilitate discovery of new knowledge. Each dataset in the Databridge has an associated name space used as a first level partitioning. In addition to testing known algorithms for SNA community building, the DataBridge project has built a message-based platform that allows users to provide their own algorithms for each of the stages in the community building process. The stages are: Signature Generation (SG): An SG algorithm creates a metadata signature for a dataset. Signature algorithms might use text metadata provided by the dataset creator or derive metadata. Relevance Algorithm (RA): An RA compares a pair of datasets and produces a similarity value between 0 and 1 for the two datasets. Sociometric Network Analysis (SNA): The SNA will operate on a similarity matrix produced by an RA to partition all of the datasets in the name space into a set of clusters. These clusters represent communities of closely related datasets. The DataBridge also includes a web application that produces a visual representation of the clustering. Future work includes a more complete application that will allow different types of searching of the network of datasets. The DataBridge approach is relevant to geoscience research and informatics. In this presentation we will outline the project, illustrate the deployment of the approach, and discuss other potential applications and next steps for the research such as applying this approach to models. In addition we will explore the relevance of DataBridge to other geoscience projects such as various EarthCube Building Blocks and DIBBS projects.

Gene-expression signature regulated by the KEAP1-NRF2-CUL3 axis is associated with a poor prognosis in head and neck squamous cell cancer.

PubMed

Namani, Akhileshwar; Matiur Rahaman, Md; Chen, Ming; Tang, Xiuwen

2018-01-06

NRF2 is the key regulator of oxidative stress in normal cells and aberrant expression of the NRF2 pathway due to genetic alterations in the KEAP1 (Kelch-like ECH-associated protein 1)-NRF2 (nuclear factor erythroid 2 like 2)-CUL3 (cullin 3) axis leads to tumorigenesis and drug resistance in many cancers including head and neck squamous cell cancer (HNSCC). The main goal of this study was to identify specific genes regulated by the KEAP1-NRF2-CUL3 axis in HNSCC patients, to assess the prognostic value of this gene signature in different cohorts, and to reveal potential biomarkers. RNA-Seq V2 level 3 data from 279 tumor samples along with 37 adjacent normal samples from patients enrolled in the The Cancer Genome Atlas (TCGA)-HNSCC study were used to identify upregulated genes using two methods (altered KEAP1-NRF2-CUL3 versus normal, and altered KEAP1-NRF2-CUL3 versus wild-type). We then used a new approach to identify the combined gene signature by integrating both datasets and subsequently tested this signature in 4 independent HNSCC datasets to assess its prognostic value. In addition, functional annotation using the DAVID v6.8 database and protein-protein interaction (PPI) analysis using the STRING v10 database were performed on the signature. A signature composed of a subset of 17 genes regulated by the KEAP1-NRF2-CUL3 axis was identified by overlapping both the upregulated genes of altered versus normal (251 genes) and altered versus wild-type (25 genes) datasets. We showed that increased expression was significantly associated with poor survival in 4 independent HNSCC datasets, including the TCGA-HNSCC dataset. Furthermore, Gene Ontology, Kyoto Encyclopedia of Genes and Genomes, and PPI analysis revealed that most of the genes in this signature are associated with drug metabolism and glutathione metabolic pathways. Altogether, our study emphasizes the discovery of a gene signature regulated by the KEAP1-NRF2-CUL3 axis which is strongly associated with tumorigenesis and drug resistance in HNSCC. This 17-gene signature provides potential biomarkers and therapeutic targets for HNSCC cases in which the NRF2 pathway is activated.

Indoor localization using magnetic fields

NASA Astrophysics Data System (ADS)

Pathapati Subbu, Kalyan Sasidhar

Indoor localization consists of locating oneself inside new buildings. GPS does not work indoors due to multipath reflection and signal blockage. WiFi based systems assume ubiquitous availability and infrastructure based systems require expensive installations, hence making indoor localization an open problem. This dissertation consists of solving the problem of indoor localization by thoroughly exploiting the indoor ambient magnetic fields comprising mainly of disturbances termed as anomalies in the Earth's magnetic field caused by pillars, doors and elevators in hallways which are ferromagnetic in nature. By observing uniqueness in magnetic signatures collected from different campus buildings, the work presents the identification of landmarks and guideposts from these signatures and further develops magnetic maps of buildings - all of which can be used to locate and navigate people indoors. To understand the reason behind these anomalies, first a comparison between the measured and model generated Earth's magnetic field is made, verifying the presence of a constant field without any disturbances. Then by modeling the magnetic field behavior of different pillars such as steel reinforced concrete, solid steel, and other structures like doors and elevators, the interaction of the Earth's field with the ferromagnetic fields is described thereby explaining the causes of the uniqueness in the signatures that comprise these disturbances. Next, by employing the dynamic time warping algorithm to account for time differences in signatures obtained from users walking at different speeds, an indoor localization application capable of classifying locations using the magnetic signatures is developed solely on the smart phone. The application required users to walk short distances of 3-6 m anywhere in hallway to be located with accuracies of 80-99%. The classification framework was further validated with over 90% accuracies using model generated magnetic signatures representing hallways with different kinds of pillars, doors and elevators. All in all, this dissertation contributes the following: 1) provides a framework for understanding the presence of ambient magnetic fields indoors and utilizing them to solve the indoor localization problem; 2) develops an application that is independent of the user and the smart phones and 3) requires no other infrastructure since it is deployed on a device that encapsulates the sensing, computing and inferring functionalities, thereby making it a novel contribution to the mobile and pervasive computing domain.

Biomarker microRNAs for prostate cancer metastasis: screened with a network vulnerability analysis model.

PubMed

Lin, Yuxin; Chen, Feifei; Shen, Li; Tang, Xiaoyu; Du, Cui; Sun, Zhandong; Ding, Huijie; Chen, Jiajia; Shen, Bairong

2018-05-21

Prostate cancer (PCa) is a fatal malignant tumor among males in the world and the metastasis is a leading cause for PCa death. Biomarkers are therefore urgently needed to detect PCa metastatic signature at the early time. MicroRNAs are small non-coding RNAs with the potential to be biomarkers for disease prediction. In addition, computer-aided biomarker discovery is now becoming an attractive paradigm for precision diagnosis and prognosis of complex diseases. In this study, we identified key microRNAs as biomarkers for predicting PCa metastasis based on network vulnerability analysis. We first extracted microRNAs and mRNAs that were differentially expressed between primary PCa and metastatic PCa (MPCa) samples. Then we constructed the MPCa-specific microRNA-mRNA network and screened microRNA biomarkers by a novel bioinformatics model. The model emphasized the characterization of systems stability changes and the network vulnerability with three measurements, i.e. the structurally single-line regulation, the functional importance of microRNA targets and the percentage of transcription factor genes in microRNA unique targets. With this model, we identified five microRNAs as putative biomarkers for PCa metastasis. Among them, miR-101-3p and miR-145-5p have been previously reported as biomarkers for PCa metastasis and the remaining three, i.e. miR-204-5p, miR-198 and miR-152, were screened as novel biomarkers for PCa metastasis. The results were further confirmed by the assessment of their predictive power and biological function analysis. Five microRNAs were identified as candidate biomarkers for predicting PCa metastasis based on our network vulnerability analysis model. The prediction performance, literature exploration and functional enrichment analysis convinced our findings. This novel bioinformatics model could be applied to biomarker discovery for other complex diseases.

Advanced Applications of Vibrational Circular Dichroism: from Small Chiral Molecules to Fibrils

NASA Astrophysics Data System (ADS)

Dukor, Rina K.

2017-06-01

Vibrational Circular Dichroism (VCD), first discovered in the early 1970s, and commercialized in the late 1990's, is finally coming of age! No longer a curiosity of the few selected academic groups, it is now used by all major pharmaceutical companies, regulatory agencies, government labs and academic institutions. The main application for the technology has been determination of absolute configuration of small pharmaceutical molecules. In more recent years, this has extended to more complicated molecules such as natural products with many chiral centers and conformational flexibility. Other applications include determination of enantiomeric purity, chiral polymers, and characterization of other biological molecules such as proteins, carohydrates and nucleic acids. One of the most fascinating discoveries in the VCD field has been been unusual enhancement in intensity for proteins that form fibrils. We have demonstrated sensitivity of VCD to in situ solution-phase probe of the process of fibrillogenesis and subsequent development that currently can only be studied in detail with dried samples by such techniques as scanning electron microscopy or atomic force microscopy. We have further shown that several different proteins, that in their native state have different secondary structures, have a very similar unique signature of mature fibrils. In this presentation, we will discuss fundamentals of VCD, demonstrate a few examples of different applications and showcase the sensitivity to structure of fibrils, including new results on micro-sampling.

Preliminary Interpretation of the MSL REMS Pressure Data

NASA Astrophysics Data System (ADS)

Haberle, Robert; Gómez-Elvira, Javier; de la Torre Juárez, Manuel; Harri, Ari-Matti; Hollingsworth, Jeffery; Kahanpää, Henrik; Kahre, Melinda; Martin-Torres, Javier; Mischna, Michael; Newman, Claire; Rafkin, Scot; Rennó, Nilton; Richardson, Mark; Rodríguez-Manfredi, Jose; Vasavada, Ashwin; Zorzano, Maria-Paz; REMS/MSL Science Teams

2013-04-01

The Rover Environmental Monitoring Station (REMS) on the Mars Science Laboratory (MSL) Curiosity rover consists of a suite of meteorological instruments that measure pressure, temperature (air and ground), wind (speed and direction), relative humidity, and the UV flux. A detailed description of the REMS sensors and their performance can be found in Gómez-Elvira et al. [2012, Space Science Reviews, 170(1-4), 583-640]. Here we focus on interpreting the first 100 sols of REMS operations with a particular emphasis on the pressure data. A unique feature of pressure data is that they reveal information on meteorological phenomena with time scales from seconds to years and spatial scales from local to global. From a single station we can learn about dust devils, regional circulations, thermal tides, synoptic weather systems, the CO2 cycle, dust storms, and interannual variability. Thus far MSL's REMS pressure sensor, provided by the Finnish Meteorological Institute and integrated into the REMS payload by Centro de Astrobiología, is performing flawlessly and our preliminary interpretation of its data includes the discovery of relatively dust-free convective vortices; a regional circulation system significantly modified by Gale crater and its central mound; the strongest thermal tides yet measured from the surface of Mars whose amplitudes and phases are very sensitive to fluctuations in global dust loading; and the classical signature of the seasonal cycling of carbon dioxide into and out of the polar caps.

Principle considerations for the use of transcriptomics in doping research.

PubMed

Neuberger, Elmo W I; Moser, Dirk A; Simon, Perikles

2011-10-01

Over the course of the past decade, technical progress has enabled scientists to investigate genome-wide RNA expression using microarray platforms. This transcriptomic approach represents a promising tool for the discovery of basic gene expression patterns and for identification of cellular signalling pathways under various conditions. Since doping substances have been shown to influence mRNA expression, it has been suggested that these changes can be detected by screening the blood transcriptome. In this review, we critically discuss the potential but also the pitfalls of this application as a tool in doping research. Transcriptomic approaches were considered to potentially provide researchers with a unique gene expression signature or with a specific biomarker for various physiological and pathophysiological conditions. Since transcriptomic approaches are considerably prone to biological and technical confounding factors that act on study subjects or samples, very strict guidelines for the use of transcriptomics in human study subjects have been developed. Typical field conditions associated with doping controls limit the feasibility of following these strict guidelines as there are too many variables counteracting a standardized procedure. After almost a decade of research using transcriptomic tools, it still remains a matter of future technological progress to identify the ultimate biomarker using technologies and/or methodologies that are sufficiently robust against typical biological and technical bias and that are valid in a court of law. Copyright © 2011 John Wiley & Sons, Ltd.

Whole transcriptome profiling reveals major cell types in the cellular immune response against acute and chronic active Epstein-Barr virus infection.

PubMed

Zhong, Huaqing; Hu, Xinran; Janowski, Andrew B; Storch, Gregory A; Su, Liyun; Cao, Lingfeng; Yu, Jinsheng; Xu, Jin

2017-12-19

Epstein-Barr virus (EBV) is a common human pathogen that infects over 95% of the population worldwide. In the present study, the whole transcriptome microarray data were generated from peripheral blood mononuclear cells from Chinese children with acute infectious mononucleosis (AIM) and chronic active EBV infection (CAEBV) that were also compared with a publicly available microarray dataset from a study of American college students with AIM. Our study characterized for the first time a broad spectrum of molecular signatures in AIM and CAEBV. The key findings from the transcriptome profiling were validated with qPCR and flow cytometry assays. The most important finding in our study is the discovery of predominant γδ TCR expression and γδ T cell expansion in AIM. This finding, in combination with the striking up-regulation of CD3, CD8 and CD94, suggests that CD8+ T cells and CD94+ NK cells may play a major role in AIM. Moreover, the unique up-regulation of CD64A/B and its significant correlation with the monocyte marker CD14 was observed in CAEBV and that implies an important role of monocytes in CAEBV. In conclusion, our study reveals major cell types (particularly γδ T cells) in the host cellular immune response against AIM and CAEBV.

Multi-frequency and polarimetric radar backscatter signatures for discrimination between agricultural crops at the Flevoland experimental test site

NASA Technical Reports Server (NTRS)

Freeman, A.; Villasenor, J.; Klein, J. D.

1991-01-01

We describe the calibration and analysis of multi-frequency, multi-polarization radar backscatter signatures over an agriculture test site in the Netherlands. The calibration procedure involved two stages: in the first stage, polarimetric and radiometric calibrations (ignoring noise) were carried out using square-base trihedral corner reflector signatures and some properties of the clutter background. In the second stage, a novel algorithm was used to estimate the noise level in the polarimetric data channels by using the measured signature of an idealized rough surface with Bragg scattering (the ocean in this case). This estimated noise level was then used to correct the measured backscatter signatures from the agriculture fields. We examine the significance of several key parameters extracted from the calibrated and noise-corrected backscatter signatures. The significance is assessed in terms of the ability to uniquely separate among classes from 13 different backscatter types selected from the test site data, including eleven different crops, one forest and one ocean area. Using the parameters with the highest separation for a given class, we use a hierarchical algorithm to classify the entire image. We find that many classes, including ocean, forest, potato, and beet, can be identified with high reliability, while the classes for which no single parameter exhibits sufficient separation have higher rates of misclassification. We expect that modified decision criteria involving simultaneous consideration of several parameters increase performance for these classes.

Archaeology: formulation of a Roman cosmetic.

PubMed

Evershed, R P; Berstan, R; Grew, F; Copley, M S; Charmant, A J H; Barham, E; Mottram, H R; Brown, G

2004-11-04

The discovery of a small tin canister in London during archaeological excavations of a Roman temple precinct, dated to the middle of the second century AD, is a landmark in the study of this class of artefact. Such discoveries from the Roman world are rare and this is the only one to be found so far with its lid and contents--a whitish medicinal or cosmetic cream--providing a unique opportunity for us to study the ancient formulation.

The cure: design and evaluation of a crowdsourcing game for gene selection for breast cancer survival prediction.

PubMed

Good, Benjamin M; Loguercio, Salvatore; Griffith, Obi L; Nanis, Max; Wu, Chunlei; Su, Andrew I

2014-07-29

Molecular signatures for predicting breast cancer prognosis could greatly improve care through personalization of treatment. Computational analyses of genome-wide expression datasets have identified such signatures, but these signatures leave much to be desired in terms of accuracy, reproducibility, and biological interpretability. Methods that take advantage of structured prior knowledge (eg, protein interaction networks) show promise in helping to define better signatures, but most knowledge remains unstructured. Crowdsourcing via scientific discovery games is an emerging methodology that has the potential to tap into human intelligence at scales and in modes unheard of before. The main objective of this study was to test the hypothesis that knowledge linking expression patterns of specific genes to breast cancer outcomes could be captured from players of an open, Web-based game. We envisioned capturing knowledge both from the player's prior experience and from their ability to interpret text related to candidate genes presented to them in the context of the game. We developed and evaluated an online game called The Cure that captured information from players regarding genes for use as predictors of breast cancer survival. Information gathered from game play was aggregated using a voting approach, and used to create rankings of genes. The top genes from these rankings were evaluated using annotation enrichment analysis, comparison to prior predictor gene sets, and by using them to train and test machine learning systems for predicting 10 year survival. Between its launch in September 2012 and September 2013, The Cure attracted more than 1000 registered players, who collectively played nearly 10,000 games. Gene sets assembled through aggregation of the collected data showed significant enrichment for genes known to be related to key concepts such as cancer, disease progression, and recurrence. In terms of the predictive accuracy of models trained using this information, these gene sets provided comparable performance to gene sets generated using other methods, including those used in commercial tests. The Cure is available on the Internet. The principal contribution of this work is to show that crowdsourcing games can be developed as a means to address problems involving domain knowledge. While most prior work on scientific discovery games and crowdsourcing in general takes as a premise that contributors have little or no expertise, here we demonstrated a crowdsourcing system that succeeded in capturing expert knowledge.

Open Science Meets Stem Cells: A New Drug Discovery Approach for Neurodegenerative Disorders

PubMed Central

Han, Chanshuai; Chaineau, Mathilde; Chen, Carol X.-Q.; Beitel, Lenore K.; Durcan, Thomas M.

2018-01-01

Neurodegenerative diseases are a challenge for drug discovery, as the biological mechanisms are complex and poorly understood, with a paucity of models that faithfully recapitulate these disorders. Recent advances in stem cell technology have provided a paradigm shift, providing researchers with tools to generate human induced pluripotent stem cells (iPSCs) from patient cells. With the potential to generate any human cell type, we can now generate human neurons and develop “first-of-their-kind” disease-relevant assays for small molecule screening. Now that the tools are in place, it is imperative that we accelerate discoveries from the bench to the clinic. Using traditional closed-door research systems raises barriers to discovery, by restricting access to cells, data and other research findings. Thus, a new strategy is required, and the Montreal Neurological Institute (MNI) and its partners are piloting an “Open Science” model. One signature initiative will be that the MNI biorepository will curate and disseminate patient samples in a more accessible manner through open transfer agreements. This feeds into the MNI open drug discovery platform, focused on developing industry-standard assays with iPSC-derived neurons. All cell lines, reagents and assay findings developed in this open fashion will be made available to academia and industry. By removing the obstacles many universities and companies face in distributing patient samples and assay results, our goal is to accelerate translational medical research and the development of new therapies for devastating neurodegenerative disorders. PMID:29467610

Open Science Meets Stem Cells: A New Drug Discovery Approach for Neurodegenerative Disorders.

PubMed

Han, Chanshuai; Chaineau, Mathilde; Chen, Carol X-Q; Beitel, Lenore K; Durcan, Thomas M

2018-01-01

Neurodegenerative diseases are a challenge for drug discovery, as the biological mechanisms are complex and poorly understood, with a paucity of models that faithfully recapitulate these disorders. Recent advances in stem cell technology have provided a paradigm shift, providing researchers with tools to generate human induced pluripotent stem cells (iPSCs) from patient cells. With the potential to generate any human cell type, we can now generate human neurons and develop "first-of-their-kind" disease-relevant assays for small molecule screening. Now that the tools are in place, it is imperative that we accelerate discoveries from the bench to the clinic. Using traditional closed-door research systems raises barriers to discovery, by restricting access to cells, data and other research findings. Thus, a new strategy is required, and the Montreal Neurological Institute (MNI) and its partners are piloting an "Open Science" model. One signature initiative will be that the MNI biorepository will curate and disseminate patient samples in a more accessible manner through open transfer agreements. This feeds into the MNI open drug discovery platform, focused on developing industry-standard assays with iPSC-derived neurons. All cell lines, reagents and assay findings developed in this open fashion will be made available to academia and industry. By removing the obstacles many universities and companies face in distributing patient samples and assay results, our goal is to accelerate translational medical research and the development of new therapies for devastating neurodegenerative disorders.

A Path to Discovery

ERIC Educational Resources Information Center

Stegemoller, William; Stegemoller, Rebecca

2004-01-01

The path taken and the turns made as a turtle traces a polygon are examined to discover an important theorem in geometry. A unique tool, the Angle Adder, is implemented in the investigation. (Contains 9 figures.)

Unique parasite aDNA in moa coprolites from New Zealand suggests mass parasite extinctions followed human-induced megafauna extinctions

USGS Publications Warehouse

Lafferty, Kevin D.; Hopkins, Skylar R.

2018-01-01

Having split early from Gondwana, Zealandia (now modern New Zealand) escaped discovery until the late 13th century, and therefore remains an important glimpse into a human-free world. Without humans or other land mammals, diverse and peculiar birds evolved in isolation, including several flightless moa species, the giant pouakai eagle (Harpagornis moorei), the kiwi (Apteryx mantelli), and the kakapo parrot (Strigops habroptila). This unique community has fascinated paleoecologists, who have spent almost two centuries devising new ways to glean information from ancient bird remains. In PNAS, Boast et al. (1) apply one recent technological advance, ancient DNA (aDNA) metabarcoding, to confirm previous discoveries and report new details about moa and kakapo diets, parasites, and niches. Their efforts confirm Zealandia was a lot different before humans arrived.

Unique plasma metabolomic signatures of individuals with inherited disorders of long-chain fatty acid oxidation

USDA-ARS?s Scientific Manuscript database

Blood and urine acylcarnitine profiles are commonly used to diagnose long-chain fatty acid oxidation disorders (FAOD: i.e., long-chain hydroxy-acyl-CoA dehydrogenase [LCHAD] and carnitine palmitoyltransferase 2 [CPT2] deficiency), but the global metabolic impact of long-chain FAOD has not been repor...

AGGREGATING FOOD SOURCES IN STABLE ISOTOPE DIETARY STUDIES: LUMP IT OR LEAVE IT?

EPA Science Inventory

A common situation when stable isotope mixing models are used to estimate food source dietary contributions is that there are too many sources to allow a unique solution. To resolve this problem one option is to combine sources with similar signatures such that the number of sou...

SOURCE AGGREGATION IN STABLE ISOTOPE MIXING MODELS: LUMP IT OR LEAVE IT?

EPA Science Inventory

A common situation when stable isotope mixing models are used to estimate source contributions to a mixture is that there are too many sources to allow a unique solution. To resolve this problem one option is to combine sources with similar signatures such that the number of sou...

22 CFR 51.1 - Definitions.

Code of Federal Regulations, 2010 CFR

2010-04-01

... photograph, a unique chip number, and a digital signature to protect the integrity of the stored information... territories and possessions. (k) U.S. citizen means a person who acquired U.S. citizenship at birth or upon naturalization as provided by law and who has not subsequently lost such citizenship. (l) U.S. national means a U...

Trusted materials using orthogonal testing. 2015 Annual report

DOE Office of Scientific and Technical Information (OSTI.GOV)

Van Benthem, Mark

2015-09-01

The purpose of this project is to prove (or disprove) that a reasonable number of simple tests can be used to provide a unique data signature for materials, changes in which could serve as a harbinger of material deviation, prompting further evaluations. The routine tests are mutually orthogonal to any currently required materials specification tests.

Past Exposure to Densely Ionizing Radiation Leaves a Unique Permanent Signature in the Genome

PubMed Central

Hande, M. Prakash; Azizova, Tamara V.; Geard, Charles R.; Burak, Ludmilla E.; Mitchell, Catherine R.; Khokhryakov, Valentin F.; Vasilenko, Evgeny K.; Brenner, David J.

2003-01-01

Speculation has long surrounded the question of whether past exposure to ionizing radiation leaves a unique permanent signature in the genome. Intrachromosomal rearrangements or deletions are produced much more efficiently by densely ionizing radiation than by chemical mutagens, x-rays, or endogenous aging processes. Until recently, such stable intrachromosomal aberrations have been very hard to detect, but a new chromosome band painting technique has made their detection practical. We report the detection and quantification of stable intrachromosomal aberrations in lymphocytes of healthy former nuclear-weapons workers who were exposed to plutonium many years ago. Even many years after occupational exposure, more than half the blood cells of the healthy plutonium workers contain large (>6 Mb) intrachromosomal rearrangements. The yield of these aberrations was highly correlated with plutonium dose to the bone marrow. The control groups contained very few such intrachromosomal aberrations. Quantification of this large-scale chromosomal damage in human populations exposed many years earlier will lead to new insights into the mechanisms and risks of cytogenetic damage. PMID:12679897

Unique human immune signature of Ebola virus disease in Guinea.

PubMed

Ruibal, Paula; Oestereich, Lisa; Lüdtke, Anja; Becker-Ziaja, Beate; Wozniak, David M; Kerber, Romy; Korva, Miša; Cabeza-Cabrerizo, Mar; Bore, Joseph A; Koundouno, Fara Raymond; Duraffour, Sophie; Weller, Romy; Thorenz, Anja; Cimini, Eleonora; Viola, Domenico; Agrati, Chiara; Repits, Johanna; Afrough, Babak; Cowley, Lauren A; Ngabo, Didier; Hinzmann, Julia; Mertens, Marc; Vitoriano, Inês; Logue, Christopher H; Boettcher, Jan Peter; Pallasch, Elisa; Sachse, Andreas; Bah, Amadou; Nitzsche, Katja; Kuisma, Eeva; Michel, Janine; Holm, Tobias; Zekeng, Elsa-Gayle; García-Dorival, Isabel; Wölfel, Roman; Stoecker, Kilian; Fleischmann, Erna; Strecker, Thomas; Di Caro, Antonino; Avšič-Županc, Tatjana; Kurth, Andreas; Meschi, Silvia; Mély, Stephane; Newman, Edmund; Bocquin, Anne; Kis, Zoltan; Kelterbaum, Anne; Molkenthin, Peter; Carletti, Fabrizio; Portmann, Jasmine; Wolff, Svenja; Castilletti, Concetta; Schudt, Gordian; Fizet, Alexandra; Ottowell, Lisa J; Herker, Eva; Jacobs, Thomas; Kretschmer, Birte; Severi, Ettore; Ouedraogo, Nobila; Lago, Mar; Negredo, Anabel; Franco, Leticia; Anda, Pedro; Schmiedel, Stefan; Kreuels, Benno; Wichmann, Dominic; Addo, Marylyn M; Lohse, Ansgar W; De Clerck, Hilde; Nanclares, Carolina; Jonckheere, Sylvie; Van Herp, Michel; Sprecher, Armand; Xiaojiang, Gao; Carrington, Mary; Miranda, Osvaldo; Castro, Carlos M; Gabriel, Martin; Drury, Patrick; Formenty, Pierre; Diallo, Boubacar; Koivogui, Lamine; Magassouba, N'Faly; Carroll, Miles W; Günther, Stephan; Muñoz-Fontela, César

2016-05-05

Despite the magnitude of the Ebola virus disease (EVD) outbreak in West Africa, there is still a fundamental lack of knowledge about the pathophysiology of EVD. In particular, very little is known about human immune responses to Ebola virus. Here we evaluate the physiology of the human T cell immune response in EVD patients at the time of admission to the Ebola Treatment Center in Guinea, and longitudinally until discharge or death. Through the use of multiparametric flow cytometry established by the European Mobile Laboratory in the field, we identify an immune signature that is unique in EVD fatalities. Fatal EVD was characterized by a high percentage of CD4(+) and CD8(+) T cells expressing the inhibitory molecules CTLA-4 and PD-1, which correlated with elevated inflammatory markers and high virus load. Conversely, surviving individuals showed significantly lower expression of CTLA-4 and PD-1 as well as lower inflammation, despite comparable overall T cell activation. Concomitant with virus clearance, survivors mounted a robust Ebola-virus-specific T cell response. Our findings suggest that dysregulation of the T cell response is a key component of EVD pathophysiology.

Agricultural trade networks and patterns of economic development.

PubMed

Shutters, Shade T; Muneepeerakul, Rachata

2012-01-01

International trade networks are manifestations of a complex combination of diverse underlying factors, both natural and social. Here we apply social network analytics to the international trade network of agricultural products to better understand the nature of this network and its relation to patterns of international development. Using a network tool known as triadic analysis we develop triad significance profiles for a series of agricultural commodities traded among countries. Results reveal a novel network "superfamily" combining properties of biological information processing networks and human social networks. To better understand this unique network signature, we examine in more detail the degree and triadic distributions within the trade network by country and commodity. Our results show that countries fall into two very distinct classes based on their triadic frequencies. Roughly 165 countries fall into one class while 18, all highly isolated with respect to international agricultural trade, fall into the other. Only Vietnam stands out as a unique case. Finally, we show that as a country becomes less isolated with respect to number of trading partners, the country's triadic signature follows a predictable trajectory that may correspond to a trajectory of development.

Genome-wide scans between two honeybee populations reveal putative signatures of human-mediated selection.

PubMed

Parejo, M; Wragg, D; Henriques, D; Vignal, A; Neuditschko, M

2017-12-01

Human-mediated selection has left signatures in the genomes of many domesticated animals, including the European dark honeybee, Apis mellifera mellifera, which has been selected by apiculturists for centuries. Using whole-genome sequence information, we investigated selection signatures in spatially separated honeybee subpopulations (Switzerland, n = 39 and France, n = 17). Three different test statistics were calculated in windows of 2 kb (fixation index, cross-population extended haplotype homozygosity and cross-population composite likelihood ratio) and combined into a recently developed composite selection score. Applying a stringent false discovery rate of 0.01, we identified six significant selective sweeps distributed across five chromosomes covering eight genes. These genes are associated with multiple molecular and biological functions, including regulation of transcription, receptor binding and signal transduction. Of particular interest is a selection signature on chromosome 1, which corresponds to the WNT4 gene, the family of which is conserved across the animal kingdom with a variety of functions. In Drosophila melanogaster, WNT4 alleles have been associated with differential wing, cross vein and abdominal phenotypes. Defining phenotypic characteristics of different Apis mellifera ssp., which are typically used as selection criteria, include colour and wing venation pattern. This signal is therefore likely to be a good candidate for human mediated-selection arising from different applied breeding practices in the two managed populations. © 2017 The Authors. Animal Genetics published by John Wiley & Sons Ltd on behalf of Stichting International Foundation for Animal Genetics.

Testing eternal inflation with the kinetic Sunyaev Zel'dovich effect

NASA Astrophysics Data System (ADS)

Zhang, Pengjie; Johnson, Matthew C.

2015-06-01

Perhaps the most controversial idea in modern cosmology is that our observable universe is contained within one bubble among many, all inhabiting the eternally inflating multiverse. One of the few way to test this idea is to look for evidence of the relic inhomogeneities left by the collisions between other bubbles and our own. Such relic inhomogeneities will induce a coherent bulk flow over Gpc scales. Therefore, bubble collisions leave unique imprints in the cosmic microwave background (CMB) through the kinetic Sunyaev Zel'dovich (kSZ) effect, temperature anisotropies induced by the scattering of photons from coherently moving free electrons in the diffuse intergalactic medium. The kSZ signature produced by bubble collisions has a unique directional dependence and is tightly correlated with the galaxy distribution; it can therefore be distinguished from other contributions to the CMB anisotropies. An important advantage of the kSZ signature is that it peaks on arcminute angular scales, where the limiting factors in making a detection are instrumental noise and foreground subtraction. This is in contrast to the collision signature in the primary CMB, which peaks on angular scales much larger than one degree, and whose detection is therefore limited by cosmic variance. In this paper, we examine the prospects for probing the inhomogeneities left by bubble collisions using the kSZ effect. We provide a forecast for detection using cross-correlations between CMB and galaxy surveys, finding that the detectability using the kSZ effect can be competitive with constraints from CMB temperature and polarization data.

Thermal signatures of voluntary deception in ecological conditions

PubMed Central

Panasiti, Maria Serena; Cardone, Daniela; Pavone, Enea F.; Mancini, Alessandra; Merla, Arcangelo; Aglioti, Salvatore M.

2016-01-01

Deception is a pervasive phenomenon that greatly influences dyadic, groupal and societal interactions. Behavioural, physiological and neural signatures of this phenomenon have imporant implications for theoretical and applied research, but, because it is difficult for a laboratory to replicate the natural context in which deception occurs, contemporary research is still struggling to find such signatures. In this study, we tracked the facial temperature of participants who decided whether or not to deceive another person, in situations where their reputation was at risk or not. We used a high-sensitivity infrared device to track temperature changes to check for unique patterns of autonomic reactivity. Using a region-of-interest based approach we found that prior to any response there was a minimal increase in periorbital temperature (which indexes sympathetic activation, together with reduced cheek temperature) for the self-gain lies in the reputation-risk condition. Crucially, we found a rise in nose temperature (which indexes parasympathetic activation) for self-gain lies in the reputation-risk condition, not only during response preparation but also after the choice was made. This finding suggests that the entire deception process may be tracked by the nose region. Furthermore, this nasal temperature modulation was negatively correlated with machiavellian traits, indicating that sympathetic/parasympathetic regulation is less important for manipulative individuals who may care less about the consequences of lie-related moral violations. Our results highlight a unique pattern of autonomic reactivity for spontaneous deception in ecological contexts. PMID:27734927

Lifeomics leads the age of grand discoveries.

PubMed

He, Fuchu

2013-03-01

When our knowledge of a field accumulates to a certain level, we are bound to see the rise of one or more great scientists. They will make a series of grand discoveries/breakthroughs and push the discipline into an 'age of grand discoveries'. Mathematics, geography, physics and chemistry have all experienced their ages of grand discoveries; and in life sciences, the age of grand discoveries has appeared countless times since the 16th century. Thanks to the ever-changing development of molecular biology over the past 50 years, contemporary life science is once again approaching its breaking point and the trigger for this is most likely to be 'lifeomics'. At the end of the 20th century, genomics wrote out the 'script of life'; proteomics decoded the script; and RNAomics, glycomics and metabolomics came into bloom. These 'omics', with their unique epistemology and methodology, quickly became the thrust of life sciences, pushing the discipline to new high. Lifeomics, which encompasses all omics, has taken shape and is now signalling the dawn of a new era, the age of grand discoveries.

Seeking heavy Higgs bosons through cascade decays

NASA Astrophysics Data System (ADS)

Coleppa, Baradhwaj; Fuks, Benjamin; Poulose, P.; Sahoo, Shibananda

2018-04-01

We investigate the LHC discovery prospects for a heavy Higgs boson decaying into the standard model Higgs boson and additional weak bosons. We consider a generic model-independent new physics configuration where this decay proceeds via a cascade involving other intermediate scalar bosons and focus on an LHC final-state signature comprised either of four b -jets and two charged leptons or of four charged leptons and two b -jets. We design two analyses of the corresponding signals, and demonstrate that a 5 σ discovery at the 14 TeV LHC is possible for various combinations of the parent and daughter Higgs-boson masses. We moreover find that the standard model backgrounds can be sufficiently rejected to guarantee the reconstruction of the parent Higgs boson mass. We apply our analyses to the Type-II two-Higgs-doublet model and identify the regions of the parameter space to which the LHC is sensitive.

Taus and the Trigger for Discovery at ATLAS

DOE Office of Scientific and Technical Information (OSTI.GOV)

Demers, Sarah

This five year grant allowed Yale Professor Sarah Demers and her students and postdocs to contribute to the ATLAS Experiment at CERN's Large Hadron Collider. We worked on a particular mode of the Higgs Boson decay, contributing to the discovery of this particle as well as measuring the particle's properties. We also performed a "first of its kind" measurement at a hadron collider in the measurement of tau polarization, which increased the sensitivity of ATLAS in a number of exciting ways, both for making measurements of known particles and for hunting for new ones. We also contributed to the taumore » trigger - the real-time selection that chooses data that includes the signature of the tau lepton. Four PhD students in the Yale Physics Department received their PhDs during the term of this grant, with at least partial support from the grant.« less

An Automated Peak Identification/Calibration Procedure for High-Dimensional Protein Measures From Mass Spectrometers.

PubMed

Yasui, Yutaka; McLerran, Dale; Adam, Bao-Ling; Winget, Marcy; Thornquist, Mark; Feng, Ziding

2003-01-01

Discovery of "signature" protein profiles that distinguish disease states (eg, malignant, benign, and normal) is a key step towards translating recent advancements in proteomic technologies into clinical utilities. Protein data generated from mass spectrometers are, however, large in size and have complex features due to complexities in both biological specimens and interfering biochemical/physical processes of the measurement procedure. Making sense out of such high-dimensional complex data is challenging and necessitates the use of a systematic data analytic strategy. We propose here a data processing strategy for two major issues in the analysis of such mass-spectrometry-generated proteomic data: (1) separation of protein "signals" from background "noise" in protein intensity measurements and (2) calibration of protein mass/charge measurements across samples. We illustrate the two issues and the utility of the proposed strategy using data from a prostate cancer biomarker discovery project as an example.

Challenges of Antibacterial Discovery

PubMed Central

Silver, Lynn L.

2011-01-01

Summary: The discovery of novel small-molecule antibacterial drugs has been stalled for many years. The purpose of this review is to underscore and illustrate those scientific problems unique to the discovery and optimization of novel antibacterial agents that have adversely affected the output of the effort. The major challenges fall into two areas: (i) proper target selection, particularly the necessity of pursuing molecular targets that are not prone to rapid resistance development, and (ii) improvement of chemical libraries to overcome limitations of diversity, especially that which is necessary to overcome barriers to bacterial entry and proclivity to be effluxed, especially in Gram-negative organisms. Failure to address these problems has led to a great deal of misdirected effort. PMID:21233508

Manipulation of the mouse genome: a multiple impact resource for drug discovery and development.

PubMed

Prosser, Haydn; Rastan, Sohaila

2003-05-01

Few would deny that the pharmaceutical industry's investment in genomics throughout the 1990s has yet to deliver in terms of drugs on the market. The reasons are complex and beyond the scope of this review. The unique ability to manipulate the mouse genome, however, has already had a positive impact on all stages of the drug discovery process and, increasingly, on the drug development process too. We give an overview of some recent applications of so-called 'transgenic' mouse technology in pharmaceutical research and development. We show how genetic manipulation in the mouse can be employed at multiple points in the drug discovery and development process, providing new solutions to old problems.

Detection of experimental brain tumors using time-resolved laser-induced fluorescence spectroscopy

NASA Astrophysics Data System (ADS)

Thompson, Reid C.; Black, Keith L.; Kateb, Babak; Marcu, Laura

2002-05-01

Time-Resolved Laser-Induced Fluorescence Spectroscopy (TR-LIFS) has the potential to provide a non- invasive characterization and detection of tumors. We utilized TR-LIFS to detect gliomas in-vivo in the rat C6 glioma model. Time-resolved emission spectra of both normal brain and tumor were analyzed to determine if unique fluorescence signatures could be used to distinguish the two. Fluorescence parameters derived from both spectral and time domain were used for tissue characterization. Our results show that in the rat C6 glioma model, TR-LIFS can be used to differentiate brain tumors from normal tissue (gray and white mater) based upon time- resolved fluorescence signatures seen in brain tumors.

A system identification technique based on the random decrement signatures. Part 1: Theory and simulation

NASA Technical Reports Server (NTRS)

Bedewi, Nabih E.; Yang, Jackson C. S.

1987-01-01

Identification of the system parameters of a randomly excited structure may be treated using a variety of statistical techniques. Of all these techniques, the Random Decrement is unique in that it provides the homogeneous component of the system response. Using this quality, a system identification technique was developed based on a least-squares fit of the signatures to estimate the mass, damping, and stiffness matrices of a linear randomly excited system. The mathematics of the technique is presented in addition to the results of computer simulations conducted to demonstrate the prediction of the response of the system and the random forcing function initially introduced to excite the system.

Advanced process and defect characterization methodology to support process development of advanced patterning structures

NASA Astrophysics Data System (ADS)

Ketkar, Supriya; Lee, Junhan; Asokamani, Sen; Cho, Winston; Mishra, Shailendra

2018-03-01

This paper discusses the approach and solution adopted by GLOBALFOUNDRIES, a high volume manufacturing (HVM) foundry, for dry-etch related edge-signature surface particle defects issue facing the sub-nm node in the gate-etch sector. It is one of the highest die killers for the company in the 14-nm node. We have used different approaches to attack and rectify the edge signature surface particle defect. Several process-related & hardware changes have been successively implemented to achieve defect reduction improvement by 63%. Each systematic process and/or hardware approach has its own unique downstream issues and they have been dealt in a route-cause-effect technique to address the issue.

Security authentication with a three-dimensional optical phase code using random forest classifier: an overview

NASA Astrophysics Data System (ADS)

Markman, Adam; Carnicer, Artur; Javidi, Bahram

2017-05-01

We overview our recent work [1] on utilizing three-dimensional (3D) optical phase codes for object authentication using the random forest classifier. A simple 3D optical phase code (OPC) is generated by combining multiple diffusers and glass slides. This tag is then placed on a quick-response (QR) code, which is a barcode capable of storing information and can be scanned under non-uniform illumination conditions, rotation, and slight degradation. A coherent light source illuminates the OPC and the transmitted light is captured by a CCD to record the unique signature. Feature extraction on the signature is performed and inputted into a pre-trained random-forest classifier for authentication.

Distinguishing Signatures of Multipathway Conformational Transitions

NASA Astrophysics Data System (ADS)

Pierse, Christopher A.; Dudko, Olga K.

2017-02-01

The folding and binding of biomolecules into functional conformations are thought to be commonly mediated by multiple pathways rather than a unique route. Yet even in experiments where one can "see" individual conformational transitions, their stochastic nature generally precludes one from determining whether the transitions occurred through one or multiple pathways. We establish model-free, observable signatures in the response of macromolecules to force that unambiguously identify multiple pathways—even when the pathways themselves cannot be resolved. The unified analytical description reveals that, through multiple pathways, the response of molecules to external forces can be shaped in diverse ways, resulting in a rich design space for a tailored biological function already at the single-molecule level.

Complex logic functions implemented with quantum dot bionanophotonic circuits.

PubMed

Claussen, Jonathan C; Hildebrandt, Niko; Susumu, Kimihiro; Ancona, Mario G; Medintz, Igor L

2014-03-26

We combine quantum dots (QDs) with long-lifetime terbium complexes (Tb), a near-IR Alexa Fluor dye (A647), and self-assembling peptides to demonstrate combinatorial and sequential bionanophotonic logic devices that function by time-gated Förster resonance energy transfer (FRET). Upon excitation, the Tb-QD-A647 FRET-complex produces time-dependent photoluminescent signatures from multi-FRET pathways enabled by the capacitor-like behavior of the Tb. The unique photoluminescent signatures are manipulated by ratiometrically varying dye/Tb inputs and collection time. Fluorescent output is converted into Boolean logic states to create complex arithmetic circuits including the half-adder/half-subtractor, 2:1 multiplexer/1:2 demultiplexer, and a 3-digit, 16-combination keypad lock.

Successes in drug discovery and design.

PubMed

2004-04-01

The Society for Medicines Research (SMR) held a one-day meeting on case histories in drug discovery on December 4, 2003, at the National Heart and Lung Institute in London. These meetings have been organized by the SMR biannually for many years, and this latest meeting proved extremely popular, attracting a capacity audience of more than 130 registrants. The purpose of these meetings is educational; they allow those interested in drug discovery to hear key learnings from recent successful drug discovery programs. There was no overall linking theme between the talks, other than each success story has led to the introduction of a new and improved product of therapeutic use. The drug discovery stories covered in the meeting were extremely varied and, put together, they emphasized that each successful story is unique and special. This meeting is also special for the SMR because it presents the "SMR Award for Drug Discovery" in recognition of outstanding achievement and contribution in the area. It should be remembered that drug discovery is an extremely risky business and an extremely costly and complicated process in which the success rate is, at best, low. (c) 2004 Prous Science. All rights reserved.

Mars scouts: an overview

NASA Technical Reports Server (NTRS)

Matousek, S.

2001-01-01

The Mars program institutes the Mars Scout Missions in order to address science goals in the program not otherwise covered in the baseline Mars plan. Mars Scout Missions will be Principle-Investigator (PI) led science missions. Analogous to the Discovery Program, PI led investigations optimize the use of limited resources to accomplish the best focused science and allow the flexibility to quickly respond to discoveries at Mars. Scout missions also require unique investments in technology and reliance upon Mars-based infrastructure such as telecom relay orbiters.

Latitudinal Trends in Stable Isotope Signatures of Northeast Atlantic Rhodoliths

NASA Astrophysics Data System (ADS)

Hofmann, Laurie

2017-04-01

Rhodoliths are free-living calcifying red algae that form extensive beds in shallow marine benthic environments (< 200 m) that provide important habitats and nurseries for marine organisms and contribute to carbonate sediment accumulation. There is growing concern that these organisms are sensitive to global climate change, which will have important consequences for coastal productivity and stability. Despite their significance and sensitivity, their basic photosynthetic and calcification mechanisms are not well understood. The goal of this study was to determine the plasticity of dissolved inorganic carbon (DIC) uptake mechanisms of rhodoliths along a latitudinal gradient in the Northeast (NE) Atlantic using natural stable isotope signatures. The delta 13C signature of macroalgae can be used to provide an indication of the preferred inorganic carbon source (CO2 vs. HCO3-). Here we present the total and organic delta 13C signatures of NE Atlantic rhodoliths with respect to changing temperature and light along the latitudinal gradient from the Canary Islands to Spitsbergen. A decreasing trend in delta 13C signatures with increasing latitude suggests that rhodoliths rely solely on CO2 as an inorganic carbon source at mid latitudes, while those at low latitudes may be able to utilize HCO3-. Polar rhodoliths deviate from this trend, suggesting they may have unique physiological mechanisms related to inorganic carbon acquisition and assimilation, which may have important implications for calcification in an environment undergoing rapid changing ocean chemistry.

Reduced isothermal feature set for long wave infrared (LWIR) face recognition

NASA Astrophysics Data System (ADS)

Donoso, Ramiro; San Martín, Cesar; Hermosilla, Gabriel

2017-06-01

In this paper, we introduce a new concept in the thermal face recognition area: isothermal features. This consists of a feature vector built from a thermal signature that depends on the emission of the skin of the person and its temperature. A thermal signature is the appearance of the face to infrared sensors and is unique to each person. The infrared face is decomposed into isothermal regions that present the thermal features of the face. Each isothermal region is modeled as circles within a center representing the pixel of the image, and the feature vector is composed of a maximum radius of the circles at the isothermal region. This feature vector corresponds to the thermal signature of a person. The face recognition process is built using a modification of the Expectation Maximization (EM) algorithm in conjunction with a proposed probabilistic index to the classification process. Results obtained using an infrared database are compared with typical state-of-the-art techniques showing better performance, especially in uncontrolled acquisition conditions scenarios.

Methods and computer executable instructions for marking a downhole elongate line and detecting same

DOEpatents

Watkins, Arthur D.

2003-05-13

Methods and computer executable instructions are provided for making an elongate line (22) with a plurality of marks (30) and detecting those marks (30) to determine a distance of the elongate line (22) in a downhole or a physical integrity thereof. In a preferred embodiment, each mark comprises a plurality of particles (44) having a substantially permanent magnetizing capability adhered to an exterior surface of the elongate line (22) at preselected intervals with an epoxy paint. The particles (44) are arranged at each interval as a plurality of bands (40). Thereafter, the particles are oriented into a magnetic signature for that interval by magnetizing the particles to create a magnetic field substantially normal to the exterior surface. This facilitates detection by a Hall effect probe. The magnetic signatures are stored in a computing configuration and, once a mark is detected, a correlation is made to a unique position on the elongate line by comparison with the stored magnetic signatures. Preferred particles include samarium-cobalt and neodymium-iron-boride.

Experimental Identification of Actinobacillus pleuropneumoniae Strains L20 and JL03 Heptosyltransferases, Evidence for a New Heptosyltransferase Signature Sequence

PubMed Central

Merino, Susana; Knirel, Yuriy A.; Regué, Miguel; Tomás, Juan M.

2013-01-01

We experimentally identified the activities of six predicted heptosyltransferases in Actinobacillus pleuropneumoniae genome serotype 5b strain L20 and serotype 3 strain JL03. The initial identification was based on a bioinformatic analysis of the amino acid similarity between these putative heptosyltrasferases with others of known function from enteric bacteria and Aeromonas. The putative functions of all the Actinobacillus pleuropneumoniae heptosyltrasferases were determined by using surrogate LPS acceptor molecules from well-defined A. hydrophyla AH-3 and A. salmonicida A450 mutants. Our results show that heptosyltransferases APL_0981 and APJL_1001 are responsible for the transfer of the terminal outer core D-glycero-D-manno-heptose (D,D-Hep) residue although they are not currently included in the CAZY glycosyltransferase 9 family. The WahF heptosyltransferase group signature sequence [S(T/S)(GA)XXH] differs from the heptosyltransferases consensus signature sequence [D(TS)(GA)XXH], because of the substitution of D261 for S261, being unique. PMID:23383222

Recent advances in the discovery of potent and selective HDAC6 inhibitors.

PubMed

Wang, Xiu-Xiu; Wan, Ren-Zhong; Liu, Zhao-Peng

2018-01-01

Histone deacetylase HDAC6, a member of the class IIb HDAC family, is unique among HDAC enzymes in having two active catalytic domains, and has unique physiological function. In addition to the modification of histone, HDAC6 targets specific substrates including α-tubulin and HSP90, and are involved in protein trafficking and degradation, cell shape and migration. Selective HDAC6 inhibitors are an emerging class of pharmaceuticals due to the involvement of HDAC6 in different pathways related to neurodegenerative diseases, cancer, and immunology. Therefore, extensive investigations have been made in the discovery of selective HDAC6 inhibitors. Based on their different zinc binding groups (ZBGs), in this review, HDAC6 inhibitors are grouped as hydroxamic acids, a sulfur containing ZBG based derivatives and other ZBG-derived compounds, and their enzymatic inhibitory activity, selectivity and other biological activities are introduced and summarized. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Pharmacokinetic and pharmacodynamic considerations for the next generation protein therapeutics.

PubMed

Shah, Dhaval K

2015-10-01

Increasingly sophisticated protein engineering efforts have been undertaken lately to generate protein therapeutics with desired properties. This has resulted in the discovery of the next generation of protein therapeutics, which include: engineered antibodies, immunoconjugates, bi/multi-specific proteins, antibody mimetic novel scaffolds, and engineered ligands/receptors. These novel protein therapeutics possess unique physicochemical properties and act via a unique mechanism-of-action, which collectively makes their pharmacokinetics (PK) and pharmacodynamics (PD) different than other established biological molecules. Consequently, in order to support the discovery and development of these next generation molecules, it becomes important to understand the determinants controlling their PK/PD. This review discusses the determinants that a PK/PD scientist should consider during the design and development of next generation protein therapeutics. In addition, the role of systems PK/PD models in enabling rational development of the next generation protein therapeutics is emphasized.

Pharmacokinetic and pharmacodynamic considerations for the next generation protein therapeutics

PubMed Central

Shah, Dhaval K.

2015-01-01

Increasingly sophisticated protein engineering efforts have been undertaken lately to generate protein therapeutics with desired properties. This has resulted in the discovery of the next generation of protein therapeutics, which include: engineered antibodies, immunoconjugates, bi/multi-specific proteins, antibody mimetic novel scaffolds, and engineered ligands/receptors. These novel protein therapeutics possess unique physicochemical properties and act via a unique mechanism-of-action, which collectively makes their pharmacokinetics (PK) and pharmacodynamics (PD) different than other established biological molecules. Consequently, in order to support the discovery and development of these next generation molecules, it becomes important to understand the determinants controlling their PK/PD. This review discusses the determinants that a PK/PD scientist should consider during the design and development of next generation protein therapeutics. In addition, the role of systems PK/PD models in enabling rational development of the next generation protein therapeutics is emphasized. PMID:26373957

Genomic DNA Methylation Signatures Enable Concurrent Diagnosis and Clinical Genetic Variant Classification in Neurodevelopmental Syndromes.

PubMed

Aref-Eshghi, Erfan; Rodenhiser, David I; Schenkel, Laila C; Lin, Hanxin; Skinner, Cindy; Ainsworth, Peter; Paré, Guillaume; Hood, Rebecca L; Bulman, Dennis E; Kernohan, Kristin D; Boycott, Kym M; Campeau, Philippe M; Schwartz, Charles; Sadikovic, Bekim

2018-01-04

Pediatric developmental syndromes present with systemic, complex, and often overlapping clinical features that are not infrequently a consequence of Mendelian inheritance of mutations in genes involved in DNA methylation, establishment of histone modifications, and chromatin remodeling (the "epigenetic machinery"). The mechanistic cross-talk between histone modification and DNA methylation suggests that these syndromes might be expected to display specific DNA methylation signatures that are a reflection of those primary errors associated with chromatin dysregulation. Given the interrelated functions of these chromatin regulatory proteins, we sought to identify DNA methylation epi-signatures that could provide syndrome-specific biomarkers to complement standard clinical diagnostics. In the present study, we examined peripheral blood samples from a large cohort of individuals encompassing 14 Mendelian disorders displaying mutations in the genes encoding proteins of the epigenetic machinery. We demonstrated that specific but partially overlapping DNA methylation signatures are associated with many of these conditions. The degree of overlap among these epi-signatures is minimal, further suggesting that, consistent with the initial event, the downstream changes are unique to every syndrome. In addition, by combining these epi-signatures, we have demonstrated that a machine learning tool can be built to concurrently screen for multiple syndromes with high sensitivity and specificity, and we highlight the utility of this tool in solving ambiguous case subjects presenting with variants of unknown significance, along with its ability to generate accurate predictions for subjects presenting with the overlapping clinical and molecular features associated with the disruption of the epigenetic machinery. Copyright © 2017 American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.

A bio-molecular inspired electronic architecture: bio-based device concepts for enhanced sensing (Invited Paper)

NASA Astrophysics Data System (ADS)

Woolard, Dwight L.; Luo, Ying; Gelmont, Boris L.; Globus, Tatiana; Jensen, James O.

2005-05-01

A biological(bio)-molecular inspired electronic architecture is presented that offers the potential for defining nanoscale sensor platforms with enhanced capabilities for sensing terahertz (THz) frequency bio-signatures. This architecture makes strategic use of integrated biological elements to enable communication and high-level function within densely-packed nanoelectronic systems. In particular, this architecture introduces a new paradigm for establishing hybrid Electro-THz-Optical (ETO) communication channels where the THz-frequency spectral characteristics that are uniquely associated with the embedded bio-molecules are utilized directly. Since the functionality of this architecture is built upon the spectral characteristics of bio-molecules, this immediately allows for defining new methods for enhanced sensing of THz bio-signatures. First, this integrated sensor concept greatly facilitates the collection of THz bio-signatures associated with embedded bio-molecules via interactions with the time-dependent signals propagating through the nanoelectronic circuit. Second, it leads to a new Multi-State Spectral Sensing (MS3) approach where bio-signature information can be collected from multiple metastable state conformations. This paper will also introduce a new class of prototype devices that utilize THz-sensitive bio-molecules to achieve molecular-level sensing and functionality. Here, new simulation results are presented for a class of bio-molecular components that exhibit the prescribed type of ETO characteristics required for realizing integrated sensor platforms. Most noteworthy, this research derives THz spectral bio-signatures for organic molecules that are amenable to photo-induced metastable-state conformations and establishes an initial scientific foundation and design blueprint for an enhanced THz bio-signature sensing capability.

Microwave signatures of ice hydrometeors from ground-based observations above Summit, Greenland

DOE PAGES

Pettersen, Claire; Bennartz, Ralf; Kulie, Mark S.; ...

2016-04-15

Multi-instrument, ground-based measurements provide unique and comprehensive data sets of the atmosphere for a specific location over long periods of time and resulting data compliment past and existing global satellite observations. Our paper explores the effect of ice hydrometeors on ground-based, high-frequency passive microwave measurements and attempts to isolate an ice signature for summer seasons at Summit, Greenland, from 2010 to 2013. Furthermore, data from a combination of passive microwave, cloud radar, radiosonde, and ceilometer were examined to isolate the ice signature at microwave wavelengths. By limiting the study to a cloud liquid water path of 40 g m -2more » or less, the cloud radar can identify cases where the precipitation was dominated by ice. These cases were examined using liquid water and gas microwave absorption models, and brightness temperatures were calculated for the high-frequency microwave channels: 90, 150, and 225GHz. By comparing the measured brightness temperatures from the microwave radiometers and the calculated brightness temperature using only gas and liquid contributions, any residual brightness temperature difference is due to emission and scattering of microwave radiation from the ice hydrometeors in the column. The ice signature in the 90, 150, and 225 GHz channels for the Summit Station summer months was isolated. Then, this measured ice signature was compared to an equivalent brightness temperature difference calculated with a radiative transfer model including microwave single-scattering properties for several ice habits. Furthermore, initial model results compare well against the 4 years of summer season isolated ice signature in the high-frequency microwave channels.« less

Graph Theory Meets Ab Initio Molecular Dynamics: Atomic Structures and Transformations at the Nanoscale

NASA Astrophysics Data System (ADS)

Pietrucci, Fabio; Andreoni, Wanda

2011-08-01

Social permutation invariant coordinates are introduced describing the bond network around a given atom. They originate from the largest eigenvalue and the corresponding eigenvector of the contact matrix, are invariant under permutation of identical atoms, and bear a clear signature of an order-disorder transition. Once combined with ab initio metadynamics, these coordinates are shown to be a powerful tool for the discovery of low-energy isomers of molecules and nanoclusters as well as for a blind exploration of isomerization, association, and dissociation reactions.

New decay modes of heavy Higgs bosons in a two Higgs doublet model with vectorlike leptons

DOE PAGES

Dermíšek, Radovan; Lunghi, Enrico; Shin, Seodong

2016-05-25

In models with extended Higgs sector and additional matter fields, the decay modes of heavy Higgs bosons can be dominated by cascade decays through the new fermions rendering present search strategies ineffective. Here, we investigate new decay topologies of heavy neutral Higgses in two Higgs doublet model with vectorlike leptons. We also discus constraints from existing searches and discovery prospects. Among the most interesting signatures are monojet, mono Z, mono Higgs, and Z and Higgs bosons produced with a pair of charged leptons.

Update on Merkel Cell Carcinoma.

PubMed

Harms, Paul W

2017-09-01

Merkel cell carcinoma (MCC) is a rare, aggressive cutaneous neuroendocrine malignancy. Merkel cell polyomavirus, a tumorigenic DNA virus, is present in most MCC tumors, with implications for tumor biology, diagnosis, and management. Merkel cell polyomavirus-negative tumors have a high burden of UV-signature mutations, similar to melanoma. The histopathologic diagnosis of MCC requires immunohistochemistry to exclude morphologically similar entities. Therapies for advanced disease are currently lacking. Here, the features of MCC are reviewed, including recent molecular discoveries with implications for improved therapy for advanced disease. Copyright © 2017 Elsevier Inc. All rights reserved.

Repertoire of novel sequence signatures for the detection of Candidatus Liberibacter asiaticus by quantitative real-time PCR

PubMed Central

2014-01-01

Background Huanglongbing (HLB) or citrus greening is a devastating disease of citrus. The gram-negative bacterium Candidatus Liberibacter asiaticus (Las) belonging to the α-proteobacteria is responsible for HLB in North America as well as in Asia. Currently, there is no cure for this disease. Early detection and quarantine of Las-infected trees are important management strategies used to prevent HLB from invading HLB-free citrus producing regions. Quantitative real-time PCR (qRT-PCR) based molecular diagnostic assays have been routinely used in the detection and diagnosis of Las. The oligonucleotide primer pairs based on conserved genes or regions, which include 16S rDNA and the β-operon, have been widely employed in the detection of Las by qRT-PCR. The availability of whole genome sequence of Las now allows the design of primers beyond the conserved regions for the detection of Las explicitly. Results We took a complimentary approach by systematically screening the genes in a genome-wide fashion, to identify the unique signatures that are only present in Las by an exhaustive sequence based similarity search against the nucleotide sequence database. Our search resulted in 34 probable unique signatures. Furthermore, by designing the primer pair specific to the identified signatures, we showed that most of our primer sets are able to detect Las from the infected plant and psyllid materials collected from the USA and China by qRT-PCR. Overall, 18 primer pairs of the 34 are found to be highly specific to Las with no cross reactivity to the closely related species Ca. L. americanus (Lam) and Ca. L. africanus (Laf). Conclusions We have designed qRT-PCR primers based on Las specific genes. Among them, 18 are suitable for the detection of Las from Las-infected plant and psyllid samples. The repertoire of primers that we have developed and characterized in this study enhanced the qRT-PCR based molecular diagnosis of HLB. PMID:24533511

Metabolite profiles of repeatedly sampled urine from male fathead minnows (Pimephales promelas) contain unique lipid signatures following exposure to anti-androgens

EPA Science Inventory

The purpose of this study was twofold. First, we sought to identify candidate markers of exposure to anti-androgens by analyzing endogenous metabolite profiles in the urine of male fathead minnows (mFHM, Pimephales promelas). Based on earlier work, we hypothesized that unidentifi...

Invasive species detection in Hawaiian rainforests using airborne imaging spectroscopy and LiDAR

Treesearch

Gregory P. Asner; David E. Knapp; Ty Kennedy-Bodoin; Matthew O. Jones; Roberta E. Martin; Joseph Boardman; Flint Hughes

2008-01-01

Remote sensing of invasive species is a critical component of conservation and management efforts, but reliable methods for the detection of invaders have not been widely established. In Hawaiian forests, we recently found that invasive trees often have hyperspectral signatures unique from that of native trees, but mapping based on spectral reflectance properties alone...

LINCS Canvas Browser: interactive web app to query, browse and interrogate LINCS L1000 gene expression signatures.

PubMed

Duan, Qiaonan; Flynn, Corey; Niepel, Mario; Hafner, Marc; Muhlich, Jeremy L; Fernandez, Nicolas F; Rouillard, Andrew D; Tan, Christopher M; Chen, Edward Y; Golub, Todd R; Sorger, Peter K; Subramanian, Aravind; Ma'ayan, Avi

2014-07-01

For the Library of Integrated Network-based Cellular Signatures (LINCS) project many gene expression signatures using the L1000 technology have been produced. The L1000 technology is a cost-effective method to profile gene expression in large scale. LINCS Canvas Browser (LCB) is an interactive HTML5 web-based software application that facilitates querying, browsing and interrogating many of the currently available LINCS L1000 data. LCB implements two compacted layered canvases, one to visualize clustered L1000 expression data, and the other to display enrichment analysis results using 30 different gene set libraries. Clicking on an experimental condition highlights gene-sets enriched for the differentially expressed genes from the selected experiment. A search interface allows users to input gene lists and query them against over 100 000 conditions to find the top matching experiments. The tool integrates many resources for an unprecedented potential for new discoveries in systems biology and systems pharmacology. The LCB application is available at http://www.maayanlab.net/LINCS/LCB. Customized versions will be made part of the http://lincscloud.org and http://lincs.hms.harvard.edu websites. © The Author(s) 2014. Published by Oxford University Press on behalf of Nucleic Acids Research.

Do two machine-learning based prognostic signatures for breast cancer capture the same biological processes?

PubMed

Drier, Yotam; Domany, Eytan

2011-03-14

The fact that there is very little if any overlap between the genes of different prognostic signatures for early-discovery breast cancer is well documented. The reasons for this apparent discrepancy have been explained by the limits of simple machine-learning identification and ranking techniques, and the biological relevance and meaning of the prognostic gene lists was questioned. Subsequently, proponents of the prognostic gene lists claimed that different lists do capture similar underlying biological processes and pathways. The present study places under scrutiny the validity of this claim, for two important gene lists that are at the focus of current large-scale validation efforts. We performed careful enrichment analysis, controlling the effects of multiple testing in a manner which takes into account the nested dependent structure of gene ontologies. In contradiction to several previous publications, we find that the only biological process or pathway for which statistically significant concordance can be claimed is cell proliferation, a process whose relevance and prognostic value was well known long before gene expression profiling. We found that the claims reported by others, of wider concordance between the biological processes captured by the two prognostic signatures studied, were found either to be lacking statistical rigor or were in fact based on addressing some other question.

Bead-based screening in chemical biology and drug discovery.

PubMed

Komnatnyy, Vitaly V; Nielsen, Thomas E; Qvortrup, Katrine

2018-06-11

High-throughput screening is an important component of the drug discovery process. The screening of libraries containing hundreds of thousands of compounds requires assays amenable to miniaturisation and automization. Combinatorial chemistry holds a unique promise to deliver structurally diverse libraries for early drug discovery. Among the various library forms, the one-bead-one-compound (OBOC) library, where each bead carries many copies of a single compound, holds the greatest potential for the rapid identification of novel hits against emerging drug targets. However, this potential has not yet been fully realized due to a number of technical obstacles. In this feature article, we review the progress that has been made in bead-based library screening and its application to the discovery of bioactive compounds. We identify the key challenges of this approach and highlight key steps needed for making a greater impact in the field.

KSC-2011-6400

NASA Image and Video Library

2011-08-11

CAPE CANAVERAL, Fla. -- At NASA's Kennedy Space Center in Florida, space shuttles Discovery and Endeavour, their noses encased in protective plastic where their forward reaction control systems (FRCS) once resided, pause outside Orbiter Processing Facility-3 (OPF-3) for a unique photo opportunity. Discovery, which temporarily was being stored in the Vehicle Assembly Building (VAB), is switching places with Endeavour, which has been undergoing decommissioning in OPF-1. Discovery then will be rolled into OPF-1 and Endeavour into the VAB. In OPF-1, Discovery will undergo further preparations for public display at the Smithsonian's National Air and Space Museum Steven F. Udvar-Hazy Center in Virginia. Endeavour will be stored in the VAB until October when it will be moved into OPF-2 for further work to get it ready for public display at the California Science Center in Los Angeles. For more information, visit http://www.nasa.gov/shuttle. Photo credit: NASA/Jim Grossmann

Mining the human urine proteome for monitoring renal transplant injury

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sigdel, Tara K.; Gao, Yuqian; He, Jintang

The human urinary proteome reflects systemic and inherent renal injury perturbations and can be analyzed to harness specific biomarkers for different kidney transplant injury states. 396 unique urine samples were collected contemporaneously with an allograft biopsy from 396 unique kidney transplant recipients. Centralized, blinded histology on the graft was used to classify matched urine samples into categories of acute rejection (AR), chronic allograft nephropathy (CAN), BK virus nephritis (BKVN), and stable graft (STA). Liquid chromatography–mass spectrometry (LC-MS) based proteomics using iTRAQ based discovery (n=108) and global label-free LC-MS analyses of individual samples (n=137) for quantitative proteome assessment were used inmore » the discovery step. Selected reaction monitoring (SRM) was applied to identify and validate minimal urine protein/peptide biomarkers to accurately segregate organ injury causation and pathology on unique urine samples (n=151). A total of 958 proteins were initially quantified by iTRAQ, 87% of which were also identified among 1574 urine proteins detected in LC-MS validation. 103 urine proteins were significantly (p<0.05) perturbed in injury and enriched for humoral immunity, complement activation, and lymphocyte trafficking. A set of 131 peptides corresponding to 78 proteins were assessed by SRM for their significance in an independent sample cohort. A minimal set of 35 peptides mapping to 33 proteins, were modeled to segregate different injury groups (AUC =93% for AR, 99% for CAN, 83% for BKVN). Urinary proteome discovery and targeted validation identified urine protein fingerprints for non-invasive differentiation of kidney transplant injuries, thus opening the door for personalized immune risk assessment and therapy.« less

Keep Your Voice Sound: How to Prevent and Avoid Voice Problems

MedlinePlus

... ways, your voice is as unique as your fingerprint. It’s produced in your throat by 2 bands ... Act No Fear Act Office of Inspector General USA.gov – Government Made Easy NIH…Turning Discovery Into ...

New Science in Plain Sight: Optical Manifestations of Coupled Subauroral Features Documented by Citizen Scientists

NASA Astrophysics Data System (ADS)

MacDonald, E.; Heavner, M.; Kosar, B.; Case, N.; Donovan, E.; Spanswick, E.; Nishimura, Y.; Gallardo-Lacourt, B.

2017-12-01

Aurora has been observed and recorded by people for thousands of years. Recently, citizen scientists captured features of aurora-like arc events not previously described in the literature at subauroral latitudes. Amateur photo sequences show unusual flow, unstable composition changes, and field aligned structures. Observations from the Swarm satellite crossing the arc reveals thermal enhancement, density depletion, and strong westward ion flow. These signatures resemble features previously described from in situ observation however the optical manifestation is surprising and contains rich, unstable signatures as well. The relevant observations have presented important implications on a variety of open questions, including the fundamental definition of aurora, and limitations of jargon and subfield distinctions. This paper covers the discovery, its context, and the significant implications for the application of public participation measurement modes to the natural sciences whereby they can form a disruptive gap to expose new observing perspectives. Photo Credit: Notanee Bourassa, Alberta Aurora Chasers

Stem cell and neurogenic gene-expression profiles link prostate basal cells to aggressive prostate cancer

PubMed Central

Zhang, Dingxiao; Park, Daechan; Zhong, Yi; Lu, Yue; Rycaj, Kiera; Gong, Shuai; Chen, Xin; Liu, Xin; Chao, Hsueh-Ping; Whitney, Pamela; Calhoun-Davis, Tammy; Takata, Yoko; Shen, Jianjun; Iyer, Vishwanath R.; Tang, Dean G.

2016-01-01

The prostate gland mainly contains basal and luminal cells constructed as a pseudostratified epithelium. Annotation of prostate epithelial transcriptomes provides a foundation for discoveries that can impact disease understanding and treatment. Here we describe a genome-wide transcriptome analysis of human benign prostatic basal and luminal epithelial populations using deep RNA sequencing. Through molecular and biological characterizations, we show that the differential gene-expression profiles account for their distinct functional properties. Strikingly, basal cells preferentially express gene categories associated with stem cells, neurogenesis and ribosomal RNA (rRNA) biogenesis. Consistent with this profile, basal cells functionally exhibit intrinsic stem-like and neurogenic properties with enhanced rRNA transcription activity. Of clinical relevance, the basal cell gene-expression profile is enriched in advanced, anaplastic, castration-resistant and metastatic prostate cancers. Therefore, we link the cell-type-specific gene signatures to aggressive subtypes of prostate cancer and identify gene signatures associated with adverse clinical features. PMID:26924072

Stem cell and neurogenic gene-expression profiles link prostate basal cells to aggressive prostate cancer.

PubMed

Zhang, Dingxiao; Park, Daechan; Zhong, Yi; Lu, Yue; Rycaj, Kiera; Gong, Shuai; Chen, Xin; Liu, Xin; Chao, Hsueh-Ping; Whitney, Pamela; Calhoun-Davis, Tammy; Takata, Yoko; Shen, Jianjun; Iyer, Vishwanath R; Tang, Dean G

2016-02-29

The prostate gland mainly contains basal and luminal cells constructed as a pseudostratified epithelium. Annotation of prostate epithelial transcriptomes provides a foundation for discoveries that can impact disease understanding and treatment. Here we describe a genome-wide transcriptome analysis of human benign prostatic basal and luminal epithelial populations using deep RNA sequencing. Through molecular and biological characterizations, we show that the differential gene-expression profiles account for their distinct functional properties. Strikingly, basal cells preferentially express gene categories associated with stem cells, neurogenesis and ribosomal RNA (rRNA) biogenesis. Consistent with this profile, basal cells functionally exhibit intrinsic stem-like and neurogenic properties with enhanced rRNA transcription activity. Of clinical relevance, the basal cell gene-expression profile is enriched in advanced, anaplastic, castration-resistant and metastatic prostate cancers. Therefore, we link the cell-type-specific gene signatures to aggressive subtypes of prostate cancer and identify gene signatures associated with adverse clinical features.

Seesaw at Lhc Through Left-Right Symmetry

NASA Astrophysics Data System (ADS)

Senjanović, Goran

I argue that LHC may shed light on the nature of neutrino mass through the probe of the seesaw mechanism. The smoking gun signature is lepton number violation through the production of same sign lepton pairs, a collider analogy of the neutrinoless double beta decay. I discuss this in the context of left-right symmetric theories, which led originally to neutrino mass and the seesaw mechanism. A WR gauge boson with a mass in a few TeV region could easily dominate neutrinoless double beta decay, and its discovery at LHC would have spectacular signatures of parity restoration and lepton number violation. Moreover, LHC can measure the masses of the right-handed neutrinos and the right-handed leptonic mixing matrix, which could in turn be used to predict the rates for neutrinoless double decay and lepton flavor violating violating processes. The LR scale at the LHC energies offers great hope of observing these low energy processes in the present and upcoming experiments.

Hereditary family signature of facial expression

PubMed Central

Peleg, Gili; Katzir, Gadi; Peleg, Ofer; Kamara, Michal; Brodsky, Leonid; Hel-Or, Hagit; Keren, Daniel; Nevo, Eviatar

2006-01-01

Although facial expressions of emotion are universal, individual differences create a facial expression “signature” for each person; but, is there a unique family facial expression signature? Only a few family studies on the heredity of facial expressions have been performed, none of which compared the gestalt of movements in various emotional states; they compared only a few movements in one or two emotional states. No studies, to our knowledge, have compared movements of congenitally blind subjects with their relatives to our knowledge. Using two types of analyses, we show a correlation between movements of congenitally blind subjects with those of their relatives in think-concentrate, sadness, anger, disgust, joy, and surprise and provide evidence for a unique family facial expression signature. In the analysis “in-out family test,” a particular movement was compared each time across subjects. Results show that the frequency of occurrence of a movement of a congenitally blind subject in his family is significantly higher than that outside of his family in think-concentrate, sadness, and anger. In the analysis “the classification test,” in which congenitally blind subjects were classified to their families according to the gestalt of movements, results show 80% correct classification over the entire interview and 75% in anger. Analysis of the movements' frequencies in anger revealed a correlation between the movements' frequencies of congenitally blind individuals and those of their relatives. This study anticipates discovering genes that influence facial expressions, understanding their evolutionary significance, and elucidating repair mechanisms for syndromes lacking facial expression, such as autism. PMID:17043232

Comparison of the Functional microRNA Expression in Immune Cell Subsets of Neonates and Adults

PubMed Central

Yu, Hong-Ren; Hsu, Te-Yao; Huang, Hsin-Chun; Kuo, Ho-Chang; Li, Sung-Chou; Yang, Kuender D.; Hsieh, Kai-Sheng

2016-01-01

Diversity of biological molecules in newborn and adult immune cells contributes to differences in cell function and atopic properties. Micro RNAs (miRNAs) are reported to involve in the regulation of immune system. Therefore, determining the miRNA expression profile of leukocyte subpopulations is important for understanding immune system regulation. In order to explore the unique miRNA profiling that contribute to altered immune in neonates, we comprehensively analyzed the functional miRNA signatures of eight leukocyte subsets (polymorphonuclear cells, monocytes, CD4+ T cells, CD8+ T cells, natural killer cells, B cells, plasmacytoid dendritic cells, and myeloid dendritic cells) from both neonatal and adult umbilical cord and peripheral blood samples, respectively. We observed distinct miRNA profiles between adult and neonatal blood leukocyte subsets, including unique miRNA signatures for each cell lineage. Leukocyte miRNA signatures were altered after stimulation. Adult peripheral leukocytes had higher let-7b-5p expression levels compared to neonatal cord leukocytes across multiple subsets, irrespective of stimulation. Transfecting neonatal monocytes with a let-7b-5p mimic resulted in a reduction of LPS-induced interleukin (IL)-6 and TNF-α production, while transfection of a let-7b-5p inhibitor into adult monocytes enhanced IL-6 and TNF-α production. With this functional approach, we provide intact differential miRNA expression profiling of specific immune cell subsets between neonates and adults. These studies serve as a basis to further understand the altered immune response observed in neonates and advance the development of therapeutic strategies. PMID:28066425

Testing eternal inflation with the kinetic Sunyaev Zel'dovich effect

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zhang, Pengjie; Johnson, Matthew C., E-mail: zhangpj@sjtu.edu.cn, E-mail: mjohnson@perimeterinstitute.ca

2015-06-01

Perhaps the most controversial idea in modern cosmology is that our observable universe is contained within one bubble among many, all inhabiting the eternally inflating multiverse. One of the few way to test this idea is to look for evidence of the relic inhomogeneities left by the collisions between other bubbles and our own. Such relic inhomogeneities will induce a coherent bulk flow over Gpc scales. Therefore, bubble collisions leave unique imprints in the cosmic microwave background (CMB) through the kinetic Sunyaev Zel'dovich (kSZ) effect, temperature anisotropies induced by the scattering of photons from coherently moving free electrons in themore » diffuse intergalactic medium. The kSZ signature produced by bubble collisions has a unique directional dependence and is tightly correlated with the galaxy distribution; it can therefore be distinguished from other contributions to the CMB anisotropies. An important advantage of the kSZ signature is that it peaks on arcminute angular scales, where the limiting factors in making a detection are instrumental noise and foreground subtraction. This is in contrast to the collision signature in the primary CMB, which peaks on angular scales much larger than one degree, and whose detection is therefore limited by cosmic variance. In this paper, we examine the prospects for probing the inhomogeneities left by bubble collisions using the kSZ effect. We provide a forecast for detection using cross-correlations between CMB and galaxy surveys, finding that the detectability using the kSZ effect can be competitive with constraints from CMB temperature and polarization data.« less

Analytical design of a hyper-spectral imaging spectrometer utilizing a convex grating

NASA Astrophysics Data System (ADS)

Kim, Seo H.; Kong, Hong J.; Ku, Hana; Lee, Jun H.

2012-09-01

This paper describes about the new design method for hyper-spectral Imaging spectrometers utilizing convex grating. Hyper-spectral imaging systems are power tools in the field of remote sensing. HSI systems collect at least 100 spectral bands of 10~20 nm width. Because the spectral signature is different and induced unique for each material, it should be possible to discriminate between one material and another based on difference in spectral signature of material. I mathematically analyzed parameters for the intellectual initial design. Main concept of this is the derivative of "ring of minimum aberration without vignetting". This work is a kind of analytical design of an Offner imaging spectrometer. Also, several experiment methods will be contrived to evaluate the performance of imaging spectrometer.

Molecular Biology In Young Women With Breast Cancer: From Tumor Gene Expression To DNA Mutations.

PubMed

Gómez-Flores-Ramos, Liliana; Castro-Sánchez, Andrea; Peña-Curiel, Omar; Mohar-Betancourt, Alejandro

2017-01-01

Young women with breast cancer (YWBC) represent roughly 15% of breast cancer (BC) cases in Latin America and other developing regions. Breast tumors occurring at an early age are more aggressive and have an overall worse prognosis compared to breast tumors in postmenopausal women. The expression of relevant proliferation biomarkers such as endocrine receptors and human epidermal growth factor receptor 2 appears to be unique in YWBC. Moreover, histopathological, molecular, genetic, and genomic studies have shown that YWBC exhibit a higher frequency of aggressive subtypes, differential tumor gene expression, increased genetic susceptibility, and specific genomic signatures, compared to older women with BC. This article reviews the current knowledge on tumor biology and genomic signatures in YWBC.

Finding overlapping communities in multilayer networks

PubMed Central

Liu, Weiyi; Suzumura, Toyotaro; Ji, Hongyu; Hu, Guangmin

2018-01-01

Finding communities in multilayer networks is a vital step in understanding the structure and dynamics of these layers, where each layer represents a particular type of relationship between nodes in the natural world. However, most community discovery methods for multilayer networks may ignore the interplay between layers or the unique topological structure in a layer. Moreover, most of them can only detect non-overlapping communities. In this paper, we propose a new community discovery method for multilayer networks, which leverages the interplay between layers and the unique topology in a layer to reveal overlapping communities. Through a comprehensive analysis of edge behaviors within and across layers, we first calculate the similarities for edges from the same layer and the cross layers. Then, by leveraging these similarities, we can construct a dendrogram for the multilayer networks that takes both the unique topological structure and the important interplay into consideration. Finally, by introducing a new community density metric for multilayer networks, we can cut the dendrogram to get the overlapping communities for these layers. By applying our method on both synthetic and real-world datasets, we demonstrate that our method has an accurate performance in discovering overlapping communities in multilayer networks. PMID:29694387

Finding overlapping communities in multilayer networks.

PubMed

Liu, Weiyi; Suzumura, Toyotaro; Ji, Hongyu; Hu, Guangmin

2018-01-01

Finding communities in multilayer networks is a vital step in understanding the structure and dynamics of these layers, where each layer represents a particular type of relationship between nodes in the natural world. However, most community discovery methods for multilayer networks may ignore the interplay between layers or the unique topological structure in a layer. Moreover, most of them can only detect non-overlapping communities. In this paper, we propose a new community discovery method for multilayer networks, which leverages the interplay between layers and the unique topology in a layer to reveal overlapping communities. Through a comprehensive analysis of edge behaviors within and across layers, we first calculate the similarities for edges from the same layer and the cross layers. Then, by leveraging these similarities, we can construct a dendrogram for the multilayer networks that takes both the unique topological structure and the important interplay into consideration. Finally, by introducing a new community density metric for multilayer networks, we can cut the dendrogram to get the overlapping communities for these layers. By applying our method on both synthetic and real-world datasets, we demonstrate that our method has an accurate performance in discovering overlapping communities in multilayer networks.

Development and Validation of a Novel Platform-Independent Metastasis Signature in Human Breast Cancer

PubMed Central

Speers, Corey; Liu, Meilan; Wilder-Romans, Kari; Lawrence, Theodore S.; Pierce, Lori J.; Feng, Felix Y.

2015-01-01

Purpose The molecular drivers of metastasis in breast cancer are not well understood. Therefore, we sought to identify the biological processes underlying distant progression and define a prognostic signature for metastatic potential in breast cancer. Experimental design In vivo screening for metastases was performed using Chick Chorioallantoic Membrane assays in 21 preclinical breast cancer models. Expressed genes associated with metastatic potential were identified using high-throughput analysis. Correlations with biological function were determined using the Database for Annotation, Visualization and Integrated Discovery. Results We identified a broad range of metastatic potential that was independent of intrinsic breast cancer subtypes. 146 genes were significantly associated with metastasis progression and were linked to cancer-related biological functions, including cell migration/adhesion, Jak-STAT, TGF-beta, and Wnt signaling. These genes were used to develop a platform-independent gene expression signature (M-Sig), which was trained and subsequently validated on 5 independent cohorts totaling nearly 1800 breast cancer patients with all p-values < 0.005 and hazard ratios ranging from approximately 2.5 to 3. On multivariate analysis accounting for standard clinicopathologic prognostic variables, M-Sig remained the strongest prognostic factor for metastatic progression, with p-values < 0.001 and hazard ratios > 2 in three different cohorts. Conclusion M-Sig is strongly prognostic for metastatic progression, and may provide clinical utility in combination with treatment prediction tools to better guide patient care. In addition, the platform-independent nature of the signature makes it an excellent research tool as it can be directly applied onto existing, and future, datasets. PMID:25974184

Gene signature associated with benign neurofibroma transformation to malignant peripheral nerve sheath tumors

PubMed Central

Sorzano, Carlos O. S.; Pascual-Montano, Alberto; Carazo, Jose M.

2017-01-01

Benign neurofibromas, the main phenotypic manifestations of the rare neurological disorder neurofibromatosis type 1, degenerate to malignant tumors associated to poor prognosis in about 10% of patients. Despite efforts in the field of (epi)genomics, the lack of prognostic biomarkers with which to predict disease evolution frustrates the adoption of appropriate early therapeutic measures. To identify potential biomarkers of malignant neurofibroma transformation, we integrated four human experimental studies and one for mouse, using a gene score-based meta-analysis method, from which we obtained a score-ranked signature of 579 genes. Genes with the highest absolute scores were classified as promising disease biomarkers. By grouping genes with similar neurofibromatosis-related profiles, we derived panels of potential biomarkers. The addition of promoter methylation data to gene profiles indicated a panel of genes probably silenced by hypermethylation. To identify possible therapeutic treatments, we used the gene signature to query drug expression databases. Trichostatin A and other histone deacetylase inhibitors, as well as cantharidin and tamoxifen, were retrieved as putative therapeutic means to reverse the aberrant regulation that drives to malignant cell proliferation and metastasis. This in silico prediction corroborated reported experimental results that suggested the inclusion of these compounds in clinical trials. This experimental validation supported the suitability of the meta-analysis method used to integrate several sources of public genomic information, and the reliability of the gene signature associated to the malignant evolution of neurofibromas to generate working hypotheses for prognostic and drug-responsive biomarkers or therapeutic measures, thus showing the potential of this in silico approach for biomarker discovery. PMID:28542306

Detection of Chorus Elements and other Wave Signatures Using Geometric Computational Techniques in the Van Allen radiation belts

NASA Astrophysics Data System (ADS)

Sengupta, A.; Kletzing, C.; Howk, R.; Kurth, W. S.

2017-12-01

An important goal of the Van Allen Probes mission is to understand wave particle interactions that can energize relativistic electron in the Earth's Van Allen radiation belts. The EMFISIS instrumentation suite provides measurements of wave electric and magnetic fields of wave features such as chorus that participate in these interactions. Geometric signal processing discovers structural relationships, e.g. connectivity across ridge-like features in chorus elements to reveal properties such as dominant angles of the element (frequency sweep rate) and integrated power along the a given chorus element. These techniques disambiguate these wave features against background hiss-like chorus. This enables autonomous discovery of chorus elements across the large volumes of EMFISIS data. At the scale of individual or overlapping chorus elements, topological pattern recognition techniques enable interpretation of chorus microstructure by discovering connectivity and other geometric features within the wave signature of a single chorus element or between overlapping chorus elements. Thus chorus wave features can be quantified and studied at multiple scales of spectral geometry using geometric signal processing techniques. We present recently developed computational techniques that exploit spectral geometry of chorus elements and whistlers to enable large-scale automated discovery, detection and statistical analysis of these events over EMFISIS data. Specifically, we present different case studies across a diverse portfolio of chorus elements and discuss the performance of our algorithms regarding precision of detection as well as interpretation of chorus microstructure. We also provide large-scale statistical analysis on the distribution of dominant sweep rates and other properties of the detected chorus elements.

No Limit: Exploring the Science of the Universe

ScienceCinema

Meinecke, Jena; Remington, Bruce; Zylstra, Alex; Falcone, Roger; Rinderknecht, Hans; Casner, Alexis

2018-06-13

Scientists who conduct unique, cutting-edge Discovery Science experiments on Lawrence Livermore National Laboratory’s National Ignition Facility (NIF) describe the excitement of doing research on the world’s largest and highest-energy laser system.

Interspecies chimeras.

PubMed

Suchy, Fabian; Nakauchi, Hiromitsu

2018-05-30

By probing early embryogenesis and regeneration, interspecies chimeras provide a unique platform for discovery and clinical use. Although efficient generation of human:animal chimeric embryos remains elusive, recent advancements attempt to overcome incompatibilities in xenogeneic development and transplantation. Copyright © 2018 Elsevier Ltd. All rights reserved.

Ultrasonic Methods for Human Motion Detection

DTIC Science & Technology

2006-10-01

contacts. The active method utilizes continuous wave ultrasonic Doppler sonar . Human motions have unique Doppler signatures and their combination...The present article reports results of human motion investigations with help of CW ultrasonic Doppler sonar . Low-cost, low-power ultrasonic motion...have been developed for operation in air [10]. Benefits of using ultrasonic CW Doppler sonar included the low-cost, low-electric noise, small size

Stable isotope fingerprinting: a novel method for identifying plant, fungal, or bacterial origins of amino acids

Treesearch

Thomas Larsen; D. Lee Taylor; Mary Beth Leigh; Diane M. O' Brien

2009-01-01

Amino acids play an important role in ecology as essential nutrients for animals and as currencies in symbiotic associations. Here we present a new approach to tracing the origins of amino acids by identifying unique patterns of carbon isotope signatures generated by amino acid synthesis in plants, fungi, and bacteria ("13C fingerprints...

A Learning System for Discriminating Variants of Malicious Network Traffic

DOE Office of Scientific and Technical Information (OSTI.GOV)

Beaver, Justin M; Symons, Christopher T; Gillen, Rob

Modern computer network defense systems rely primarily on signature-based intrusion detection tools, which generate alerts when patterns that are pre-determined to be malicious are encountered in network data streams. Signatures are created reactively, and only after in-depth manual analysis of a network intrusion. There is little ability for signature-based detectors to identify intrusions that are new or even variants of an existing attack, and little ability to adapt the detectors to the patterns unique to a network environment. Due to these limitations, the need exists for network intrusion detection techniques that can more comprehensively address both known unknown networkbased attacksmore » and can be optimized for the target environment. This work describes a system that leverages machine learning to provide a network intrusion detection capability that analyzes behaviors in channels of communication between individual computers. Using examples of malicious and non-malicious traffic in the target environment, the system can be trained to discriminate between traffic types. The machine learning provides insight that would be difficult for a human to explicitly code as a signature because it evaluates many interdependent metrics simultaneously. With this approach, zero day detection is possible by focusing on similarity to known traffic types rather than mining for specific bit patterns or conditions. This also reduces the burden on organizations to account for all possible attack variant combinations through signatures. The approach is presented along with results from a third-party evaluation of its performance.« less

Novel algorithm to identify and differentiate specific digital signature of breath sound in patients with diffuse parenchymal lung disease.

PubMed

Bhattacharyya, Parthasarathi; Mondal, Ashok; Dey, Rana; Saha, Dipanjan; Saha, Goutam

2015-05-01

Auscultation is an important part of the clinical examination of different lung diseases. Objective analysis of lung sounds based on underlying characteristics and its subsequent automatic interpretations may help a clinical practice. We collected the breath sounds from 8 normal subjects and 20 diffuse parenchymal lung disease (DPLD) patients using a newly developed instrument and then filtered off the heart sounds using a novel technology. The collected sounds were thereafter analysed digitally on several characteristics as dynamical complexity, texture information and regularity index to find and define their unique digital signatures for differentiating normality and abnormality. For convenience of testing, these characteristic signatures of normal and DPLD lung sounds were transformed into coloured visual representations. The predictive power of these images has been validated by six independent observers that include three physicians. The proposed method gives a classification accuracy of 100% for composite features for both the normal as well as lung sound signals from DPLD patients. When tested by independent observers on the visually transformed images, the positive predictive value to diagnose the normality and DPLD remained 100%. The lung sounds from the normal and DPLD subjects could be differentiated and expressed according to their digital signatures. On visual transformation to coloured images, they retain 100% predictive power. This technique may assist physicians to diagnose DPLD from visual images bearing the digital signature of the condition. © 2015 Asian Pacific Society of Respirology.

Opposing Development of Cytotoxic and Follicular Helper CD4 T Cells Controlled by the TCF-1-Bcl6 Nexus.

PubMed

Donnarumma, Tiziano; Young, George R; Merkenschlager, Julia; Eksmond, Urszula; Bongard, Nadine; Nutt, Stephen L; Boyer, Claude; Dittmer, Ulf; Le-Trilling, Vu Thuy Khanh; Trilling, Mirko; Bayer, Wibke; Kassiotis, George

2016-11-01

CD4 + T cells develop distinct and often contrasting helper, regulatory, or cytotoxic activities. Typically a property of CD8 + T cells, granzyme-mediated cytotoxic T cell (CTL) potential is also exerted by CD4 + T cells. However, the conditions that induce CD4 + CTLs are not entirely understood. Using single-cell transcriptional profiling, we uncover a unique signature of Granzyme B (GzmB) + CD4 + CTLs, which distinguishes them from other CD4 + T helper (Th) cells, including Th1 cells, and strongly contrasts with the follicular helper T (Tfh) cell signature. The balance between CD4 + CTL and Tfh differentiation heavily depends on the class of infecting virus and is jointly regulated by the Tfh-related transcription factors Bcl6 and Tcf7 (encoding TCF-1) and by the expression of the inhibitory receptors PD-1 and LAG3. This unique profile of CD4 + CTLs offers targets for their study, and its antagonism by the Tfh program separates CD4 + T cells with either helper or killer functions. Copyright © 2016 The Author(s). Published by Elsevier Inc. All rights reserved.

Universal Majorana thermoelectric noise

NASA Astrophysics Data System (ADS)

Smirnov, Sergey

2018-04-01

Thermoelectric phenomena resulting from an interplay between particle flows induced by electric fields and temperature inhomogeneities are extremely insightful as a tool providing substantial knowledge about the microscopic structure of a given system. By tuning, e.g., parameters of a nanoscopic system coupled via tunneling mechanisms to two contacts, one may achieve various situations where the electric current induced by an external bias voltage competes with the electric current excited by the temperature difference of the two contacts. Even more exciting physics emerges when the system's electronic degrees freedom split to form Majorana fermions which make the thermoelectric dynamics universal. Here, we propose revealing these unique universal signatures of Majorana fermions in strongly nonequilibrium quantum dots via noise of the thermoelectric transport beyond linear response. It is demonstrated that whereas mean thermoelectric quantities are only universal at large-bias voltages, the noise of the electric current excited by an external bias voltage and the temperature difference of the contacts is universal at any bias voltage. We provide truly universal, i.e., independent of the system's parameters, thermoelectric ratios between nonlinear response coefficients of the noise and mean current at large-bias voltages where experiments may easily be performed to uniquely detect these truly universal Majorana thermoelectric signatures.

Optical properties of dissolved organic matter (DOM): Effects of biological and photolytic degradation

USGS Publications Warehouse

Hansen, Angela; Kraus, Tamara; Pellerin, Brian; Fleck, Jacob; Downing, Bryan D.; Bergamaschi, Brian

2016-01-01

Advances in spectroscopic techniques have led to an increase in the use of optical properties (absorbance and fluorescence) to assess dissolved organic matter (DOM) composition and infer sources and processing. However, little information is available to assess the impact of biological and photolytic processing on the optical properties of original DOM source materials. We measured changes in commonly used optical properties and indices in DOM leached from peat soil, plants, and algae following biological and photochemical degradation to determine whether they provide unique signatures that can be linked to original DOM source. Changes in individual optical parameters varied by source material and process, with biodegradation and photodegradation often causing values to shift in opposite directions. Although values for different source materials overlapped at the end of the 111-day lab experiment, multivariate statistical analyses showed that unique optical signatures could be linked to original DOM source material even after degradation, with 17 optical properties determined by discriminant analysis to be significant (p<0.05) in distinguishing between DOM source and environmental processing. These results demonstrate that inferring the source material from optical properties is possible when parameters are evaluated in combination even after extensive biological and photochemical alteration.

Agricultural Trade Networks and Patterns of Economic Development

PubMed Central

Shutters, Shade T.; Muneepeerakul, Rachata

2012-01-01

International trade networks are manifestations of a complex combination of diverse underlying factors, both natural and social. Here we apply social network analytics to the international trade network of agricultural products to better understand the nature of this network and its relation to patterns of international development. Using a network tool known as triadic analysis we develop triad significance profiles for a series of agricultural commodities traded among countries. Results reveal a novel network “superfamily” combining properties of biological information processing networks and human social networks. To better understand this unique network signature, we examine in more detail the degree and triadic distributions within the trade network by country and commodity. Our results show that countries fall into two very distinct classes based on their triadic frequencies. Roughly 165 countries fall into one class while 18, all highly isolated with respect to international agricultural trade, fall into the other. Only Vietnam stands out as a unique case. Finally, we show that as a country becomes less isolated with respect to number of trading partners, the country's triadic signature follows a predictable trajectory that may correspond to a trajectory of development. PMID:22768310

Signature properties of water: Their molecular electronic origins

PubMed Central

Jones, Andrew P.; Cipcigan, Flaviu S.; Crain, Jason; Martyna, Glenn J.

2015-01-01

Water challenges our fundamental understanding of emergent materials properties from a molecular perspective. It exhibits a uniquely rich phenomenology including dramatic variations in behavior over the wide temperature range of the liquid into water’s crystalline phases and amorphous states. We show that many-body responses arising from water’s electronic structure are essential mechanisms harnessed by the molecule to encode for the distinguishing features of its condensed states. We treat the complete set of these many-body responses nonperturbatively within a coarse-grained electronic structure derived exclusively from single-molecule properties. Such a “strong coupling” approach generates interaction terms of all symmetries to all orders, thereby enabling unique transferability to diverse local environments such as those encountered along the coexistence curve. The symmetries of local motifs that can potentially emerge are not known a priori. Consequently, electronic responses unfiltered by artificial truncation are then required to embody the terms that tip the balance to the correct set of structures. Therefore, our fully responsive molecular model produces, a simple, accurate, and intuitive picture of water’s complexity and its molecular origin, predicting water’s signature physical properties from ice, through liquid–vapor coexistence, to the critical point. PMID:25941394

Kepler Planet Detection Metrics: Window and One-Sigma Depth Functions for Data Release 25

NASA Technical Reports Server (NTRS)

Burke, Christopher J.; Catanzarite, Joseph

2017-01-01

This document describes the window and one-sigma depth functions relevant to the Transiting Planet Search (TPS) algorithm in the Kepler pipeline (Jenkins 2002; Jenkins et al. 2017). The window function specifies the fraction of unique orbital ephemeris epochs over which three transits are observable as a function of orbital period. In this context, the epoch and orbital period, together, comprise the ephemeris of an orbiting companion, and ephemerides with the same period are considered equivalent if their epochs differ by an integer multiple of the period. The one-sigma depth function specifies the depth of a signal (in ppm) for a given light curve that results in a one-sigma detection of a transit signature as a function of orbital period when averaged over all unique orbital ephemerides. These planet detection metrics quantify the ability of TPS to detect a transiting planet signature on a star-by-star basis. They are uniquely applicable to a specific Kepler data release, since they are dependent on the details of the light curves searched and the functionality of the TPS algorithm used to perform the search. This document describes the window and one-sigma depth functions relevant to Kepler Data Release 25 (DR25), where the data were processed (Thompson et al. 2016) and searched (Twicken et al. 2016) with the SOC 9.3 pipeline. In Section 4, we describe significant differences from those reported in Kepler Data Release 24 (Burke Seader 2016) and document our verification method.

Mechatronics technology in predictive maintenance method

NASA Astrophysics Data System (ADS)

Majid, Nurul Afiqah A.; Muthalif, Asan G. A.

2017-11-01

This paper presents recent mechatronics technology that can help to implement predictive maintenance by combining intelligent and predictive maintenance instrument. Vibration Fault Simulation System (VFSS) is an example of mechatronics system. The focus of this study is the prediction on the use of critical machines to detect vibration. Vibration measurement is often used as the key indicator of the state of the machine. This paper shows the choice of the appropriate strategy in the vibration of diagnostic process of the mechanical system, especially rotating machines, in recognition of the failure during the working process. In this paper, the vibration signature analysis is implemented to detect faults in rotary machining that includes imbalance, mechanical looseness, bent shaft, misalignment, missing blade bearing fault, balancing mass and critical speed. In order to perform vibration signature analysis for rotating machinery faults, studies have been made on how mechatronics technology is used as predictive maintenance methods. Vibration Faults Simulation Rig (VFSR) is designed to simulate and understand faults signatures. These techniques are based on the processing of vibrational data in frequency-domain. The LabVIEW-based spectrum analyzer software is developed to acquire and extract frequency contents of faults signals. This system is successfully tested based on the unique vibration fault signatures that always occur in a rotating machinery.

NF-κB gene signature predicts prostate cancer progression

PubMed Central

Jin, Renjie; Yi, Yajun; Yull, Fiona E.; Blackwell, Timothy S.; Clark, Peter E.; Koyama, Tatsuki; Smith, Joseph A.; Matusik, Robert J.

2014-01-01

In many prostate cancer (PCa) patients, the cancer will be recurrent and eventually progress to lethal metastatic disease after primary treatment, such as surgery or radiation therapy. Therefore, it would be beneficial to better predict which patients with early-stage PCa would progress or recur after primary definitive treatment. In addition, many studies indicate that activation of NF-κB signaling correlates with PCa progression; however, the precise underlying mechanism is not fully understood. Our studies show that activation of NF-κB signaling via deletion of one allele of its inhibitor, IκBα, did not induce prostatic tumorigenesis in our mouse model. However, activation of NF-κB signaling did increase the rate of tumor progression in the Hi-Myc mouse PCa model when compared to Hi-Myc alone. Using the non-malignant NF-κB activated androgen depleted mouse prostate, a NF-κB Activated Recurrence Predictor 21 (NARP21) gene signature was generated. The NARP21 signature successfully predicted disease-specific survival and distant metastases-free survival in patients with PCa. This transgenic mouse model derived gene signature provides a useful and unique molecular profile for human PCa prognosis, which could be used on a prostatic biopsy to predict indolent versus aggressive behavior of the cancer after surgery. PMID:24686169

The (BETA) Pictoris Phenomenon Among Herbig Ae/Be Stars

NASA Technical Reports Server (NTRS)

Grady, C. A.; Perez, M. R.; Talavera, A.; Bjorkman, K. S.; deWinter, D.; The, P.-S.; Molster, F. J.; vandenAncker, M. E.; Sitko, M. L.; Morrison, N. D.;

Hyperspectral imagery for observing spectral signature change in Aspergillus flavus

NASA Astrophysics Data System (ADS)

DiCrispino, Kevin; Yao, Haibo; Hruska, Zuzana; Brabham, Kori; Lewis, David; Beach, Jim; Brown, Robert L.; Cleveland, Thomas E.

2005-11-01

Aflatoxin contaminated corn is dangerous for domestic animals when used as feed and cause liver cancer when consumed by human beings. Therefore, the ability to detect A. flavus and its toxic metabolite, aflatoxin, is important. The objective of this study is to measure A. flavus growth using hyperspectral technology and develop spectral signatures for A. flavus. Based on the research group's previous experiments using hyperspectral imaging techniques, it has been confirmed that the spectral signature of A. flavus is unique and readily identifiable against any background or surrounding surface and among other fungal strains. This study focused on observing changes in the A. flavus spectral signature over an eight-day growth period. The study used a visible-near-infrared hyperspectral image system for data acquisition. This image system uses focal plane pushbroom scanning for high spatial and high spectral resolution imaging. Procedures previously developed by the research group were used for image calibration and image processing. The results showed that while A. flavus gradually progressed along the experiment timeline, the day-to-day surface reflectance of A. flavus displayed significant difference in discreet regions of the wavelength spectrum. External disturbance due to environmental changes also altered the growth and subsequently changed the reflectance patterns of A. flavus.

Phylogenomic and Molecular Demarcation of the Core Members of the Polyphyletic Pasteurellaceae Genera Actinobacillus, Haemophilus, and Pasteurella

PubMed Central

Naushad, Sohail; Adeolu, Mobolaji; Goel, Nisha; Khadka, Bijendra; Al-Dahwi, Aqeel; Gupta, Radhey S.

2015-01-01

The genera Actinobacillus, Haemophilus, and Pasteurella exhibit extensive polyphyletic branching in phylogenetic trees and do not represent coherent clusters of species. In this study, we have utilized molecular signatures identified through comparative genomic analyses in conjunction with genome based and multilocus sequence based phylogenetic analyses to clarify the phylogenetic and taxonomic boundary of these genera. We have identified large clusters of Actinobacillus, Haemophilus, and Pasteurella species which represent the “sensu stricto” members of these genera. We have identified 3, 7, and 6 conserved signature indels (CSIs), which are specifically shared by sensu stricto members of Actinobacillus, Haemophilus, and Pasteurella, respectively. We have also identified two different sets of CSIs that are unique characteristics of the pathogen containing genera Aggregatibacter and Mannheimia, respectively. It is now possible to demarcate the genera Actinobacillus sensu stricto, Haemophilus sensu stricto, and Pasteurella sensu stricto on the basis of discrete molecular signatures. The other members of the genera Actinobacillus, Haemophilus, and Pasteurella that do not fall within the “sensu stricto” clades and do not contain these molecular signatures should be reclassified as other genera. The CSIs identified here also provide useful diagnostic targets for the identification of current and novel members of the indicated genera. PMID:25821780

The LncRNA Connectivity Map: Using LncRNA Signatures to Connect Small Molecules, LncRNAs, and Diseases.

PubMed

Yang, Haixiu; Shang, Desi; Xu, Yanjun; Zhang, Chunlong; Feng, Li; Sun, Zeguo; Shi, Xinrui; Zhang, Yunpeng; Han, Junwei; Su, Fei; Li, Chunquan; Li, Xia

2017-07-27

Well characterized the connections among diseases, long non-coding RNAs (lncRNAs) and drugs are important for elucidating the key roles of lncRNAs in biological mechanisms in various biological states. In this study, we constructed a database called LNCmap (LncRNA Connectivity Map), available at http://www.bio-bigdata.com/LNCmap/ , to establish the correlations among diseases, physiological processes, and the action of small molecule therapeutics by attempting to describe all biological states in terms of lncRNA signatures. By reannotating the microarray data from the Connectivity Map database, the LNCmap obtained 237 lncRNA signatures of 5916 instances corresponding to 1262 small molecular drugs. We provided a user-friendly interface for the convenient browsing, retrieval and download of the database, including detailed information and the associations of drugs and corresponding affected lncRNAs. Additionally, we developed two enrichment analysis methods for users to identify candidate drugs for a particular disease by inputting the corresponding lncRNA expression profiles or an associated lncRNA list and then comparing them to the lncRNA signatures in our database. Overall, LNCmap could significantly improve our understanding of the biological roles of lncRNAs and provide a unique resource to reveal the connections among drugs, lncRNAs and diseases.

Temporal measurement and analysis of high-resolution spectral signatures of plants and relationships to biophysical characteristics

NASA Astrophysics Data System (ADS)

Bostater, Charles R., Jr.; Rebbman, Jan; Hall, Carlton; Provancha, Mark; Vieglais, David

1995-11-01

Measurements of temporal reflectance signatures as a function of growing season for sand live oak (Quercus geminata), myrtle oak (Q. myrtifolia, and saw palmetto (Serenoa repens) were collected during a two year study period. Canopy level spectral reflectance signatures, as a function of 252 channels between 368 and 1115 nm, were collected using near nadir viewing geometry and a consistent sun illumination angle. Leaf level reflectance measurements were made in the laboratory using a halogen light source and an environmental optics chamber with a barium sulfate reflectance coating. Spectral measurements were related to several biophysical measurements utilizing optimal passive ambient correlation spectroscopy (OPACS) technique. Biophysical parameters included percent moisture, water potential (MPa), total chlorophyll, and total Kjeldahl nitrogen. Quantitative data processing techniques were used to determine optimal bands based on the utilization of a second order derivative or inflection estimator. An optical cleanup procedure was then employed that computes the double inflection ratio (DIR) spectra for all possible three band combinations normalized to the previously computed optimal bands. These results demonstrate a unique approach to the analysis of high spectral resolution reflectance signatures for estimation of several biophysical measures of plants at the leaf and canopy level from optimally selected bands or bandwidths.

The Cure: Design and Evaluation of a Crowdsourcing Game for Gene Selection for Breast Cancer Survival Prediction

PubMed Central

Loguercio, Salvatore; Griffith, Obi L; Nanis, Max; Wu, Chunlei; Su, Andrew I

2014-01-01

Background Molecular signatures for predicting breast cancer prognosis could greatly improve care through personalization of treatment. Computational analyses of genome-wide expression datasets have identified such signatures, but these signatures leave much to be desired in terms of accuracy, reproducibility, and biological interpretability. Methods that take advantage of structured prior knowledge (eg, protein interaction networks) show promise in helping to define better signatures, but most knowledge remains unstructured. Crowdsourcing via scientific discovery games is an emerging methodology that has the potential to tap into human intelligence at scales and in modes unheard of before. Objective The main objective of this study was to test the hypothesis that knowledge linking expression patterns of specific genes to breast cancer outcomes could be captured from players of an open, Web-based game. We envisioned capturing knowledge both from the player’s prior experience and from their ability to interpret text related to candidate genes presented to them in the context of the game. Methods We developed and evaluated an online game called The Cure that captured information from players regarding genes for use as predictors of breast cancer survival. Information gathered from game play was aggregated using a voting approach, and used to create rankings of genes. The top genes from these rankings were evaluated using annotation enrichment analysis, comparison to prior predictor gene sets, and by using them to train and test machine learning systems for predicting 10 year survival. Results Between its launch in September 2012 and September 2013, The Cure attracted more than 1000 registered players, who collectively played nearly 10,000 games. Gene sets assembled through aggregation of the collected data showed significant enrichment for genes known to be related to key concepts such as cancer, disease progression, and recurrence. In terms of the predictive accuracy of models trained using this information, these gene sets provided comparable performance to gene sets generated using other methods, including those used in commercial tests. The Cure is available on the Internet. Conclusions The principal contribution of this work is to show that crowdsourcing games can be developed as a means to address problems involving domain knowledge. While most prior work on scientific discovery games and crowdsourcing in general takes as a premise that contributors have little or no expertise, here we demonstrated a crowdsourcing system that succeeded in capturing expert knowledge. PMID:25654473

Identification of Hip BMD Loss and Fracture Risk Markers Through Population-Based Serum Proteomics: HIP BMD LOSS & FRACTURE RISK MARKERS BY POPULATION-BASED SERUM PROTEOMICS

DOE Office of Scientific and Technical Information (OSTI.GOV)

Nielson, Carrie M.; Wiedrick, Jack; Shen, Jian

Accelerated bone loss significantly increases the risk of osteoporosis and fracture. The mechanisms underlying bone loss remain incompletely understood, and there are few available biomarkers. We utilized a novel proteomics approach to identify serum peptides and proteins associated with bone loss in 1967 older men who were randomly chosen from the Osteoporotic Fracture in Men Study (MrOS study) (age ≥ 65 yrs). Men had 2-3 measures of femoral neck BMD over an average follow-up of 4.6 years. Change in BMD was estimated and then categorized into three groups: maintained BMD (n=453), expected loss (n=1185) and accelerated loss (n=237). A liquidmore » chromatography–ion mobility separation-mass spectrometry (LC-IMS-MS) proteomics platform was used to identify and quantify peptides from serum proteins. The whole cohort was randomly divided into discovery (N= 960) and validation (N= 915) sub-cohorts. Linear regression models and a random forest approach were used to discover differentially abundant individual peptides and a proteomic signature that distinguished individuals with accelerated bone loss from those who maintained BMD. Network analyses were performed using the MetaCore knowledgebase. We identified 12 peptides that were associated with BMD loss in both discovery (P< 0.1 FDR) and replication sub-cohorts (P<0.05). Those 12 peptides mapped to the following proteins: ALS, LYVE1, RNAS1, C2, ICOSL, C163A, C7, HEMO, CD14, CERU, CRAC1 and CD59. Meta-analysis of peptidesassociated with bone loss identified 6 additional proteins including GRP78, IGF-2, SHBG, ENPP2, IBP2 and IBP6. We also identified a proteomic signature that was predictive of BMD loss with a discriminative value similar to serum bone marker carboxy-terminal collagen crosslink peptide (CTX). Interestingly, combining the proteomic signature with CTX significantly improved the ability to discriminate men with accelerated loss. In summary, we have identified potential new biomarkers for bone loss that provide a more in depth understanding of its pathophysiology.« less

The discovery of a class of novel HIV-1 maturation inhibitors and their potential in the therapy of HIV.

PubMed

Yu, Donglei; Wild, Carl T; Martin, David E; Morris-Natschke, Susan L; Chen, Chin-Ho; Allaway, Graham P; Lee, Kuo-Hsiung

2005-06-01

Although HIV infection is now primarily treated with reverse transcriptase and protease inhibitors, HIV therapy must look toward new drugs with novel mechanism(s) of action to both improve efficacy and address the growing problem of drug resistance. Using natural products as a source of biologically active compounds, our drug discovery program has successfully optimised the natural product betulinic acid to the first-in-class maturation inhibitor 3-O-(3',3'-dimethylsuccinyl)-betulinic acid (DSB). DSB's unique viral target has been identified as a late step in Gag processing. Specifically, it inhibits the cleavage of the capsid precursor, CA-SP1, resulting in a block to the processing of mature capsid protein leading to a defect in viral core condensation. DSB represents a unique class of anti-HIV compounds that inhibit virus maturation and provide additional opportunities for anti-HIV therapy. In this review, the discovery of DSB and its mode of action are summarised. Anti-AIDS Agents part 64. For part 63 in the series, see YU D, LEE KH: Recent progress and prospects on plant-derived anti-HIV agents and analogs. In: Medicinal Chemistry of Bioactive Natural Products. XT Liang, WS Fang (Eds), Wiley, New York, USA (2005) (In Press).

Phylogenomics and Comparative Genomic Studies Robustly Support Division of the Genus Mycobacterium into an Emended Genus Mycobacterium and Four Novel Genera

PubMed Central

Gupta, Radhey S.; Lo, Brian; Son, Jeen

2018-01-01

The genus Mycobacterium contains 188 species including several major human pathogens as well as numerous other environmental species. We report here comprehensive phylogenomics and comparative genomic analyses on 150 genomes of Mycobacterium species to understand their interrelationships. Phylogenetic trees were constructed for the 150 species based on 1941 core proteins for the genus Mycobacterium, 136 core proteins for the phylum Actinobacteria and 8 other conserved proteins. Additionally, the overall genome similarity amongst the Mycobacterium species was determined based on average amino acid identity of the conserved protein families. The results from these analyses consistently support the existence of five distinct monophyletic groups within the genus Mycobacterium at the highest level, which are designated as the “Tuberculosis-Simiae,” “Terrae,” “Triviale,” “Fortuitum-Vaccae,” and “Abscessus-Chelonae” clades. Some of these clades have also been observed in earlier phylogenetic studies. Of these clades, the “Abscessus-Chelonae” clade forms the deepest branching lineage and does not form a monophyletic grouping with the “Fortuitum-Vaccae” clade of fast-growing species. In parallel, our comparative analyses of proteins from mycobacterial genomes have identified 172 molecular signatures in the form of conserved signature indels and conserved signature proteins, which are uniquely shared by either all Mycobacterium species or by members of the five identified clades. The identified molecular signatures (or synapomorphies) provide strong independent evidence for the monophyly of the genus Mycobacterium and the five described clades and they provide reliable means for the demarcation of these clades and for their diagnostics. Based on the results of our comprehensive phylogenomic analyses and numerous identified molecular signatures, which consistently and strongly support the division of known mycobacterial species into the five described clades, we propose here division of the genus Mycobacterium into an emended genus Mycobacterium encompassing the “Tuberculosis-Simiae” clade, which includes all of the major human pathogens, and four novel genera viz. Mycolicibacterium gen. nov., Mycolicibacter gen. nov., Mycolicibacillus gen. nov. and Mycobacteroides gen. nov. corresponding to the “Fortuitum-Vaccae,” “Terrae,” “Triviale,” and “Abscessus-Chelonae” clades, respectively. With the division of mycobacterial species into these five distinct groups, attention can now be focused on unique genetic and molecular characteristics that differentiate members of these groups. PMID:29497402

Human plasma and serum extracellular small RNA reference profiles and their clinical utility.

PubMed

Max, Klaas E A; Bertram, Karl; Akat, Kemal Marc; Bogardus, Kimberly A; Li, Jenny; Morozov, Pavel; Ben-Dov, Iddo Z; Li, Xin; Weiss, Zachary R; Azizian, Azadeh; Sopeyin, Anuoluwapo; Diacovo, Thomas G; Adamidi, Catherine; Williams, Zev; Tuschl, Thomas

2018-06-05

Circulating extracellular RNAs (exRNAs) have the potential to serve as biomarkers for a wide range of medical conditions. However, limitations in existing exRNA isolation methods and a lack of knowledge on parameters affecting exRNA variability in human samples may hinder their successful discovery and clinical implementation. Using combinations of denaturants, reducing agents, proteolysis, and revised organic extraction, we developed an automated, high-throughput approach for recovery of exRNAs and exDNA from the same biofluid sample. We applied this method to characterize exRNAs from 312 plasma and serum samples collected from 13 healthy volunteers at 12 time points over a 2-month period. Small RNA cDNA library sequencing identified nearly twofold increased epithelial-, muscle-, and neuroendocrine-cell-specific miRNAs in females, while fasting and hormonal cycle showed little effect. External standardization helped to detect quantitative differences in erythrocyte and platelet-specific miRNA contributions and in miRNA concentrations between biofluids. It also helped to identify a study participant with a unique exRNA phenotype featuring a miRNA signature of up to 20-fold elevated endocrine-cell-specific miRNAs and twofold elevated total miRNA concentrations stable for over 1 year. Collectively, these results demonstrate an efficient and quantitative method to discern exRNA phenotypes and suggest that plasma and serum RNA profiles are stable over months and can be routinely monitored in long-term clinical studies. Copyright © 2018 the Author(s). Published by PNAS.

Extraterrestrial amino acids in Cretaceous/Tertiary boundary sediments at Stevns Klint, Denmark

NASA Astrophysics Data System (ADS)

Zhao, Meixun; Bada, Jeffrey L.

1989-06-01

SINCE the discovery1 nearly a decade ago that Cretaceous/Tertiary (K/T) boundary layers are greatly enriched in iridium, a rare element in the Earth's crust, there has been intense controversy on the relationship between this Ir anomaly and the massive extinction of organisms ranging from dinosaurs to marine plankton that characterizes the K/T boundary. Convincing evidence suggests that both the Ir spike and the extinction event were caused by the collision of a large bolide (>10 km in diameter) with the Earth1-11. Alternative explanations claim that extensive, violent volcanism12-14 can account for the Ir, and that other independent causes were responsible for the mass extinctions15,16. We surmise that the collision of a massive extraterrestrial object with the Earth may have produced a unique organic chemical signature because certain meteorites, and probably comets, contain organic compounds which are either rare or non-existent on the Earth17. In contrast, no organic compounds would be expected to be associated with volcanic processes. Here we find that K/T boundary sediments at Stevns Klint, Denmark, contain both α-amino-isobutyric acid [AIB, (CH3)2CNH2COOH] and racemic isovaline [ISOVAL, CH3CH2(CH3)CNH2COOH], two amino acids that are exceedingly rare on the Earth but which are major amino acids in carbonaceous chondrites17,18. An extraterrestrial source is the most reasonable explanation for the presence of these amino acids.

Shape Analysis of Planar Multiply-Connected Objects Using Conformal Welding.

PubMed

Lok Ming Lui; Wei Zeng; Shing-Tung Yau; Xianfeng Gu

2014-07-01

Shape analysis is a central problem in the field of computer vision. In 2D shape analysis, classification and recognition of objects from their observed silhouettes are extremely crucial but difficult. It usually involves an efficient representation of 2D shape space with a metric, so that its mathematical structure can be used for further analysis. Although the study of 2D simply-connected shapes has been subject to a corpus of literatures, the analysis of multiply-connected shapes is comparatively less studied. In this work, we propose a representation for general 2D multiply-connected domains with arbitrary topologies using conformal welding. A metric can be defined on the proposed representation space, which gives a metric to measure dissimilarities between objects. The main idea is to map the exterior and interior of the domain conformally to unit disks and circle domains (unit disk with several inner disks removed), using holomorphic 1-forms. A set of diffeomorphisms of the unit circle S(1) can be obtained, which together with the conformal modules are used to define the shape signature. A shape distance between shape signatures can be defined to measure dissimilarities between shapes. We prove theoretically that the proposed shape signature uniquely determines the multiply-connected objects under suitable normalization. We also introduce a reconstruction algorithm to obtain shapes from their signatures. This completes our framework and allows us to move back and forth between shapes and signatures. With that, a morphing algorithm between shapes can be developed through the interpolation of the Beltrami coefficients associated with the signatures. Experiments have been carried out on shapes extracted from real images. Results demonstrate the efficacy of our proposed algorithm as a stable shape representation scheme.

Argon Collection And Purification For Proliferation Detection

DOE Office of Scientific and Technical Information (OSTI.GOV)

Achey, R.; Hunter, D.

2015-10-09

In order to determine whether a seismic event was a declared/undeclared underground nuclear weapon test, environmental samples must be taken and analyzed for signatures that are unique to a nuclear explosion. These signatures are either particles or gases. Particle samples are routinely taken and analyzed under the Comprehensive Nuclear-Test-Ban Treaty Organization (CTBTO) verification regime as well as by individual countries. Gas samples are analyzed for signature gases, especially radioactive xenon. Underground nuclear tests also produce radioactive argon, but that signature is not well monitored. A radioactive argon signature, along with other signatures, can more conclusively determine whether an event wasmore » a nuclear test. This project has developed capabilities for collecting and purifying argon samples for ultra-low-background proportional counting. SRNL has developed a continuous gas enrichment system that produces an output stream containing 97% argon from whole air using adsorbent separation technology (the flow diagram for the system is shown in the figure). The vacuum swing adsorption (VSA) enrichment system is easily scalable to produce ten liters or more of 97% argon within twelve hours. A gas chromatographic separation using a column of modified hydrogen mordenite molecular sieve has been developed that can further purify the sample to better than 99% purity after separation from the helium carrier gas. The combination of these concentration and purification systems has the capability of being used for a field-deployable system for collecting argon samples suitable for ultra-low-background proportional counting for detecting nuclear detonations under the On-Site Inspection program of the CTBTO verification regime. The technology also has applications for the bulk argon separation from air for industrial purposes such as the semi-conductor industry.« less

matK-QR classifier: a patterns based approach for plant species identification.

PubMed

More, Ravi Prabhakar; Mane, Rupali Chandrashekhar; Purohit, Hemant J

2016-01-01

DNA barcoding is widely used and most efficient approach that facilitates rapid and accurate identification of plant species based on the short standardized segment of the genome. The nucleotide sequences of maturaseK ( matK ) and ribulose-1, 5-bisphosphate carboxylase ( rbcL ) marker loci are commonly used in plant species identification. Here, we present a new and highly efficient approach for identifying a unique set of discriminating nucleotide patterns to generate a signature (i.e. regular expression) for plant species identification. In order to generate molecular signatures, we used matK and rbcL loci datasets, which encompass 125 plant species in 52 genera reported by the CBOL plant working group. Initially, we performed Multiple Sequence Alignment (MSA) of all species followed by Position Specific Scoring Matrix (PSSM) for both loci to achieve a percentage of discrimination among species. Further, we detected Discriminating Patterns (DP) at genus and species level using PSSM for the matK dataset. Combining DP and consecutive pattern distances, we generated molecular signatures for each species. Finally, we performed a comparative assessment of these signatures with the existing methods including BLASTn, Support Vector Machines (SVM), Jrip-RIPPER, J48 (C4.5 algorithm), and the Naïve Bayes (NB) methods against NCBI-GenBank matK dataset. Due to the higher discrimination success obtained with the matK as compared to the rbcL , we selected matK gene for signature generation. We generated signatures for 60 species based on identified discriminating patterns at genus and species level. Our comparative assessment results suggest that a total of 46 out of 60 species could be correctly identified using generated signatures, followed by BLASTn (34 species), SVM (18 species), C4.5 (7 species), NB (4 species) and RIPPER (3 species) methods As a final outcome of this study, we converted signatures into QR codes and developed a software matK -QR Classifier (http://www.neeri.res.in/matk_classifier/index.htm), which search signatures in the query matK gene sequences and predict corresponding plant species. This novel approach of employing pattern-based signatures opens new avenues for the classification of species. In addition to existing methods, we believe that matK -QR Classifier would be a valuable tool for molecular taxonomists enabling precise identification of plant species.

Fundamental Properties of the Red Square

NASA Astrophysics Data System (ADS)

Tuthill, Peter; Barnes, Peter; Cohen, Martin; Schmidt, Timothy

2007-04-01

This proposal follows the exciting recent discovery of the Red Square, the first near-sibling to the illustrious Red Rectangle; and also a potential example progenitor system for supernovae such as SN 1987A. Exploiting the unique extremely wide bandwidth correlator available at Mopra, we propose to rapidly and efficiently explore the molecular environment of this unique new object at 3 mm. This should reveal the fundamental properties of the gas in the underlying stellar system, and will provide the necessary springboard for future spatially-resolved work with interferometers.

Balmer Absorption Lines in FeLoBALs

NASA Astrophysics Data System (ADS)

Aoki, K.; Iwata, I.; Ohta, K.; Tamura, N.; Ando, M.; Akiyama, M.; Kiuchi, G.; Nakanishi, K.

2007-10-01

We discovered non-stellar Balmer absorption lines in two many-narrow-trough FeLoBALs (mntBALs) by the near-infrared spectroscopy with Subaru/CISCO. Presence of the non-stellar Balmer absorption lines is known to date only in the Seyfert galaxy NGC 4151; thus our discovery is the first cases for quasars. Since all known active galactic nuclei with Balmer absorption lines share similar characteristics, it is suggested that there is a population of BAL quasars which have unique structures at their nuclei or unique evolutionary phase.

The unexpected discovery of the Mg(HMDS) 2 /MgCl 2 complex as a magnesium electrolyte for rechargeable magnesium batteries

DOE PAGES

Liao, Chen; Sa, Niya; Key, Baris; ...

2015-02-02

We developed a unique class of non-Grignard, aluminum-free magnesium electrolytes based on a simple mixture of magnesium compounds: magnesium hexamethyldisilazide (Mg(HMDS) 2) and magnesium chloride (MgCl 2).

Recent Advances in the Discovery and Development of Marine Microbial Natural Products

PubMed Central

Xiong, Zhi-Qiang; Wang, Jian-Feng; Hao, Yu-You; Wang, Yong

2013-01-01

Marine microbial natural products (MMNPs) have attracted increasing attention from microbiologists, taxonomists, ecologists, agronomists, chemists and evolutionary biologists during the last few decades. Numerous studies have indicated that diverse marine microbes appear to have the capacity to produce an impressive array of MMNPs exhibiting a wide variety of biological activities such as antimicrobial, anti-tumor, anti-inflammatory and anti-cardiovascular agents. Marine microorganisms represent an underexplored reservoir for the discovery of MMNPs with unique scaffolds and for exploitation in the pharmaceutical and agricultural industries. This review focuses on MMNPs discovery and development over the past decades, including innovative isolation and culture methods, strategies for discovering novel MMNPs via routine screenings, metagenomics, genomics, combinatorial biosynthesis, and synthetic biology. The potential problems and future directions for exploring MMNPs are also discussed. PMID:23528949

Commentary: charting a course for success: excellence in clinical care and discovery in academic departments.

PubMed

Cooper, William O; Gitlin, Jonathan D

2011-05-01

The current shifts in academics not only invite new challenges but create previously unexplored opportunities for unique discoveries in health. Leaders in academic departments must consider changes in academic medicine as new courses to be charted rather than an inevitable shifting of the ground beneath them. Under this model, clinical excellence is coupled with discovery, where trainees, faculty, and patients and families are continually exposed to asking questions and identifying ways to move science forward to improve health. Academic pediatrics remains today a vibrant and exciting discipline with extraordinary leaders and committed trainees. We must continue to inspire on the voyage to excellence, keeping our eyes on the horizon and not the gathering storms. Copyright © by the Association of American medical Colleges.

General view of the underside of the Orbiter Discovery on ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

General view of the underside of the Orbiter Discovery on the port side looking toward the starboard side and slightly forward. Note the landing gear assemblies, the jack stands attached to the External Tank (ET) attach points in on the Orbiter/ET propellant interface plate and the black High-Temperature Reusable Surface Insulation. The varying degrees of darkness of the tiles is due to the age of the tiles, the more recently replaced tiles are darker than the older tiles. The pattern created by the tile replacement is unique to each orbiter and becomes their "fingerprint". This view was taken in the Orbiter Processing Facility at Kennedy Space Center. - Space Transportation System, Orbiter Discovery (OV-103), Lyndon B. Johnson Space Center, 2101 NASA Parkway, Houston, Harris County, TX

Recent advances in the discovery and development of marine microbial natural products.

PubMed

Xiong, Zhi-Qiang; Wang, Jian-Feng; Hao, Yu-You; Wang, Yong

2013-03-08

Marine microbial natural products (MMNPs) have attracted increasing attention from microbiologists, taxonomists, ecologists, agronomists, chemists and evolutionary biologists during the last few decades. Numerous studies have indicated that diverse marine microbes appear to have the capacity to produce an impressive array of MMNPs exhibiting a wide variety of biological activities such as antimicrobial, anti-tumor, anti-inflammatory and anti-cardiovascular agents. Marine microorganisms represent an underexplored reservoir for the discovery of MMNPs with unique scaffolds and for exploitation in the pharmaceutical and agricultural industries. This review focuses on MMNPs discovery and development over the past decades, including innovative isolation and culture methods, strategies for discovering novel MMNPs via routine screenings, metagenomics, genomics, combinatorial biosynthesis, and synthetic biology. The potential problems and future directions for exploring MMNPs are also discussed.

In Vivo Detection of EGFRvIII in Glioblastoma via Perfusion Magnetic Resonance Imaging Signature Consistent with Deep Peritumoral Infiltration: The φ-Index.

PubMed

Bakas, Spyridon; Akbari, Hamed; Pisapia, Jared; Martinez-Lage, Maria; Rozycki, Martin; Rathore, Saima; Dahmane, Nadia; O'Rourke, Donald M; Davatzikos, Christos

2017-08-15

Purpose: The epidermal growth factor receptor variant III ( EGFRvIII ) mutation has been considered a driver mutation and therapeutic target in glioblastoma, the most common and aggressive brain cancer. Currently, detecting EGFRvIII requires postoperative tissue analyses, which are ex vivo and unable to capture the tumor's spatial heterogeneity. Considering the increasing evidence of in vivo imaging signatures capturing molecular characteristics of cancer, this study aims to detect EGFRvIII in primary glioblastoma noninvasively, using routine clinically acquired imaging. Experimental Design: We found peritumoral infiltration and vascularization patterns being related to EGFRvIII status. We therefore constructed a quantitative within-patient peritumoral heterogeneity index (PHI/φ-index), by contrasting perfusion patterns of immediate and distant peritumoral edema. Application of φ-index in preoperative perfusion scans of independent discovery ( n = 64) and validation ( n = 78) cohorts, revealed the generalizability of this EGFRvIII imaging signature. Results: Analysis in both cohorts demonstrated that the obtained signature is highly accurate (89.92%), specific (92.35%), and sensitive (83.77%), with significantly distinctive ability ( P = 4.0033 × 10 -10 , AUC = 0.8869). Findings indicated a highly infiltrative-migratory phenotype for EGFRvIII + tumors, which displayed similar perfusion patterns throughout peritumoral edema. Contrarily, EGFRvIII - tumors displayed perfusion dynamics consistent with peritumorally confined vascularization, suggesting potential benefit from extensive peritumoral resection/radiation. Conclusions: This EGFRvIII signature is potentially suitable for clinical translation, since obtained from analysis of clinically acquired images. Use of within-patient heterogeneity measures, rather than population-based associations, renders φ-index potentially resistant to inter-scanner variations. Overall, our findings enable noninvasive evaluation of EGFRvIII for patient selection for targeted therapy, stratification into clinical trials, personalized treatment planning, and potentially treatment-response evaluation. Clin Cancer Res; 23(16); 4724-34. ©2017 AACR . ©2017 American Association for Cancer Research.

Advances in the Kepler Transit Search Engine

NASA Astrophysics Data System (ADS)

Jenkins, Jon M.

2016-10-01

Twenty years ago, no planets were known outside our own solar system. Since then, the discoveries of ~1500 exoplanets have radically altered our views of planets and planetary systems. This revolution is due in no small part to the Kepler Mission, which has discovered >1000 of these planets and >4000 planet candidates. While Kepler has shown that small rocky planets and planetary systems are quite common, the quest to find Earth's closest cousins and characterize their atmospheres presses forward with missions such as NASA Explorer Program's Transiting Exoplanet Survey Satellite (TESS) slated for launch in 2017 and ESA's PLATO mission scheduled for launch in 2024. These future missions pose daunting data processing challenges in terms of the number of stars, the amount of data, and the difficulties in detecting weak signatures of transiting small planets against a roaring background. These complications include instrument noise and systematic effects as well as the intrinsic stellar variability of the subjects under scrutiny. In this paper we review recent developments in the Kepler transit search pipeline improving both the yield and reliability of detected transit signatures. Many of the phenomena in light curves that represent noise can also trigger transit detection algorithms. The Kepler Mission has expended great effort in suppressing false positives from its planetary candidate catalogs. Over 18,000 transit-like signatures can be identified for a search across 4 years of data. Most of these signatures are artifacts, not planets. Vetting all such signatures historically takes several months' effort by many individuals. We describe the application of machine learning approaches for the automated vetting and production of planet candidate catalogs. These algorithms can improve the efficiency of the human vetting effort as well as quantifying the likelihood that each candidate is truly a planet. This information is crucial for obtaining valid planet occurrence rates. Machine learning approaches may prove to be critical to the success of future missions such as TESS and PLATO.

Jupiter's Auroras Acceleration Processes

NASA Image and Video Library

2017-09-06

This image, created with data from Juno's Ultraviolet Imaging Spectrometer (UVS), marks the path of Juno's readings of Jupiter's auroras, highlighting the electron measurements that show the discovery of the so-called discrete auroral acceleration processes indicated by the "inverted Vs" in the lower panel (Figure 1). This signature points to powerful magnetic-field-aligned electric potentials that accelerate electrons toward the atmosphere to energies that are far greater than what drive the most intense aurora at Earth. Scientists are looking into why the same processes are not the main factor in Jupiter's most powerful auroras. https://photojournal.jpl.nasa.gov/catalog/PIA21937

Detecting Axionlike Particles with Gamma Ray Telescopes

NASA Astrophysics Data System (ADS)

Hooper, Dan; Serpico, Pasquale D.

2007-12-01

We propose that axionlike particles (ALPs) with a two-photon vertex, consistent with all astrophysical and laboratory bounds, may lead to a detectable signature in the spectra of high-energy gamma-ray sources. This occurs as a result of gamma rays being converted into ALPs in the magnetic fields of efficient astrophysical accelerators according to the “Hillas criterion”, such as jets of active galactic nuclei or hot spots of radio galaxies. The discovery of such an effect is possible by GLAST in the 1 100 GeV range and by ground-based gamma-ray telescopes in the TeV range.

Single-Cell Genomics Unravels Brain Cell-Type Complexity.

PubMed

Guillaumet-Adkins, Amy; Heyn, Holger

2017-01-01

The brain is the most complex tissue in terms of cell types that it comprises, to the extent that it is still poorly understood. Single cell genome and transcriptome profiling allow to disentangle the neuronal heterogeneity, enabling the categorization of individual neurons into groups with similar molecular signatures. Herein, we unravel the current state of knowledge in single cell neurogenomics. We describe the molecular understanding of the cellular architecture of the mammalian nervous system in health and in disease; from the discovery of unrecognized cell types to the validation of known ones, applying these state-of-the-art technologies.

Anomalous single production of the fourth generation quarks at the CERN LHC

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ciftci, R.

Possible anomalous single productions of the fourth standard model generation up and down type quarks at CERN Large Hadron Collider are studied. Namely, pp{yields}u{sub 4}(d{sub 4})X with subsequent u{sub 4}{yields}bW{sup +} process followed by the leptonic decay of the W boson and d{sub 4}{yields}b{gamma} (and its H.c.) decay channel are considered. Signatures of these processes and corresponding standard model backgrounds are discussed in detail. Discovery limits for the quark mass and achievable values of the anomalous coupling strength are determined.

Gender, Contraceptives and Individual Metabolic Predisposition Shape a Healthy Plasma Lipidome.

PubMed

Sales, Susanne; Graessler, Juergen; Ciucci, Sara; Al-Atrib, Rania; Vihervaara, Terhi; Schuhmann, Kai; Kauhanen, Dimple; Sysi-Aho, Marko; Bornstein, Stefan R; Bickle, Marc; Cannistraci, Carlo V; Ekroos, Kim; Shevchenko, Andrej

2016-06-14

Lipidomics of human blood plasma is an emerging biomarker discovery approach that compares lipid profiles under pathological and physiologically normal conditions, but how a healthy lipidome varies within the population is poorly understood. By quantifying 281 molecular species from 27 major lipid classes in the plasma of 71 healthy young Caucasians whose 35 clinical blood test and anthropometric indices matched the medical norm, we provided a comprehensive, expandable and clinically relevant resource of reference molar concentrations of individual lipids. We established that gender is a major lipidomic factor, whose impact is strongly enhanced by hormonal contraceptives and mediated by sex hormone-binding globulin. In lipidomics epidemiological studies should avoid mixed-gender cohorts and females taking hormonal contraceptives should be considered as a separate sub-cohort. Within a gender-restricted cohort lipidomics revealed a compositional signature that indicates the predisposition towards an early development of metabolic syndrome in ca. 25% of healthy male individuals suggesting a healthy plasma lipidome as resource for early biomarker discovery.

Dip in the gene pool: metagenomic survey of natural coccolithovirus communities.

PubMed

Pagarete, António; Kusonmano, Kanthida; Petersen, Kjell; Kimmance, Susan A; Martínez Martínez, Joaquín; Wilson, William H; Hehemann, Jan-Hendrik; Allen, Michael J; Sandaa, Ruth-Anne

2014-10-01

Despite the global oceanic distribution and recognised biogeochemical impact of coccolithoviruses (EhV), their diversity remains poorly understood. Here we employed a metagenomic approach to study the occurrence and progression of natural EhV community genomic variability. Analysis of EhV metagenomes from the early and late stages of an induced bloom led to three main discoveries. First, we observed resilient and specific genomic signatures in the EhV community associated with the Norwegian coast, which reinforce the existence of limitations to the capacity of dispersal and genomic exchange among EhV populations. Second, we identified a hyper-variable region (approximately 21kbp long) in the coccolithovirus genome. Third, we observed a clear trend for EhV relative amino-acid diversity to reduce from early to late stages of the bloom. This study validated two new methodological combinations, and proved very useful in the discovery of new genomic features associated with coccolithovirus natural communities. Copyright © 2014 Elsevier Inc. All rights reserved.

Systems analysis of arrestin pathway functions.

PubMed

Maudsley, Stuart; Siddiqui, Sana; Martin, Bronwen

2013-01-01

To fully appreciate the diversity and specificity of complex cellular signaling events, such as arrestin-mediated signaling from G protein-coupled receptor activation, a complex systems-level investigation currently appears to be the best option. A rational combination of transcriptomics, proteomics, and interactomics, all coherently integrated with applied next-generation bioinformatics, is vital for the future understanding of the development, translation, and expression of GPCR-mediated arrestin signaling events in physiological contexts. Through a more nuanced, systems-level appreciation of arrestin-mediated signaling, the creation of arrestin-specific molecular response "signatures" should be made simple and ultimately amenable to drug discovery processes. Arrestin-based signaling paradigms possess important aspects, such as its specific temporal kinetics and ability to strongly affect transcriptional activity, that make it an ideal test bed for next-generation of drug discovery bioinformatic approaches such as multi-parallel dose-response analysis, data texturization, and latent semantic indexing-based natural language data processing and feature extraction. Copyright © 2013 Elsevier Inc. All rights reserved.

Gut Microbiome-Based Metagenomic Signature for Non-invasive Detection of Advanced Fibrosis in Human Nonalcoholic Fatty Liver Disease.

PubMed

Loomba, Rohit; Seguritan, Victor; Li, Weizhong; Long, Tao; Klitgord, Niels; Bhatt, Archana; Dulai, Parambir Singh; Caussy, Cyrielle; Bettencourt, Richele; Highlander, Sarah K; Jones, Marcus B; Sirlin, Claude B; Schnabl, Bernd; Brinkac, Lauren; Schork, Nicholas; Chen, Chi-Hua; Brenner, David A; Biggs, William; Yooseph, Shibu; Venter, J Craig; Nelson, Karen E

2017-05-02

The presence of advanced fibrosis in nonalcoholic fatty liver disease (NAFLD) is the most important predictor of liver mortality. There are limited data on the diagnostic accuracy of gut microbiota-derived signature for predicting the presence of advanced fibrosis. In this prospective study, we characterized the gut microbiome compositions using whole-genome shotgun sequencing of DNA extracted from stool samples. This study included 86 uniquely well-characterized patients with biopsy-proven NAFLD, of which 72 had mild/moderate (stage 0-2 fibrosis) NAFLD, and 14 had advanced fibrosis (stage 3 or 4 fibrosis). We identified a set of 40 features (p < 0.006), which included 37 bacterial species that were used to construct a Random Forest classifier model to distinguish mild/moderate NAFLD from advanced fibrosis. The model had a robust diagnostic accuracy (AUC 0.936) for detecting advanced fibrosis. This study provides preliminary evidence for a fecal-microbiome-derived metagenomic signature to detect advanced fibrosis in NAFLD. Copyright © 2017 Elsevier Inc. All rights reserved.

The chromatin accessibility signature of human immune aging stems from CD8+ T cells.

PubMed

Ucar, Duygu; Márquez, Eladio J; Chung, Cheng-Han; Marches, Radu; Rossi, Robert J; Uyar, Asli; Wu, Te-Chia; George, Joshy; Stitzel, Michael L; Palucka, A Karolina; Kuchel, George A; Banchereau, Jacques

2017-10-02

Aging is linked to deficiencies in immune responses and increased systemic inflammation. To unravel the regulatory programs behind these changes, we applied systems immunology approaches and profiled chromatin accessibility and the transcriptome in PBMCs and purified monocytes, B cells, and T cells. Analysis of samples from 77 young and elderly donors revealed a novel and robust aging signature in PBMCs, with simultaneous systematic chromatin closing at promoters and enhancers associated with T cell signaling and a potentially stochastic chromatin opening mostly found at quiescent and repressed sites. Combined analyses of chromatin accessibility and the transcriptome uncovered immune molecules activated/inactivated with aging and identified the silencing of the IL7R gene and the IL-7 signaling pathway genes as potential biomarkers. This signature is borne by memory CD8 + T cells, which exhibited an aging-related loss in binding of NF-κB and STAT factors. Thus, our study provides a unique and comprehensive approach to identifying candidate biomarkers and provides mechanistic insights into aging-associated immunodeficiency. © 2017 Ucar et al.

The chromatin accessibility signature of human immune aging stems from CD8+ T cells

PubMed Central

Marches, Radu; Rossi, Robert J.; Uyar, Asli; Wu, Te-Chia; Stitzel, Michael L.; Palucka, A. Karolina

2017-01-01

Aging is linked to deficiencies in immune responses and increased systemic inflammation. To unravel the regulatory programs behind these changes, we applied systems immunology approaches and profiled chromatin accessibility and the transcriptome in PBMCs and purified monocytes, B cells, and T cells. Analysis of samples from 77 young and elderly donors revealed a novel and robust aging signature in PBMCs, with simultaneous systematic chromatin closing at promoters and enhancers associated with T cell signaling and a potentially stochastic chromatin opening mostly found at quiescent and repressed sites. Combined analyses of chromatin accessibility and the transcriptome uncovered immune molecules activated/inactivated with aging and identified the silencing of the IL7R gene and the IL-7 signaling pathway genes as potential biomarkers. This signature is borne by memory CD8+ T cells, which exhibited an aging-related loss in binding of NF-κB and STAT factors. Thus, our study provides a unique and comprehensive approach to identifying candidate biomarkers and provides mechanistic insights into aging-associated immunodeficiency. PMID:28904110

Persistence of social signatures in human communication.

PubMed

Saramäki, Jari; Leicht, E A; López, Eduardo; Roberts, Sam G B; Reed-Tsochas, Felix; Dunbar, Robin I M

2014-01-21

The social network maintained by a focal individual, or ego, is intrinsically dynamic and typically exhibits some turnover in membership over time as personal circumstances change. However, the consequences of such changes on the distribution of an ego's network ties are not well understood. Here we use a unique 18-mo dataset that combines mobile phone calls and survey data to track changes in the ego networks and communication patterns of students making the transition from school to university or work. Our analysis reveals that individuals display a distinctive and robust social signature, captured by how interactions are distributed across different alters. Notably, for a given ego, these social signatures tend to persist over time, despite considerable turnover in the identity of alters in the ego network. Thus, as new network members are added, some old network members either are replaced or receive fewer calls, preserving the overall distribution of calls across network members. This is likely to reflect the consequences of finite resources such as the time available for communication, the cognitive and emotional effort required to sustain close relationships, and the ability to make emotional investments.

Persistence of social signatures in human communication

PubMed Central

Saramäki, Jari; Leicht, E. A.; López, Eduardo; Roberts, Sam G. B.; Reed-Tsochas, Felix; Dunbar, Robin I. M.

2014-01-01

The social network maintained by a focal individual, or ego, is intrinsically dynamic and typically exhibits some turnover in membership over time as personal circumstances change. However, the consequences of such changes on the distribution of an ego’s network ties are not well understood. Here we use a unique 18-mo dataset that combines mobile phone calls and survey data to track changes in the ego networks and communication patterns of students making the transition from school to university or work. Our analysis reveals that individuals display a distinctive and robust social signature, captured by how interactions are distributed across different alters. Notably, for a given ego, these social signatures tend to persist over time, despite considerable turnover in the identity of alters in the ego network. Thus, as new network members are added, some old network members either are replaced or receive fewer calls, preserving the overall distribution of calls across network members. This is likely to reflect the consequences of finite resources such as the time available for communication, the cognitive and emotional effort required to sustain close relationships, and the ability to make emotional investments. PMID:24395777

Signatures from Tissue-specific MPSS Libraries Identify Transcripts Preferentially Expressed in the Mouse Inner Ear

PubMed Central

Peters, Linda M.; Belyantseva, Inna A.; Lagziel, Ayala; Battey, James F.; Friedman, Thomas B.; Morell, Robert J.

2007-01-01

Specialization in cell function and morphology is influenced by the differential expression of mRNAs, many of which are expressed at low abundance and restricted to certain cell types. Detecting such transcripts in cDNA libraries may require sequencing millions of clones. Massively parallel signature sequencing (MPSS) is well-suited for identifying transcripts that are expressed in discrete cell types and in low abundance. We have made MPSS libraries from microdissections of three inner ear tissues. By comparing these MPSS libraries to those of 87 other tissues included in the Mouse Reference Transcriptome (MRT) online resource, we have identified genes that are highly enriched in, or specific to, the inner ear. We show by RT-PCR and in situ hybridization that signatures unique to the inner ear libraries identify transcripts with highly specific cell-type localizations. These transcripts serve to illustrate the utility of a resource that is available to the research community. Utilization of these resources will increase the number of known transcription units and expand our knowledge of the tissue-specific regulation of the transcriptome. PMID:17049805

Remote sensing change detection methods to track deforestation and growth in threatened rainforests in Madre de Dios, Peru

USGS Publications Warehouse

Shermeyer, Jacob S.; Haack, Barry N.

2015-01-01

Two forestry-change detection methods are described, compared, and contrasted for estimating deforestation and growth in threatened forests in southern Peru from 2000 to 2010. The methods used in this study rely on freely available data, including atmospherically corrected Landsat 5 Thematic Mapper and Moderate Resolution Imaging Spectroradiometer (MODIS) vegetation continuous fields (VCF). The two methods include a conventional supervised signature extraction method and a unique self-calibrating method called MODIS VCF guided forest/nonforest (FNF) masking. The process chain for each of these methods includes a threshold classification of MODIS VCF, training data or signature extraction, signature evaluation, k-nearest neighbor classification, analyst-guided reclassification, and postclassification image differencing to generate forest change maps. Comparisons of all methods were based on an accuracy assessment using 500 validation pixels. Results of this accuracy assessment indicate that FNF masking had a 5% higher overall accuracy and was superior to conventional supervised classification when estimating forest change. Both methods succeeded in classifying persistently forested and nonforested areas, and both had limitations when classifying forest change.

Protein Interactome of Muscle Invasive Bladder Cancer

PubMed Central

Bhat, Akshay; Heinzel, Andreas; Mayer, Bernd; Perco, Paul; Mühlberger, Irmgard; Husi, Holger; Merseburger, Axel S.; Zoidakis, Jerome; Vlahou, Antonia; Schanstra, Joost P.; Mischak, Harald; Jankowski, Vera

2015-01-01

Muscle invasive bladder carcinoma is a complex, multifactorial disease caused by disruptions and alterations of several molecular pathways that result in heterogeneous phenotypes and variable disease outcome. Combining this disparate knowledge may offer insights for deciphering relevant molecular processes regarding targeted therapeutic approaches guided by molecular signatures allowing improved phenotype profiling. The aim of the study is to characterize muscle invasive bladder carcinoma on a molecular level by incorporating scientific literature screening and signatures from omics profiling. Public domain omics signatures together with molecular features associated with muscle invasive bladder cancer were derived from literature mining to provide 286 unique protein-coding genes. These were integrated in a protein-interaction network to obtain a molecular functional map of the phenotype. This feature map educated on three novel disease-associated pathways with plausible involvement in bladder cancer, namely Regulation of actin cytoskeleton, Neurotrophin signalling pathway and Endocytosis. Systematic integration approaches allow to study the molecular context of individual features reported as associated with a clinical phenotype and could potentially help to improve the molecular mechanistic description of the disorder. PMID:25569276

Enhancing nuclear quadrupole resonance (NQR) signature detection leveraging interference suppression algorithms

NASA Astrophysics Data System (ADS)

DeBardelaben, James A.; Miller, Jeremy K.; Myrick, Wilbur L.; Miller, Joel B.; Gilbreath, G. Charmaine; Bajramaj, Blerta

2012-06-01

Nuclear quadrupole resonance (NQR) is a radio frequency (RF) magnetic spectroscopic technique that has been shown to detect and identify a wide range of explosive materials containing quadrupolar nuclei. The NQR response signal provides a unique signature of the material of interest. The signal is, however, very weak and can be masked by non-stationary RF interference (RFI) and thermal noise, limiting detection distance. In this paper, we investigate the bounds on the NQR detection range for ammonium nitrate. We leverage a low-cost RFI data acquisition system composed of inexpensive B-field sensing and commercial-off-the-shelf (COTS) software-defined radios (SDR). Using collected data as RFI reference signals, we apply adaptive filtering algorithms to mitigate RFI and enable NQR detection techniques to approach theoretical range bounds in tactical environments.

The signature of a black hole transit

NASA Technical Reports Server (NTRS)

Dolan, Joseph F.

1989-01-01

This paper considers the possibility of identifying a black hole on the basis of the detection of some unique effect occurring during the transit of a black hole across the stellar disk of a companion star in a binary system. The results of Monte-Carlo calculations show that the amplitude of the photometric and polarimetric light curves in a typical X-ray binary is too small to be observed with present instrumentation, but that a black hole transit might be detectable in a binary having a large separation of the components. No binary system suggested as containing a stellar-mass-sized black hole is a like candidate to exhibit an observable transit signature, with the possible exception of X Persei/4U0352+30 described by White et al. (1976).

Deciphering cGMP signatures and cGMP-dependent pathways in plant defence

PubMed Central

Meier, Stuart; Madeo, Laura; Ederli, Luisa; Donaldson, Lara; Gehring, Chris

2009-01-01

The second messenger, 3′,5′-cyclic monophosphate (cGMP), is a critical component of many different processes in plants while guanylyl cyclases that catalyse the formation of cGMP from GTP have remained somewhat elusive in higher plants. Consequently, two major aims are the discovery of novel GCs and the identification of cGMP mediated processes. Recently, we have reported temporal signatures of ozone (O3)-induced hydrogen peroxide (H2O2) and nitric oxide (NO) generation, their effect on cGMP generation, and consequent transcriptional changes of genes diagnostic for stress responses in tobacco. We demonstrated that O3 and NO induced early transcriptional activation of the scavenger encoding proteins, alternative oxidase (AOX1a), glutathione peroxidase (GPX) and the induction of ethylene production through aminocyclopropancarboxylic acid synthase (ACS2) are cGMP-independent. By contrast, the early response of the phenylalanine ammonia lyase gene (PALa) and the late response of the gene encoding the pathogenesis-related protein (PR1a) show critical dependence on cGMP. Here we show differential cGMP responses to virulent and avirulent Pseudomonas syringae strains and propose that host-pathogen recognition and/or down-stream processes are transduced by complex cGMP signatures. This is in accordance with the identification of a growing number of multi-domain molecules in Arabidopsis that are reported to contain putative functional GC catalytic centers. PMID:19794847

PAGER 2.0: an update to the pathway, annotated-list and gene-signature electronic repository for Human Network Biology

PubMed Central

Yue, Zongliang; Zheng, Qi; Neylon, Michael T; Yoo, Minjae; Shin, Jimin; Zhao, Zhiying; Tan, Aik Choon

2018-01-01

Abstract Integrative Gene-set, Network and Pathway Analysis (GNPA) is a powerful data analysis approach developed to help interpret high-throughput omics data. In PAGER 1.0, we demonstrated that researchers can gain unbiased and reproducible biological insights with the introduction of PAGs (Pathways, Annotated-lists and Gene-signatures) as the basic data representation elements. In PAGER 2.0, we improve the utility of integrative GNPA by significantly expanding the coverage of PAGs and PAG-to-PAG relationships in the database, defining a new metric to quantify PAG data qualities, and developing new software features to simplify online integrative GNPA. Specifically, we included 84 282 PAGs spanning 24 different data sources that cover human diseases, published gene-expression signatures, drug–gene, miRNA–gene interactions, pathways and tissue-specific gene expressions. We introduced a new normalized Cohesion Coefficient (nCoCo) score to assess the biological relevance of genes inside a PAG, and RP-score to rank genes and assign gene-specific weights inside a PAG. The companion web interface contains numerous features to help users query and navigate the database content. The database content can be freely downloaded and is compatible with third-party Gene Set Enrichment Analysis tools. We expect PAGER 2.0 to become a major resource in integrative GNPA. PAGER 2.0 is available at http://discovery.informatics.uab.edu/PAGER/. PMID:29126216

Orbital Evolution and Physical Characteristics of Object "Peggy" at the Edge of Saturn's A Ring

NASA Astrophysics Data System (ADS)

Murray, C.; Cooper, N. J.; Noyelles, B.; Renner, S.; Araujo, N.

2016-12-01

Images taken with the Cassini ISS instrument on 2013 April 15 showed the presence of a bright, extended object at the edge of Saturn's A ring. The gravitational signature of the object often appears as a discontinuity in the azimuthal profile of the ring edge and a subsequent analysis revealed that the object (nicknamed "Peggy") was detectable in ISS images as far back as 2012. The morphology of the signature is a function of the orbital phase suggesting that the object has a relative eccentricity or periapse with respect to the surrounding ring material. Tracking the signature allows a determination of the object's semi-major axis and following the initial detection this has varied by as much as 5 km. At no stage has the object been as bright as it was at the time of its discovery, suggesting that a collisional event had recently occurred. Here we report on the latest Cassini ISS observations of "Peggy" and their interpretation. These will include the calculated changes in its semi-major axis since 2013, constraints on its mass based on numerical integrations of its perturbing effect on adjacent ring particles, and what has been learned from a recent 8 h sequence of high resolution ISS images specially designed to track "Peggy" for more than half an orbital period.

Evaluation of plasma proteomic data for Alzheimer disease state classification and for the prediction of progression from mild cognitive impairment to Alzheimer disease.

PubMed

Llano, Daniel A; Devanarayan, Viswanath; Simon, Adam J

2013-01-01

Previous studies that have examined the potential for plasma markers to serve as biomarkers for Alzheimer disease (AD) have studied single analytes and focused on the amyloid-β and τ isoforms and have failed to yield conclusive results. In this study, we performed a multivariate analysis of 146 plasma analytes (the Human DiscoveryMAP v 1.0 from Rules-Based Medicine) in 527 subjects with AD, mild cognitive impairment (MCI), or cognitively normal elderly subjects from the Alzheimer's Disease Neuroimaging Initiative database. We identified 4 different proteomic signatures, each using 5 to 14 analytes, that differentiate AD from control patients with sensitivity and specificity ranging from 74% to 85%. Five analytes were common to all 4 signatures: apolipoprotein A-II, apolipoprotein E, serum glutamic oxaloacetic transaminase, α-1-microglobulin, and brain natriuretic peptide. None of the signatures adequately predicted progression from MCI to AD over a 12- and 24-month period. A new panel of analytes, optimized to predict MCI to AD conversion, was able to provide 55% to 60% predictive accuracy. These data suggest that a simple panel of plasma analytes may provide an adjunctive tool to differentiate AD from controls, may provide mechanistic insights to the etiology of AD, but cannot adequately predict MCI to AD conversion.

Photoreceptor disc shedding in the living human eye

PubMed Central

Kocaoglu, Omer P.; Liu, Zhuolin; Zhang, Furu; Kurokawa, Kazuhiro; Jonnal, Ravi S.; Miller, Donald T.

2016-01-01

Cone photoreceptors undergo a daily cycle of renewal and shedding of membranous discs in their outer segments (OS), the portion responsible for light capture. These physiological processes are fundamental to maintaining photoreceptor health, and their dysfunction is associated with numerous retinal diseases. While both processes have been extensively studied in animal models and postmortem eyes, little is known about them in the living eye, in particular human. In this study, we report discovery of the optical signature associated with disc shedding using a method based on adaptive optics optical coherence tomography (AO-OCT) in conjunction with post-processing methods to track and monitor individual cone cells in 4D. The optical signature of disc shedding is characterized by an abrupt transient loss in the cone outer segment tip (COST) reflection followed by its return that is axially displaced anteriorly. Using this signature, we measured the temporal and spatial properties of shedding events in three normal subjects. Average duration of the shedding event was 8.8 ± 13.4 minutes, and average length loss of the OS was 2.1 μm (7.0% of OS length). Prevalence of cone shedding was highest in the morning (14.3%) followed by the afternoon (5.7%) and evening (4.0%), with load distributed across the imaged patch. To the best of our knowledge these are the first images of photoreceptor disc shedding in the living retina. PMID:27895995

Australia’s Submarine Design Capabilities and Capacities: Challenges and Options for the Future Submarine

DTIC Science & Technology

2011-01-01

stealth features requiring specialised noise and vibra- tion skills and propulsion plants requiring other unique skill sets. Personnel with these...analysis Acoustic, wake , thermal, electromagnetic, and other signature analysis Combat systems and ship control Combat system integration, combat system...to-diagnose flow-induced radiated noise Own-sensor performance degradation Note: Risks can be reduced for given designs using scale models

Applications That Participate in Their Own Defense (APOD)

DTIC Science & Technology

2003-05-01

bandwidth requirements from multiple applications and uses ssh to directly login the RSVP routers to reconfigure the priority queues. This approach...detect flooding. 3 Emerald makes use of some signature matching techniques on BSM logs, but the unique strength of Emerald technology is in event...mechanisms that provide awareness, and IDSs form an important class of these4. We investigated several COTS and research IDSs including Emerald

Extending human perception of electromagnetic radiation to the UV region through biologically inspired photochromic fuzzy logic (BIPFUL) systems.

PubMed

Gentili, Pier Luigi; Rightler, Amanda L; Heron, B Mark; Gabbutt, Christopher D

2016-01-25

Photochromic fuzzy logic systems have been designed that extend human visual perception into the UV region. The systems are founded on a detailed knowledge of the activation wavelengths and quantum yields of a series of thermally reversible photochromic compounds. By appropriate matching of the photochromic behaviour unique colour signatures are generated in response differing UV activation frequencies.

Drug Discovery in Fish, Flies, and Worms

PubMed Central

Strange, Kevin

2016-01-01

Abstract Nonmammalian model organisms such as the nematode Caenorhabditis elegans, the fruit fly Drosophila melanogaster, and the zebrafish Danio rerio provide numerous experimental advantages for drug discovery including genetic and molecular tractability, amenability to high-throughput screening methods and reduced experimental costs and increased experimental throughput compared to traditional mammalian models. An interdisciplinary approach that strategically combines the study of nonmammalian and mammalian animal models with diverse experimental tools has and will continue to provide deep molecular and genetic understanding of human disease and will significantly enhance the discovery and application of new therapies to treat those diseases. This review will provide an overview of C. elegans, Drosophila, and zebrafish biology and husbandry and will discuss how these models are being used for phenotype-based drug screening and for identification of drug targets and mechanisms of action. The review will also describe how these and other nonmammalian model organisms are uniquely suited for the discovery of drug-based regenerative medicine therapies. PMID:28053067

Integration of lyoplate based flow cytometry and computational analysis for standardized immunological biomarker discovery.

PubMed

Villanova, Federica; Di Meglio, Paola; Inokuma, Margaret; Aghaeepour, Nima; Perucha, Esperanza; Mollon, Jennifer; Nomura, Laurel; Hernandez-Fuentes, Maria; Cope, Andrew; Prevost, A Toby; Heck, Susanne; Maino, Vernon; Lord, Graham; Brinkman, Ryan R; Nestle, Frank O

2013-01-01

Discovery of novel immune biomarkers for monitoring of disease prognosis and response to therapy in immune-mediated inflammatory diseases is an important unmet clinical need. Here, we establish a novel framework for immunological biomarker discovery, comparing a conventional (liquid) flow cytometry platform (CFP) and a unique lyoplate-based flow cytometry platform (LFP) in combination with advanced computational data analysis. We demonstrate that LFP had higher sensitivity compared to CFP, with increased detection of cytokines (IFN-γ and IL-10) and activation markers (Foxp3 and CD25). Fluorescent intensity of cells stained with lyophilized antibodies was increased compared to cells stained with liquid antibodies. LFP, using a plate loader, allowed medium-throughput processing of samples with comparable intra- and inter-assay variability between platforms. Automated computational analysis identified novel immunophenotypes that were not detected with manual analysis. Our results establish a new flow cytometry platform for standardized and rapid immunological biomarker discovery with wide application to immune-mediated diseases.

Integration of Lyoplate Based Flow Cytometry and Computational Analysis for Standardized Immunological Biomarker Discovery

PubMed Central

Villanova, Federica; Di Meglio, Paola; Inokuma, Margaret; Aghaeepour, Nima; Perucha, Esperanza; Mollon, Jennifer; Nomura, Laurel; Hernandez-Fuentes, Maria; Cope, Andrew; Prevost, A. Toby; Heck, Susanne; Maino, Vernon; Lord, Graham; Brinkman, Ryan R.; Nestle, Frank O.

2013-01-01

Discovery of novel immune biomarkers for monitoring of disease prognosis and response to therapy in immune-mediated inflammatory diseases is an important unmet clinical need. Here, we establish a novel framework for immunological biomarker discovery, comparing a conventional (liquid) flow cytometry platform (CFP) and a unique lyoplate-based flow cytometry platform (LFP) in combination with advanced computational data analysis. We demonstrate that LFP had higher sensitivity compared to CFP, with increased detection of cytokines (IFN-γ and IL-10) and activation markers (Foxp3 and CD25). Fluorescent intensity of cells stained with lyophilized antibodies was increased compared to cells stained with liquid antibodies. LFP, using a plate loader, allowed medium-throughput processing of samples with comparable intra- and inter-assay variability between platforms. Automated computational analysis identified novel immunophenotypes that were not detected with manual analysis. Our results establish a new flow cytometry platform for standardized and rapid immunological biomarker discovery with wide application to immune-mediated diseases. PMID:23843942

The history of aerobic ammonia oxidizers: from the first discoveries to today.

PubMed

Monteiro, Maria; Séneca, Joana; Magalhães, Catarina

2014-07-01

Nitrification, the oxidation of ammonia to nitrite and nitrate, has long been considered a central biological process in the global nitrogen cycle, with its first description dated 133 years ago. Until 2005, bacteria were considered the only organisms capable of nitrification. However, the recent discovery of a chemoautotrophic ammonia-oxidizing archaeon, Nitrosopumilus maritimus, changed our concept of the range of organisms involved in nitrification, highlighting the importance of ammonia-oxidizing archaea (AOA) as potential players in global biogeochemical nitrogen transformations. The uniqueness of these archaea justified the creation of a novel archaeal phylum, Thaumarchaeota. These recent discoveries increased the global scientific interest within the microbial ecology society and have triggered an analysis of the importance of bacterial vs archaeal ammonia oxidation in a wide range of natural ecosystems. In this mini review we provide a chronological perspective of the current knowledge on the ammonia oxidation pathway of nitrification, based on the main physiological, ecological and genomic discoveries.

Cis-regulatory signatures of orthologous stress-associated bZIP transcription factors from rice, sorghum and Arabidopsis based on phylogenetic footprints

PubMed Central

2012-01-01

Background The potential contribution of upstream sequence variation to the unique features of orthologous genes is just beginning to be unraveled. A core subset of stress-associated bZIP transcription factors from rice (Oryza sativa) formed ten clusters of orthologous groups (COG) with genes from the monocot sorghum (Sorghum bicolor) and dicot Arabidopsis (Arabidopsis thaliana). The total cis-regulatory information content of each stress-associated COG was examined by phylogenetic footprinting to reveal ortholog-specific, lineage-specific and species-specific conservation patterns. Results The most apparent pattern observed was the occurrence of spatially conserved ‘core modules’ among the COGs but not among paralogs. These core modules are comprised of various combinations of two to four putative transcription factor binding site (TFBS) classes associated with either developmental or stress-related functions. Outside the core modules are specific stress (ABA, oxidative, abiotic, biotic) or organ-associated signals, which may be functioning as ‘regulatory fine-tuners’ and further define lineage-specific and species-specific cis-regulatory signatures. Orthologous monocot and dicot promoters have distinct TFBS classes involved in disease and oxidative-regulated expression, while the orthologous rice and sorghum promoters have distinct combinations of root-specific signals, a pattern that is not particularly conserved in Arabidopsis. Conclusions Patterns of cis-regulatory conservation imply that each ortholog has distinct signatures, further suggesting that they are potentially unique in a regulatory context despite the presumed conservation of broad biological function during speciation. Based on the observed patterns of conservation, we postulate that core modules are likely primary determinants of basal developmental programming, which may be integrated with and further elaborated by additional intrinsic or extrinsic signals in conjunction with lineage-specific or species-specific regulatory fine-tuners. This synergy may be critical for finer-scale spatio-temporal regulation, hence unique expression profiles of homologous transcription factors from different species with distinct zones of ecological adaptation such as rice, sorghum and Arabidopsis. The patterns revealed from these comparisons set the stage for further empirical validation by functional genomics. PMID:22992304

Synthesis-Spectroscopy Roadmap Problems: Discovering Organic Chemistry

ERIC Educational Resources Information Center

Kurth, Laurie L.; Kurth, Mark J.

2014-01-01

Organic chemistry problems that interrelate and integrate synthesis with spectroscopy are presented. These synthesis-spectroscopy roadmap (SSR) problems uniquely engage second-year undergraduate organic chemistry students in the personal discovery of organic chemistry. SSR problems counter the memorize-or-bust strategy that many students tend to…

Comparative expression profiling in grape (Vitis vinifera) berries derived from frequency analysis of ESTs and MPSS signatures.

PubMed

Iandolino, Alberto; Nobuta, Kan; da Silva, Francisco Goes; Cook, Douglas R; Meyers, Blake C

2008-05-12

Vitis vinifera (V. vinifera) is the primary grape species cultivated for wine production, with an industry valued annually in the billions of dollars worldwide. In order to sustain and increase grape production, it is necessary to understand the genetic makeup of grape species. Here we performed mRNA profiling using Massively Parallel Signature Sequencing (MPSS) and combined it with available Expressed Sequence Tag (EST) data. These tag-based technologies, which do not require a priori knowledge of genomic sequence, are well-suited for transcriptional profiling. The sequence depth of MPSS allowed us to capture and quantify almost all the transcripts at a specific stage in the development of the grape berry. The number and relative abundance of transcripts from stage II grape berries was defined using Massively Parallel Signature Sequencing (MPSS). A total of 2,635,293 17-base and 2,259,286 20-base signatures were obtained, representing at least 30,737 and 26,878 distinct sequences. The average normalized abundance per signature was approximately 49 TPM (Transcripts Per Million). Comparisons of the MPSS signatures with available Vitis species' ESTs and a unigene set demonstrated that 6,430 distinct contigs and 2,190 singletons have a perfect match to at least one MPSS signature. Among the matched sequences, ESTs were identified from tissues other than berries or from berries at different developmental stages. Additional MPSS signatures not matching to known grape ESTs can extend our knowledge of the V. vinifera transcriptome, particularly when these data are used to assist in annotation of whole genome sequences from Vitis vinifera. The MPSS data presented here not only achieved a higher level of saturation than previous EST based analyses, but in doing so, expand the known set of transcripts of grape berries during the unique stage in development that immediately precedes the onset of ripening. The MPSS dataset also revealed evidence of antisense expression not previously reported in grapes but comparable to that reported in other plant species. Finally, we developed a novel web-based, public resource for utilization of the grape MPSS data [1].

Genome signature analysis of thermal virus metagenomes reveals Archaea and thermophilic signatures

PubMed Central

Pride, David T; Schoenfeld, Thomas

2008-01-01

Background Metagenomic analysis provides a rich source of biological information for otherwise intractable viral communities. However, study of viral metagenomes has been hampered by its nearly complete reliance on BLAST algorithms for identification of DNA sequences. We sought to develop algorithms for examination of viral metagenomes to identify the origin of sequences independent of BLAST algorithms. We chose viral metagenomes obtained from two hot springs, Bear Paw and Octopus, in Yellowstone National Park, as they represent simple microbial populations where comparatively large contigs were obtained. Thermal spring metagenomes have high proportions of sequences without significant Genbank homology, which has hampered identification of viruses and their linkage with hosts. To analyze each metagenome, we developed a method to classify DNA fragments using genome signature-based phylogenetic classification (GSPC), where metagenomic fragments are compared to a database of oligonucleotide signatures for all previously sequenced Bacteria, Archaea, and viruses. Results From both Bear Paw and Octopus hot springs, each assembled contig had more similarity to other metagenome contigs than to any sequenced microbial genome based on GSPC analysis, suggesting a genome signature common to each of these extreme environments. While viral metagenomes from Bear Paw and Octopus share some similarity, the genome signatures from each locale are largely unique. GSPC using a microbial database predicts most of the Octopus metagenome has archaeal signatures, while bacterial signatures predominate in Bear Paw; a finding consistent with those of Genbank BLAST. When using a viral database, the majority of the Octopus metagenome is predicted to belong to archaeal virus Families Globuloviridae and Fuselloviridae, while none of the Bear Paw metagenome is predicted to belong to archaeal viruses. As expected, when microbial and viral databases are combined, each of the Octopus and Bear Paw metagenomic contigs are predicted to belong to viruses rather than to any Bacteria or Archaea, consistent with the apparent viral origin of both metagenomes. Conclusion That BLAST searches identify no significant homologs for most metagenome contigs, while GSPC suggests their origin as archaeal viruses or bacteriophages, indicates GSPC provides a complementary approach in viral metagenomic analysis. PMID:18798991

Genome signature analysis of thermal virus metagenomes reveals Archaea and thermophilic signatures.

PubMed

Pride, David T; Schoenfeld, Thomas

2008-09-17

Metagenomic analysis provides a rich source of biological information for otherwise intractable viral communities. However, study of viral metagenomes has been hampered by its nearly complete reliance on BLAST algorithms for identification of DNA sequences. We sought to develop algorithms for examination of viral metagenomes to identify the origin of sequences independent of BLAST algorithms. We chose viral metagenomes obtained from two hot springs, Bear Paw and Octopus, in Yellowstone National Park, as they represent simple microbial populations where comparatively large contigs were obtained. Thermal spring metagenomes have high proportions of sequences without significant Genbank homology, which has hampered identification of viruses and their linkage with hosts. To analyze each metagenome, we developed a method to classify DNA fragments using genome signature-based phylogenetic classification (GSPC), where metagenomic fragments are compared to a database of oligonucleotide signatures for all previously sequenced Bacteria, Archaea, and viruses. From both Bear Paw and Octopus hot springs, each assembled contig had more similarity to other metagenome contigs than to any sequenced microbial genome based on GSPC analysis, suggesting a genome signature common to each of these extreme environments. While viral metagenomes from Bear Paw and Octopus share some similarity, the genome signatures from each locale are largely unique. GSPC using a microbial database predicts most of the Octopus metagenome has archaeal signatures, while bacterial signatures predominate in Bear Paw; a finding consistent with those of Genbank BLAST. When using a viral database, the majority of the Octopus metagenome is predicted to belong to archaeal virus Families Globuloviridae and Fuselloviridae, while none of the Bear Paw metagenome is predicted to belong to archaeal viruses. As expected, when microbial and viral databases are combined, each of the Octopus and Bear Paw metagenomic contigs are predicted to belong to viruses rather than to any Bacteria or Archaea, consistent with the apparent viral origin of both metagenomes. That BLAST searches identify no significant homologs for most metagenome contigs, while GSPC suggests their origin as archaeal viruses or bacteriophages, indicates GSPC provides a complementary approach in viral metagenomic analysis.

Using Quantum Confinement to Uniquely Identify Devices

PubMed Central

Roberts, J.; Bagci, I. E.; Zawawi, M. A. M.; Sexton, J.; Hulbert, N.; Noori, Y. J.; Young, M. P.; Woodhead, C. S.; Missous, M.; Migliorato, M. A.; Roedig, U.; Young, R. J.

2015-01-01

Modern technology unintentionally provides resources that enable the trust of everyday interactions to be undermined. Some authentication schemes address this issue using devices that give a unique output in response to a challenge. These signatures are generated by hard-to-predict physical responses derived from structural characteristics, which lend themselves to two different architectures, known as unique objects (UNOs) and physically unclonable functions (PUFs). The classical design of UNOs and PUFs limits their size and, in some cases, their security. Here we show that quantum confinement lends itself to the provision of unique identities at the nanoscale, by using fluctuations in tunnelling measurements through quantum wells in resonant tunnelling diodes (RTDs). This provides an uncomplicated measurement of identity without conventional resource limitations whilst providing robust security. The confined energy levels are highly sensitive to the specific nanostructure within each RTD, resulting in a distinct tunnelling spectrum for every device, as they contain a unique and unpredictable structure that is presently impossible to clone. This new class of authentication device operates with minimal resources in simple electronic structures above room temperature. PMID:26553435

Revolutionary Science

PubMed Central

Fang, Ferric C.

2016-01-01

ABSTRACT On rare occasions in the history of science, remarkable discoveries transform human society and forever alter mankind’s view of the world. Examples of such discoveries include the heliocentric theory, Newtonian physics, the germ theory of disease, quantum theory, plate tectonics and the discovery that DNA carries genetic information. The science philosopher Thomas Kuhn famously described science as long periods of normality punctuated by times of crisis, when anomalous observations culminate in revolutionary changes that replace one paradigm with another. This essay examines several transformative discoveries in the light of Kuhn’s formulation. We find that each scientific revolution is unique, with disparate origins that may include puzzle solving, serendipity, inspiration, or a convergence of disparate observations. The causes of revolutionary science are varied and lack an obvious common structure. Moreover, it can be difficult to draw a clear distinction between so-called normal and revolutionary science. Revolutionary discoveries often emerge from basic science and are critically dependent on nonrevolutionary research. Revolutionary discoveries may be conceptual or technological in nature, lead to the creation of new fields, and have a lasting impact on many fields in addition to the field from which they emerge. In contrast to political revolutions, scientific revolutions do not necessarily require the destruction of the previous order. For humanity to continue to benefit from revolutionary discoveries, a broad palette of scientific inquiry with a particular emphasis on basic science should be supported. PMID:26933052

Common characteristics of open source software development and applicability for drug discovery: a systematic review.

PubMed

Ardal, Christine; Alstadsæter, Annette; Røttingen, John-Arne

2011-09-28

Innovation through an open source model has proven to be successful for software development. This success has led many to speculate if open source can be applied to other industries with similar success. We attempt to provide an understanding of open source software development characteristics for researchers, business leaders and government officials who may be interested in utilizing open source innovation in other contexts and with an emphasis on drug discovery. A systematic review was performed by searching relevant, multidisciplinary databases to extract empirical research regarding the common characteristics and barriers of initiating and maintaining an open source software development project. Common characteristics to open source software development pertinent to open source drug discovery were extracted. The characteristics were then grouped into the areas of participant attraction, management of volunteers, control mechanisms, legal framework and physical constraints. Lastly, their applicability to drug discovery was examined. We believe that the open source model is viable for drug discovery, although it is unlikely that it will exactly follow the form used in software development. Hybrids will likely develop that suit the unique characteristics of drug discovery. We suggest potential motivations for organizations to join an open source drug discovery project. We also examine specific differences between software and medicines, specifically how the need for laboratories and physical goods will impact the model as well as the effect of patents.

NCI Program for Natural Product Discovery: A Publicly-Accessible Library of Natural Product Fractions for High-Throughput Screening.

PubMed

Thornburg, Christopher C; Britt, John R; Evans, Jason R; Akee, Rhone K; Whitt, James A; Trinh, Spencer K; Harris, Matthew J; Thompson, Jerell R; Ewing, Teresa L; Shipley, Suzanne M; Grothaus, Paul G; Newman, David J; Schneider, Joel P; Grkovic, Tanja; O'Keefe, Barry R

2018-06-13

The US National Cancer Institute's (NCI) Natural Product Repository is one of the world's largest, most diverse collections of natural products containing over 230,000 unique extracts derived from plant, marine, and microbial organisms that have been collected from biodiverse regions throughout the world. Importantly, this national resource is available to the research community for the screening of extracts and the isolation of bioactive natural products. However, despite the success of natural products in drug discovery, compatibility issues that make extracts challenging for liquid handling systems, extended timelines that complicate natural product-based drug discovery efforts and the presence of pan-assay interfering compounds have reduced enthusiasm for the high-throughput screening (HTS) of crude natural product extract libraries in targeted assay systems. To address these limitations, the NCI Program for Natural Product Discovery (NPNPD), a newly launched, national program to advance natural product discovery technologies and facilitate the discovery of structurally defined, validated lead molecules ready for translation will create a prefractionated library from over 125,000 natural product extracts with the aim of producing a publicly-accessible, HTS-amenable library of >1,000,000 fractions. This library, representing perhaps the largest accumulation of natural-product based fractions in the world, will be made available free of charge in 384-well plates for screening against all disease states in an effort to reinvigorate natural product-based drug discovery.

Revolutionary Science.

PubMed

Casadevall, Arturo; Fang, Ferric C

2016-03-01

On rare occasions in the history of science, remarkable discoveries transform human society and forever alter mankind's view of the world. Examples of such discoveries include the heliocentric theory, Newtonian physics, the germ theory of disease, quantum theory, plate tectonics and the discovery that DNA carries genetic information. The science philosopher Thomas Kuhn famously described science as long periods of normality punctuated by times of crisis, when anomalous observations culminate in revolutionary changes that replace one paradigm with another. This essay examines several transformative discoveries in the light of Kuhn's formulation. We find that each scientific revolution is unique, with disparate origins that may include puzzle solving, serendipity, inspiration, or a convergence of disparate observations. The causes of revolutionary science are varied and lack an obvious common structure. Moreover, it can be difficult to draw a clear distinction between so-called normal and revolutionary science. Revolutionary discoveries often emerge from basic science and are critically dependent on nonrevolutionary research. Revolutionary discoveries may be conceptual or technological in nature, lead to the creation of new fields, and have a lasting impact on many fields in addition to the field from which they emerge. In contrast to political revolutions, scientific revolutions do not necessarily require the destruction of the previous order. For humanity to continue to benefit from revolutionary discoveries, a broad palette of scientific inquiry with a particular emphasis on basic science should be supported. Copyright © 2016 Casadevall and Fang.

Metabolic cancer biology: structural-based analysis of cancer as a metabolic disease, new sights and opportunities for disease treatment.

PubMed

Masoudi-Nejad, Ali; Asgari, Yazdan

2015-02-01

The cancer cell metabolism or the Warburg effect discovery goes back to 1924 when, for the first time Otto Warburg observed, in contrast to the normal cells, cancer cells have different metabolism. With the initiation of high throughput technologies and computational systems biology, cancer cell metabolism renaissances and many attempts were performed to revise the Warburg effect. The development of experimental and analytical tools which generate high-throughput biological data including lots of information could lead to application of computational models in biological discovery and clinical medicine especially for cancer. Due to the recent availability of tissue-specific reconstructed models, new opportunities in studying metabolic alteration in various kinds of cancers open up. Structural approaches at genome-scale levels seem to be suitable for developing diagnostic and prognostic molecular signatures, as well as in identifying new drug targets. In this review, we have considered these recent advances in structural-based analysis of cancer as a metabolic disease view. Two different structural approaches have been described here: topological and constraint-based methods. The ultimate goal of this type of systems analysis is not only the discovery of novel drug targets but also the development of new systems-based therapy strategies. Copyright © 2014 Elsevier Ltd. All rights reserved.

Integrated multi-cohort transcriptional meta-analysis of neurodegenerative diseases.

PubMed

Li, Matthew D; Burns, Terry C; Morgan, Alexander A; Khatri, Purvesh

2014-09-04

Neurodegenerative diseases share common pathologic features including neuroinflammation, mitochondrial dysfunction and protein aggregation, suggesting common underlying mechanisms of neurodegeneration. We undertook a meta-analysis of public gene expression data for neurodegenerative diseases to identify a common transcriptional signature of neurodegeneration. Using 1,270 post-mortem central nervous system tissue samples from 13 patient cohorts covering four neurodegenerative diseases, we identified 243 differentially expressed genes, which were similarly dysregulated in 15 additional patient cohorts of 205 samples including seven neurodegenerative diseases. This gene signature correlated with histologic disease severity. Metallothioneins featured prominently among differentially expressed genes, and functional pathway analysis identified specific convergent themes of dysregulation. MetaCore network analyses revealed various novel candidate hub genes (e.g. STAU2). Genes associated with M1-polarized macrophages and reactive astrocytes were strongly enriched in the meta-analysis data. Evaluation of genes enriched in neurons revealed 70 down-regulated genes, over half not previously associated with neurodegeneration. Comparison with aging brain data (3 patient cohorts, 221 samples) revealed 53 of these to be unique to neurodegenerative disease, many of which are strong candidates to be important in neuropathogenesis (e.g. NDN, NAP1L2). ENCODE ChIP-seq analysis predicted common upstream transcriptional regulators not associated with normal aging (REST, RBBP5, SIN3A, SP2, YY1, ZNF143, IKZF1). Finally, we removed genes common to neurodegeneration from disease-specific gene signatures, revealing uniquely robust immune response and JAK-STAT signaling in amyotrophic lateral sclerosis. Our results implicate pervasive bioenergetic deficits, M1-type microglial activation and gliosis as unifying themes of neurodegeneration, and identify numerous novel genes associated with neurodegenerative processes.

Spectral mapping tools from the earth sciences applied to spectral microscopy data.

PubMed

Harris, A Thomas

2006-08-01

Spectral imaging, originating from the field of earth remote sensing, is a powerful tool that is being increasingly used in a wide variety of applications for material identification. Several workers have used techniques like linear spectral unmixing (LSU) to discriminate materials in images derived from spectral microscopy. However, many spectral analysis algorithms rely on assumptions that are often violated in microscopy applications. This study explores algorithms originally developed as improvements on early earth imaging techniques that can be easily translated for use with spectral microscopy. To best demonstrate the application of earth remote sensing spectral analysis tools to spectral microscopy data, earth imaging software was used to analyze data acquired with a Leica confocal microscope with mechanical spectral scanning. For this study, spectral training signatures (often referred to as endmembers) were selected with the ENVI (ITT Visual Information Solutions, Boulder, CO) "spectral hourglass" processing flow, a series of tools that use the spectrally over-determined nature of hyperspectral data to find the most spectrally pure (or spectrally unique) pixels within the data set. This set of endmember signatures was then used in the full range of mapping algorithms available in ENVI to determine locations, and in some cases subpixel abundances of endmembers. Mapping and abundance images showed a broad agreement between the spectral analysis algorithms, supported through visual assessment of output classification images and through statistical analysis of the distribution of pixels within each endmember class. The powerful spectral analysis algorithms available in COTS software, the result of decades of research in earth imaging, are easily translated to new sources of spectral data. Although the scale between earth imagery and spectral microscopy is radically different, the problem is the same: mapping material locations and abundances based on unique spectral signatures. (c) 2006 International Society for Analytical Cytology.

Hubble Space Telescope - Scientific, Technological and Social Contributions to the Public Discourse on Science

NASA Technical Reports Server (NTRS)

Wiseman, Jennifer

2012-01-01

The Hubble Space Telescope has unified the world with a sense of awe and wonder for 2 I years and is currently more scientifically powerful than ever. I will present highlights of discoveries made with the Hubble Space Telescope, including details of planetary weather, star formation, extra-solar planets, colliding galaxies, and a universe expanding with the acceleration of dark energy. I will also present the unique technical challenges and triumphs of this phenomenal observatory, and discuss how our discoveries in the cosmos affect our sense of human unity, significance, and wonder.

CREDO: a structural interactomics database for drug discovery

PubMed Central

Schreyer, Adrian M.; Blundell, Tom L.

2013-01-01

CREDO is a unique relational database storing all pairwise atomic interactions of inter- as well as intra-molecular contacts between small molecules and macromolecules found in experimentally determined structures from the Protein Data Bank. These interactions are integrated with further chemical and biological data. The database implements useful data structures and algorithms such as cheminformatics routines to create a comprehensive analysis platform for drug discovery. The database can be accessed through a web-based interface, downloads of data sets and web services at http://www-cryst.bioc.cam.ac.uk/credo. Database URL: http://www-cryst.bioc.cam.ac.uk/credo PMID:23868908

Introduction: Nipah virus--discovery and origin.

PubMed

Chua, Kaw Bing

2012-01-01

Until the Nipah outbreak in Malaysia in 1999, knowledge of human infections with the henipaviruses was limited to the small number of cases associated with the emergence of Hendra virus in Australia in 1994. The Nipah outbreak in Malaysia alerted the global public health community to the severe pathogenic potential and widespread distribution of these unique paramyxoviruses. This chapter briefly describes the initial discovery of Nipah virus and the challenges encountered during the initial identification and characterisation of the aetiological agent responsible for the outbreak of febrile encephalitis. The initial attempts to isolate Nipah virus from the bat reservoir host are also described.

Microarray-based gene expression profiling in patients with cryopyrin-associated periodic syndromes defines a disease-related signature and IL-1-responsive transcripts.

PubMed

Balow, James E; Ryan, John G; Chae, Jae Jin; Booty, Matthew G; Bulua, Ariel; Stone, Deborah; Sun, Hong-Wei; Greene, James; Barham, Beverly; Goldbach-Mansky, Raphaela; Kastner, Daniel L; Aksentijevich, Ivona

2013-06-01

To analyse gene expression patterns and to define a specific gene expression signature in patients with the severe end of the spectrum of cryopyrin-associated periodic syndromes (CAPS). The molecular consequences of interleukin 1 inhibition were examined by comparing gene expression patterns in 16 CAPS patients before and after treatment with anakinra. We collected peripheral blood mononuclear cells from 22 CAPS patients with active disease and from 14 healthy children. Transcripts that passed stringent filtering criteria (p values≤false discovery rate 1%) were considered as differentially expressed genes (DEG). A set of DEG was validated by quantitative reverse transcription PCR and functional studies with primary cells from CAPS patients and healthy controls. We used 17 CAPS and 66 non-CAPS patient samples to create a set of gene expression models that differentiates CAPS patients from controls and from patients with other autoinflammatory conditions. Many DEG include transcripts related to the regulation of innate and adaptive immune responses, oxidative stress, cell death, cell adhesion and motility. A set of gene expression-based models comprising the CAPS-specific gene expression signature correctly classified all 17 samples from an independent dataset. This classifier also correctly identified 15 of 16 post-anakinra CAPS samples despite the fact that these CAPS patients were in clinical remission. We identified a gene expression signature that clearly distinguished CAPS patients from controls. A number of DEG were in common with other systemic inflammatory diseases such as systemic onset juvenile idiopathic arthritis. The CAPS-specific gene expression classifiers also suggest incomplete suppression of inflammation at low doses of anakinra.

Microarray-based gene expression profiling in patients with cryopyrin-associated periodic syndromes defines a disease-related signature and IL-1-responsive transcripts

PubMed Central

Balow, James E; Ryan, John G; Chae, Jae Jin; Booty, Matthew G; Bulua, Ariel; Stone, Deborah; Sun, Hong-Wei; Greene, James; Barham, Beverly; Goldbach-Mansky, Raphaela; Kastner, Daniel L; Aksentijevich, Ivona

2014-01-01

Objective To analyse gene expression patterns and to define a specific gene expression signature in patients with the severe end of the spectrum of cryopyrin-associated periodic syndromes (CAPS). The molecular consequences of interleukin 1 inhibition were examined by comparing gene expression patterns in 16 CAPS patients before and after treatment with anakinra. Methods We collected peripheral blood mononuclear cells from 22 CAPS patients with active disease and from 14 healthy children. Transcripts that passed stringent filtering criteria (p values ≤ false discovery rate 1%) were considered as differentially expressed genes (DEG). A set of DEG was validated by quantitative reverse transcription PCR and functional studies with primary cells from CAPS patients and healthy controls. We used 17 CAPS and 66 non-CAPS patient samples to create a set of gene expression models that differentiates CAPS patients from controls and from patients with other autoinflammatory conditions. Results Many DEG include transcripts related to the regulation of innate and adaptive immune responses, oxidative stress, cell death, cell adhesion and motility. A set of gene expression-based models comprising the CAPS-specific gene expression signature correctly classified all 17 samples from an independent dataset. This classifier also correctly identified 15 of 16 postanakinra CAPS samples despite the fact that these CAPS patients were in clinical remission. Conclusions We identified a gene expression signature that clearly distinguished CAPS patients from controls. A number of DEG were in common with other systemic inflammatory diseases such as systemic onset juvenile idiopathic arthritis. The CAPS-specific gene expression classifiers also suggest incomplete suppression of inflammation at low doses of anakinra. PMID:23223423

Technetium-99 and strontium-90: Abundance determination at ultratrace sensitivity by AMS as signatures of undeclared nuclear reprocessing activity

DOE Office of Scientific and Technical Information (OSTI.GOV)

McAninch, J.E.; Proctor, I.D.

1995-03-01

The purpose of this White Paper is to examine the use of the ultratrace technique Accelerator Mass Spectrometry (AMS) to lower detection limits for {sup 99}Tc and {sup 90}Sr, and to examine the utility of these isotopes as signatures of a convert reprocessing facility. The International Atomic Energy Agency (IAEA) has committed to improving the effectiveness of the IAEA Safeguards System. This is in some degree a result of the discovery in 1991 of an undeclared Iraqi EMIS program. Recommendations from the March 1993 Consultants Group Meeting have resulted in several studies and follow on field trials to identify environmentalmore » signatures from covert nuclear fuel reprocessing activity. In particular, the April, 1993 reports of the Standing Advisory Group on Safeguards Implementation (SAGSI) identified the long-lived radioisotopes Technetium-99 and strontium-90 as two reliable signatures of fuel reprocessing activity. This report also suggested pathways in the chemical processing of irradiated fuel where these elements would be volatilized and potentially released in amounts detectable with ultratrace sensitivity techniques. Based on measured {sup 99}Tc background levels compiled from a variety of sources, it is estimated that AMS can provide 10% measurements of environmental levels of {sup 99}Tc in a few minutes using modestly sized samples: a few grams for soils, plants, or animal tissues; one to several liters for rain or seawater samples; and tens to hundreds of cubic meters for air sampling. Small sample sizes and high sample throughput result in significant increases in feasibility, cost effectiveness, and quality of data for a regional monitoring program. Similar results are expected for {sup 90}Sr.« less

Novel recurrently mutated genes and a prognostic mutation signature in colorectal cancer.

PubMed

Yu, Jun; Wu, William K K; Li, Xiangchun; He, Jun; Li, Xiao-Xing; Ng, Simon S M; Yu, Chang; Gao, Zhibo; Yang, Jie; Li, Miao; Wang, Qiaoxiu; Liang, Qiaoyi; Pan, Yi; Tong, Joanna H; To, Ka F; Wong, Nathalie; Zhang, Ning; Chen, Jie; Lu, Youyong; Lai, Paul B S; Chan, Francis K L; Li, Yingrui; Kung, Hsiang-Fu; Yang, Huanming; Wang, Jun; Sung, Joseph J Y

2015-04-01

Characterisation of colorectal cancer (CRC) genomes by next-generation sequencing has led to the discovery of novel recurrently mutated genes. Nevertheless, genomic data has not yet been used for CRC prognostication. To identify recurrent somatic mutations with prognostic significance in patients with CRC. Exome sequencing was performed to identify somatic mutations in tumour tissues of 22 patients with CRC, followed by validation of 187 recurrent and pathway-related genes using targeted capture sequencing in additional 160 cases. Seven significantly mutated genes, including four reported (APC, TP53, KRAS and SMAD4) and three novel recurrently mutated genes (CDH10, FAT4 and DOCK2), exhibited high mutation prevalence (6-14% for novel cancer genes) and higher-than-expected number of non-silent mutations in our CRC cohort. For prognostication, a five-gene-signature (CDH10, COL6A3, SMAD4, TMEM132D, VCAN) was devised, in which mutation(s) in one or more of these genes was significantly associated with better overall survival independent of tumor-node-metastasis (TNM) staging. The median survival time was 80.4 months in the mutant group versus 42.4 months in the wild type group (p=0.0051). The prognostic significance of this signature was successfully verified using the data set from the Cancer Genome Atlas study. The application of next-generation sequencing has led to the identification of three novel significantly mutated genes in CRC and a mutation signature that predicts survival outcomes for stratifying patients with CRC independent of TNM staging. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Urban microbial ecology of a freshwater estuary of Lake Michigan.

PubMed

Fisher, Jenny C; Newton, Ryan J; Dila, Deborah K; McLellan, Sandra L

Freshwater estuaries throughout the Great Lakes region receive stormwater runoff and riverine inputs from heavily urbanized population centers. While human and animal feces contained in this runoff are often the focus of source tracking investigations, non-fecal bacterial loads from soil, aerosols, urban infrastructure, and other sources are also transported to estuaries and lakes. We quantified and characterized this non-fecal urban microbial component using bacterial 16S rRNA gene sequences from sewage, stormwater, rivers, harbor/estuary, and the lake surrounding Milwaukee, WI, USA. Bacterial communities from each of these environments had a distinctive composition, but some community members were shared among environments. We used a statistical biomarker discovery tool to identify the components of the microbial community that were most strongly associated with stormwater and sewage to describe an "urban microbial signature," and measured the presence and relative abundance of these organisms in the rivers, estuary, and lake. This urban signature increased in magnitude in the estuary and harbor with increasing rainfall levels, and was more apparent in lake samples with closest proximity to the Milwaukee estuary. The dominant bacterial taxa in the urban signature were Acinetobacter, Aeromonas , and Pseudomonas , which are organisms associated with pipe infrastructure and soil and not typically found in pelagic freshwater environments. These taxa were highly abundant in stormwater and sewage, but sewage also contained a high abundance of Arcobacter and Trichococcus that appeared in lower abundance in stormwater outfalls and in trace amounts in aquatic environments. Urban signature organisms comprised 1.7% of estuary and harbor communities under baseflow conditions, 3.5% after rain, and >10% after a combined sewer overflow. With predicted increases in urbanization across the Great Lakes, further alteration of freshwater communities is likely to occur with potential long term impacts on the function of estuarine and nearshore ecosystems.

Using Functional Signatures to Identify Repositioned Drugs for Breast, Myelogenous Leukemia and Prostate Cancer

PubMed Central

Shigemizu, Daichi; Hu, Zhenjun; Hung, Jui-Hung; Huang, Chia-Ling; Wang, Yajie; DeLisi, Charles

2012-01-01

The cost and time to develop a drug continues to be a major barrier to widespread distribution of medication. Although the genomic revolution appears to have had little impact on this problem, and might even have exacerbated it because of the flood of additional and usually ineffective leads, the emergence of high throughput resources promises the possibility of rapid, reliable and systematic identification of approved drugs for originally unintended uses. In this paper we develop and apply a method for identifying such repositioned drug candidates against breast cancer, myelogenous leukemia and prostate cancer by looking for inverse correlations between the most perturbed gene expression levels in human cancer tissue and the most perturbed expression levels induced by bioactive compounds. The method uses variable gene signatures to identify bioactive compounds that modulate a given disease. This is in contrast to previous methods that use small and fixed signatures. This strategy is based on the observation that diseases stem from failed/modified cellular functions, irrespective of the particular genes that contribute to the function, i.e., this strategy targets the functional signatures for a given cancer. This function-based strategy broadens the search space for the effective drugs with an impressive hit rate. Among the 79, 94 and 88 candidate drugs for breast cancer, myelogenous leukemia and prostate cancer, 32%, 13% and 17% respectively are either FDA-approved/in-clinical-trial drugs, or drugs with suggestive literature evidences, with an FDR of 0.01. These findings indicate that the method presented here could lead to a substantial increase in efficiency in drug discovery and development, and has potential application for the personalized medicine. PMID:22346740

Radiogenomics analysis identifies correlations of digital mammography with clinical molecular signatures in breast cancer.

PubMed

Tamez-Peña, Jose-Gerardo; Rodriguez-Rojas, Juan-Andrés; Gomez-Rueda, Hugo; Celaya-Padilla, Jose-Maria; Rivera-Prieto, Roxana-Alicia; Palacios-Corona, Rebeca; Garza-Montemayor, Margarita; Cardona-Huerta, Servando; Treviño, Victor

2018-01-01

In breast cancer, well-known gene expression subtypes have been related to a specific clinical outcome. However, their impact on the breast tissue phenotype has been poorly studied. Here, we investigate the association of imaging data of tumors to gene expression signatures from 71 patients with breast cancer that underwent pre-treatment digital mammograms and tumor biopsies. From digital mammograms, a semi-automated radiogenomics analysis generated 1,078 features describing the shape, signal distribution, and texture of tumors along their contralateral image used as control. From tumor biopsy, we estimated the OncotypeDX and PAM50 recurrence scores using gene expression microarrays. Then, we used multivariate analysis under stringent cross-validation to train models predicting recurrence scores. Few univariate features reached Spearman correlation coefficients above 0.4. Nevertheless, multivariate analysis yielded significantly correlated models for both signatures (correlation of OncotypeDX = 0.49 ± 0.07 and PAM50 = 0.32 ± 0.10 in stringent cross-validation and OncotypeDX = 0.83 and PAM50 = 0.78 for a unique model). Equivalent models trained from the unaffected contralateral breast were not correlated suggesting that the image signatures were tumor-specific and that overfitting was not a considerable issue. We also noted that models were improved by combining clinical information (triple negative status and progesterone receptor). The models used mostly wavelets and fractal features suggesting their importance to capture tumor information. Our results suggest that molecular-based recurrence risk and breast cancer subtypes have observable radiographic phenotypes. To our knowledge, this is the first study associating mammographic information to gene expression recurrence signatures.

Classification of micro-Doppler signatures of human aquatic activity through simulation and measurement using transferred learning

NASA Astrophysics Data System (ADS)

Kim, Youngwook; Park, Jinhee; Moon, Taesup

2017-05-01

Remote detection of human aquatic activity can be applied not only to ocean surveillance but also to rescue operations. When a human is illuminated by electromagnetic waves, a Doppler signal is generated from his or her moving parts. Indeed, bodily movements are what make humans' micro-Doppler signatures unique, offering a chance to classify human motions. Certain studies have analyzed and attempted to recognize human aquatic activity, but the topic has yet to be extensively studied. In the present research, we simulate the micro-Doppler signatures of a swimming person in an attempt to investigate those signatures' characteristics. We model human arms as point scatterers while assuming a simple arm motion. By means of such a simulation, we can obtain spectrograms from a swimming person, then extend our measurement to multiple participants. Measurements are taken from five aquatic activities featuring five participants, comprising freestyle, backstroke, and breaststroke, pulling a boat, and rowing. As suggested by the simulation study, the spectrograms for the five activities show different micro-Doppler signatures; hence, we propose to classify them using a deep convolutional neural network (DCNN). In particular, we suggest the use of a transfer-learned DCNN, which is based on a DCNN pretrained by a large-scale RGB image dataset that is, ImageNet. The classification accuracy is calculated using fivefold cross-validation on our dataset. We find that a DCNN trained through transfer learning achieves the highest accuracy while also providing a significant performance boost over the conventional classification method.