HTO and OBT activity concentrations in soil at the historical atmospheric HT release site (Chalk River Laboratories).

PubMed

Kim, S B; Bredlaw, M; Korolevych, V Y

2012-01-01

Tritium is routinely released by the Chalk River Laboratories (CRL) nuclear facilities. Three International HT release experiments have been conducted at the CRL site in the past. The site has not been disturbed since the last historical atmospheric testing in 1994 and presents an opportunity to assess the retention of tritium in soil. This study is devoted to the measurement of HTO and OBT activity concentration profiles in the subsurface 25 cm of soil. In terms of soil HTO, there is no evidence from the past HT release experiments that HTO was retained. The HTO activity concentration in the soil pore water appears similar to concentrations found in background areas in Ontario. In contrast, OBT activity concentrations in soil at the same site were significantly higher than HTO activity concentrations in soil. Elevated OBT appears to reside in the top layer of the soil (0-5 cm). In addition, OBT activity concentrations in the top soil layer did not fluctuate much with season, again, quite in contrast with soil HTO. This result suggests that OBT activity concentrations retained the signature of the historical tritium releases. Crown Copyright © 2011. Published by Elsevier Ltd. All rights reserved.

Peripheral Blood Signatures of Lead Exposure

PubMed Central

LaBreche, Heather G.; Meadows, Sarah K.; Nevins, Joseph R.; Chute, John P.

2011-01-01

Background Current evidence indicates that even low-level lead (Pb) exposure can have detrimental effects, especially in children. We tested the hypothesis that Pb exposure alters gene expression patterns in peripheral blood cells and that these changes reflect dose-specific alterations in the activity of particular pathways. Methodology/Principal Finding Using Affymetrix Mouse Genome 430 2.0 arrays, we examined gene expression changes in the peripheral blood of female Balb/c mice following exposure to per os lead acetate trihydrate or plain drinking water for two weeks and after a two-week recovery period. Data sets were RMA-normalized and dose-specific signatures were generated using established methods of supervised classification and binary regression. Pathway activity was analyzed using the ScoreSignatures module from GenePattern. Conclusions/Significance The low-level Pb signature was 93% sensitive and 100% specific in classifying samples a leave-one-out crossvalidation. The high-level Pb signature demonstrated 100% sensitivity and specificity in the leave-one-out crossvalidation. These two signatures exhibited dose-specificity in their ability to predict Pb exposure and had little overlap in terms of constituent genes. The signatures also seemed to reflect current levels of Pb exposure rather than past exposure. Finally, the two doses showed differential activation of cellular pathways. Low-level Pb exposure increased activity of the interferon-gamma pathway, whereas high-level Pb exposure increased activity of the E2F1 pathway. PMID:21829687

A Serum Circulating miRNA Signature for Short-Term Risk of Progression to Active Tuberculosis Among Household Contacts.

PubMed

Duffy, Fergal J; Thompson, Ethan; Downing, Katrina; Suliman, Sara; Mayanja-Kizza, Harriet; Boom, W Henry; Thiel, Bonnie; Weiner Iii, January; Kaufmann, Stefan H E; Dover, Drew; Tabb, David L; Dockrell, Hazel M; Ottenhoff, Tom H M; Tromp, Gerard; Scriba, Thomas J; Zak, Daniel E; Walzl, Gerhard

2018-01-01

Biomarkers that predict who among recently Mycobacterium tuberculosis (MTB)-exposed individuals will progress to active tuberculosis are urgently needed. Intracellular microRNAs (miRNAs) regulate the host response to MTB and circulating miRNAs (c-miRNAs) have been developed as biomarkers for other diseases. We performed machine-learning analysis of c-miRNA measurements in the serum of adult household contacts (HHCs) of TB index cases from South Africa and Uganda and developed a c-miRNA-based signature of risk for progression to active TB. This c-miRNA-based signature significantly discriminated HHCs within 6 months of progression to active disease from HHCs that remained healthy in an independent test set [ROC area under the ROC curve (AUC) 0.74, progressors < 6 Mo to active TB and ROC AUC 0.66, up to 24 Mo to active TB], and complements the predictions of a previous cellular mRNA-based signature of TB risk.

Differential signatures of bacterial and mammalian IMP dehydrogenase enzymes.

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

Zhang, R.; Evans, G.; Rotella, F.

1999-06-01

IMP dehydrogenase (IMPDH) is an essential enzyme of de novo guanine nucleotide synthesis. IMPDH inhibitors have clinical utility as antiviral, anticancer or immunosuppressive agents. The essential nature of this enzyme suggests its therapeutic applications may be extended to the development of antimicrobial agents. Bacterial IMPDH enzymes show bio- chemical and kinetic characteristics that are different than the mammalian IMPDH enzymes, suggesting IMPDH may be an attractive target for the development of antimicrobial agents. We suggest that the biochemical and kinetic differences between bacterial and mammalian enzymes are a consequence of the variance of specific, identifiable amino acid residues. Identification ofmore » these residues or combination of residues that impart this mammalian or bacterial enzyme signature is a prerequisite for the rational identification of agents that specifically target the bacterial enzyme. We used sequence alignments of IMPDH proteins to identify sequence signatures associated with bacterial or eukaryotic IMPDH enzymes. These selections were further refined to discern those likely to have a role in catalysis using information derived from the bacterial and mammalian IMPDH crystal structures and site-specific mutagenesis. Candidate bacterial sequence signatures identified by this process include regions involved in subunit interactions, the active site flap and the NAD binding region. Analysis of sequence alignments in these regions indicates a pattern of catalytic residues conserved in all enzymes and a secondary pattern of amino acid conservation associated with the major phylogenetic groups. Elucidation of the basis for this mammalian/bacterial IMPDH signature will provide insight into the catalytic mechanism of this enzyme and the foundation for the development of highly specific inhibitors.« less

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.

Active Site Detection by Spatial Conformity and Electrostatic Analysis—Unravelling a Proteolytic Function in Shrimp Alkaline Phosphatase

PubMed Central

Chakraborty, Sandeep; Minda, Renu; Salaye, Lipika; Bhattacharjee, Swapan K.; Rao, Basuthkar J.

2011-01-01

Computational methods are increasingly gaining importance as an aid in identifying active sites. Mostly these methods tend to have structural information that supplement sequence conservation based analyses. Development of tools that compute electrostatic potentials has further improved our ability to better characterize the active site residues in proteins. We have described a computational methodology for detecting active sites based on structural and electrostatic conformity - C ata L ytic A ctive S ite P rediction (CLASP). In our pipelined model, physical 3D signature of any particular enzymatic function as defined by its active sites is used to obtain spatially congruent matches. While previous work has revealed that catalytic residues have large pKa deviations from standard values, we show that for a given enzymatic activity, electrostatic potential difference (PD) between analogous residue pairs in an active site taken from different proteins of the same family are similar. False positives in spatially congruent matches are further pruned by PD analysis where cognate pairs with large deviations are rejected. We first present the results of active site prediction by CLASP for two enzymatic activities - β-lactamases and serine proteases, two of the most extensively investigated enzymes. The results of CLASP analysis on motifs extracted from Catalytic Site Atlas (CSA) are also presented in order to demonstrate its ability to accurately classify any protein, putative or otherwise, with known structure. The source code and database is made available at www.sanchak.com/clasp/. Subsequently, we probed alkaline phosphatases (AP), one of the well known promiscuous enzymes, for additional activities. Such a search has led us to predict a hitherto unknown function of shrimp alkaline phosphatase (SAP), where the protein acts as a protease. Finally, we present experimental evidence of the prediction by CLASP by showing that SAP indeed has protease activity in vitro

Sites Inferred by Metabolic Background Assertion Labeling (SIMBAL): adapting the Partial Phylogenetic Profiling algorithm to scan sequences for signatures that predict protein function

PubMed Central

2010-01-01

Background Comparative genomics methods such as phylogenetic profiling can mine powerful inferences from inherently noisy biological data sets. We introduce Sites Inferred by Metabolic Background Assertion Labeling (SIMBAL), a method that applies the Partial Phylogenetic Profiling (PPP) approach locally within a protein sequence to discover short sequence signatures associated with functional sites. The approach is based on the basic scoring mechanism employed by PPP, namely the use of binomial distribution statistics to optimize sequence similarity cutoffs during searches of partitioned training sets. Results Here we illustrate and validate the ability of the SIMBAL method to find functionally relevant short sequence signatures by application to two well-characterized protein families. In the first example, we partitioned a family of ABC permeases using a metabolic background property (urea utilization). Thus, the TRUE set for this family comprised members whose genome of origin encoded a urea utilization system. By moving a sliding window across the sequence of a permease, and searching each subsequence in turn against the full set of partitioned proteins, the method found which local sequence signatures best correlated with the urea utilization trait. Mapping of SIMBAL "hot spots" onto crystal structures of homologous permeases reveals that the significant sites are gating determinants on the cytosolic face rather than, say, docking sites for the substrate-binding protein on the extracellular face. In the second example, we partitioned a protein methyltransferase family using gene proximity as a criterion. In this case, the TRUE set comprised those methyltransferases encoded near the gene for the substrate RF-1. SIMBAL identifies sequence regions that map onto the substrate-binding interface while ignoring regions involved in the methyltransferase reaction mechanism in general. Neither method for training set construction requires any prior experimental

The magnetic signature of ultramafic-hosted hydrothermal systems (Invited)

NASA Astrophysics Data System (ADS)

Szitkar, F.; Dyment, J.; Honsho, C.; Horen, H.; Fouquet, Y.

2013-12-01

While the magnetic response of basalt-hosted hydrothermal sites is well known, that of ultramafic-hosted hydrothermal sites (UMHS) remains poorly documented. Here we present the magnetic signature of three of the six UMHS investigated to date on the Mid-Atlantic Ridge, i.e. sites Rainbow, Ashadze (1 and 2), and Logachev. Two magnetic signatures are observed. Sites Rainbow and Ashadze 1 are both characterized by a positive reduced-to-the-pole magnetic anomaly, i.e. a positive magnetization contrast. Conversely, sites Ashadze 2 and Logachev do not exhibit any clear magnetic signature. Rock-magnetic measurements on samples from site Rainbow reveal a strong magnetization (~30 A/m adding induced and remanent contributions) borne by sulfide-impregnated serpentinites; the magnetic carrier being magnetite. This observation can be explained by three (non exclusive) processes: (1) higher temperature serpentinization at the site resulting in the formation of more abundant / more strongly magnetized magnetite; (2) the reducing hydrothermal fluid protecting magnetite at the site from the oxidation which otherwise affects magnetite in contact with seawater; and (3) the formation of primary (hydrothermal) magnetite. We apply a new inversion method developed by Honsho et al. (2012) to the high-resolution magnetic anomalies acquired 10 m above seafloor at sites Rainbow and Ashadze 1. This method uses the Akaike Bayesian Information Criterion (ABIC) and takes full advantage of the near-seafloor measurements, avoiding the upward-continuation (i.e. loss of resolution) of other inversion schemes. This inversion reveals a difference in the intensity of equivalent magnetization obtained assuming a 100 m thick magnetic layer, ~30 A/m at site Rainbow and only 8A/m at site Ashadze, suggesting a thinner or less magnetized source for the latter. Hydrothermal sites at Ashadze 2 and Logachev are much smaller (of the order of 10 m) than the previous ones (several 100 m). These sites, known as

Building predictive gene signatures through simultaneous assessment of transcription factor activation and gene expression.

EPA Science Inventory

Building predictive gene signatures through simultaneous assessment of transcription factor activation and gene expression Exposure to many drugs and environmentally-relevant chemicals can cause adverse outcomes. These adverse outcomes, such as cancer, have been linked to mol...

A COL11A1-correlated pan-cancer gene signature of activated fibroblasts for the prioritization of therapeutic targets

PubMed Central

Jia, Dongyu; Liu, Zhenqiu; Deng, Nan; Tan, Tuan Zea; Huang, Ruby Yun-Ju; Taylor-Harding, Barbie; Cheon, Dong-Joo; Lawrenson, Kate; Wiedemeyer, Wolf R.; Walts, Ann E.; Karlan, Beth Y.; Orsulic, Sandra

2016-01-01

Although cancer-associated fibroblasts (CAFs) are viewed as a promising therapeutic target, the design of rational therapy has been hampered by two key obstacles. First, attempts to ablate CAFs have resulted in significant toxicity because currently used biomarkers cannot effectively distinguish activated CAFs from non-cancer associated fibroblasts and mesenchymal progenitor cells. Second, it is unclear whether CAFs in different organs have different molecular and functional properties that necessitate organ-specific therapeutic designs. Our analyses uncovered COL11A1 as a highly specific biomarker of activated CAFs. Using COL11A1 as a ‘seed’, we identified co-expressed genes in 13 types of primary carcinoma in The Cancer Genome Atlas. We demonstrated that a molecular signature of activated CAFs is conserved in epithelial cancers regardless of organ site and transforming events within cancer cells, suggesting that targeting fibroblast activation should be effective in multiple cancers. We prioritized several potential pan-cancer therapeutic targets that are likely to have high specificity for activated CAFs and minimal toxicity in normal tissues. PMID:27609069

15 CFR 908.16 - Signature.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 15 Commerce and Foreign Trade 3 2010-01-01 2010-01-01 false Signature. 908.16 Section 908.16 Commerce and Foreign Trade Regulations Relating to Commerce and Foreign Trade (Continued) NATIONAL OCEANIC... SUBMITTING REPORTS ON WEATHER MODIFICATION ACTIVITIES § 908.16 Signature. All reports filed with the National...

Computational Account of Spontaneous Activity as a Signature of Predictive Coding

PubMed Central

Koren, Veronika

2017-01-01

Spontaneous activity is commonly observed in a variety of cortical states. Experimental evidence suggested that neural assemblies undergo slow oscillations with Up ad Down states even when the network is isolated from the rest of the brain. Here we show that these spontaneous events can be generated by the recurrent connections within the network and understood as signatures of neural circuits that are correcting their internal representation. A noiseless spiking neural network can represent its input signals most accurately when excitatory and inhibitory currents are as strong and as tightly balanced as possible. However, in the presence of realistic neural noise and synaptic delays, this may result in prohibitively large spike counts. An optimal working regime can be found by considering terms that control firing rates in the objective function from which the network is derived and then minimizing simultaneously the coding error and the cost of neural activity. In biological terms, this is equivalent to tuning neural thresholds and after-spike hyperpolarization. In suboptimal working regimes, we observe spontaneous activity even in the absence of feed-forward inputs. In an all-to-all randomly connected network, the entire population is involved in Up states. In spatially organized networks with local connectivity, Up states spread through local connections between neurons of similar selectivity and take the form of a traveling wave. Up states are observed for a wide range of parameters and have similar statistical properties in both active and quiescent state. In the optimal working regime, Up states are vanishing, leaving place to asynchronous activity, suggesting that this working regime is a signature of maximally efficient coding. Although they result in a massive increase in the firing activity, the read-out of spontaneous Up states is in fact orthogonal to the stimulus representation, therefore interfering minimally with the network function. PMID:28114353

Genetic Signatures of HIV-1 Envelope-mediated Bystander Apoptosis

PubMed Central

Joshi, Anjali; Lee, Raphael T. C.; Mohl, Jonathan; Sedano, Melina; Khong, Wei Xin; Ng, Oon Tek; Maurer-Stroh, Sebastian; Garg, Himanshu

2014-01-01

The envelope (Env) glycoprotein of HIV is an important determinant of viral pathogenesis. Several lines of evidence support the role of HIV-1 Env in inducing bystander apoptosis that may be a contributing factor in CD4+ T cell loss. However, most of the studies testing this phenomenon have been conducted with laboratory-adapted HIV-1 isolates. This raises the question of whether primary Envs derived from HIV-infected patients are capable of inducing bystander apoptosis and whether specific Env signatures are associated with this phenomenon. We developed a high throughput assay to determine the bystander apoptosis inducing activity of a panel of primary Envs. We tested 38 different Envs for bystander apoptosis, virion infectivity, neutralizing antibody sensitivity, and putative N-linked glycosylation sites along with a comprehensive sequence analysis to determine if specific sequence signatures within the viral Env are associated with bystander apoptosis. Our studies show that primary Envs vary considerably in their bystander apoptosis-inducing potential, a phenomenon that correlates inversely with putative N-linked glycosylation sites and positively with virion infectivity. By use of a novel phylogenetic analysis that avoids subtype bias coupled with structural considerations, we found specific residues like Arg-476 and Asn-425 that were associated with differences in bystander apoptosis induction. A specific role of these residues was also confirmed experimentally. These data demonstrate for the first time the potential of primary R5 Envs to mediate bystander apoptosis in CD4+ T cells. Furthermore, we identify specific genetic signatures within the Env that may be associated with the bystander apoptosis-inducing phenotype. PMID:24265318

Fruit and Juice Epigenetic Signatures Are Associated with Independent Immunoregulatory Pathways.

PubMed

Nicodemus-Johnson, Jessie; Sinnott, Robert A

2017-07-14

Epidemiological evidence strongly suggests that fruit consumption promotes many health benefits. Despite the general consensus that fruit and juice are nutritionally similar, epidemiological results for juice consumption are conflicting. Our objective was to use DNA methylation marks to characterize fruit and juice epigenetic signatures within PBMCs and identify shared and independent signatures associated with these groups. Genome-wide DNA methylation marks (Illumina Human Methylation 450k chip) for 2,148 individuals that participated in the Framingham Offspring exam 8 were analyzed for correlations between fruit or juice consumption using standard linear regression. CpG sites with low P -values ( P < 0.01) were characterized using Gene Set Enrichment Analysis (GSEA), Ingenuity Pathway Analysis (IPA), and epigenetic Functional element Overlap analysis of the Results of Genome Wide Association Study Experiments (eFORGE). Fruit and juice-specific low P -value epigenetic signatures were largely independent. Genes near the fruit-specific epigenetic signature were enriched among pathways associated with antigen presentation and chromosome or telomere maintenance, while the juice-specific epigenetic signature was enriched for proinflammatory pathways. IPA and eFORGE analyses implicate fruit and juice-specific epigenetic signatures in the modulation of macrophage (fruit) and B or T cell (juice) activities. These data suggest a role for epigenetic regulation in fruit and juice-specific health benefits and demonstrate independent associations with distinct immune functions and cell types, suggesting that these groups may not confer the same health benefits. Identification of such differences between foods is the first step toward personalized nutrition and ultimately the improvement of human health and longevity.

Fruit and Juice Epigenetic Signatures Are Associated with Independent Immunoregulatory Pathways

PubMed Central

Nicodemus-Johnson, Jessie; Sinnott, Robert A.

2017-01-01

Epidemiological evidence strongly suggests that fruit consumption promotes many health benefits. Despite the general consensus that fruit and juice are nutritionally similar, epidemiological results for juice consumption are conflicting. Our objective was to use DNA methylation marks to characterize fruit and juice epigenetic signatures within PBMCs and identify shared and independent signatures associated with these groups. Genome-wide DNA methylation marks (Illumina Human Methylation 450k chip) for 2,148 individuals that participated in the Framingham Offspring exam 8 were analyzed for correlations between fruit or juice consumption using standard linear regression. CpG sites with low P-values (P < 0.01) were characterized using Gene Set Enrichment Analysis (GSEA), Ingenuity Pathway Analysis (IPA), and epigenetic Functional element Overlap analysis of the Results of Genome Wide Association Study Experiments (eFORGE). Fruit and juice-specific low P-value epigenetic signatures were largely independent. Genes near the fruit-specific epigenetic signature were enriched among pathways associated with antigen presentation and chromosome or telomere maintenance, while the juice-specific epigenetic signature was enriched for proinflammatory pathways. IPA and eFORGE analyses implicate fruit and juice-specific epigenetic signatures in the modulation of macrophage (fruit) and B or T cell (juice) activities. These data suggest a role for epigenetic regulation in fruit and juice-specific health benefits and demonstrate independent associations with distinct immune functions and cell types, suggesting that these groups may not confer the same health benefits. Identification of such differences between foods is the first step toward personalized nutrition and ultimately the improvement of human health and longevity. PMID:28708104

Isotopic signatures: An important tool in today`s world

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

Rokop, D.J.; Efurd, D.W.; Benjamin, T.M.

1995-12-01

High-sensitivity/high-accuracy actinide measurement techniques developed to support weapons diagnostic capabilities at the Los Alamos National Laboratory are now being used for environmental monitoring. The measurement techniques used are Thermal Ionization Mass Spectrometry (TIMS), Alpha Spectrometry(AS), and High Resolution Gamma Spectrometry(HRGS). These techniques are used to address a wide variety of actinide inventory issues: Environmental surveillance, site characterizations, food chain member determination, sedimentary records of activities, and treaty compliance concerns. As little as 10 femtograms of plutonium can be detected in samples and isotopic signatures determined on samples containing sub-100 femtogram amounts. Uranium, present in all environmental samples, can generally yieldmore » isotopic signatures of anthropogenic origin when present at the 40 picogam/gram level. Solid samples (soils, sediments, fauna, and tissue) can range from a few particles to several kilograms in size. Water samples can range from a few milliliters to as much as 200 liters.« less

(234)U/(238)U signatures associated with uranium ore bodies: part 3 Koongarra.

PubMed

Lowson, Richard T

2013-04-01

The Koongarra ore body is an early Proterozoic U ore body in the Alligator Rivers U province, Northern Territory, Australia. It has surface expression with a redox front located ∼30 m below the surface. The (234)U/(238)U activity ratios (AR) for the ground water and the amorphous phase of the solid have been analysed for the ore zone and dispersion halo as a function of depth. The results display a (234)U/(238)U AR signature with depth which may be common to all U ore bodies. The (234)U/(238)U AR is depressed below secular equilibrium in the weathered material above the redox front; rises significantly above secular equilibrium in the vicinity of the redox front; and is followed by a gradual decrease with depth below the redox front. The amplitude of the profile is a function of local conditions. A model is proposed for the signature in which oxidising waters preferentially leach the (234)U sites at the redox front due to preconditioning of the (234)U sites by α recoil during the decay of (23)(8)U to (23)(4)U. Mass balance requires the solid material left behind the redox front to have a (234)U/(238)U AR reduced below 1. Local second order effects may be superimposed on the signature. The signature may have application to calibrating scenarios for nuclear waste repositories, assisting in understanding historical climates, economic evaluation of U ore bodies and U exploration. Copyright © 2012 Elsevier Ltd. All rights reserved.

12 CFR 7.2017 - Facsimile signatures on bank stock certificates.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 12 Banks and Banking 1 2010-01-01 2010-01-01 false Facsimile signatures on bank stock certificates... ACTIVITIES AND OPERATIONS Corporate Practices § 7.2017 Facsimile signatures on bank stock certificates. The... stock certificate. The signatures may be manual or facsimile, including electronic means of signature...

Physical activity classification using time-frequency signatures of motion artifacts in multi-channel electrical impedance plethysmographs.

PubMed

Khan, Hassan Aqeel; Gore, Amit; Ashe, Jeff; Chakrabartty, Shantanu

2017-07-01

Physical activities are known to introduce motion artifacts in electrical impedance plethysmographic (EIP) sensors. Existing literature considers motion artifacts as a nuisance and generally discards the artifact containing portion of the sensor output. This paper examines the notion of exploiting motion artifacts for detecting the underlying physical activities which give rise to the artifacts in question. In particular, we investigate whether the artifact pattern associated with a physical activity is unique; and does it vary from one human-subject to another? Data was recorded from 19 adult human-subjects while conducting 5 distinct, artifact inducing, activities. A set of novel features based on the time-frequency signatures of the sensor outputs are then constructed. Our analysis demonstrates that these features enable high accuracy detection of the underlying physical activity. Using an SVM classifier we are able to differentiate between 5 distinct physical activities (coughing, reaching, walking, eating and rolling-on-bed) with an average accuracy of 85.46%. Classification is performed solely using features designed specifically to capture the time-frequency signatures of different physical activities. This enables us to measure both respiratory and motion information using only one type of sensor. This is in contrast to conventional approaches to physical activity monitoring; which rely on additional hardware such as accelerometers to capture activity information.

Discovery of metabolic signatures for predicting whole organism toxicology.

PubMed

Hines, Adam; Staff, Fred J; Widdows, John; Compton, Russell M; Falciani, Francesco; Viant, Mark R

2010-06-01

Toxicological studies in sentinel organisms frequently use biomarkers to assess biological effect. Development of "omic" technologies has enhanced biomarker discovery at the molecular level, providing signatures unique to toxicant mode-of-action (MOA). However, these signatures often lack relevance to organismal responses, such as growth or reproduction, limiting their value for environmental monitoring. Our primary objective was to discover metabolic signatures in chemically exposed organisms that can predict physiological toxicity. Marine mussels (Mytilus edulis) were exposed for 7 days to 12 and 50 microg/l copper and 50 and 350 microg/l pentachlorophenol (PCP), toxicants with unique MOAs. Physiological responses comprised an established measure of organism energetic fitness, scope for growth (SFG). Metabolic fingerprints were measured in the same individuals using nuclear magnetic resonance-based metabolomics. Metabolic signatures predictive of SFG were sought using optimal variable selection strategies and multivariate regression and then tested upon independently field-sampled mussels from rural and industrialized sites. Copper and PCP induced rational metabolic and physiological changes. Measured and predicted SFG were highly correlated for copper (r(2) = 0.55, P = 2.82 x 10(-7)) and PCP (r(2) = 0.66, P = 3.20 x 10(-6)). Predictive metabolites included methionine and arginine/phosphoarginine for copper and allantoin, valine, and methionine for PCP. When tested on field-sampled animals, metabolic signatures predicted considerably reduced fitness of mussels from the contaminated (SFG = 6.0 J/h/g) versus rural (SFG = 15.2 J/h/g) site. We report the first successful discovery of metabolic signatures in chemically exposed environmental organisms that inform on molecular MOA and that can predict physiological toxicity. This could have far-reaching implications for monitoring impacts on environmental health.

Sequence signatures of allosteric proteins towards rational design.

PubMed

Namboodiri, Saritha; Verma, Chandra; Dhar, Pawan K; Giuliani, Alessandro; Nair, Achuthsankar S

2010-12-01

Allostery is the phenomenon of changes in the structure and activity of proteins that appear as a consequence of ligand binding at sites other than the active site. Studying mechanistic basis of allostery leading to protein design with predetermined functional endpoints is an important unmet need of synthetic biology. Here, we screened the amino acid sequence landscape in search of sequence-signatures of allostery using Recurrence Quantitative Analysis (RQA) method. A characteristic vector, comprised of 10 features extracted from RQA was defined for amino acid sequences. Using Principal Component Analysis, four factors were found to be important determinants of allosteric behavior. Our sequence-based predictor method shows 82.6% accuracy, 85.7% sensitivity and 77.9% specificity with the current dataset. Further, we show that Laminarity-Mean-hydrophobicity representing repeated hydrophobic patches is the most crucial indicator of allostery. To our best knowledge this is the first report that describes sequence determinants of allostery based on hydrophobicity. As an outcome of these findings, we plan to explore possibility of inducing allostery in proteins.

Clustered Mutation Signatures Reveal that Error-Prone DNA Repair Targets Mutations to Active Genes.

PubMed

Supek, Fran; Lehner, Ben

2017-07-27

Many processes can cause the same nucleotide change in a genome, making the identification of the mechanisms causing mutations a difficult challenge. Here, we show that clustered mutations provide a more precise fingerprint of mutagenic processes. Of nine clustered mutation signatures identified from >1,000 tumor genomes, three relate to variable APOBEC activity and three are associated with tobacco smoking. An additional signature matches the spectrum of translesion DNA polymerase eta (POLH). In lymphoid cells, these mutations target promoters, consistent with AID-initiated somatic hypermutation. In solid tumors, however, they are associated with UV exposure and alcohol consumption and target the H3K36me3 chromatin of active genes in a mismatch repair (MMR)-dependent manner. These regions normally have a low mutation rate because error-free MMR also targets H3K36me3 chromatin. Carcinogens and error-prone repair therefore redistribute mutations to the more important regions of the genome, contributing a substantial mutation load in many tumors, including driver mutations. Copyright © 2017 Elsevier Inc. All rights reserved.

Normal Modes Expose Active Sites in Enzymes.

PubMed

Glantz-Gashai, Yitav; Meirson, Tomer; Samson, Abraham O

2016-12-01

Accurate prediction of active sites is an important tool in bioinformatics. Here we present an improved structure based technique to expose active sites that is based on large changes of solvent accessibility accompanying normal mode dynamics. The technique which detects EXPOsure of active SITes through normal modEs is named EXPOSITE. The technique is trained using a small 133 enzyme dataset and tested using a large 845 enzyme dataset, both with known active site residues. EXPOSITE is also tested in a benchmark protein ligand dataset (PLD) comprising 48 proteins with and without bound ligands. EXPOSITE is shown to successfully locate the active site in most instances, and is found to be more accurate than other structure-based techniques. Interestingly, in several instances, the active site does not correspond to the largest pocket. EXPOSITE is advantageous due to its high precision and paves the way for structure based prediction of active site in enzymes.

Normal Modes Expose Active Sites in Enzymes

PubMed Central

Glantz-Gashai, Yitav; Samson, Abraham O.

2016-01-01

Accurate prediction of active sites is an important tool in bioinformatics. Here we present an improved structure based technique to expose active sites that is based on large changes of solvent accessibility accompanying normal mode dynamics. The technique which detects EXPOsure of active SITes through normal modEs is named EXPOSITE. The technique is trained using a small 133 enzyme dataset and tested using a large 845 enzyme dataset, both with known active site residues. EXPOSITE is also tested in a benchmark protein ligand dataset (PLD) comprising 48 proteins with and without bound ligands. EXPOSITE is shown to successfully locate the active site in most instances, and is found to be more accurate than other structure-based techniques. Interestingly, in several instances, the active site does not correspond to the largest pocket. EXPOSITE is advantageous due to its high precision and paves the way for structure based prediction of active site in enzymes. PMID:28002427

Stable carbon isotopic signature of methane from high-emitting wetland sites in discontinuous permafrost landscape

NASA Astrophysics Data System (ADS)

Marushchak, Maija; Liimatainen, Maarit; Lind, Saara; Biasi, Christina; Martikainen, Pertti

2017-04-01

The rising methane concentration in the atmosphere during the past years has been associated with a concurrent change in the carbon isotopic signature: The atmospheric methane is getting more and more depleted in the heavy carbon isotope. The decreasing 13C/12C ratio indicates an increasing contribution of methane from biogenic sources, most importantly wetlands and inland waters, whose global emissions are still poorly constrained. From the climate change perspective, arctic and subarctic wetlands are particularly interesting due to the strong warming and permafrost thaw predicted for these regions that will cause changes in the methane dynamics. Coupling methane flux inventories with determination of the stable isotopic signature can provide useful information about the pathways of methane production, consumption and transport in these ecosystems. Here, we present data on the emissions and carbon isotopic composition of methane from subarctic tundra wetlands at the Seida study site, Northeast European Russia. In this landscape, underlain by discontinuous permafrost, waterlogged fens represent sites of high carbon turnover and high methane release. Despite they cover less than 15% of the region, their methane emissions comprise 98% of the regional mean (± SD) release of 6.7 (± 1.8) g CH4 m-2 y-1 (Marushchak et al. 2016). The methane emission from the studied fens was clearly depleted in 13C compared to the pore water methane. The bulk mean δ13CH4 (± SD) over the growing season was -68.2 (± 2.0) ‰ which is similar to the relatively few values previously reported from tundra wetlands. We explain the depleted methane emissions by the high importance of passive transport via aerenchymous plants, a process that discriminates against the heavier isotopes. This idea is supported by the strong positive correlation observed between the methane emission and the vascular leaf area index (LAI), and the inverse relationship between the δ13CH4 of emitted methane and LAI

Embryonic mammary signature subsets are activated in Brca1-/- and basal-like breast cancers

PubMed Central

2013-01-01

Introduction Cancer is often suggested to result from development gone awry. Links between normal embryonic development and cancer biology have been postulated, but no defined genetic basis has been established. We recently published the first transcriptomic analysis of embryonic mammary cell populations. Embryonic mammary epithelial cells are an immature progenitor cell population, lacking differentiation markers, which is reflected in their very distinct genetic profiles when compared with those of their postnatal descendents. Methods We defined an embryonic mammary epithelial signature that incorporates the most highly expressed genes from embryonic mammary epithelium when compared with the postnatal mammary epithelial cells. We looked for activation of the embryonic mammary epithelial signature in mouse mammary tumors that formed in mice in which Brca1 had been conditionally deleted from the mammary epithelium and in human breast cancers to determine whether any genetic links exist between embryonic mammary cells and breast cancers. Results Small subsets of the embryonic mammary epithelial signature were consistently activated in mouse Brca1-/- tumors and human basal-like breast cancers, which encoded predominantly transcriptional regulators, cell-cycle, and actin cytoskeleton components. Other embryonic gene subsets were found activated in non-basal-like tumor subtypes and repressed in basal-like tumors, including regulators of neuronal differentiation, transcription, and cell biosynthesis. Several embryonic genes showed significant upregulation in estrogen receptor (ER)-negative, progesterone receptor (PR)-negative, and/or grade 3 breast cancers. Among them, the transcription factor, SOX11, a progenitor cell and lineage regulator of nonmammary cell types, is found highly expressed in some Brca1-/- mammary tumors. By using RNA interference to silence SOX11 expression in breast cancer cells, we found evidence that SOX11 regulates breast cancer cell

Identification of crops in Central Arkansas using visual and infrared spectral reflectance signatures

NASA Technical Reports Server (NTRS)

1977-01-01

The spectral reflectance signatures of principle crops of central Arkansas were calibrated. Data were collected by conducting ground based reflectance signatures at well controlled test sites. Data collected were primarily for soybeans, therefore, additional measurements are essential to the acquisition of significant results.

Molecular signatures database (MSigDB) 3.0.

PubMed

Liberzon, Arthur; Subramanian, Aravind; Pinchback, Reid; Thorvaldsdóttir, Helga; Tamayo, Pablo; Mesirov, Jill P

2011-06-15

Well-annotated gene sets representing the universe of the biological processes are critical for meaningful and insightful interpretation of large-scale genomic data. The Molecular Signatures Database (MSigDB) is one of the most widely used repositories of such sets. We report the availability of a new version of the database, MSigDB 3.0, with over 6700 gene sets, a complete revision of the collection of canonical pathways and experimental signatures from publications, enhanced annotations and upgrades to the web site. MSigDB is freely available for non-commercial use at http://www.broadinstitute.org/msigdb.

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

Discriminative Features Mining for Offline Handwritten Signature Verification

NASA Astrophysics Data System (ADS)

Neamah, Karrar; Mohamad, Dzulkifli; Saba, Tanzila; Rehman, Amjad

2014-03-01

Signature verification is an active research area in the field of pattern recognition. It is employed to identify the particular person with the help of his/her signature's characteristics such as pen pressure, loops shape, speed of writing and up down motion of pen, writing speed, pen pressure, shape of loops, etc. in order to identify that person. However, in the entire process, features extraction and selection stage is of prime importance. Since several signatures have similar strokes, characteristics and sizes. Accordingly, this paper presents combination of orientation of the skeleton and gravity centre point to extract accurate pattern features of signature data in offline signature verification system. Promising results have proved the success of the integration of the two methods.

Automatic removal of cosmic ray signatures in Deep Impact images

NASA Astrophysics Data System (ADS)

Ipatov, S. I.; A'Hearn, M. F.; Klaasen, K. P.

The results of recognition of cosmic ray (CR) signatures on single images made during the Deep Impact mission were analyzed for several codes written by several authors. For automatic removal of CR signatures on many images, we suggest using the code imgclean ( http://pdssbn.astro.umd.edu/volume/didoc_0001/document/calibration_software/dical_v5/) written by E. Deutsch as other codes considered do not work properly automatically with a large number of images and do not run to completion for some images; however, other codes can be better for analysis of certain specific images. Sometimes imgclean detects false CR signatures near the edge of a comet nucleus, and it often does not recognize all pixels of long CR signatures. Our code rmcr is the only code among those considered that allows one to work with raw images. For most visual images made during low solar activity at exposure time t > 4 s, the number of clusters of bright pixels on an image per second per sq. cm of CCD was about 2-4, both for dark and normal sky images. At high solar activity, it sometimes exceeded 10. The ratio of the number of CR signatures consisting of n pixels obtained at high solar activity to that at low solar activity was greater for greater n. The number of clusters detected as CR signatures on a single infrared image is by at least a factor of several greater than the actual number of CR signatures; the number of clusters based on analysis of two successive dark infrared frames is in agreement with an expected number of CR signatures. Some glitches of false CR signatures include bright pixels repeatedly present on different infrared images. Our interactive code imr allows a user to choose the regions on a considered image where glitches detected by imgclean as CR signatures are ignored. In other regions chosen by the user, the brightness of some pixels is replaced by the local median brightness if the brightness of these pixels is greater by some factor than the median brightness. The

Real Traceable Signatures

NASA Astrophysics Data System (ADS)

Chow, Sherman S. M.

Traceable signature scheme extends a group signature scheme with an enhanced anonymity management mechanism. The group manager can compute a tracing trapdoor which enables anyone to test if a signature is signed by a given misbehaving user, while the only way to do so for group signatures requires revealing the signer of all signatures. Nevertheless, it is not tracing in a strict sense. For all existing schemes, T tracing agents need to recollect all N' signatures ever produced and perform RN' “checks” for R revoked users. This involves a high volume of transfer and computations. Increasing T increases the degree of parallelism for tracing but also the probability of “missing” some signatures in case some of the agents are dishonest.

Observation of a 27-day solar signature in noctilucent cloud altitude

NASA Astrophysics Data System (ADS)

Köhnke, Merlin C.; von Savigny, Christian; Robert, Charles E.

2018-05-01

Previous studies have identified solar 27-day signatures in several parameters in the Mesosphere/Lower thermosphere region, including temperature and Noctilucent cloud (NLC) occurrence frequency. In this study we report on a solar 27-day signature in NLC altitude with peak-to-peak variations of about 400 m. We use SCIAMACHY limb-scatter observations from 2002 to 2012 to detect NLCs. The superposed epoch analysis method is applied to extract solar 27-day signatures. A 27-day signature in NLC altitude can be identified in both hemispheres in the SCIAMACHY dataset, but the signature is more pronounced in the northern hemisphere. The solar signature in NLC altitude is found to be in phase with solar activity and temperature for latitudes ≳ 70 ° N. We provide a qualitative explanation for the positive correlation between solar activity and NLC altitude based on published model simulations.

Signature molecular descriptor : advanced applications.

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

Visco, Donald Patrick, Jr.

provides details on a technique to describe molecules on a computer, called Signature, as well as the computer-aided molecule design algorithm built around Signature. Two applications are provided of the CAMD algorithm with Signature. The first describes the design of green solvents based on data in the GlaxoSmithKline (GSK) Solvent Selection Guide. The second provides novel non-steroidal glucocorticoid receptor ligands with some optimally predicted properties. In addition to using the CAMD algorithm with Signature, it is demonstrated how to employ Signature in a high-throughput screening study. Here, after classifying both active and inactive inhibitors for the protein Factor XIa using Signature, the model developed is used to screen a large, publicly-available database called PubChem for the most active compounds.« less

Stromal-Based Signatures for the Classification of Gastric Cancer.

PubMed

Uhlik, Mark T; Liu, Jiangang; Falcon, Beverly L; Iyer, Seema; Stewart, Julie; Celikkaya, Hilal; O'Mahony, Marguerita; Sevinsky, Christopher; Lowes, Christina; Douglass, Larry; Jeffries, Cynthia; Bodenmiller, Diane; Chintharlapalli, Sudhakar; Fischl, Anthony; Gerald, Damien; Xue, Qi; Lee, Jee-Yun; Santamaria-Pang, Alberto; Al-Kofahi, Yousef; Sui, Yunxia; Desai, Keyur; Doman, Thompson; Aggarwal, Amit; Carter, Julia H; Pytowski, Bronislaw; Jaminet, Shou-Ching; Ginty, Fiona; Nasir, Aejaz; Nagy, Janice A; Dvorak, Harold F; Benjamin, Laura E

2016-05-01

Treatment of metastatic gastric cancer typically involves chemotherapy and monoclonal antibodies targeting HER2 (ERBB2) and VEGFR2 (KDR). However, reliable methods to identify patients who would benefit most from a combination of treatment modalities targeting the tumor stroma, including new immunotherapy approaches, are still lacking. Therefore, we integrated a mouse model of stromal activation and gastric cancer genomic information to identify gene expression signatures that may inform treatment strategies. We generated a mouse model in which VEGF-A is expressed via adenovirus, enabling a stromal response marked by immune infiltration and angiogenesis at the injection site, and identified distinct stromal gene expression signatures. With these data, we designed multiplexed IHC assays that were applied to human primary gastric tumors and classified each tumor to a dominant stromal phenotype representative of the vascular and immune diversity found in gastric cancer. We also refined the stromal gene signatures and explored their relation to the dominant patient phenotypes identified by recent large-scale studies of gastric cancer genomics (The Cancer Genome Atlas and Asian Cancer Research Group), revealing four distinct stromal phenotypes. Collectively, these findings suggest that a genomics-based systems approach focused on the tumor stroma can be used to discover putative predictive biomarkers of treatment response, especially to antiangiogenesis agents and immunotherapy, thus offering an opportunity to improve patient stratification. Cancer Res; 76(9); 2573-86. ©2016 AACR. ©2016 American Association for Cancer Research.

A gene expression signature of RAS pathway dependence predicts response to PI3K and RAS pathway inhibitors and expands the population of RAS pathway activated tumors.

PubMed

Loboda, Andrey; Nebozhyn, Michael; Klinghoffer, Rich; Frazier, Jason; Chastain, Michael; Arthur, William; Roberts, Brian; Zhang, Theresa; Chenard, Melissa; Haines, Brian; Andersen, Jannik; Nagashima, Kumiko; Paweletz, Cloud; Lynch, Bethany; Feldman, Igor; Dai, Hongyue; Huang, Pearl; Watters, James

2010-06-30

Hyperactivation of the Ras signaling pathway is a driver of many cancers, and RAS pathway activation can predict response to targeted therapies. Therefore, optimal methods for measuring Ras pathway activation are critical. The main focus of our work was to develop a gene expression signature that is predictive of RAS pathway dependence. We used the coherent expression of RAS pathway-related genes across multiple datasets to derive a RAS pathway gene expression signature and generate RAS pathway activation scores in pre-clinical cancer models and human tumors. We then related this signature to KRAS mutation status and drug response data in pre-clinical and clinical datasets. The RAS signature score is predictive of KRAS mutation status in lung tumors and cell lines with high (> 90%) sensitivity but relatively low (50%) specificity due to samples that have apparent RAS pathway activation in the absence of a KRAS mutation. In lung and breast cancer cell line panels, the RAS pathway signature score correlates with pMEK and pERK expression, and predicts resistance to AKT inhibition and sensitivity to MEK inhibition within both KRAS mutant and KRAS wild-type groups. The RAS pathway signature is upregulated in breast cancer cell lines that have acquired resistance to AKT inhibition, and is downregulated by inhibition of MEK. In lung cancer cell lines knockdown of KRAS using siRNA demonstrates that the RAS pathway signature is a better measure of dependence on RAS compared to KRAS mutation status. In human tumors, the RAS pathway signature is elevated in ER negative breast tumors and lung adenocarcinomas, and predicts resistance to cetuximab in metastatic colorectal cancer. These data demonstrate that the RAS pathway signature is superior to KRAS mutation status for the prediction of dependence on RAS signaling, can predict response to PI3K and RAS pathway inhibitors, and is likely to have the most clinical utility in lung and breast tumors.

A gene expression signature of RAS pathway dependence predicts response to PI3K and RAS pathway inhibitors and expands the population of RAS pathway activated tumors

PubMed Central

2010-01-01

Background Hyperactivation of the Ras signaling pathway is a driver of many cancers, and RAS pathway activation can predict response to targeted therapies. Therefore, optimal methods for measuring Ras pathway activation are critical. The main focus of our work was to develop a gene expression signature that is predictive of RAS pathway dependence. Methods We used the coherent expression of RAS pathway-related genes across multiple datasets to derive a RAS pathway gene expression signature and generate RAS pathway activation scores in pre-clinical cancer models and human tumors. We then related this signature to KRAS mutation status and drug response data in pre-clinical and clinical datasets. Results The RAS signature score is predictive of KRAS mutation status in lung tumors and cell lines with high (> 90%) sensitivity but relatively low (50%) specificity due to samples that have apparent RAS pathway activation in the absence of a KRAS mutation. In lung and breast cancer cell line panels, the RAS pathway signature score correlates with pMEK and pERK expression, and predicts resistance to AKT inhibition and sensitivity to MEK inhibition within both KRAS mutant and KRAS wild-type groups. The RAS pathway signature is upregulated in breast cancer cell lines that have acquired resistance to AKT inhibition, and is downregulated by inhibition of MEK. In lung cancer cell lines knockdown of KRAS using siRNA demonstrates that the RAS pathway signature is a better measure of dependence on RAS compared to KRAS mutation status. In human tumors, the RAS pathway signature is elevated in ER negative breast tumors and lung adenocarcinomas, and predicts resistance to cetuximab in metastatic colorectal cancer. Conclusions These data demonstrate that the RAS pathway signature is superior to KRAS mutation status for the prediction of dependence on RAS signaling, can predict response to PI3K and RAS pathway inhibitors, and is likely to have the most clinical utility in lung and breast

Dissecting the active site of a photoreceptor protein

NASA Astrophysics Data System (ADS)

Hoff, Wouter; Hara, Miwa; Ren, Jie; Moghadam, Farzaneh; Xie, Aihua; Kumauchi, Masato

While enzymes are quite large molecules, functionally important chemical events are often limited to a small region of the protein: the active site. The physical and chemical properties of residues at such active sites are often strongly altered compared to the same groups dissolved in water. Understanding such effects is important for unraveling the mechanisms underlying protein function and for protein engineering, but has proven challenging. Here we report on our ongoing efforts on using photoactive yellow protein (PYP), a bacterial photoreceptor, as a model system for such effects. We will report on the following questions: How many residues affect active site properties? Are these residues in direct physical contact with the active site? Can functionally important residues be recognized in the crystal structure of a protein? What structural resolution is needed to understand active sites? What spectroscopic techniques are most informative? Which weak interactions dominate active site properties?

Mechanistic considerations on the wavelength-dependent variations of UVR genotoxicity and mutagenesis in skin: the discrimination of UVA-signature from UV-signature mutation.

PubMed

Ikehata, Hironobu

2018-05-31

Ultraviolet radiation (UVR) predominantly induces UV-signature mutations, C → T and CC → TT base substitutions at dipyrimidine sites, in the cellular and skin genome. I observed in our in vivo mutation studies of mouse skin that these UVR-specific mutations show a wavelength-dependent variation in their sequence-context preference. The C → T mutation occurs most frequently in the 5'-TCG-3' sequence regardless of the UVR wavelength, but is recovered more preferentially there as the wavelength increases, resulting in prominent occurrences exclusively in the TCG sequence in the UVA wavelength range, which I will designate as a "UVA signature" in this review. The preference of the UVB-induced C → T mutation for the sequence contexts shows a mixed pattern of UVC- and UVA-induced mutations, and a similar pattern is also observed for natural sunlight, in which UVB is the most genotoxic component. In addition, the CC → TT mutation hardly occurs at UVA1 wavelengths, although it is detected rarely but constantly in the UVC and UVB ranges. This wavelength-dependent variation in the sequence-context preference of the UVR-specific mutations could be explained by two different photochemical mechanisms of cyclobutane pyrimidine dimer (CPD) formation. The UV-signature mutations observed in the UVC and UVB ranges are known to be caused mainly by CPDs produced through the conventional singlet/triplet excitation of pyrimidine bases after the direct absorption of the UVC/UVB photon energy in those bases. On the other hand, a novel photochemical mechanism through the direct absorption of the UVR energy to double-stranded DNA, which is called "collective excitation", has been proposed for the UVA-induced CPD formation. The UVA photons directly absorbed by DNA produce CPDs with a sequence context preference different from that observed for CPDs caused by the UVC/UVB-mediated singlet/triplet excitation, causing CPD formation preferentially at thymine-containing dipyrimidine

Small-scale studies of roasted ore waste reveal extreme ranges of stable mercury isotope signatures

NASA Astrophysics Data System (ADS)

Smith, Robin S.; Wiederhold, Jan G.; Jew, Adam D.; Brown, Gordon E.; Bourdon, Bernard; Kretzschmar, Ruben

2014-07-01

Active and closed Hg mines are significant sources of Hg contamination to the environment, mainly due to large volumes of mine waste material disposed of on-site. The application of Hg isotopes as source tracer from such contaminated sites requires knowledge of the Hg isotope signatures of different materials potentially released to the environment. Previous work has shown that calcine, the waste residue of the on-site ore roasting process, can exhibit distinct Hg isotope signatures compared with the primary ore. Here, we report results from a detailed small-scale study of Hg isotope variations in calcine collected from the closed New Idria Hg mine, San Benito County, CA, USA. The calcine samples exhibited different internal layering features which were investigated using optical microscopy, micro X-ray fluorescence, micro X-ray absorption spectroscopy (μ-XAS), and stable Hg isotope analysis. Significant Fe, S, and Hg concentration gradients were found across the different internal layers. Isotopic analyses revealed an extreme variation with pronounced isotopic gradients across the internal layered features. Overall, δ202Hg (±0.10‰, 2 SD) describing mass-dependent fractionation (MDF) ranged from -5.96 to 14.49‰, which is by far the largest range of δ202Hg values reported for any environmental sample. In addition, Δ199Hg (±0.06‰, 2 SD) describing mass-independent fractionation (MIF) ranged from -0.17 to 0.21‰. The μ-XAS analyses suggested that cinnabar and metacinnabar are the dominant Hg-bearing phases in the calcine. Our results demonstrate that the incomplete roasting of HgS ores in Hg mines can cause extreme mass-dependent Hg isotope fractionations at the scale of individual calcine pieces with enrichments in both light and heavy Hg isotopes relative to the primary ore signatures. This finding has important implications for the application of Hg isotopes as potential source tracers for Hg released to the environment from closed Hg mines and

Monoamine oxidase A (MAO-A): a signature marker of alternatively activated monocytes/macrophages

PubMed Central

Cathcart, Martha K.; Bhattacharjee, Ashish

2015-01-01

Monocytes/macrophages are versatile cells centrally involved in host defense and immunity. Th1 cytokines induce a classical activation program in monocytes/macrophages leading to a proinflammatory M1 macrophage phenotype while Th2 cytokines IL-4 and IL-13 promote monocyte differentiation into an alternatively activated, anti-inflammatory M2 macrophage phenotype. Although monoamine oxidase A (MAO-A) is primarily known for its action in the nervous system, several recent studies have identified MAO-A as a signature marker of alternative activation of monocytes/macrophages. In this brief review we explore the signaling pathways/molecules that regulate MAO-A expression in alternatively activated monocytes/macrophages. We further discuss the contribution of MAO-A to the resolution of inflammation and identify potential therapeutic targets for controlling inflammation. Altogether this review provides deeper insight into the role of MAO-A in alternative activation of monocytes/macrophages and their participation in the inflammatory response. PMID:26052543

Monoamine oxidase A (MAO-A): a signature marker of alternatively activated monocytes/macrophages.

PubMed

Cathcart, Martha K; Bhattacharjee, Ashish

Monocytes/macrophages are versatile cells centrally involved in host defense and immunity. Th1 cytokines induce a classical activation program in monocytes/macrophages leading to a proinflammatory M1 macrophage phenotype while Th2 cytokines IL-4 and IL-13 promote monocyte differentiation into an alternatively activated, anti-inflammatory M2 macrophage phenotype. Although monoamine oxidase A (MAO-A) is primarily known for its action in the nervous system, several recent studies have identified MAO-A as a signature marker of alternative activation of monocytes/macrophages. In this brief review we explore the signaling pathways/molecules that regulate MAO-A expression in alternatively activated monocytes/macrophages. We further discuss the contribution of MAO-A to the resolution of inflammation and identify potential therapeutic targets for controlling inflammation. Altogether this review provides deeper insight into the role of MAO-A in alternative activation of monocytes/macrophages and their participation in the inflammatory response.

Active site dynamics of ribonuclease.

PubMed Central

Brünger, A T; Brooks, C L; Karplus, M

1985-01-01

The stochastic boundary molecular dynamics method is used to study the structure, dynamics, and energetics of the solvated active site of bovine pancreatic ribonuclease A. Simulations of the native enzyme and of the enzyme complexed with the dinucleotide substrate CpA and the transition-state analog uridine vanadate are compared. Structural features and dynamical couplings for ribonuclease residues found in the simulation are consistent with experimental data. Water molecules, most of which are not observed in crystallographic studies, are shown to play an important role in the active site. Hydrogen bonding of residues with water molecules in the free enzyme is found to mimic the substrate-enzyme interactions of residues involved in binding. Networks of water stabilize the cluster of positively charged active site residues. Correlated fluctuations between the uridine vanadate complex and the distant lysine residues are mediated through water and may indicate a possible role for these residues in stabilizing the transition state. Images PMID:3866234

Crystal structures reveal metal-binding plasticity at the metallo-β-lactamase active site of PqqB from Pseudomonas putida

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

Tu, Xiongying; Latham, John A.; Klema, Valerie J.

PqqB is an enzyme involved in the biosynthesis of pyrroloquinoline quinone and a distal member of the metallo-β-lactamase (MBL) superfamily. PqqB lacks two residues in the conserved signature motif HxHxDH that makes up the key metal-chelating elements that can bind up to two metal ions at the active site of MBLs and other members of its superfamily. Here, we report crystal structures of PqqB bound to Mn2+, Mg2+, Cu2+, and Zn2+. These structures demonstrate that PqqB can still bind metal ions at the canonical MBL active site. The fact that PqqB can adapt its side chains to chelate a widemore » spectrum of metal ions with different coordination features on a uniform main chain scaffold demonstrates its metal-binding plasticity. This plasticity may provide insights into the structural basis of promiscuous activities found in ensembles of metal complexes within this superfamily. Furthermore, PqqB belongs to a small subclass of MBLs that contain an additional CxCxxC motif that binds a structural Zn2+. Our data support a key role for this motif in dimerization.« less

Low dielectric response in enzyme active site

PubMed Central

Mertz, Edward L.; Krishtalik, Lev I.

2000-01-01

The kinetics of charge transfer depend crucially on the dielectric reorganization of the medium. In enzymatic reactions that involve charge transfer, atomic dielectric response of the active site and of its surroundings determines the efficiency of the protein as a catalyst. We report direct spectroscopic measurements of the reorganization energy associated with the dielectric response in the active site of α-chymotrypsin. A chromophoric inhibitor of the enzyme is used as a spectroscopic probe. We find that water strongly affects the dielectric reorganization in the active site of the enzyme in solution. The reorganization energy of the protein matrix in the vicinity of the active site is similar to that of low-polarity solvents. Surprisingly, water exhibits an anomalously high dielectric response that cannot be described in terms of the dielectric continuum theory. As a result, sequestering the active site from the aqueous environment inside low-dielectric enzyme body dramatically reduces the dielectric reorganization. This reduction is particularly important for controlling the rate of enzymatic reactions. PMID:10681440

Prevalence of interferon type I signature in CD14 monocytes of patients with Sjögren's syndrome and association with disease activity and BAFF gene expression

PubMed Central

Brkic, Zana; Maria, Naomi I; van Helden-Meeuwsen, Cornelia G; van de Merwe, Joop P; van Daele, Paul L; Dalm, Virgil A; Wildenberg, Manon E; Beumer, Wouter; Drexhage, Hemmo A; Versnel, Marjan A

2013-01-01

Objective To determine the prevalence of upregulation of interferon (IFN) type I inducible genes, the so called ‘IFN type I signature’, in CD14 monocytes in 69 patients with primary Sjögren's syndrome (pSS) and 44 healthy controls (HC) and correlate it with disease manifestations and expression of B cell activating factor (BAFF). Methods Expression of IFI44L, IFI44, IFIT3, LY6E and MX1 was measured using real time quantitative PCR in monocytes. Expression values were used to calculate IFN type I scores for each subject. pSS patients positive for the IFN type I signature (IFN score≥10) and patients negative for the signature (IFN score<10) were then compared for clinical disease manifestations and BAFF expression. A bioassay using a monocytic cell line was performed to study whether BAFF mRNA expression was inducible by IFN type I activity in serum of patients with pSS. Results An IFN type I signature was present in 55% of patients with pSS compared with 4.5% of HC. Patients with the IFN type I signature showed: (a) higher EULAR Sjögren's Syndrome Disease Activity Index scores; higher anti-Ro52, anti-Ro60 and anti-La autoantibodies; higher rheumatoid factor; higher serum IgG; lower C3, lower absolute lymphocyte and neutrophil counts; (b)higher BAFF gene expression in monocytes. In addition, serum of signature-positive patients induced BAFF gene expression in monocytes. Conclusions The monocyte IFN type I signature identifies a subgroup of patients with pSS with a higher clinical disease activity together with higher BAFF mRNA expression. Such patients might benefit from treatment blocking IFN type I production or activity. PMID:22736090

Methanopyrus kandleri topoisomerase V contains three distinct AP lyase active sites in addition to the topoisomerase active site

PubMed Central

Rajan, Rakhi; Osterman, Amy; Mondragón, Alfonso

2016-01-01

Topoisomerase V (Topo-V) is the only topoisomerase with both topoisomerase and DNA repair activities. The topoisomerase activity is conferred by a small alpha-helical domain, whereas the AP lyase activity is found in a region formed by 12 tandem helix-hairpin-helix ((HhH)2) domains. Although it was known that Topo-V has multiple repair sites, only one had been mapped. Here, we show that Topo-V has three AP lyase sites. The atomic structure and Small Angle X-ray Scattering studies of a 97 kDa fragment spanning the topoisomerase and 10 (HhH)2 domains reveal that the (HhH)2 domains extend away from the topoisomerase domain. A combination of biochemical and structural observations allow the mapping of the second repair site to the junction of the 9th and 10th (HhH)2 domains. The second site is structurally similar to the first one and to the sites found in other AP lyases. The 3rd AP lyase site is located in the 12th (HhH)2 domain. The results show that Topo-V is an unusual protein: it is the only known protein with more than one (HhH)2 domain, the only known topoisomerase with dual activities and is also unique by having three AP lyase repair sites in the same polypeptide. PMID:26908655

A Simple Model-Based Approach to Inferring and Visualizing Cancer Mutation Signatures

PubMed Central

Shiraishi, Yuichi; Tremmel, Georg; Miyano, Satoru; Stephens, Matthew

2015-01-01

Recent advances in sequencing technologies have enabled the production of massive amounts of data on somatic mutations from cancer genomes. These data have led to the detection of characteristic patterns of somatic mutations or “mutation signatures” at an unprecedented resolution, with the potential for new insights into the causes and mechanisms of tumorigenesis. Here we present new methods for modelling, identifying and visualizing such mutation signatures. Our methods greatly simplify mutation signature models compared with existing approaches, reducing the number of parameters by orders of magnitude even while increasing the contextual factors (e.g. the number of flanking bases) that are accounted for. This improves both sensitivity and robustness of inferred signatures. We also provide a new intuitive way to visualize the signatures, analogous to the use of sequence logos to visualize transcription factor binding sites. We illustrate our new method on somatic mutation data from urothelial carcinoma of the upper urinary tract, and a larger dataset from 30 diverse cancer types. The results illustrate several important features of our methods, including the ability of our new visualization tool to clearly highlight the key features of each signature, the improved robustness of signature inferences from small sample sizes, and more detailed inference of signature characteristics such as strand biases and sequence context effects at the base two positions 5′ to the mutated site. The overall framework of our work is based on probabilistic models that are closely connected with “mixed-membership models” which are widely used in population genetic admixture analysis, and in machine learning for document clustering. We argue that recognizing these relationships should help improve understanding of mutation signature extraction problems, and suggests ways to further improve the statistical methods. Our methods are implemented in an R package pmsignature (https

Magma Differentiation Processes That Develop an "Enriched" Signature in the Izu Bonin Rear Arc: Evidence from Drilling at IODP Site U1437

NASA Astrophysics Data System (ADS)

Heywood, L. J.; DeBari, S. M.; Schindlbeck, J. C.; Escobar-Burciaga, R. D.

2015-12-01

The Izu Bonin rear arc represents a unique laboratory to study the development of continental crust precursors at an intraoceanic subduction zone., Volcanic output in the Izu Bonin rear arc is compositionally distinct from the Izu Bonin main volcanic front, with med- to high-K and LREE-enrichment similar to the average composition of the continental crust. Drilling at IODP Expedition 350 Site U1437 in the Izu Bonin rear arc obtained volcaniclastic material that was deposited from at least 13.5 Ma to present. IODP Expedition 350 represents the first drilling mission in the Izu Bonin rear arc region. This study presents fresh glass and mineral compositions (obtained via EMP and LA-ICP-MS) from unaltered tephra layers in mud/mudstone (Lithostratigraphic Unit I) and lapillistone (Lithostratigraphic Unit II) <4.5 Ma to examine the geochemical signature of Izu Bonin rear arc magmas. Unit II samples are coarse-grained tephras that are mainly rhyolitic in composition (72.1-77.5 wt. % SiO2, 3.2-3.9 wt. % K2O and average Mg# 24) and LREE-enriched. These rear-arc rhyolites have an average La/Sm of 2.6 with flat HREEs, average Th/La of 0.15, and Zr/Y of 4.86. Rear-arc rhyolite trace element signature is distinct from felsic eruptive products from the Izu Bonin main volcanic front, which have lower La/Sm and Th/La as well as significantly lower incompatible element concentrations. Rear arc rhyolites have similar trace element ratios to rhyolites from the adjacent but younger backarc knolls and actively-extending rift regions, but the latter is typified by lower K2O, as well as a smaller degree of enrichment in incompatible elements. Given these unique characteristics, we explore models for felsic magma formation and intracrustal differentiation in the Izu Bonin rear arc.

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

Mechanistic insights into the active site and allosteric communication pathways in human nonmuscle myosin-2C

PubMed Central

Preller, Matthias

2017-01-01

Despite a generic, highly conserved motor domain, ATP turnover kinetics and their activation by F-actin vary greatly between myosin-2 isoforms. Here, we present a 2.25 Å pre-powerstroke state (ADP⋅VO4) crystal structure of the human nonmuscle myosin-2C motor domain, one of the slowest myosins characterized. In combination with integrated mutagenesis, ensemble-solution kinetics, and molecular dynamics simulation approaches, the structure reveals an allosteric communication pathway that connects the distal end of the motor domain with the active site. Disruption of this pathway by mutation of hub residue R788, which forms the center of a cluster of interactions connecting the converter, the SH1-SH2 helix, the relay helix, and the lever, abolishes nonmuscle myosin-2 specific kinetic signatures. Our results provide insights into structural changes in the myosin motor domain that are triggered upon F-actin binding and contribute critically to the mechanochemical behavior of stress fibers, actin arcs, and cortical actin-based structures. PMID:29256864

ADAGE signature analysis: differential expression analysis with data-defined gene sets.

PubMed

Tan, Jie; Huyck, Matthew; Hu, Dongbo; Zelaya, René A; Hogan, Deborah A; Greene, Casey S

2017-11-22

Gene set enrichment analysis and overrepresentation analyses are commonly used methods to determine the biological processes affected by a differential expression experiment. This approach requires biologically relevant gene sets, which are currently curated manually, limiting their availability and accuracy in many organisms without extensively curated resources. New feature learning approaches can now be paired with existing data collections to directly extract functional gene sets from big data. Here we introduce a method to identify perturbed processes. In contrast with methods that use curated gene sets, this approach uses signatures extracted from public expression data. We first extract expression signatures from public data using ADAGE, a neural network-based feature extraction approach. We next identify signatures that are differentially active under a given treatment. Our results demonstrate that these signatures represent biological processes that are perturbed by the experiment. Because these signatures are directly learned from data without supervision, they can identify uncurated or novel biological processes. We implemented ADAGE signature analysis for the bacterial pathogen Pseudomonas aeruginosa. For the convenience of different user groups, we implemented both an R package (ADAGEpath) and a web server ( http://adage.greenelab.com ) to run these analyses. Both are open-source to allow easy expansion to other organisms or signature generation methods. We applied ADAGE signature analysis to an example dataset in which wild-type and ∆anr mutant cells were grown as biofilms on the Cystic Fibrosis genotype bronchial epithelial cells. We mapped active signatures in the dataset to KEGG pathways and compared with pathways identified using GSEA. The two approaches generally return consistent results; however, ADAGE signature analysis also identified a signature that revealed the molecularly supported link between the MexT regulon and Anr. We designed

The cytidine deaminase signature HxE(x)n CxxC of DYW1 binds zinc and is necessary for RNA editing of ndhD-1.

PubMed

Boussardon, Clément; Avon, Alexandra; Kindgren, Peter; Bond, Charles S; Challenor, Michael; Lurin, Claire; Small, Ian

2014-09-01

In flowering plants, RNA editing involves deamination of specific cytidines to uridines in both mitochondrial and chloroplast transcripts. Pentatricopeptide repeat (PPR) proteins and multiple organellar RNA editing factor (MORF) proteins have been shown to be involved in RNA editing but none have been shown to possess cytidine deaminase activity. The DYW domain of some PPR proteins contains a highly conserved signature resembling the zinc-binding active site motif of known nucleotide deaminases. We modified these highly conserved amino acids in the DYW motif of DYW1, an editing factor required for editing of the ndhD-1 site in Arabidopsis chloroplasts. We demonstrate that several amino acids of this signature motif are required for RNA editing in vivo and for zinc binding in vitro. We conclude that the DYW domain of DYW1 has features in common with cytidine deaminases, reinforcing the hypothesis that this domain forms part of the active enzyme that carries out RNA editing in plants. © 2014 The Authors. New Phytologist © 2014 New Phytologist Trust.

Feasibility study for locating archaeological village sites by satellite remote sensing techniques. [multispectral photography of Alaska

NASA Technical Reports Server (NTRS)

Cook, J. P. (Principal Investigator); Stringer, W. J.

1974-01-01

The author has identified the following significant results. The objective is to determine the feasibility of detecting large Alaskan archaeological sites by satellite remote sensing techniques and mapping such sites. The approach used is to develop digital multispectral signatures of dominant surface features including vegetation, exposed soils and rock, hydrological patterns and known archaeological sites. ERTS-1 scenes are then printed out digitally in a map-like array with a letter reflecting the most appropriate classification representing each pixel. Preliminary signatures were developed and tested. It was determined that there was a need to tighten up the archaeological site signature by developing accurate signatures for all naturally-occurring vegetation and surface conditions in the vicinity of the test area. These second generation signatures have been tested by means of computer printouts and classified tape displays on the University of Alaska CDU-200 and by comparison with aerial photography. It has been concluded that the archaeological signatures now in use are as good as can be developed. Plans are to print out signatures for the entire test area and locate on topographic maps the likely locations of archaeological sites within the test area.

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

-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.

Activation of phenylalanine hydroxylase by phenylalanine does not require binding in the active site.

PubMed

Roberts, Kenneth M; Khan, Crystal A; Hinck, Cynthia S; Fitzpatrick, Paul F

2014-12-16

Phenylalanine hydroxylase (PheH), a liver enzyme that catalyzes the hydroxylation of excess phenylalanine in the diet to tyrosine, is activated by phenylalanine. The lack of activity at low levels of phenylalanine has been attributed to the N-terminus of the protein's regulatory domain acting as an inhibitory peptide by blocking substrate access to the active site. The location of the site at which phenylalanine binds to activate the enzyme is unknown, and both the active site in the catalytic domain and a separate site in the N-terminal regulatory domain have been proposed. Binding of catecholamines to the active-site iron was used to probe the accessibility of the active site. Removal of the regulatory domain increases the rate constants for association of several catecholamines with the wild-type enzyme by ∼2-fold. Binding of phenylalanine in the active site is effectively abolished by mutating the active-site residue Arg270 to lysine. The k(cat)/K(phe) value is down 10⁴ for the mutant enzyme, and the K(m) value for phenylalanine for the mutant enzyme is >0.5 M. Incubation of the R270K enzyme with phenylalanine also results in a 2-fold increase in the rate constants for catecholamine binding. The change in the tryptophan fluorescence emission spectrum seen in the wild-type enzyme upon activation by phenylalanine is also seen with the R270K mutant enzyme in the presence of phenylalanine. Both results establish that activation of PheH by phenylalanine does not require binding of the amino acid in the active site. This is consistent with a separate allosteric site, likely in the regulatory domain.

Activation of Phenylalanine Hydroxylase by Phenylalanine Does Not Require Binding in the Active Site

PubMed Central

2015-01-01

Phenylalanine hydroxylase (PheH), a liver enzyme that catalyzes the hydroxylation of excess phenylalanine in the diet to tyrosine, is activated by phenylalanine. The lack of activity at low levels of phenylalanine has been attributed to the N-terminus of the protein’s regulatory domain acting as an inhibitory peptide by blocking substrate access to the active site. The location of the site at which phenylalanine binds to activate the enzyme is unknown, and both the active site in the catalytic domain and a separate site in the N-terminal regulatory domain have been proposed. Binding of catecholamines to the active-site iron was used to probe the accessibility of the active site. Removal of the regulatory domain increases the rate constants for association of several catecholamines with the wild-type enzyme by ∼2-fold. Binding of phenylalanine in the active site is effectively abolished by mutating the active-site residue Arg270 to lysine. The kcat/Kphe value is down 104 for the mutant enzyme, and the Km value for phenylalanine for the mutant enzyme is >0.5 M. Incubation of the R270K enzyme with phenylalanine also results in a 2-fold increase in the rate constants for catecholamine binding. The change in the tryptophan fluorescence emission spectrum seen in the wild-type enzyme upon activation by phenylalanine is also seen with the R270K mutant enzyme in the presence of phenylalanine. Both results establish that activation of PheH by phenylalanine does not require binding of the amino acid in the active site. This is consistent with a separate allosteric site, likely in the regulatory domain. PMID:25453233

Non-competitive inhibition by active site binders.

PubMed

Blat, Yuval

2010-06-01

Classical enzymology has been used for generations to understand the interactions of inhibitors with their enzyme targets. Enzymology tools enabled prediction of the biological impact of inhibitors as well as the development of novel, more potent, ones. Experiments designed to examine the competition between the tested inhibitor and the enzyme substrate(s) are the tool of choice to identify inhibitors that bind in the active site. Competition between an inhibitor and a substrate is considered a strong evidence for binding of the inhibitor in the active site, while the lack of competition suggests binding to an alternative site. Nevertheless, exceptions to this notion do exist. Active site-binding inhibitors can display non-competitive inhibition patterns. This unusual behavior has been observed with enzymes utilizing an exosite for substrate binding, isomechanism enzymes, enzymes with multiple substrates and/or products and two-step binding inhibitors. In many of these cases, the mechanisms underlying the lack of competition between the substrate and the inhibitor are well understood. Tools like alternative substrates, testing the enzyme reaction in the reverse direction and monitoring inhibition time dependence can be applied to enable distinction between 'badly behaving' active site binders and true exosite inhibitors.

Safety Oversight of Decommissioning Activities at DOE Nuclear Sites

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

Zull, Lawrence M.; Yeniscavich, William

2008-01-15

The Defense Nuclear Facilities Safety Board (Board) is an independent federal agency established by Congress in 1988 to provide nuclear safety oversight of activities at U.S. Department of Energy (DOE) defense nuclear facilities. The activities under the Board's jurisdiction include the design, construction, startup, operation, and decommissioning of defense nuclear facilities at DOE sites. This paper reviews the Board's safety oversight of decommissioning activities at DOE sites, identifies the safety problems observed, and discusses Board initiatives to improve the safety of decommissioning activities at DOE sites. The decommissioning of former defense nuclear facilities has reduced the risk of radioactive materialmore » contamination and exposure to the public and site workers. In general, efforts to perform decommissioning work at DOE defense nuclear sites have been successful, and contractors performing decommissioning work have a good safety record. Decommissioning activities have recently been completed at sites identified for closure, including the Rocky Flats Environmental Technology Site, the Fernald Closure Project, and the Miamisburg Closure Project (the Mound site). The Rocky Flats and Fernald sites, which produced plutonium parts and uranium materials for defense needs (respectively), have been turned into wildlife refuges. The Mound site, which performed R and D activities on nuclear materials, has been converted into an industrial and technology park called the Mound Advanced Technology Center. The DOE Office of Legacy Management is responsible for the long term stewardship of these former EM sites. The Board has reviewed many decommissioning activities, and noted that there are valuable lessons learned that can benefit both DOE and the contractor. As part of its ongoing safety oversight responsibilities, the Board and its staff will continue to review the safety of DOE and contractor decommissioning activities at DOE defense nuclear sites.« less

Chemical Signatures of and Precursors to Fractures Using Fluid Inclusion Stratigraphy

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

Lorie M. Dilley

Enhanced Geothermal Systems (EGS) are designed to recover heat from the subsurface by mechanically creating fractures in subsurface rocks. Open or recently closed fractures would be more susceptible to enhancing the permeability of the system. Identifying dense fracture areas as well as large open fractures from small fracture systems will assist in fracture stimulation site selection. Geothermal systems are constantly generating fractures (Moore, Morrow et al. 1987), and fluids and gases passing through rocks in these systems leave small fluid and gas samples trapped in healed microfractures. These fluid inclusions are faithful records of pore fluid chemistry. Fluid inclusions trappedmore » in minerals as the fractures heal are characteristic of the fluids that formed them, and this signature can be seen in fluid inclusion gas analysis. This report presents the results of the project to determine fracture locations by the chemical signatures from gas analysis of fluid inclusions. With this project we hope to test our assumptions that gas chemistry can distinguish if the fractures are open and bearing production fluids or represent prior active fractures and whether there are chemical signs of open fracture systems in the wall rock above the fracture. Fluid Inclusion Stratigraphy (FIS) is a method developed for the geothermal industry which applies the mass quantification of fluid inclusion gas data from drill cuttings and applying known gas ratios and compositions to determine depth profiles of fluid barriers in a modern geothermal system (Dilley, 2009; Dilley et al., 2005; Norman et al., 2005). Identifying key gas signatures associated with fractures for isolating geothermal fluid production is the latest advancement in the application of FIS to geothermal systems (Dilley and Norman, 2005; Dilley and Norman, 2007). Our hypothesis is that peaks in FIS data are related to location of fractures. Previous work (DOE Grant DE-FG36-06GO16057) has indicated differences

Trafficking receptor signatures define blood plasmablasts responding to tissue-specific immune challenge

PubMed Central

Seong, Yekyung; Lazarus, Nicole H.; Sutherland, Lusijah; Habtezion, Aida; Abramson, Tzvia; He, Xiao-Song; Greenberg, Harry B.

2017-01-01

Antibody-secreting cells are generated in regional lymphoid tissues and traffic as plasmablasts (PBs) via lymph and blood to target sites for local immunity. We used multiparameter flow cytometry to define PB trafficking programs (TPs, combinations of adhesion molecules and chemoattractant receptors) and their imprinting in patients in response to localized infection or immune insults. TPs enriched after infection or autoimmune inflammation of mucosae correlate with sites of immune response or symptoms, with different TPs imprinted during small intestinal, colon, throat, and upper respiratory immune challenge. PBs induced after intramuscular or intradermal influenza vaccination, including flu-specific antibody–secreting cells, display TPs characterized by the lack of mucosal homing receptors. PBs of healthy donors display diverse mucosa-associated TPs, consistent with homeostatic immune activity. Identification of TP signatures of PBs may facilitate noninvasive monitoring of organ-specific immune responses. PMID:28352656

Decoding a Signature-Based Model of Transcription Cofactor Recruitment Dictated by Cardinal Cis-Regulatory Elements in Proximal Promoter Regions

PubMed Central

Benner, Christopher; Hutt, Kasey R.; Stunnenberg, Rieka; Garcia-Bassets, Ivan

2013-01-01

Genome-wide maps of DNase I hypersensitive sites (DHSs) reveal that most human promoters contain perpetually active cis-regulatory elements between −150 bp and +50 bp (−150/+50 bp) relative to the transcription start site (TSS). Transcription factors (TFs) recruit cofactors (chromatin remodelers, histone/protein-modifying enzymes, and scaffold proteins) to these elements in order to organize the local chromatin structure and coordinate the balance of post-translational modifications nearby, contributing to the overall regulation of transcription. However, the rules of TF-mediated cofactor recruitment to the −150/+50 bp promoter regions remain poorly understood. Here, we provide evidence for a general model in which a series of cis-regulatory elements (here termed ‘cardinal’ motifs) prefer acting individually, rather than in fixed combinations, within the −150/+50 bp regions to recruit TFs that dictate cofactor signatures distinctive of specific promoter subsets. Subsequently, human promoters can be subclassified based on the presence of cardinal elements and their associated cofactor signatures. In this study, furthermore, we have focused on promoters containing the nuclear respiratory factor 1 (NRF1) motif as the cardinal cis-regulatory element and have identified the pervasive association of NRF1 with the cofactor lysine-specific demethylase 1 (LSD1/KDM1A). This signature might be distinctive of promoters regulating nuclear-encoded mitochondrial and other particular genes in at least some cells. Together, we propose that decoding a signature-based, expanded model of control at proximal promoter regions should lead to a better understanding of coordinated regulation of gene transcription. PMID:24244184

Coupling Between Doppler Radar Signatures and Tornado Damage Tracks

NASA Technical Reports Server (NTRS)

Jedlovec, Gary J.; Molthan, Andrew L.; Carey, Lawrence; Carcione, Brian; Smith, Matthew; Schultz, Elise V.; Schultz, Christopher; Lafontaine, Frank

2011-01-01

On April 27, 2011, the southeastern United States was raked with several episodes of severe weather. Numerous tornadoes caused extensive damage, and tragically, the deaths of over 300 people. In Alabama alone, there were 61 confirmed tornados, 4 of them produced EF5 damage, and several were on the ground an hour or more with continuous damage tracks exceeding 80km. The use of Doppler radars covering the region provided reflectivity and velocity signatures that allowed forecasters to monitors the severe storms from beginning to end issuing hundreds of severe weather warnings throughout the day. Meteorologists from the the NWS performed extensive surveys to assess the intensity, duration, and ground track of tornadoes reported during the event. Survey activities included site visits to the affected locations, analysis of radar and satellite data, aerial surveys, and interviews with eyewitnesses. Satellite data from NASA's MODIS and ASTER instruments played a helpful role in determining the location of tornado damage paths and in the assessment. High resolution multispectral and temporal composites helped forecasters corroborate their damage assessments, determine starting and ending points for tornado touchdowns, and helped to provide forecasters with a better big-picture view of the damage region. The imagery also helped to separate damage from the April 27th tornados from severe weather that occurred earlier that month. In a post analysis of the outbreak, tornado damage path signatures observed in the NASA satellite data have been correlated to "debris ball" signatures in the NWS Doppler radars and a special ARMOR dual-polarization radar operated by the University of Alabama Huntsville during the event. The Doppler radar data indicates a circular enhanced reflectivity signal and rotational couplet in the radial velocity likely associated with the tornado that is spatially correlated with the damage tracks in the observed satellite data. An algorithm to detect and

Stability across environments of the coffee variety near infrared spectral signature.

PubMed

Posada, H; Ferrand, M; Davrieux, F; Lashermes, P; Bertrand, B

2009-02-01

Previous study on food plants has shown that near infrared (NIR) spectral methods seem effective for authenticating coffee varieties. We confirm that result, but also show that inter-variety differences are not stable from one harvest to the next. We put forward the hypothesis that the spectral signature is affected by environmental factors. The purpose of this study was to find a way of reducing this environmental variance to increase the method's reliability and to enable practical application in breeding. Spectral collections were obtained from ground green coffee samples from multilocation trials. Two harvests of bean samples from 11 homozygous introgressed lines, and the cv 'Caturra' as the control, supplied from three different sites, were compared. For each site, squared Euclidean distances among the 12 varieties were estimated from the NIR spectra. Matrix correlation coefficients were assessed by the Mantel test. We obtained very good stability (high correlations) for inter-variety differences across the sites when using the two harvests data. If only the most heritable zones of the spectrum were used, there was a marked improvement in the efficiency of the method. This improvement was achieved by treating the spectrum as succession of phenotypic variables, each resulting from an environmental and genetic effect. Heritabilities were calculated with confidence intervals. A near infrared spectroscopy signature, acquired over a set of harvests, can therefore effectively characterize a coffee variety. We indicated how this typical signature can be used in breeding to assist in selection.

Pose-oblivious shape signature.

PubMed

Gal, Ran; Shamir, Ariel; Cohen-Or, Daniel

2007-01-01

A 3D shape signature is a compact representation for some essence of a shape. Shape signatures are commonly utilized as a fast indexing mechanism for shape retrieval. Effective shape signatures capture some global geometric properties which are scale, translation, and rotation invariant. In this paper, we introduce an effective shape signature which is also pose-oblivious. This means that the signature is also insensitive to transformations which change the pose of a 3D shape such as skeletal articulations. Although some topology-based matching methods can be considered pose-oblivious as well, our new signature retains the simplicity and speed of signature indexing. Moreover, contrary to topology-based methods, the new signature is also insensitive to the topology change of the shape, allowing us to match similar shapes with different genus. Our shape signature is a 2D histogram which is a combination of the distribution of two scalar functions defined on the boundary surface of the 3D shape. The first is a definition of a novel function called the local-diameter function. This function measures the diameter of the 3D shape in the neighborhood of each vertex. The histogram of this function is an informative measure of the shape which is insensitive to pose changes. The second is the centricity function that measures the average geodesic distance from one vertex to all other vertices on the mesh. We evaluate and compare a number of methods for measuring the similarity between two signatures, and demonstrate the effectiveness of our pose-oblivious shape signature within a 3D search engine application for different databases containing hundreds of models.

Source identification of uranium-containing materials at mine legacy sites in Portugal.

PubMed

Keatley, A C; Martin, P G; Hallam, K R; Payton, O D; Awbery, R; Carvalho, F P; Oliveira, J M; Silva, L; Malta, M; Scott, T B

2018-03-01

Whilst prior nuclear forensic studies have focused on identifying signatures to distinguish between different uranium deposit types, this paper focuses on providing a scientific basis for source identification of materials from different uranium mine sites within a single region, which can then be potentially used within nuclear forensics. A number of different tools, including gamma spectrometry, alpha spectrometry, mineralogy and major and minor elemental analysis, have been utilised to determine the provenance of uranium mineral samples collected at eight mine sites, located within three different uranium provinces, in Portugal. A radiation survey was initially conducted by foot and/or unmanned aerial vehicle at each site to assist sample collection. The results from each mine site were then compared to determine if individual mine sites could be distinguished based on characteristic elemental and isotopic signatures. Gamma and alpha spectrometry were used to differentiate between samples from different sites and also give an indication of past milling and mining activities. Ore samples from the different mine sites were found to be very similar in terms of gangue and uranium mineralogy. However, rarer minerals or specific impurity elements, such as calcium and copper, did permit some separation of the sites examined. In addition, classification rates using linear discriminant analysis were comparable to those in the literature. Crown Copyright © 2018. Published by Elsevier Ltd. All rights reserved.

Ionospheric plasma deterioration in the area of enhanced seismic activity as compared to antipodal sites far from seismicity

NASA Astrophysics Data System (ADS)

Gulyaeva, Tamara; Arikan, Feza; Poustovalova, Ljubov; Stanislawska, Iwona

2016-07-01

The early magnetogram records from two nearly antipodal sites at Greenwich and Melbourne corresponding to the activity level at the invariant magnetic latitude of 50 deg give a long series of geomagnetic aa indices since 1868. The aa index derived from magnetic perturbation values at only two observatories (as distinct from the planetary ap index) experiences larger extreme values if either input site is well situated to the overhead ionospheric and/or field aligned current systems producing the magnetic storm effects. Analysis of the earthquakes catalogues since 1914 has shown the area of the peak global earthquake occurrence in the Pacific Ocean southwards from the magnetic equator, and, in particular, at Australia. In the present study the ionospheric critical frequency, foF2, is analyzed from the ionosonde measurements at the nearby observatories, Canberra and Slough (Chilton), and Moscow (control site) since 1944 to 2015. The daily-hourly-annual percentage occurrence of positive ionospheric W index (pW+) and negative index (pW-) is determined. It is found that the ionospheric plasma depletion pW- of the instant foF2 as compared to the monthly median is well correlated to the aa index at all three sites but the positive storm signatures show drastic difference at Canberra (no correlation of pW+ with aa index) as compared to two other sites where the high correlation is found of the ionospheric plasma density enhancement with the geomagnetic activity. A possible suppression of the enhanced ionospheric variability over the region of intense seismicity is discussed in the paper. This study is supported by TUBITAK EEEAG 115E915.

Ionizable Side Chains at Catalytic Active Sites of Enzymes

PubMed Central

Jimenez-Morales, David; Liang, Jie

2012-01-01

Catalytic active sites of enzymes of known structure can be well defined by a modern program of computational geometry. The CASTp program was used to define and measure the volume of the catalytic active sites of 573 enzymes in the Catalytic Site Atlas database. The active sites are identified as catalytic because the amino acids they contain are known to participate in the chemical reaction catalyzed by the enzyme. Acid and base side chains are reliable markers of catalytic active sites. The catalytic active sites have 4 acid and 5 base side chains, in an average volume of 1072 Å3. The number density of acid side chains is 8.3 M (in chemical units); the number density of basic side chains is 10.6 M. The catalytic active site of these enzymes is an unusual electrostatic and steric environment in which side chains and reactants are crowded together in a mixture more like an ionic liquid than an ideal infinitely dilute solution. The electrostatics and crowding of reactants and side chains seems likely to be important for catalytic function. In three types of analogous ion channels, simulation of crowded charges accounts for the main properties of selectivity measured in a wide range of solutions and concentrations. It seems wise to use mathematics designed to study interacting complex fluids when making models of the catalytic active sites of enzymes. PMID:22484856

Discriminative structural approaches for enzyme active-site prediction.

PubMed

Kato, Tsuyoshi; Nagano, Nozomi

2011-02-15

Predicting enzyme active-sites in proteins is an important issue not only for protein sciences but also for a variety of practical applications such as drug design. Because enzyme reaction mechanisms are based on the local structures of enzyme active-sites, various template-based methods that compare local structures in proteins have been developed to date. In comparing such local sites, a simple measurement, RMSD, has been used so far. This paper introduces new machine learning algorithms that refine the similarity/deviation for comparison of local structures. The similarity/deviation is applied to two types of applications, single template analysis and multiple template analysis. In the single template analysis, a single template is used as a query to search proteins for active sites, whereas a protein structure is examined as a query to discover the possible active-sites using a set of templates in the multiple template analysis. This paper experimentally illustrates that the machine learning algorithms effectively improve the similarity/deviation measurements for both the analyses.

Magnetic Oscillations Mark Sites of Magnetic Transients in an Acoustically Active Flare

NASA Astrophysics Data System (ADS)

Lindsey, Charles A.; Donea, A.; Hudson, H. S.; Martinez Oliveros, J.; Hanson, C.

2011-05-01

The flare of 2011 February 15, in NOAA AR11158, was the first acoustically active flare of solar cycle 24, and the first observed by the Solar Dynamics Observatory (SDO). It was exceptional in a number of respects (Kosovichev 2011a,b). Sharp ribbon-like transient Doppler, and magnetic signatures swept over parts of the active region during the impulsive phase of the flare. We apply seismic holography to a 2-hr time series of HMI observations encompassing the flare. The acoustic source distribution appears to have been strongly concentrated in a single highly compact penumbral region in which the continuum-intensity signature was unusually weak. The line-of-sight magnetic transient was strong in parts of the active region, but relatively weak in the seismic-source region. On the other hand, the neighbourhoods of the regions visited by the strongest magnetic transients maintained conspicuous 5-minutes-period variations in the line of sight magnetic signature for the full 2-hr duration of the time series, before the flare as well as after. We apply standard helioseismic control diagnostics for clues as to the physics underlying 5-minute magnetic oscillations in regions conducive to magnetic transients during a flare and consider the prospective development of this property as an indicator of flare potentiality on some time scale. We make use of high-resolution data from AIA, using diffracted images where necessary to obtain good photometry where the image is otherwise saturated. This is relevant to seismic emission driven by thick-target heating in the absence of back-warming. We also use RHESSI imaging spectroscopy to compare the source distributions of HXR and seismic emission.

Adaptation of a RAS pathway activation signature from FF to FFPE tissues in colorectal cancer.

PubMed

Omolo, Bernard; Yang, Mingli; Lo, Fang Yin; Schell, Michael J; Austin, Sharon; Howard, Kellie; Madan, Anup; Yeatman, Timothy J

2016-10-19

The KRAS gene is mutated in about 40 % of colorectal cancer (CRC) cases, which has been clinically validated as a predictive mutational marker of intrinsic resistance to anti-EGFR inhibitor (EGFRi) therapy. Since nearly 60 % of patients with a wild type KRAS fail to respond to EGFRi combination therapies, there is a need to develop more reliable molecular signatures to better predict response. Here we address the challenge of adapting a gene expression signature predictive of RAS pathway activation, created using fresh frozen (FF) tissues, for use with more widely available formalin fixed paraffin-embedded (FFPE) tissues. In this study, we evaluated the translation of an 18-gene RAS pathway signature score from FF to FFPE in 54 CRC cases, using a head-to-head comparison of five technology platforms. FFPE-based technologies included the Affymetrix GeneChip (Affy), NanoString nCounter™ (NanoS), Illumina whole genome RNASeq (RNA-Acc), Illumina targeted RNASeq (t-RNA), and Illumina stranded Total RNA-rRNA-depletion (rRNA). Using Affy_FF as the "gold" standard, initial analysis of the 18-gene RAS scores on all 54 samples shows varying pairwise Spearman correlations, with (1) Affy_FFPE (r = 0.233, p = 0.090); (2) NanoS_FFPE (r = 0.608, p < 0.0001); (3) RNA-Acc_FFPE (r = 0.175, p = 0.21); (4) t-RNA_FFPE (r = -0.237, p = 0.085); (5) and t-RNA (r = -0.012, p = 0.93). These results suggest that only NanoString has successful FF to FFPE translation. The subsequent removal of identified "problematic" samples (n = 15) and genes (n = 2) further improves the correlations of Affy_FF with three of the five technologies: Affy_FFPE (r = 0.672, p < 0.0001); NanoS_FFPE (r = 0.738, p < 0.0001); and RNA-Acc_FFPE (r = 0.483, p = 0.002). Of the five technology platforms tested, NanoString technology provides a more faithful translation of the RAS pathway gene expression signature from FF to FFPE than the Affymetrix

New Surface-Enhanced Raman Sensing Chip Designed for On-Site Detection of Active Ricin in Complex Matrices Based on Specific Depurination.

PubMed

Tang, Ji-Jun; Sun, Jie-Fang; Lui, Rui; Zhang, Zong-Mian; Liu, Jing-Fu; Xie, Jian-Wei

2016-01-27

Quick and accurate on-site detection of active ricin has very important realistic significance in view of national security and defense. In this paper, optimized single-stranded oligodeoxynucleotides named poly(21dA), which function as a depurination substrate of active ricin, were screened and chemically attached on gold nanoparticles (AuNPs, ∼100 nm) via the Au-S bond [poly(21dA)-AuNPs]. Subsequently, poly(21dA)-AuNPs were assembled on a dihydrogen lipoic-acid-modified Si wafer (SH-Si), thus forming the specific surface-enhanced Raman spectroscopy (SERS) chip [poly(21dA)-AuNPs@SH-Si] for depurination of active ricin. Under optimized conditions, active ricin could specifically hydrolyze multiple adenines from poly(21dA) on the chip. This depurination-induced composition change could be conveniently monitored by measuring the distinct attenuation of the SERS signature corresponding to adenine. To improve sensitivity of this method, a silver nanoshell was deposited on post-reacted poly(21dA)-AuNPs, which lowered the limit of detection to 8.9 ng mL(-1). The utility of this well-controlled SERS chip was successfully demonstrated in food and biological matrices spiked with different concentrations of active ricin, thus showing to be very promising assay for reliable and rapid on-site detection of active ricin.

Unconditionally Secure Blind Signatures

NASA Astrophysics Data System (ADS)

Hara, Yuki; Seito, Takenobu; Shikata, Junji; Matsumoto, Tsutomu

The blind signature scheme introduced by Chaum allows a user to obtain a valid signature for a message from a signer such that the message is kept secret for the signer. Blind signature schemes have mainly been studied from a viewpoint of computational security so far. In this paper, we study blind signatures in unconditional setting. Specifically, we newly introduce a model of unconditionally secure blind signature schemes (USBS, for short). Also, we propose security notions and their formalization in our model. Finally, we propose a construction method for USBS that is provably secure in our security notions.

Ionizable side chains at catalytic active sites of enzymes.

PubMed

Jimenez-Morales, David; Liang, Jie; Eisenberg, Bob

2012-05-01

Catalytic active sites of enzymes of known structure can be well defined by a modern program of computational geometry. The CASTp program was used to define and measure the volume of the catalytic active sites of 573 enzymes in the Catalytic Site Atlas database. The active sites are identified as catalytic because the amino acids they contain are known to participate in the chemical reaction catalyzed by the enzyme. Acid and base side chains are reliable markers of catalytic active sites. The catalytic active sites have 4 acid and 5 base side chains, in an average volume of 1,072 Å(3). The number density of acid side chains is 8.3 M (in chemical units); the number density of basic side chains is 10.6 M. The catalytic active site of these enzymes is an unusual electrostatic and steric environment in which side chains and reactants are crowded together in a mixture more like an ionic liquid than an ideal infinitely dilute solution. The electrostatics and crowding of reactants and side chains seems likely to be important for catalytic function. In three types of analogous ion channels, simulation of crowded charges accounts for the main properties of selectivity measured in a wide range of solutions and concentrations. It seems wise to use mathematics designed to study interacting complex fluids when making models of the catalytic active sites of enzymes.

Signature program: a platform of basket trials.

PubMed

Slosberg, Eric D; Kang, Barinder P; Peguero, Julio; Taylor, Matthew; Bauer, Todd M; Berry, Donald A; Braiteh, Fadi; Spira, Alexander; Meric-Bernstam, Funda; Stein, Steven; Piha-Paul, Sarina A; Salvado, August

2018-04-20

Investigating targeted therapies can be challenging due to diverse tumor mutations and slow patient accrual for clinical studies. The Signature Program is a series of 8 phase 2, agent-specific basket protocols using a rapid study start-up approach involving no predetermined study sites. Each protocol evaluated 1 agent (buparlisib, dovitinib, binimetinib, encorafenib, sonidegib, BGJ398, ceritinib, or ribociclib) in patients with solid or hematologic malignancies and an actionable mutation. The primary endpoint of each study was the clinical benefit rate (ie, complete or partial response, or stable disease) at 16 weeks. A total of 192 individual sites were opened in the United States, with a median start-up time of 3.6 weeks. The most common tumor types among the 595 treated patients were colorectal (9.2%), non-small cell lung adenocarcinoma (9.1%), and ovarian (8.4%). Frequent genetic alterations were in PIK3CA , RAS , p16 , and PTEN . Overall, 30 partial or complete responses were observed with 6 compounds in 16 tumor types. The Signature Program presents a unique and successful approach for rapid signal finding across multiple tumors and allowed various agents to be evaluated in patients with rare alterations. Incorporating these program features in conventional studies could lead to improved trial efficiencies and patient outcomes.

Signature program: a platform of basket trials

PubMed Central

Peguero, Julio; Taylor, Matthew; Bauer, Todd M.; Berry, Donald A.; Braiteh, Fadi; Spira, Alexander; Meric-Bernstam, Funda; Stein, Steven; Piha-Paul, Sarina A.; Salvado, August

2018-01-01

Investigating targeted therapies can be challenging due to diverse tumor mutations and slow patient accrual for clinical studies. The Signature Program is a series of 8 phase 2, agent-specific basket protocols using a rapid study start-up approach involving no predetermined study sites. Each protocol evaluated 1 agent (buparlisib, dovitinib, binimetinib, encorafenib, sonidegib, BGJ398, ceritinib, or ribociclib) in patients with solid or hematologic malignancies and an actionable mutation. The primary endpoint of each study was the clinical benefit rate (ie, complete or partial response, or stable disease) at 16 weeks. A total of 192 individual sites were opened in the United States, with a median start-up time of 3.6 weeks. The most common tumor types among the 595 treated patients were colorectal (9.2%), non-small cell lung adenocarcinoma (9.1%), and ovarian (8.4%). Frequent genetic alterations were in PIK3CA, RAS, p16, and PTEN. Overall, 30 partial or complete responses were observed with 6 compounds in 16 tumor types. The Signature Program presents a unique and successful approach for rapid signal finding across multiple tumors and allowed various agents to be evaluated in patients with rare alterations. Incorporating these program features in conventional studies could lead to improved trial efficiencies and patient outcomes. PMID:29765547

Contextualising the topographic signature of historic mining, a scaling analysis

NASA Astrophysics Data System (ADS)

Reinhardt, Liam

2017-04-01

Mining is globally one of the most significant means by which humans alter landscapes; we do so through erosion (mining), transport, and deposition of extracted sediments (waste). The iconic Dartmoor mountain landscape of SW England ( 700km2) has experienced over 1000 years of shallow (Cu & Sn) mining that has left a pervasive imprint on the landscape. The availability of high resolution digital elevation models (<=1m) and aerial photographs @12.5 cm resolution) combined with historic records of mining activity and output make this an ideal location to investigate the topographic signature of mining. Conceptually I ask the question: how much (digital elevation model) smoothing is required to remove the human imprint from this landscape ? While we may have entered the Anthropocene other gravity driven process have imparted distinct scale-dependant signatures. How might the human signature differ from these processes and how pervasive is it at the landscape scale? Spatial scaling analysis (curvature & semi-variance) was used to quantify the topographic signature of historic mining and to determine how it differs to a) natural landforms such as bedrock tors; and b) the morphology of biological activity (e.g. peat formation). Other forms of historic activity such as peat cutting and quarrying were also investigated. The existence of 400 years of mine activity archives also makes it possible to distinguish between the imprint of differing forms of mine technology and their spatio-temporal signature. Interestingly the higher technology 19th C mines have left a much smaller topographic legacy than Medieval miners; though the former had a much greater impact in terms of heavy metal contamination.

Space Object Radiometric Modeling for Hardbody Optical Signature Database Generation

DTIC Science & Technology

2009-09-01

Introduction This presentation summarizes recent activity in monitoring spacecraft health status using passive remote optical nonimaging ...Approved for public release; distribution is unlimited. Space Object Radiometric Modeling for Hardbody Optical Signature Database Generation...It is beneficial to the observer/analyst to understand the fundamental optical signature variability associated with these detection and

Factor models for cancer signatures

NASA Astrophysics Data System (ADS)

Kakushadze, Zura; Yu, Willie

2016-11-01

We present a novel method for extracting cancer signatures by applying statistical risk models (http://ssrn.com/abstract=2732453) from quantitative finance to cancer genome data. Using 1389 whole genome sequenced samples from 14 cancers, we identify an ;overall; mode of somatic mutational noise. We give a prescription for factoring out this noise and source code for fixing the number of signatures. We apply nonnegative matrix factorization (NMF) to genome data aggregated by cancer subtype and filtered using our method. The resultant signatures have substantially lower variability than those from unfiltered data. Also, the computational cost of signature extraction is cut by about a factor of 10. We find 3 novel cancer signatures, including a liver cancer dominant signature (96% contribution) and a renal cell carcinoma signature (70% contribution). Our method accelerates finding new cancer signatures and improves their overall stability. Reciprocally, the methods for extracting cancer signatures could have interesting applications in quantitative finance.

Signatures of local adaptation along environmental gradients in a range-expanding damselfly (Ischnura elegans).

PubMed

Dudaniec, Rachael Y; Yong, Chuan Ji; Lancaster, Lesley T; Svensson, Erik I; Hansson, Bengt

2018-06-01

Insect distributions are shifting rapidly in response to climate change and are undergoing rapid evolutionary change. We investigate the molecular signatures underlying local adaptation in the range-expanding damselfly, Ischnura elegans. Using a landscape genomic approach combined with generalized dissimilarity modelling (GDM), we detect selection signatures on loci via allelic frequency change along environmental gradients. We analyse 13,612 single nucleotide polymorphisms (SNPs), derived from restriction site-associated DNA sequencing (RADseq), in 426 individuals from 25 sites spanning the I. elegans distribution in Sweden, including its expanding northern range edge. Environmental association analysis (EAA) and the magnitude of allele frequency change along the range expansion gradient revealed significant signatures of selection in relation to high maximum summer temperature, high mean annual precipitation and low wind speeds at the range edge. SNP annotations with significant signatures of selection revealed gene functions associated with ongoing range expansion, including heat shock proteins (HSP40 and HSP70), ion transport (V-ATPase) and visual processes (long-wavelength-sensitive opsin), which have implications for thermal stress response, salinity tolerance and mate discrimination, respectively. We also identified environmental thresholds where climate-mediated selection is likely to be strong, and indicate that I. elegans is rapidly adapting to the climatic environment during its ongoing range expansion. Our findings empirically validate an integrative approach for detecting spatially explicit signatures of local adaptation along environmental gradients. © 2018 John Wiley & Sons Ltd.

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

An Overview of ARL’s Multimodal Signatures Database and Web Interface

DTIC Science & Technology

2007-12-01

ActiveX components, which hindered distribution due to license agreements and run-time license software to use such components. g. Proprietary...Overview The database consists of multimodal signature data files in the HDF5 format. Generally, each signature file contains all the ancillary...only contains information in the database, Web interface, and signature files that is releasable to the public. The Web interface consists of static

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.

A prospective blood RNA signature for tuberculosis disease risk

PubMed Central

Zak, Daniel E.; Penn-Nicholson, Adam; Scriba, Thomas J.; Thompson, Ethan; Suliman, Sara; Amon, Lynn M.; Mahomed, Hassan; Erasmus, Mzwandile; Whatney, Wendy; Hussey, Gregory D.; Abrahams, Deborah; Kafaar, Fazlin; Hawkridge, Tony; Verver, Suzanne; Hughes, E. Jane; Ota, Martin; Sutherland, Jayne; Howe, Rawleigh; Dockrell, Hazel M.; Boom, W. Henry; Thiel, Bonnie; Ottenhoff, Tom H.M.; Mayanja-Kizza, Harriet; Crampin, Amelia C; Downing, Katrina; Hatherill, Mark; Valvo, Joe; Shankar, Smitha; Parida, Shreemanta K; Kaufmann, Stefan H.E.; Walzl, Gerhard; Aderem, Alan; Hanekom, Willem A.

2016-01-01

Background Identification of blood biomarkers that prospectively predict progression of Mycobacterium tuberculosis infection to tuberculosis disease may lead to interventions that impact the epidemic. Methods Healthy, M. tuberculosis infected South African adolescents were followed for 2 years; blood was collected every 6 months. A prospective signature of risk was derived from whole blood RNA-Sequencing data by comparing participants who ultimately developed active tuberculosis disease (progressors) with those who remained healthy (matched controls). After adaptation to multiplex qRT-PCR, the signature was used to predict tuberculosis disease in untouched adolescent samples and in samples from independent cohorts of South African and Gambian adult progressors and controls. The latter participants were household contacts of adults with active pulmonary tuberculosis disease. Findings Of 6,363 adolescents screened, 46 progressors and 107 matched controls were identified. A 16 gene signature of risk was identified. The signature predicted tuberculosis progression with a sensitivity of 66·1% (95% confidence interval, 63·2–68·9) and a specificity of 80·6% (79·2–82·0) in the 12 months preceding tuberculosis diagnosis. The risk signature was validated in an untouched group of adolescents (p=0·018 for RNA-Seq and p=0·0095 for qRT-PCR) and in the independent South African and Gambian cohorts (p values <0·0001 by qRT-PCR) with a sensitivity of 53·7% (42·6–64·3) and a specificity of 82·8% (76·7–86) in 12 months preceding tuberculosis. Interpretation The whole blood tuberculosis risk signature prospectively identified persons at risk of developing active tuberculosis, opening the possibility for targeted intervention to prevent the disease. Funding Bill and Melinda Gates Foundation, the National Institutes of Health, Aeras, the European Union and the South African Medical Research Council (detail at end of text). PMID:27017310

Metal active site elasticity linked to activation of homocysteine in methionine synthases

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

Koutmos, Markos; Pejchal, Robert; Bomer, Theresa M.

2008-04-02

Enzymes possessing catalytic zinc centers perform a variety of fundamental processes in nature, including methyl transfer to thiols. Cobalamin-independent (MetE) and cobalamin-dependent (MetH) methionine synthases are two such enzyme families. Although they perform the same net reaction, transfer of a methyl group from methyltetrahydrofolate to homocysteine (Hcy) to form methionine, they display markedly different catalytic strategies, modular organization, and active site zinc centers. Here we report crystal structures of zinc-replete MetE and MetH, both in the presence and absence of Hcy. Structural investigation of the catalytic zinc sites of these two methyltransferases reveals an unexpected inversion of zinc geometry uponmore » binding of Hcy and displacement of an endogenous ligand in both enzymes. In both cases a significant movement of the zinc relative to the protein scaffold accompanies inversion. These structures provide new information on the activation of thiols by zinc-containing enzymes and have led us to propose a paradigm for the mechanism of action of the catalytic zinc sites in these and related methyltransferases. Specifically, zinc is mobile in the active sites of MetE and MetH, and its dynamic nature helps facilitate the active site conformational changes necessary for thiol activation and methyl transfer.« less

Electronic Signature Policy

EPA Pesticide Factsheets

Establishes the United States Environmental Protection Agency's approach to adopting electronic signature technology and best practices to ensure electronic signatures applied to official Agency documents are legally valid and enforceable

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

Baseline shifts in coral skeletal oxygen isotopic composition: a signature of symbiont shuffling?

NASA Astrophysics Data System (ADS)

Carilli, J. E.; Charles, C. D.; Garren, M.; McField, M.; Norris, R. D.

2013-06-01

Decades-long records of the stable isotopic composition of coral skeletal cores were analyzed from four sites on the Mesoamerican Reef. Two of the sites exhibited baseline shifts in oxygen isotopic composition after known coral bleaching events. Changes in pH at the calcification site caused by a change in the associated symbiont community are invoked to explain the observed shift in the isotopic composition. To test the hypothesis that changes in symbiont clade could affect skeletal chemistry, additional coral samples were collected from Belize for paired Symbiodinium identification and skeletal stable isotopic analysis. We found some evidence that skeletal stable isotopic composition may be affected by symbiont clade and suggest this is an important topic for future investigation. If different Symbiodinium clades leave consistent signatures in skeletal geochemical composition, the signature will provide a method to quantify past symbiont shuffling events, important for understanding how corals are likely to respond to climate change.

The use of spectral skin reflectivity and laser doppler vibrometry data to determine the optimal site and wavelength to collect human vital sign signatures

NASA Astrophysics Data System (ADS)

Byrd, Kenneth A.; Kaur, Balvinder; Hodgkin, Van A.

2012-06-01

The carotid artery has been used extensively by researchers to demonstrate that Laser Doppler Vibrometry (LDV) is capable of exploiting vital sign signatures from cooperative human subjects at stando. Research indicates that, the carotid, although good for cooperative and non-traumatic scenarios, is one of the first vital signs to become absent or irregular when a casualty is hemorrhaging and in progress to circulatory (hypovolemic) shock. In an effort to determine the optimal site and wavelength to measure vital signs off human skin, a human subject data collection was executed whereby 14 subjects had their spectral skin reflectivity and vital signs measured at five collection sites (carotid artery, chest, back, right wrist and left wrist). In this paper, we present our findings on using LDV and re ectivity data to determine the optimal collection site and wavelength that should be used to sense pulse signals from quiet and relatively motionless human subjects at stando. In particular, we correlate maximum levels of re ectivity across the ensemble of 14 subjects with vital sign measurements made with an LDV at two ranges, for two scenarios.

Littoral assessment of mine burial signatures (LAMBS): buried landmine/background spectral-signature analyses

NASA Astrophysics Data System (ADS)

Kenton, Arthur C.; Geci, Duane M.; Ray, Kristofer J.; Thomas, Clayton M.; Salisbury, John W.; Mars, John C.; Crowley, James K.; Witherspoon, Ned H.; Holloway, John H., Jr.

2004-09-01

The objective of the Office of Naval Research (ONR) Rapid Overt Reconnaissance (ROR) program and the Airborne Littoral Reconnaissance Technologies (ALRT) project's LAMBS effort is to determine if electro-optical spectral discriminants exist that are useful for the detection of land mines in littoral regions. Statistically significant buried mine overburden and background signature data were collected over a wide spectral range (0.35 to 14 μm) to identify robust spectral features that might serve as discriminants for new airborne sensor concepts. LAMBS has expanded previously collected databases to littoral areas - primarily dry and wet sandy soils - where tidal, surf, and wind conditions can severely modify spectral signatures. At AeroSense 2003, we reported completion of three buried mine collections at an inland bay, Atlantic and Gulf of Mexico beach sites. We now report LAMBS spectral database analyses results using metrics which characterize the detection performance of general types of spectral detection algorithms. These metrics include mean contrast, spectral signal-to-clutter, covariance, information content, and spectral matched filter analyses. Detection performance of the buried land mines was analyzed with regard to burial age, background type, and environmental conditions. These analyses considered features observed due to particle size differences, surface roughness, surface moisture, and compositional differences.

Nicotinamide Cofactors Suppress Active-Site Labeling of Aldehyde Dehydrogenases.

PubMed

Stiti, Naim; Chandrasekar, Balakumaran; Strubl, Laura; Mohammed, Shabaz; Bartels, Dorothea; van der Hoorn, Renier A L

2016-06-17

Active site labeling by (re)activity-based probes is a powerful chemical proteomic tool to globally map active sites in native proteomes without using substrates. Active site labeling is usually taken as a readout for the active state of the enzyme because labeling reflects the availability and reactivity of active sites, which are hallmarks for enzyme activities. Here, we show that this relationship holds tightly, but we also reveal an important exception to this rule. Labeling of Arabidopsis ALDH3H1 with a chloroacetamide probe occurs at the catalytic Cys, and labeling is suppressed upon nitrosylation and oxidation, and upon treatment with other Cys modifiers. These experiments display a consistent and strong correlation between active site labeling and enzymatic activity. Surprisingly, however, labeling is suppressed by the cofactor NAD(+), and this property is shared with other members of the ALDH superfamily and also detected for unrelated GAPDH enzymes with an unrelated hydantoin-based probe in crude extracts of plant cell cultures. Suppression requires cofactor binding to its binding pocket. Labeling is also suppressed by ALDH modulators that bind at the substrate entrance tunnel, confirming that labeling occurs through the substrate-binding cavity. Our data indicate that cofactor binding adjusts the catalytic Cys into a conformation that reduces the reactivity toward chloroacetamide probes.

Quantum mechanical design of enzyme active sites.

PubMed

Zhang, Xiyun; DeChancie, Jason; Gunaydin, Hakan; Chowdry, Arnab B; Clemente, Fernando R; Smith, Adam J T; Handel, T M; Houk, K N

2008-02-01

The design of active sites has been carried out using quantum mechanical calculations to predict the rate-determining transition state of a desired reaction in presence of the optimal arrangement of catalytic functional groups (theozyme). Eleven versatile reaction targets were chosen, including hydrolysis, dehydration, isomerization, aldol, and Diels-Alder reactions. For each of the targets, the predicted mechanism and the rate-determining transition state (TS) of the uncatalyzed reaction in water is presented. For the rate-determining TS, a catalytic site was designed using naturalistic catalytic units followed by an estimation of the rate acceleration provided by a reoptimization of the catalytic site. Finally, the geometries of the sites were compared to the X-ray structures of related natural enzymes. Recent advances in computational algorithms and power, coupled with successes in computational protein design, have provided a powerful context for undertaking such an endeavor. We propose that theozymes are excellent candidates to serve as the active site models for design processes.

1 CFR 18.7 - Signature.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 1 General Provisions 1 2010-01-01 2010-01-01 false Signature. 18.7 Section 18.7 General Provisions... PREPARATION AND TRANSMITTAL OF DOCUMENTS GENERALLY § 18.7 Signature. The original and each duplicate original... stamped beneath the signature. Initialed or impressed signatures will not be accepted. Documents submitted...

Experimental study of ELF signatures developed by ballistic missile launch

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

Peglow, S.G.; Rynne, T.M.

1993-04-08

The Lawrence Livermore National Laboratory (Livermore, CA) and SARA, Inc. participated in the ATMD missile launch activities that occurred at WSMR during January 1993. These tests involved the launch of Lance missiles with a subsequent direction of F-15Es into the launch area for subsequent detection and simulated destruction of redeployed missile launchers, LLNL and SARA deployed SARN`s ELF sensors and various data acquisition systems for monitoring of basic phenomena. On 25 January 1993, a single missile launch allowed initial measurements of the phenomena and an assessment of appropriate sensor sensitivity settings as well as the appropriateness of the sensor deploymentmore » sites (e.g., with respect to man-made ELF sources such as power distributions and communication lines). On 27 January 1993, a measurement of a double launch of Lance missiles was performed. This technical report covers the results of the analysis of latter measurements. An attempt was made to measure low frequency electromagnetic signatures that may be produced during a missile launch. Hypothetical signature production mechanisms include: (1) Perturbations of the earth geo-potential during the launch of the missile. This signature may arise from the interaction of the ambient electric field with the conducting body of the missile as well as the partially ionized exhaust plume. (2) Production of spatial, charge sources from triboelectric-like mechanisms. Such effects may occur during the initial interaction of the missile plume with the ground material and lead to an initial {open_quotes}spike{close_quotes} output, Additionally, there may exist charge transfer mechanisms produced during the exhausting of the burnt fuel oxidizer.« less

Utility of Characterizing and Monitoring Suspected Underground Nuclear Sites with VideoSAR

NASA Astrophysics Data System (ADS)

Dauphin, S. M.; Yocky, D. A.; Riley, R.; Calloway, T. M.; Wahl, D. E.

2016-12-01

Sandia National Laboratories proposed using airborne synthetic aperture RADAR (SAR) collected in VideoSAR mode to characterize the Underground Nuclear Explosion Signature Experiment (UNESE) test bed site at the Nevada National Security Site (NNSS). The SNL SAR collected airborne, Ku-band (16.8 GHz center frequency), 0.2032 meter ground resolution over NNSS in August 2014 and X-band (9.6 GHz), 0.1016 meter ground resolution fully-polarimetric SAR in April 2015. This paper reports the findings of processing and exploiting VideoSAR for creating digital elevation maps, detecting cultural artifacts and exploiting full-circle polarimetric signatures. VideoSAR collects a continuous circle of phase history data, therefore, imagery can be formed over the 360-degrees of the site. Since the Ku-band VideoSAR had two antennas suitable for interferometric digital elevation mapping (DEM), DEMs could be generated over numerous aspect angles, filling in holes created by targets with height by imaging from all sides. Also, since the X-band VideoSAR was fully-polarimetric, scattering signatures could be gleaned from all angles also. Both of these collections can be used to find man-made objects and changes in elevation that might indicate testing activities. VideoSAR provides a unique, coherent measure of ground objects allowing one to create accurate DEMS, locate man-made objects, and identify scattering signatures via polarimetric exploitation. Sandia National Laboratories is a multi-program laboratory managed and operated by Sandia Corporation, a wholly owned subsidiary of Lockheed Martin Corporation, for the U.S. Department of Energy's National Nuclear Security Administration under contract DE-AC04-94AL85000. The authors would like to thank the National Nuclear Security Administration, Defense Nuclear Nonproliferation Research and Development, for sponsoring this work. We would also like to thank the Underground Nuclear Explosion Signatures Experiment team, a multi

Simulating realistic predator signatures in quantitative fatty acid signature analysis

USGS Publications Warehouse

Bromaghin, Jeffrey F.

2015-01-01

Diet estimation is an important field within quantitative ecology, providing critical insights into many aspects of ecology and community dynamics. Quantitative fatty acid signature analysis (QFASA) is a prominent method of diet estimation, particularly for marine mammal and bird species. Investigators using QFASA commonly use computer simulation to evaluate statistical characteristics of diet estimators for the populations they study. Similar computer simulations have been used to explore and compare the performance of different variations of the original QFASA diet estimator. In both cases, computer simulations involve bootstrap sampling prey signature data to construct pseudo-predator signatures with known properties. However, bootstrap sample sizes have been selected arbitrarily and pseudo-predator signatures therefore may not have realistic properties. I develop an algorithm to objectively establish bootstrap sample sizes that generates pseudo-predator signatures with realistic properties, thereby enhancing the utility of computer simulation for assessing QFASA estimator performance. The algorithm also appears to be computationally efficient, resulting in bootstrap sample sizes that are smaller than those commonly used. I illustrate the algorithm with an example using data from Chukchi Sea polar bears (Ursus maritimus) and their marine mammal prey. The concepts underlying the approach may have value in other areas of quantitative ecology in which bootstrap samples are post-processed prior to their use.

Five Guidelines for Selecting Hydrological Signatures

NASA Astrophysics Data System (ADS)

McMillan, H. K.; Westerberg, I.; Branger, F.

2017-12-01

Hydrological signatures are index values derived from observed or modeled series of hydrological data such as rainfall, flow or soil moisture. They are designed to extract relevant information about hydrological behavior, such as to identify dominant processes, and to determine the strength, speed and spatiotemporal variability of the rainfall-runoff response. Hydrological signatures play an important role in model evaluation. They allow us to test whether particular model structures or parameter sets accurately reproduce the runoff generation processes within the watershed of interest. Most modeling studies use a selection of different signatures to capture different aspects of the catchment response, for example evaluating overall flow distribution as well as high and low flow extremes and flow timing. Such studies often choose their own set of signatures, or may borrow subsets of signatures used in multiple other works. The link between signature values and hydrological processes is not always straightforward, leading to uncertainty and variability in hydrologists' signature choices. In this presentation, we aim to encourage a more rigorous approach to hydrological signature selection, which considers the ability of signatures to represent hydrological behavior and underlying processes for the catchment and application in question. To this end, we propose a set of guidelines for selecting hydrological signatures. We describe five criteria that any hydrological signature should conform to: Identifiability, Robustness, Consistency, Representativeness, and Discriminatory Power. We describe an example of the design process for a signature, assessing possible signature designs against the guidelines above. Due to their ubiquity, we chose a signature related to the Flow Duration Curve, selecting the FDC mid-section slope as a proposed signature to quantify catchment overall behavior and flashiness. We demonstrate how assessment against each guideline could be used to

Signatures of coronal rain observed in the chromosphere of an Active Region Filament

NASA Astrophysics Data System (ADS)

Pillet, V. M.; McAteer, J.

2016-12-01

Using He 10830A spectropolarimetric data from the Tenerife Infrared Polarimeter (TIP) in a rather compact active region neutral line, we observe a persistent chromospheric downflow on both sides of the neutral line that we interpret as the signature of rain from the Corona. The photospheric Si I line also present in this spectral region allows studying the continuation of the chromospheric downflow into the deeper areas dominated by granulation. Full reconstruction of the photospheric and chromospheric vector magnetic field showed that the active region filament was the central, axial, part of a magnetic flux rope. These observations demonstrate the potential of this spectral region to monitor the magnetic field and plasma motions in solar filaments. NMSU and NSO are teaming to start a synoptic program at the DST (Sac Peak) that uses this spectral region to track the evolution of magnetic fields and flows in solar filaments. We briefly present the characteristics of the synoptic program.

Field site selection

NASA Technical Reports Server (NTRS)

Schwarz, D. E.; Ellefsen, R. E.

1981-01-01

Several general guidelines should be kept in mind when considering the selection of field sites for teaching remote sensing fundamentals. Proximity and vantage point are two very practical considerations. Only through viewing a broad enough area to place the site in context can one make efficient use of a site. The effects of inclement weather when selecting sites should be considered. If field work is to be an effective tool to illustrate remote sensing principles, the following criteria are critical: (1) the site must represent the range of class interest; (2) the site must have a theme or add something no other site offers; (3) there should be intrasite variation within the theme; (4) ground resolution and spectral signature distinction should be illustrated; and (5) the sites should not be ordered sequentially.

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

Active and regulatory sites of cytosolic 5'-nucleotidase.

PubMed

Pesi, Rossana; Allegrini, Simone; Careddu, Maria Giovanna; Filoni, Daniela Nicole; Camici, Marcella; Tozzi, Maria Grazia

2010-12-01

Cytosolic 5'-nucleotidase (cN-II), which acts preferentially on 6-hydroxypurine nucleotides, is essential for the survival of several cell types. cN-II catalyses both the hydrolysis of nucleotides and transfer of their phosphate moiety to a nucleoside acceptor through formation of a covalent phospho-intermediate. Both activities are regulated by a number of phosphorylated compounds, such as diadenosine tetraphosphate (Ap₄A), ADP, ATP, 2,3-bisphosphoglycerate (BPG) and phosphate. On the basis of a partial crystal structure of cN-II, we mutated two residues located in the active site, Y55 and T56. We ascertained that the ability to catalyse the transfer of phosphate depends on the presence of a bulky residue in the active site very close to the aspartate residue that forms the covalent phospho-intermediate. The molecular model indicates two possible sites at which adenylic compounds may interact. We mutated three residues that mediate interaction in the first activation site (R144, N154, I152) and three in the second (F127, M436 and H428), and found that Ap₄A and ADP interact with the same site, but the sites for ATP and BPG remain uncertain. The structural model indicates that cN-II is a homotetrameric protein that results from interaction through a specific interface B of two identical dimers that have arisen from interaction of two identical subunits through interface A. Point mutations in the two interfaces and gel-filtration experiments indicated that the dimer is the smallest active oligomerization state. Finally, gel-filtration and light-scattering experiments demonstrated that the native enzyme exists as a tetramer, and no further oligomerization is required for enzyme activation. © 2010 The Authors Journal compilation © 2010 FEBS.

Water in the Active Site of Ketosteroid Isomerase

PubMed Central

Hanoian, Philip; Hammes-Schiffer, Sharon

2011-01-01

Classical molecular dynamics simulations were utilized to investigate the structural and dynamical properties of water in the active site of ketosteroid isomerase (KSI) to provide insight into the role of these water molecules in the enzyme-catalyzed reaction. This reaction is thought to proceed via a dienolate intermediate that is stabilized by hydrogen bonding with residues Tyr16 and Asp103. A comparative study was performed for the wild-type (WT) KSI and the Y16F, Y16S, and Y16F/Y32F/Y57F (FFF) mutants. These systems were studied with three different bound ligands: equilenin, which is an intermediate analog, and the intermediate states of two steroid substrates. Several distinct water occupation sites were identified in the active site of KSI for the WT and mutant systems. Three additional sites were identified in the Y16S mutant that were not occupied in WT KSI or the other mutants studied. The number of water molecules directly hydrogen bonded to the ligand oxygen was approximately two waters in the Y16S mutant, one water in the Y16F and FFF mutants, and intermittent hydrogen bonding of one water molecule in WT KSI. The molecular dynamics trajectories of the Y16F and FFF mutants reproduced the small conformational changes of residue 16 observed in the crystal structures of these two mutants. Quantum mechanical/molecular mechanical calculations of 1H NMR chemical shifts of the protons in the active site hydrogen-bonding network suggest that the presence of water in the active site does not prevent the formation of short hydrogen bonds with far-downfield chemical shifts. The molecular dynamics simulations indicate that the active site water molecules exchange much more frequently for WT KSI and the FFF mutant than for the Y16F and Y16S mutants. This difference is most likely due to the hydrogen-bonding interaction between Tyr57 and an active site water molecule that is persistent in the Y16F and Y16S mutants but absent in the FFF mutant and significantly less

Water in the active site of ketosteroid isomerase.

PubMed

Hanoian, Philip; Hammes-Schiffer, Sharon

2011-08-09

Classical molecular dynamics simulations were utilized to investigate the structural and dynamical properties of water in the active site of ketosteroid isomerase (KSI) to provide insight into the role of these water molecules in the enzyme-catalyzed reaction. This reaction is thought to proceed via a dienolate intermediate that is stabilized by hydrogen bonding with residues Tyr16 and Asp103. A comparative study was performed for the wild-type (WT) KSI and the Y16F, Y16S, and Y16F/Y32F/Y57F (FFF) mutants. These systems were studied with three different bound ligands: equilenin, which is an intermediate analog, and the intermediate states of two steroid substrates. Several distinct water occupation sites were identified in the active site of KSI for the WT and mutant systems. Three additional sites were identified in the Y16S mutant that were not occupied in WT KSI or the other mutants studied. The number of water molecules directly hydrogen bonded to the ligand oxygen was approximately two in the Y16S mutant and one in the Y16F and FFF mutants, with intermittent hydrogen bonding of one water molecule in WT KSI. The molecular dynamics trajectories of the Y16F and FFF mutants reproduced the small conformational changes of residue 16 observed in the crystal structures of these two mutants. Quantum mechanical/molecular mechanical calculations of (1)H NMR chemical shifts of the protons in the active site hydrogen-bonding network suggest that the presence of water in the active site does not prevent the formation of short hydrogen bonds with far-downfield chemical shifts. The molecular dynamics simulations indicate that the active site water molecules exchange much more frequently for WT KSI and the FFF mutant than for the Y16F and Y16S mutants. This difference is most likely due to the hydrogen-bonding interaction between Tyr57 and an active site water molecule that is persistent in the Y16F and Y16S mutants but absent in the FFF mutant and significantly less probable

Active Site Characterization of Proteases Sequences from Different Species of Aspergillus.

PubMed

Morya, V K; Yadav, Virendra K; Yadav, Sangeeta; Yadav, Dinesh

2016-09-01

A total of 129 proteases sequences comprising 43 serine proteases, 36 aspartic proteases, 24 cysteine protease, 21 metalloproteases, and 05 neutral proteases from different Aspergillus species were analyzed for the catalytically active site residues using MEROPS database and various bioinformatics tools. Different proteases have predominance of variable active site residues. In case of 24 cysteine proteases of Aspergilli, the predominant active site residues observed were Gln193, Cys199, His364, Asn384 while for 43 serine proteases, the active site residues namely Asp164, His193, Asn284, Ser349 and Asp325, His357, Asn454, Ser519 were frequently observed. The analysis of 21 metalloproteases of Aspergilli revealed Glu298 and Glu388, Tyr476 as predominant active site residues. In general, Aspergilli species-specific active site residues were observed for different types of protease sequences analyzed. The phylogenetic analysis of these 129 proteases sequences revealed 14 different clans representing different types of proteases with diverse active site residues.

Half-of-the-sites reactivity of outer-membrane phospholipase A against an active-site-directed inhibitor.

PubMed

Ubarretxena-Belandia, I; Cox, R C; Dijkman, R; Egmond, M R; Verheij, H M; Dekker, N

1999-03-01

The reaction of a novel active-site-directed phospholipase A1 inhibitor with the outer-membrane phospholipase A (OMPLA) was investigated. The inhibitor 1-p-nitrophenyl-octylphosphonate-2-tridecylcarbamoyl-3-et hanesulfonyl -amino-3-deoxy-sn-glycerol irreversibly inactivated OMPLA. The inhibition reaction did not require the cofactor calcium or an unprotonated active-site His142. The inhibition of the enzyme solubilized in hexadecylphosphocholine micelles was characterized by a rapid (t1/2 = 20 min) and complete loss of enzymatic activity, concurrent with the covalent modification of 50% of the active-site serines, as judged from the amount of p-nitrophenolate (PNP) released. Modification of the remaining 50% occurred at a much lower rate, indicative of half-of-the-sites reactivity against the inhibitor of this dimeric enzyme. Inhibition of monomeric OMPLA solubilized in hexadecyl-N,N-dimethyl-1-ammonio-3-propanesulfonate resulted in an equimolar monophasic release of PNP, concurrent with the loss of enzymatic activity (t1/2 = 14 min). The half-of-the-sites reactivity is discussed in view of the dimeric nature of this enzyme.

Physical activity and cancer risk: dose-response and cancer, all sites and site-specific.

PubMed

Thune, I; Furberg, A S

2001-06-01

The association between physical activity and overall and site-specific cancer risk is elaborated in relation to whether any observed dose-response association between physical activity and cancer can be interpreted in terms of how much physical activity (type, intensity, duration, frequency) is needed to influence site- and gender-specific cancer risk. Observational studies were reviewed that have examined the independent effect of the volume of occupational physical activity (OPA) and/or leisure time physical activity (LPA) on overall and site-specific cancer risk. The evidence of cohort and case-control studies suggests that both leisure time and occupational physical activity protect against overall cancer risk, with a graded dose-response association suggested in both sexes. Confounding effects such as diet, body weight, and parity are often included as a covariate in the analyses, with little influence on the observed associations. A crude graded inverse dose-response association was observed between physical activity and colon cancer in 48 studies including 40,674 colon/colorectal cancer cases for both sexes. A dose-response effect of physical activity on colon cancer risk was especially observed, when participation in activities of at least moderate activity (>4.5 MET) and demonstrated by activities expressed as MET-hours per week. An observed inverse association with a dose-response relationship between physical activity and breast cancer was also identified in the majority of the 41 studies including 108,031 breast cancer cases. The dose-response relationship was in particular observed in case-control studies and supported by observations in cohort studies when participation in activities of at least moderate activity (>4.5 MET) and demonstrated by activities expressed by MET-hours per week. This association between physical activity and breast cancer risk is possibly dependent on age at exposure, age at diagnosis, menopausal status and other effect

Littoral Assessment of Mine Burial Signatures (LAMBS) buried land mine/background spectral signature analyses

USGS Publications Warehouse

Kenton, A.C.; Geci, D.M.; Ray, K.J.; Thomas, C.M.; Salisbury, J.W.; Mars, J.C.; Crowley, J.K.; Witherspoon, N.H.; Holloway, J.H.; Harmon R.S.Broach J.T.Holloway, Jr. J.H.

2004-01-01

The objective of the Office of Naval Research (ONR) Rapid Overt Reconnaissance (ROR) program and the Airborne Littoral Reconnaissance Technologies (ALRT) project's LAMBS effort is to determine if electro-optical spectral discriminants exist that are useful for the detection of land mines in littoral regions. Statistically significant buried mine overburden and background signature data were collected over a wide spectral range (0.35 to 14 ??m) to identify robust spectral features that might serve as discriminants for new airborne sensor concepts. LAMBS has expanded previously collected databases to littoral areas - primarily dry and wet sandy soils - where tidal, surf, and wind conditions can severely modify spectral signatures. At AeroSense 2003, we reported completion of three buried mine collections at an inland bay, Atlantic and Gulf of Mexico beach sites.1 We now report LAMBS spectral database analyses results using metrics which characterize the detection performance of general types of spectral detection algorithms. These metrics include mean contrast, spectral signal-to-clutter, covariance, information content, and spectral matched filter analyses. Detection performance of the buried land mines was analyzed with regard to burial age, background type, and environmental conditions. These analyses considered features observed due to particle size differences, surface roughness, surface moisture, and compositional differences.

Active Site Metal Occupancy and Cyclic Di-GMP Phosphodiesterase Activity of Thermotoga maritima HD-GYP.

PubMed

Miner, Kyle D; Kurtz, Donald M

2016-02-16

HD-GYPs make up a subclass of the metal-dependent HD phosphohydrolase superfamily and catalyze conversion of cyclic di(3',5')-guanosine monophosphate (c-di-GMP) to 5'-phosphoguanylyl-(3'→5')-guanosine (pGpG) and GMP. Until now, the only reported crystal structure of an HD-GYP that also exhibits c-di-GMP phosphodiesterase activity contains a His/carboxylate ligated triiron active site. However, other structural and phylogenetic correlations indicate that some HD-GYPs contain dimetal active sites. Here we provide evidence that an HD-GYP c-di-GMP phosphodiesterase, TM0186, from Thermotoga maritima can accommodate both di- and trimetal active sites. We show that an as-isolated iron-containing TM0186 has an oxo/carboxylato-bridged diferric site, and that the reduced (diferrous) form is necessary and sufficient to catalyze conversion of c-di-GMP to pGpG, but that conversion of pGpG to GMP requires more than two metals per active site. Similar c-di-GMP phosphodiesterase activities were obtained with divalent iron or manganese. On the basis of activity correlations with several putative metal ligand residue variants and molecular dynamics simulations, we propose that TM0186 can accommodate both di- and trimetal active sites. Our results also suggest that a Glu residue conserved in a subset of HD-GYPs is required for formation of the trimetal site and can also serve as a labile ligand to the dimetal site. Given the anaerobic growth requirement of T. maritima, we suggest that this HD-GYP can function in vivo with either divalent iron or manganese occupying di- and trimetal sites.

Identification and Characteristics of Signature Whistles in Wild Bottlenose Dolphins (Tursiops truncatus) from Namibia

PubMed Central

Elwen, Simon Harvey; Nastasi, Aurora

2014-01-01

A signature whistle type is a learned, individually distinctive whistle type in a dolphin's acoustic repertoire that broadcasts the identity of the whistle owner. The acquisition and use of signature whistles indicates complex cognitive functioning that requires wider investigation in wild dolphin populations. Here we identify signature whistle types from a population of approximately 100 wild common bottlenose dolphins (Tursiops truncatus) inhabiting Walvis Bay, and describe signature whistle occurrence, acoustic parameters and temporal production. A catalogue of 43 repeatedly emitted whistle types (REWTs) was generated by analysing 79 hrs of acoustic recordings. From this, 28 signature whistle types were identified using a method based on the temporal patterns in whistle sequences. A visual classification task conducted by 5 naïve judges showed high levels of agreement in classification of whistles (Fleiss-Kappa statistic, κ = 0.848, Z = 55.3, P<0.001) and supported our categorisation. Signature whistle structure remained stable over time and location, with most types (82%) recorded in 2 or more years, and 4 identified at Walvis Bay and a second field site approximately 450 km away. Whistle acoustic parameters were consistent with those of signature whistles documented in Sarasota Bay (Florida, USA). We provide evidence of possible two-voice signature whistle production by a common bottlenose dolphin. Although signature whistle types have potential use as a marker for studying individual habitat use, we only identified approximately 28% of those from the Walvis Bay population, despite considerable recording effort. We found that signature whistle type diversity was higher in larger dolphin groups and groups with calves present. This is the first study describing signature whistles in a wild free-ranging T. truncatus population inhabiting African waters and it provides a baseline on which more in depth behavioural studies can be based. PMID:25203814

Diffusional correlations among multiple active sites in a single enzyme.

PubMed

Echeverria, Carlos; Kapral, Raymond

2014-04-07

Simulations of the enzymatic dynamics of a model enzyme containing multiple substrate binding sites indicate the existence of diffusional correlations in the chemical reactivity of the active sites. A coarse-grain, particle-based, mesoscopic description of the system, comprising the enzyme, the substrate, the product and solvent, is constructed to study these effects. The reactive and non-reactive dynamics is followed using a hybrid scheme that combines molecular dynamics for the enzyme, substrate and product molecules with multiparticle collision dynamics for the solvent. It is found that the reactivity of an individual active site in the multiple-active-site enzyme is reduced substantially, and this effect is analyzed and attributed to diffusive competition for the substrate among the different active sites in the enzyme.

QFASAR: Quantitative fatty acid signature analysis with R

USGS Publications Warehouse

Bromaghin, Jeffrey F.

2017-01-01

Knowledge of predator diets provides essential insights into their ecology, yet diet estimation is challenging and remains an active area of research.Quantitative fatty acid signature analysis (QFASA) is a popular method of estimating diet composition that continues to be investigated and extended. However, software to implement QFASA has only recently become publicly available.I summarize a new R package, qfasar, for diet estimation using QFASA methods. The package also provides functionality to evaluate and potentially improve the performance of a library of prey signature data, compute goodness-of-fit diagnostics, and support simulation-based research. Several procedures in the package have not previously been published.qfasar makes traditional and recently published QFASA diet estimation methods accessible to ecologists for the first time. Use of the package is illustrated with signature data from Chukchi Sea polar bears and potential prey species.

Validation of a remote sensing model to identify Simulium damnosum s.l. breeding sites in Sub-Saharan Africa.

PubMed

Jacob, Benjamin G; Novak, Robert J; Toe, Laurent D; Sanfo, Moussa; Griffith, Daniel A; Lakwo, Thomson L; Habomugisha, Peace; Katabarwa, Moses N; Unnasch, Thomas R

2013-01-01

Recently, most onchocerciasis control programs have begun to focus on elimination. Developing an effective elimination strategy relies upon accurately mapping the extent of endemic foci. In areas of Africa that suffer from a lack of infrastructure and/or political instability, developing such accurate maps has been difficult. Onchocerciasis foci are localized near breeding sites for the black fly vectors of the infection. The goal of this study was to conduct ground validation studies to evaluate the sensitivity and specificity of a remote sensing model developed to predict S. damnosum s.l. breeding sites. Remote sensing images from Togo were analyzed to identify areas containing signature characteristics of S. damnosum s.l. breeding habitat. All 30 sites with the spectral signature were found to contain S. damnosum larvae, while 0/52 other sites judged as likely to contain larvae were found to contain larvae. The model was then used to predict breeding sites in Northern Uganda. This area is hyper-endemic for onchocerciasis, but political instability had precluded mass distribution of ivermectin until 2009. Ground validation revealed that 23/25 sites with the signature contained S. damnosum larvae, while 8/10 sites examined lacking the signature were larvae free. Sites predicted to have larvae contained significantly more larvae than those that lacked the signature. This study suggests that a signature extracted from remote sensing images may be used to predict the location of S. damnosum s.l. breeding sites with a high degree of accuracy. This method should be of assistance in predicting communities at risk for onchocerciasis in areas of Africa where ground-based epidemiological surveys are difficult to implement.

Validation of a Remote Sensing Model to Identify Simulium damnosum s.l. Breeding Sites in Sub-Saharan Africa

PubMed Central

Jacob, Benjamin G.; Novak, Robert J.; Toe, Laurent D.; Sanfo, Moussa; Griffith, Daniel A.; Lakwo, Thomson L.; Habomugisha, Peace; Katabarwa, Moses N.; Unnasch, Thomas R.

2013-01-01

Background Recently, most onchocerciasis control programs have begun to focus on elimination. Developing an effective elimination strategy relies upon accurately mapping the extent of endemic foci. In areas of Africa that suffer from a lack of infrastructure and/or political instability, developing such accurate maps has been difficult. Onchocerciasis foci are localized near breeding sites for the black fly vectors of the infection. The goal of this study was to conduct ground validation studies to evaluate the sensitivity and specificity of a remote sensing model developed to predict S. damnosum s.l. breeding sites. Methodology/Principal Findings Remote sensing images from Togo were analyzed to identify areas containing signature characteristics of S. damnosum s.l. breeding habitat. All 30 sites with the spectral signature were found to contain S. damnosum larvae, while 0/52 other sites judged as likely to contain larvae were found to contain larvae. The model was then used to predict breeding sites in Northern Uganda. This area is hyper-endemic for onchocerciasis, but political instability had precluded mass distribution of ivermectin until 2009. Ground validation revealed that 23/25 sites with the signature contained S. damnosum larvae, while 8/10 sites examined lacking the signature were larvae free. Sites predicted to have larvae contained significantly more larvae than those that lacked the signature. Conclusions/Significance This study suggests that a signature extracted from remote sensing images may be used to predict the location of S. damnosum s.l. breeding sites with a high degree of accuracy. This method should be of assistance in predicting communities at risk for onchocerciasis in areas of Africa where ground-based epidemiological surveys are difficult to implement. PMID:23936571

Uncertainty in hydrological signatures

NASA Astrophysics Data System (ADS)

McMillan, Hilary; Westerberg, Ida

2015-04-01

Information that summarises the hydrological behaviour or flow regime of a catchment is essential for comparing responses of different catchments to understand catchment organisation and similarity, and for many other modelling and water-management applications. Such information types derived as an index value from observed data are known as hydrological signatures, and can include descriptors of high flows (e.g. mean annual flood), low flows (e.g. mean annual low flow, recession shape), the flow variability, flow duration curve, and runoff ratio. Because the hydrological signatures are calculated from observed data such as rainfall and flow records, they are affected by uncertainty in those data. Subjective choices in the method used to calculate the signatures create a further source of uncertainty. Uncertainties in the signatures may affect our ability to compare different locations, to detect changes, or to compare future water resource management scenarios. The aim of this study was to contribute to the hydrological community's awareness and knowledge of data uncertainty in hydrological signatures, including typical sources, magnitude and methods for its assessment. We proposed a generally applicable method to calculate these uncertainties based on Monte Carlo sampling and demonstrated it for a variety of commonly used signatures. The study was made for two data rich catchments, the 50 km2 Mahurangi catchment in New Zealand and the 135 km2 Brue catchment in the UK. For rainfall data the uncertainty sources included point measurement uncertainty, the number of gauges used in calculation of the catchment spatial average, and uncertainties relating to lack of quality control. For flow data the uncertainty sources included uncertainties in stage/discharge measurement and in the approximation of the true stage-discharge relation by a rating curve. The resulting uncertainties were compared across the different signatures and catchments, to quantify uncertainty

Digital Signature Management.

ERIC Educational Resources Information Center

Hassler, Vesna; Biely, Helmut

1999-01-01

Describes the Digital Signature Project that was developed in Austria to establish an infrastructure for applying smart card-based digital signatures in banking and electronic-commerce applications. Discusses the need to conform to international standards, an international certification infrastructure, and security features for a public directory…

Direct instrumental identification of catalytically active surface sites

NASA Astrophysics Data System (ADS)

Pfisterer, Jonas H. K.; Liang, Yunchang; Schneider, Oliver; Bandarenka, Aliaksandr S.

2017-09-01

The activity of heterogeneous catalysts—which are involved in some 80 per cent of processes in the chemical and energy industries—is determined by the electronic structure of specific surface sites that offer optimal binding of reaction intermediates. Directly identifying and monitoring these sites during a reaction should therefore provide insight that might aid the targeted development of heterogeneous catalysts and electrocatalysts (those that participate in electrochemical reactions) for practical applications. The invention of the scanning tunnelling microscope (STM) and the electrochemical STM promised to deliver such imaging capabilities, and both have indeed contributed greatly to our atomistic understanding of heterogeneous catalysis. But although the STM has been used to probe and initiate surface reactions, and has even enabled local measurements of reactivity in some systems, it is not generally thought to be suited to the direct identification of catalytically active surface sites under reaction conditions. Here we demonstrate, however, that common STMs can readily map the catalytic activity of surfaces with high spatial resolution: we show that by monitoring relative changes in the tunnelling current noise, active sites can be distinguished in an almost quantitative fashion according to their ability to catalyse the hydrogen-evolution reaction or the oxygen-reduction reaction. These data allow us to evaluate directly the importance and relative contribution to overall catalyst activity of different defects and sites at the boundaries between two materials. With its ability to deliver such information and its ready applicability to different systems, we anticipate that our method will aid the rational design of heterogeneous catalysts.

The identity of the active site of oxalate decarboxylase and the importance of the stability of active-site lid conformations1

PubMed Central

Just, Victoria J.; Burrell, Matthew R.; Bowater, Laura; McRobbie, Iain; Stevenson, Clare E. M.; Lawson, David M.; Bornemann, Stephen

2007-01-01

Oxalate decarboxylase (EC 4.1.1.2) catalyses the conversion of oxalate into carbon dioxide and formate. It requires manganese and, uniquely, dioxygen for catalysis. It forms a homohexamer and each subunit contains two similar, but distinct, manganese sites termed sites 1 and 2. There is kinetic evidence that only site 1 is catalytically active and that site 2 is purely structural. However, the kinetics of enzymes with mutations in site 2 are often ambiguous and all mutant kinetics have been interpreted without structural information. Nine new site-directed mutants have been generated and four mutant crystal structures have now been solved. Most mutants targeted (i) the flexibility (T165P), (ii) favoured conformation (S161A, S164A, D297A or H299A) or (iii) presence (Δ162–163 or Δ162–164) of a lid associated with site 1. The kinetics of these mutants were consistent with only site 1 being catalytically active. This was particularly striking with D297A and H299A because they disrupted hydrogen bonds between the lid and a neighbouring subunit only when in the open conformation and were distant from site 2. These observations also provided the first evidence that the flexibility and stability of lid conformations are important in catalysis. The deletion of the lid to mimic the plant oxalate oxidase led to a loss of decarboxylase activity, but only a slight elevation in the oxalate oxidase side reaction, implying other changes are required to afford a reaction specificity switch. The four mutant crystal structures (R92A, E162A, Δ162–163 and S161A) strongly support the hypothesis that site 2 is purely structural. PMID:17680775

Role of active site rigidity in activity: MD simulation and fluorescence study on a lipase mutant.

PubMed

Kamal, Md Zahid; Mohammad, Tabrez Anwar Shamim; Krishnamoorthy, G; Rao, Nalam Madhusudhana

2012-01-01

Relationship between stability and activity of enzymes is maintained by underlying conformational flexibility. In thermophilic enzymes, a decrease in flexibility causes low enzyme activity while in less stable proteins such as mesophiles and psychrophiles, an increase in flexibility is associated with enhanced enzyme activity. Recently, we identified a mutant of a lipase whose stability and activity were enhanced simultaneously. In this work, we probed the conformational dynamics of the mutant and the wild type lipase, particularly flexibility of their active site using molecular dynamic simulations and time-resolved fluorescence techniques. In contrast to the earlier observations, our data show that active site of the mutant is more rigid than wild type enzyme. Further investigation suggests that this lipase needs minimal reorganization/flexibility of active site residues during its catalytic cycle. Molecular dynamic simulations suggest that catalytically competent active site geometry of the mutant is relatively more preserved than wild type lipase, which might have led to its higher enzyme activity. Our study implies that widely accepted positive correlation between conformation flexibility and enzyme activity need not be stringent and draws attention to the possibility that high enzyme activity can still be accomplished in a rigid active site and stable protein structures. This finding has a significant implication towards better understanding of involvement of dynamic motions in enzyme catalysis and enzyme engineering through mutations in active site.

Information processing through a bio-based redox capacitor: signatures for redox-cycling.

PubMed

Liu, Yi; Kim, Eunkyoung; White, Ian M; Bentley, William E; Payne, Gregory F

2014-08-01

Redox-cycling compounds can significantly impact biological systems and can be responsible for activities that range from pathogen virulence and contaminant toxicities, to therapeutic drug mechanisms. Current methods to identify redox-cycling activities rely on the generation of reactive oxygen species (ROS), and employ enzymatic or chemical methods to detect ROS. Here, we couple the speed and sensitivity of electrochemistry with the molecular-electronic properties of a bio-based redox-capacitor to generate signatures of redox-cycling. The redox capacitor film is electrochemically-fabricated at the electrode surface and is composed of a polysaccharide hydrogel with grafted catechol moieties. This capacitor film is redox-active but non-conducting and can engage diffusible compounds in either oxidative or reductive redox-cycling. Using standard electrochemical mediators ferrocene dimethanol (Fc) and Ru(NH3)6Cl3 (Ru(3+)) as model redox-cyclers, we observed signal amplifications and rectifications that serve as signatures of redox-cycling. Three bio-relevant compounds were then probed for these signatures: (i) ascorbate, a redox-active compound that does not redox-cycle; (ii) pyocyanin, a virulence factor well-known for its reductive redox-cycling; and (iii) acetaminophen, an analgesic that oxidatively redox-cycles but also undergoes conjugation reactions. These studies demonstrate that the redox-capacitor can enlist the capabilities of electrochemistry to generate rapid and sensitive signatures of biologically-relevant chemical activities (i.e., redox-cycling). Published by Elsevier B.V.

Signature extension studies

NASA Technical Reports Server (NTRS)

Vincent, R. K.; Thomas, G. S.; Nalepka, R. F.

1974-01-01

The importance of specific spectral regions to signature extension is explored. In the recent past, the signature extension task was focused on the development of new techniques. Tested techniques are now used to investigate this spectral aspect of the large area survey. Sets of channels were sought which, for a given technique, were the least affected by several sources of variation over four data sets and yet provided good object class separation on each individual data set. Using sets of channels determined as part of this study, signature extension was accomplished between data sets collected over a six-day period and over a range of about 400 kilometers.

Genome-wide identification of novel expression signatures reveal distinct patterns and prevalence of binding motifs for p53, nuclear factor-κB and other signal transcription factors in head and neck squamous cell carcinoma

PubMed Central

Yan, Bin; Yang, Xinping; Lee, Tin-Lap; Friedman, Jay; Tang, Jun; Van Waes, Carter; Chen, Zhong

2007-01-01

Background Differentially expressed gene profiles have previously been observed among pathologically defined cancers by microarray technologies, including head and neck squamous cell carcinomas (HNSCCs). However, the molecular expression signatures and transcriptional regulatory controls that underlie the heterogeneity in HNSCCs are not well defined. Results Genome-wide cDNA microarray profiling of ten HNSCC cell lines revealed novel gene expression signatures that distinguished cancer cell subsets associated with p53 status. Three major clusters of over-expressed genes (A to C) were defined through hierarchical clustering, Gene Ontology, and statistical modeling. The promoters of genes in these clusters exhibited different patterns and prevalence of transcription factor binding sites for p53, nuclear factor-κB (NF-κB), activator protein (AP)-1, signal transducer and activator of transcription (STAT)3 and early growth response (EGR)1, as compared with the frequency in vertebrate promoters. Cluster A genes involved in chromatin structure and function exhibited enrichment for p53 and decreased AP-1 binding sites, whereas clusters B and C, containing cytokine and antiapoptotic genes, exhibited a significant increase in prevalence of NF-κB binding sites. An increase in STAT3 and EGR1 binding sites was distributed among the over-expressed clusters. Novel regulatory modules containing p53 or NF-κB concomitant with other transcription factor binding motifs were identified, and experimental data supported the predicted transcriptional regulation and binding activity. Conclusion The transcription factors p53, NF-κB, and AP-1 may be important determinants of the heterogeneous pattern of gene expression, whereas STAT3 and EGR1 may broadly enhance gene expression in HNSCCs. Defining these novel gene signatures and regulatory mechanisms will be important for establishing new molecular classifications and subtyping, which in turn will promote development of targeted

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

40 CFR 61.154 - Standard for active waste disposal sites.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 40 Protection of Environment 8 2011-07-01 2011-07-01 false Standard for active waste disposal... for Asbestos § 61.154 Standard for active waste disposal sites. Each owner or operator of an active... visible emissions to the outside air from any active waste disposal site where asbestos-containing waste...

40 CFR 61.154 - Standard for active waste disposal sites.

Code of Federal Regulations, 2013 CFR

2013-07-01

... 40 Protection of Environment 9 2013-07-01 2013-07-01 false Standard for active waste disposal... for Asbestos § 61.154 Standard for active waste disposal sites. Each owner or operator of an active... visible emissions to the outside air from any active waste disposal site where asbestos-containing waste...

40 CFR 61.154 - Standard for active waste disposal sites.

Code of Federal Regulations, 2012 CFR

2012-07-01

... 40 Protection of Environment 9 2012-07-01 2012-07-01 false Standard for active waste disposal... for Asbestos § 61.154 Standard for active waste disposal sites. Each owner or operator of an active... visible emissions to the outside air from any active waste disposal site where asbestos-containing waste...

40 CFR 61.154 - Standard for active waste disposal sites.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 40 Protection of Environment 8 2010-07-01 2010-07-01 false Standard for active waste disposal... for Asbestos § 61.154 Standard for active waste disposal sites. Each owner or operator of an active... visible emissions to the outside air from any active waste disposal site where asbestos-containing waste...

40 CFR 61.154 - Standard for active waste disposal sites.

Code of Federal Regulations, 2014 CFR

2014-07-01

... 40 Protection of Environment 9 2014-07-01 2014-07-01 false Standard for active waste disposal... for Asbestos § 61.154 Standard for active waste disposal sites. Each owner or operator of an active... visible emissions to the outside air from any active waste disposal site where asbestos-containing waste...

Meta-Analysis of DNA Tumor-Viral Integration Site Selection Indicates a Role for Repeats, Gene Expression and Epigenetics

PubMed Central

Doolittle-Hall, Janet M.; Cunningham Glasspoole, Danielle L.; Seaman, William T.; Webster-Cyriaque, Jennifer

2015-01-01

Oncoviruses cause tremendous global cancer burden. For several DNA tumor viruses, human genome integration is consistently associated with cancer development. However, genomic features associated with tumor viral integration are poorly understood. We sought to define genomic determinants for 1897 loci prone to hosting human papillomavirus (HPV), hepatitis B virus (HBV) or Merkel cell polyomavirus (MCPyV). These were compared to HIV, whose enzyme-mediated integration is well understood. A comprehensive catalog of integration sites was constructed from the literature and experimentally-determined HPV integration sites. Features were scored in eight categories (genes, expression, open chromatin, histone modifications, methylation, protein binding, chromatin segmentation and repeats) and compared to random loci. Random forest models determined loci classification and feature selection. HPV and HBV integrants were not fragile site associated. MCPyV preferred integration near sensory perception genes. Unique signatures of integration-associated predictive genomic features were detected. Importantly, repeats, actively-transcribed regions and histone modifications were common tumor viral integration signatures. PMID:26569308

An inter-sensor comparison of the microwave signatures of Arctic sea ice

NASA Technical Reports Server (NTRS)

Onstott, R. G.

1986-01-01

Active and passive microwave and physical properties of Arctic sea ice in the marginal ice zone were measured during the summer. Results of an intercomparison of data acquired by an aircraft synthetic aperture radar, a passive microwave imager and a helicopter-mounted scatterometer indicate that early-to-mid summer sea ice microwave signatures are dominated by snowpack characteristics. Measurements show that the greatest contrast between thin first-year and multiyear sea ice occurs when operating actively between 5 and 10 GHz. Significant information about the state of melt of snow and ice is contained in the active and passive microwave signatures.

Specific Signature of Seismic Shaking in Landslide Inventories: Case of the Chichi Earthquake

NASA Astrophysics Data System (ADS)

Meunier, P.; Rault, C.; Marc, O.; Hovius, N.

2017-12-01

The 1999 Chichi earthquake triggered 10 000 landslides in its epicentral area. In addition to coseismic landsliding, directly induced by the shaking, the hillslopes response extended to several years after the main shock, during which landslide susceptibility remained higher than during the pre-seismic period. We attribute this elevated rate to weakening effects caused by the shaking. The characteristics of the coseismic landslide catalogues (clustering,slope and azimuth distribution) bears the signature of the seismic triggering. Extended landslide mapping (1994-2004) allows to track changes in these signatures in order to better interpret them. We present a summary of the change of these signatures through time and space. At the scale of the epicentral area, we show that coseismic landslide clustering did clearly occur along the fault where the shaking is strong. In 3 sub-catchments of the Choshui river, a finer analysis of the landslide time series reveals a mixed signature of both geology and shaking. Pre-quake rain-induced landslides preferentially occurred down slope and along the bedding planes while coseismic landslides locate higher in the landscape, on slopes strongly affected by site effects. However, during the post seismic period, the signature of the shaking is not present while landslide rate remains high, suggesting that weakening effects seemed homogeneously distributed in the landscape.

Specific signature of seismic shaking in landslide catalogues: Case of the Chichi earthquake

NASA Astrophysics Data System (ADS)

Meunier, Patrick; Rault, Claire; Marc, Odin; Hovius, Niels

2017-04-01

The 1999 Chichi earthquake triggered 10 000 landslides in its epicentral area. In addition to coseismic landsliding, directly induced by the shaking, the hillslopes response extended to several years after the main shock, during which landslide susceptibility remained higher than during the pre-seismic period. We attribute this elevated rate to weakening effects caused by the shaking. The characteristics of the coseismic landslide catalogues (clustering, slope and azimuth distribution) bears the signature of the seismic triggering. Extended landslide mapping (1994-2004) allows to track changes in these signatures in order to better interpret them. We present a summary of the change of these signatures through time and space. At the scale of the epicentral area, we show that coseismic landslide clustering did clearly occur along the fault where the shaking is strong. In 3 sub-catchments of the Choshui river, a finer analysis of the landslide time series reveals a mixed signature of both geology and shaking. Pre-quake rain-induced landslides preferentially occurred down slope and along the bedding planes while coseismic landslides locate higher in the landscape, on slopes strongly affected by site effects. However, during the post seismic period, the signature of the shaking is not present while landslide rate remains high, suggesting that weakening effects seemed homogeneously distributed in the landscape.

Lesson 6: Signature Validation

EPA Pesticide Factsheets

Checklist items 13 through 17 are grouped under the Signature Validation Process, and represent CROMERR requirements that the system must satisfy as part of ensuring that electronic signatures it receives are valid.

21 CFR 11.50 - Signature manifestations.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 1 2010-04-01 2010-04-01 false Signature manifestations. 11.50 Section 11.50 Food... RECORDS; ELECTRONIC SIGNATURES Electronic Records § 11.50 Signature manifestations. (a) Signed electronic...: (1) The printed name of the signer; (2) The date and time when the signature was executed; and (3...

Quality of signatures. [spectral signatures of winter wheat grown in Texas

NASA Technical Reports Server (NTRS)

Kan, E. P. F.

1974-01-01

Three conclusions are drawn on the usability, inherent variations, and noise aspects of the spectral signatures processed from data collected by the Field Signature Acquisition System (FSAS). Conclusions are based on the spectral data collected from winter wheat of the 1972/73 season, grown at Texas A and M University, College Station, Texas.

7 CFR 97.155 - Signatures.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 7 Agriculture 3 2010-01-01 2010-01-01 false Signatures. 97.155 Section 97.155 Agriculture... PLANT VARIETY AND PROTECTION Attorneys and Agents § 97.155 Signatures. Every document filed by an attorney or agent representing an applicant or party to a proceeding in the Office shall bear the signature...

21 CFR 11.70 - Signature/record linking.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 1 2010-04-01 2010-04-01 false Signature/record linking. 11.70 Section 11.70 Food... RECORDS; ELECTRONIC SIGNATURES Electronic Records § 11.70 Signature/record linking. Electronic signatures and handwritten signatures executed to electronic records shall be linked to their respective...

10 CFR 63.16 - Review of site characterization activities. 2

Code of Federal Regulations, 2012 CFR

2012-01-01

... which such activities are carried out and to observe excavations, borings, and in situ tests, as they... IN A GEOLOGIC REPOSITORY AT YUCCA MOUNTAIN, NEVADA Licenses Preapplication Review § 63.16 Review of site characterization activities. 2 2 In addition to the review of site characterization activities...

10 CFR 63.16 - Review of site characterization activities. 2

Code of Federal Regulations, 2011 CFR

2011-01-01

... which such activities are carried out and to observe excavations, borings, and in situ tests, as they... IN A GEOLOGIC REPOSITORY AT YUCCA MOUNTAIN, NEVADA Licenses Preapplication Review § 63.16 Review of site characterization activities. 2 2 In addition to the review of site characterization activities...

10 CFR 63.16 - Review of site characterization activities. 2

Code of Federal Regulations, 2013 CFR

2013-01-01

... which such activities are carried out and to observe excavations, borings, and in situ tests, as they... IN A GEOLOGIC REPOSITORY AT YUCCA MOUNTAIN, NEVADA Licenses Preapplication Review § 63.16 Review of site characterization activities. 2 2 In addition to the review of site characterization activities...

10 CFR 63.16 - Review of site characterization activities. 2

Code of Federal Regulations, 2010 CFR

2010-01-01

... which such activities are carried out and to observe excavations, borings, and in situ tests, as they... IN A GEOLOGIC REPOSITORY AT YUCCA MOUNTAIN, NEVADA Licenses Preapplication Review § 63.16 Review of site characterization activities. 2 2 In addition to the review of site characterization activities...

10 CFR 63.16 - Review of site characterization activities. 2

Code of Federal Regulations, 2014 CFR

2014-01-01

... which such activities are carried out and to observe excavations, borings, and in situ tests, as they... IN A GEOLOGIC REPOSITORY AT YUCCA MOUNTAIN, NEVADA Licenses Preapplication Review § 63.16 Review of site characterization activities. 2 2 In addition to the review of site characterization activities...

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

17 CFR 12.12 - Signature.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 17 Commodity and Securities Exchanges 1 2010-04-01 2010-04-01 false Signature. 12.12 Section 12.12... General Information and Preliminary Consideration of Pleadings § 12.12 Signature. (a) By whom. All... document on behalf of another person. (b) Effect. The signature on any document of any person acting either...

Evaluation of ERTS multispectral signatures in relation to ground control signatures using a nested-sampling approach

NASA Technical Reports Server (NTRS)

Lyon, R. J. P. (Principal Investigator)

1975-01-01

The author has identified the following significant results. Ground measured spectral signatures of wavelength bands matching ERTS MSS were collected using a radiometer at several Californian and Nevadan sites, and directly compared with similar data from ERTS CCTs. The comparison was tested at the highest possible spatial resolution for ERTS, using deconvoluted MSS data, and contrasted with that of ground measured spectra, originally from 1 meter squares. In the mobile traverses of the grassland sites, these one meter fields of view were integrated into eighty meter transects along the five km track across four major rock/soil types. Suitable software was developed to read the MSS CCT tapes, to shadeprint individual bands with user-determined greyscale stretching. Four new algorithms for unsupervised and supervised, normalized and unnormalized clustering were developed, into a program termed STANSORT. Parallel software allowed the field data to be calibrated, and by using concurrently continuously collected, upward- and downward-viewing, 4 band radiometers, bidirectional reflectances could be calculated.

Tracking riverborne sediment and contaminants in Commencement Bay, Washington, using geochemical signatures

USGS Publications Warehouse

Takesue, Renee K.; Conn, Kathleen E.; Dinicola, Richard S.

2017-09-29

Large rivers carry terrestrial sediment, contaminants, and other materials to the coastal zone where they can affect marine biogeochemical cycles and ecosystems. This U.S. Geological Survey study combined river and marine sediment geochemistry and organic contaminant analyses to identify riverborne sediment and associated contaminants at shoreline sites in Commencement Bay, Puget Sound, Washington, that could be used by adult forage fish and other marine organisms. Geochemical signatures distinguished the fine fraction (<0.063 millimeter, mm) of Puyallup River sediment—which originates from Mount Rainier, a Cascade volcano—from glacial fine sediment in lowland bluffs that supply sediment to beaches. In combination with activities of beryllium-7 (7Be), a short-lived radionuclide, geochemical signatures showed that winter 2013–14 sediment runoff from the Puyallup River was transported to and deposited along the north shore of Commencement Bay, then mixed downward into the sediment column. The three Commencement Bay sites at which organic contaminants were measured in surface sediment did not have measurable 7Be activities in that layer, so their contaminant assemblages were attributed to sources from previous years. Concentrations of organic contaminants (the most common of which were polycyclic aromatic hydrocarbons, polychlorinated biphenyls, and fecal sterols) were higher in the <0.063-mm fraction compared to the <2-mm fraction, in winter compared to summer, in river suspended sediment compared to river bar and bank sediment, and in marine sediment compared to river sediment. The geochemical property barium/aluminum (Ba/Al) showed that the median percentage of Puyallup River derived fine surface sediment along the shoreline of Commencement Bay was 77 percent. This finding, in combination with higher concentrations of organic contaminants in marine rather than river sediment, indicates that riverborne sediment-bound contaminants are retained in shallow

Geochemical signature of land-based activities in Caribbean coral surface samples

USGS Publications Warehouse

Prouty, N.G.; Hughen, K.A.; Carilli, J.

2008-01-01

Anthropogenic threats, such as increased sedimentation, agrochemical run-off, coastal development, tourism, and overfishing, are of great concern to the Mesoamerican Caribbean Reef System (MACR). Trace metals in corals can be used to quantify and monitor the impact of these land-based activities. Surface coral samples from the MACR were investigated for trace metal signatures resulting from relative differences in water quality. Samples were analyzed at three spatial scales (colony, reef, and regional) as part of a hierarchical multi-scale survey. A primary goal of the paper is to elucidate the extrapolation of information between fine-scale variation at the colony or reef scale and broad-scale patterns at the regional scale. Of the 18 metals measured, five yielded statistical differences at the colony and/or reef scale, suggesting fine-scale spatial heterogeneity not conducive to regional interpretation. Five metals yielded a statistical difference at the regional scale with an absence of a statistical difference at either the colony or reef scale. These metals are barium (Ba), manganese (Mn), chromium (Cr), copper (Cu), and antimony (Sb). The most robust geochemical indicators of land-based activities are coral Ba and Mn concentrations, which are elevated in samples from the southern region of the Gulf of Honduras relative to those from the Turneffe Islands. These findings are consistent with the occurrence of the most significant watersheds in the MACR from southern Belize to Honduras, which contribute sediment-laden freshwater to the coastal zone primarily as a result of human alteration to the landscape (e.g., deforestation and agricultural practices). Elevated levels of Cu and Sb were found in samples from Honduras and may be linked to industrial shipping activities where copper-antimony additives are commonly used in antifouling paints. Results from this study strongly demonstrate the impact of terrestrial runoff and anthropogenic activities on coastal water

Thermal signature analysis of human face during jogging activity using infrared thermography technique

NASA Astrophysics Data System (ADS)

Budiarti, Putria W.; Kusumawardhani, Apriani; Setijono, Heru

2016-11-01

Thermal imaging has been widely used for many applications. Thermal camera is used to measure object's temperature above absolute temperature of 0 Kelvin using infrared radiation emitted by the object. Thermal imaging is color mapping taken using false color that represents temperature. Human body is one of the objects that emits infrared radiation. Human infrared radiations vary according to the activity that is being done. Physical activities such as jogging is among ones that is commonly done. Therefore this experiment will investigate the thermal signature profile of jogging activity in human body, especially in the face parts. The results show that the significant increase is found in periorbital area that is near eyes and forehand by the number of 7.5%. Graphical temperature distributions show that all region, eyes, nose, cheeks, and chin at the temperature of 28.5 - 30.2°C the pixel area tends to be constant since it is the surrounding temperature. At the temperature of 30.2 - 34.7°C the pixel area tends to increase, while at the temperature of 34.7 - 37.1°C the pixel area tends to decrease because pixels at temperature of 34.7 - 37.1°C after jogging activity change into temperature of 30.2 - 34.7°C so that the pixel area increases. The trendline of jogging activity during 10 minutes period also shows the increasing of temperature. The results of each person also show variations due to physiological nature of each person, such as sweat production during physical activities.

The effects of extrinsic motivation on signature authorship opinions in forensic signature blind trials.

PubMed

Dewhurst, Tahnee N; Found, Bryan; Ballantyne, Kaye N; Rogers, Doug

2014-03-01

Expertise studies in forensic handwriting examination involve comparisons of Forensic Handwriting Examiners' (FHEs) opinions with lay-persons on blind tests. All published studies of this type have reported real and demonstrable skill differences between the specialist and lay groups. However, critics have proposed that any difference shown may be indicative of a lack of motivation on the part of lay participants, rather than a real difference in skill. It has been suggested that qualified FHEs would be inherently more motivated to succeed in blinded validation trials, as their professional reputations could be at risk, should they perform poorly on the task provided. Furthermore, critics suggest that lay-persons would be unlikely to be highly motivated to succeed, as they would have no fear of negative consequences should they perform badly. In an effort to investigate this concern, a blind signature trial was designed and administered to forty lay-persons. Participants were required to compare known (exemplar) signatures of an individual to questioned signatures and asked to express an opinion regarding whether the writer of the known signatures wrote each of the questioned signatures. The questioned signatures comprised a mixture of genuine, disguised and simulated signatures. The forty participants were divided into two separate groupings. Group 'A' were requested to complete the trial as directed and were advised that for each correct answer they would be financially rewarded, for each incorrect answer they would be financially penalized, and for each inconclusive opinion they would receive neither penalty nor reward. Group 'B' was requested to complete the trial as directed, with no mention of financial recompense or penalty. The results of this study do not support the proposition that motivation rather than skill difference is the source of the statistical difference in opinions between individuals' results in blinded signature proficiency trials. Crown

Visual signature reduction of unmanned aerial vehicles

NASA Astrophysics Data System (ADS)

Zhong, Z. W.; Ma, Z. X.; Jayawijayaningtiyas; Ngoh, J. H. H.

2016-10-01

With the emergence of unmanned aerial vehicles (UAVs) in multiple tactical defence missions, there was a need for an efficient visual signature suppression system for a more efficient stealth operation. One of our studies experimentally investigated the visual signature reduction of UAVs achieved through an active camouflage system. A prototype was constructed with newly developed operating software, Cloak, to provide active camouflage to the UAV model. The reduction of visual signature was analysed. Tests of the devices mounted on UAVs were conducted in another study. A series of experiments involved testing of the concept as well as the prototype. The experiments were conducted both in the laboratory and under normal environmental conditions. Results showed certain degrees of blending with the sky to create a camouflage effect. A mini-UAV made mostly out of transparent plastic was also designed and fabricated. Because of the transparency of the plastic material, the visibility of this UAV in the air is very small, and therefore the UAV is difficult to be detected. After re-designs and tests, eventually a practical system to reduce the visibility of UAVs viewed by human observers from the ground was developed. The system was evaluated during various outdoor tests. The scene target-to-background lightness contrast and the scene target-to-background colour contrast of the adaptive control system prototype were smaller than 10% at a stand-off viewing distance of 20-50 m.

More complete gene silencing by fewer siRNAs: transparent optimized design and biophysical signature

PubMed Central

Ladunga, Istvan

2007-01-01

Highly accurate knockdown functional analyses based on RNA interference (RNAi) require the possible most complete hydrolysis of the targeted mRNA while avoiding the degradation of untargeted genes (off-target effects). This in turn requires significant improvements to target selection for two reasons. First, the average silencing activity of randomly selected siRNAs is as low as 62%. Second, applying more than five different siRNAs may lead to saturation of the RNA-induced silencing complex (RISC) and to the degradation of untargeted genes. Therefore, selecting a small number of highly active siRNAs is critical for maximizing knockdown and minimizing off-target effects. To satisfy these needs, a publicly available and transparent machine learning tool is presented that ranks all possible siRNAs for each targeted gene. Support vector machines (SVMs) with polynomial kernels and constrained optimization models select and utilize the most predictive effective combinations from 572 sequence, thermodynamic, accessibility and self-hairpin features over 2200 published siRNAs. This tool reaches an accuracy of 92.3% in cross-validation experiments. We fully present the underlying biophysical signature that involves free energy, accessibility and dinucleotide characteristics. We show that while complete silencing is possible at certain structured target sites, accessibility information improves the prediction of the 90% active siRNA target sites. Fast siRNA activity predictions can be performed on our web server at . PMID:17169992

Computer simulation of the active site of human serum cholinesterase

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

Kefang Jiao; Song Li; Zhengzheng Lu

1996-12-31

The first 3D-structure of acetylchelinesterase from Torpedo California electric organ (T.AChE) was published by JL. Sussman in 1991. We have simulated 3D-structure of human serum cholinesterase (H.BuChE) and the active site of H.BuChE. It is discovered by experiment that the residue of H.BuChE is still active site after a part of H.BuChE is cut. For example, the part of 21KD + 20KD is active site of H.BuChE. The 20KD as it is. Studies on these peptides by Hemelogy indicate that two active peptides have same negative electrostatic potential maps diagram. These negative electrostatic areas attached by acetyl choline with positivemore » electrostatic potency. We predict that 147...236 peptide of AChE could be active site because it was as 20KD as with negative electrostatic potential maps. We look forward to proving from other ones.« less

Nonlinear instabilities of multi-site breathers in Klein-Gordon lattices

DOE PAGES

Cuevas-Maraver, Jesus; Kevrekidis, Panayotis G.; Pelinovsky, Dmitry E.

2016-08-01

Here, we explore the possibility of multi-site breather states in a nonlinear Klein–Gordon lattice to become nonlinearly unstable, even if they are found to be spectrally stable. The mechanism for this nonlinear instability is through the resonance with the wave continuum of a multiple of an internal mode eigenfrequency in the linearization of excited breather states. For the nonlinear instability, the internal mode must have its Krein signature opposite to that of the wave continuum. This mechanism is not only theoretically proposed, but also numerically corroborated through two concrete examples of the Klein–Gordon lattice with a soft (Morse) and amore » hard (Φ 4) potential. Compared to the case of the nonlinear Schrödinger lattice, the Krein signature of the internal mode relative to that of the wave continuum may change depending on the period of the multi-site breather state. For the periods for which the Krein signatures of the internal mode and the wave continuum coincide, multi-site breather states are observed to be nonlinearly stable.« less

De novo active sites for resurrected Precambrian enzymes

NASA Astrophysics Data System (ADS)

Risso, Valeria A.; Martinez-Rodriguez, Sergio; Candel, Adela M.; Krüger, Dennis M.; Pantoja-Uceda, David; Ortega-Muñoz, Mariano; Santoyo-Gonzalez, Francisco; Gaucher, Eric A.; Kamerlin, Shina C. L.; Bruix, Marta; Gavira, Jose A.; Sanchez-Ruiz, Jose M.

2017-07-01

Protein engineering studies often suggest the emergence of completely new enzyme functionalities to be highly improbable. However, enzymes likely catalysed many different reactions already in the last universal common ancestor. Mechanisms for the emergence of completely new active sites must therefore either plausibly exist or at least have existed at the primordial protein stage. Here, we use resurrected Precambrian proteins as scaffolds for protein engineering and demonstrate that a new active site can be generated through a single hydrophobic-to-ionizable amino acid replacement that generates a partially buried group with perturbed physico-chemical properties. We provide experimental and computational evidence that conformational flexibility can assist the emergence and subsequent evolution of new active sites by improving substrate and transition-state binding, through the sampling of many potentially productive conformations. Our results suggest a mechanism for the emergence of primordial enzymes and highlight the potential of ancestral reconstruction as a tool for protein engineering.

Developing chemical signatures of particulate air pollution in the Pearl River Delta region, China.

PubMed

Zheng, Mei; Cheng, Yuan; Zeng, Limin; Zhang, Yuanhang

2011-01-01

PM2.5 samples were collected in a regional sampling network with three sites in Hong Kong and four sites in the adjacent inland Pearl River Delta (PRD) or Guangdong Province during four months/seasons from 2002-2003. Trans-boundary transport between Hong Kong and the inland PRD is inevitable under the influence of Asian monsoon. In summer, Hong Kong serves as the upwind site of the inland PRD while during other seasons it is under the influence of continental emissions. Previous studies have recognized the importance of using chemical signatures to differentiate local vs. regional contributions to air pollutants in Hong Kong such as the CO/NOx ratio, ratios of different VOC species. In this study, detailed chemical speciation by gas chromatography-mass spectrometry was performed with PM2.5 samples to identify new chemical signatures to distinguish aerosols in Hong Kong from those from the inland PRD. Since Hong Kong is not influenced by the continental emissions from the inland PRD during summer, comparison focused on chemical data obtained from this season for chemical signatures. The new ratios developed from the current study include LCPI/HCPI ratio of alkanes (0.39 +/- 0.02 in Hong Kong vs. 0.78 +/- 0.08 in the inland PRD), pyrene to benzo[ghi]perylene ratio (0.97 +/- 0.21 in Hong Kong compared to 0.20 +/- 0.06 in the inland PRD), and the ratio of 1,2-benzenedioic acid to 1,4-benzenedioic acid (1.8 +/- 0.1 in Hong Kong vs. 0.6 +/- 0.05 in the inland PRD). Results from this study also revealed that Hong Kong was impacted by ship emissions as reflected by substantially high V/Ni ratio (9 +/- 2) while this ratio was about 1-2 at all sites in the inland PRD, which is very close to typical ratios from residual oil combustion.

Secure Obfuscation for Encrypted Group Signatures

PubMed Central

Fan, Hongfei; Liu, Qin

2015-01-01

In recent years, group signature techniques are widely used in constructing privacy-preserving security schemes for various information systems. However, conventional techniques keep the schemes secure only in normal black-box attack contexts. In other words, these schemes suppose that (the implementation of) the group signature generation algorithm is running in a platform that is perfectly protected from various intrusions and attacks. As a complementary to existing studies, how to generate group signatures securely in a more austere security context, such as a white-box attack context, is studied in this paper. We use obfuscation as an approach to acquire a higher level of security. Concretely, we introduce a special group signature functionality-an encrypted group signature, and then provide an obfuscator for the proposed functionality. A series of new security notions for both the functionality and its obfuscator has been introduced. The most important one is the average-case secure virtual black-box property w.r.t. dependent oracles and restricted dependent oracles which captures the requirement of protecting the output of the proposed obfuscator against collision attacks from group members. The security notions fit for many other specialized obfuscators, such as obfuscators for identity-based signatures, threshold signatures and key-insulated signatures. Finally, the correctness and security of the proposed obfuscator have been proven. Thereby, the obfuscated encrypted group signature functionality can be applied to variants of privacy-preserving security schemes and enhance the security level of these schemes. PMID:26167686

Molecular dynamics explorations of active site structure in designed and evolved enzymes.

PubMed

Osuna, Sílvia; Jiménez-Osés, Gonzalo; Noey, Elizabeth L; Houk, K N

2015-04-21

This Account describes the use of molecular dynamics (MD) simulations to reveal how mutations alter the structure and organization of enzyme active sites. As proposed by Pauling about 70 years ago and elaborated by many others since then, biocatalysis is efficient when functional groups in the active site of an enzyme are in optimal positions for transition state stabilization. Changes in mechanism and covalent interactions are often critical parts of enzyme catalysis. We describe our explorations of the dynamical preorganization of active sites using MD, studying the fluctuations between active and inactive conformations normally concealed to static crystallography. MD shows how the various arrangements of active site residues influence the free energy of the transition state and relates the populations of the catalytic conformational ensemble to the enzyme activity. This Account is organized around three case studies from our laboratory. We first describe the importance of dynamics in evaluating a series of computationally designed and experimentally evolved enzymes for the Kemp elimination, a popular subject in the enzyme design field. We find that the dynamics of the active site is influenced not only by the original sequence design and subsequent mutations but also by the nature of the ligand present in the active site. In the second example, we show how microsecond MD has been used to uncover the role of remote mutations in the active site dynamics and catalysis of a transesterase, LovD. This enzyme was evolved by Tang at UCLA and Codexis, Inc., and is a useful commercial catalyst for the production of the drug simvastatin. X-ray analysis of inactive and active mutants did not reveal differences in the active sites, but relatively long time scale MD in solution showed that the active site of the wild-type enzyme preorganizes only upon binding of the acyl carrier protein (ACP) that delivers the natural acyl group to the active site. In the absence of bound ACP

Free-Space Quantum Signatures Using Heterodyne Measurements

NASA Astrophysics Data System (ADS)

Croal, Callum; Peuntinger, Christian; Heim, Bettina; Khan, Imran; Marquardt, Christoph; Leuchs, Gerd; Wallden, Petros; Andersson, Erika; Korolkova, Natalia

2016-09-01

Digital signatures guarantee the authorship of electronic communications. Currently used "classical" signature schemes rely on unproven computational assumptions for security, while quantum signatures rely only on the laws of quantum mechanics to sign a classical message. Previous quantum signature schemes have used unambiguous quantum measurements. Such measurements, however, sometimes give no result, reducing the efficiency of the protocol. Here, we instead use heterodyne detection, which always gives a result, although there is always some uncertainty. We experimentally demonstrate feasibility in a real environment by distributing signature states through a noisy 1.6 km free-space channel. Our results show that continuous-variable heterodyne detection improves the signature rate for this type of scheme and therefore represents an interesting direction in the search for practical quantum signature schemes. For transmission values ranging from 100% to 10%, but otherwise assuming an ideal implementation with no other imperfections, the signature length is shorter by a factor of 2 to 10. As compared with previous relevant experimental realizations, the signature length in this implementation is several orders of magnitude shorter.

Free-Space Quantum Signatures Using Heterodyne Measurements.

PubMed

Croal, Callum; Peuntinger, Christian; Heim, Bettina; Khan, Imran; Marquardt, Christoph; Leuchs, Gerd; Wallden, Petros; Andersson, Erika; Korolkova, Natalia

2016-09-02

Digital signatures guarantee the authorship of electronic communications. Currently used "classical" signature schemes rely on unproven computational assumptions for security, while quantum signatures rely only on the laws of quantum mechanics to sign a classical message. Previous quantum signature schemes have used unambiguous quantum measurements. Such measurements, however, sometimes give no result, reducing the efficiency of the protocol. Here, we instead use heterodyne detection, which always gives a result, although there is always some uncertainty. We experimentally demonstrate feasibility in a real environment by distributing signature states through a noisy 1.6 km free-space channel. Our results show that continuous-variable heterodyne detection improves the signature rate for this type of scheme and therefore represents an interesting direction in the search for practical quantum signature schemes. For transmission values ranging from 100% to 10%, but otherwise assuming an ideal implementation with no other imperfections, the signature length is shorter by a factor of 2 to 10. As compared with previous relevant experimental realizations, the signature length in this implementation is several orders of magnitude shorter.

CD137+CD154- Expression As a Regulatory T Cell (Treg)-Specific Activation Signature for Identification and Sorting of Stable Human Tregs from In Vitro Expansion Cultures.

PubMed

Nowak, Anna; Lock, Dominik; Bacher, Petra; Hohnstein, Thordis; Vogt, Katrin; Gottfreund, Judith; Giehr, Pascal; Polansky, Julia K; Sawitzki, Birgit; Kaiser, Andrew; Walter, Jörn; Scheffold, Alexander

2018-01-01

Regulatory T cells (Tregs) are an attractive therapeutic tool for several different immune pathologies. Therapeutic Treg application often requires prolonged in vitro culture to generate sufficient Treg numbers or to optimize their functionality, e.g., via genetic engineering of their antigen receptors. However, purity of clinical Treg expansion cultures is highly variable, and currently, it is impossible to identify and separate stable Tregs from contaminating effector T cells, either ex vivo or after prior expansion. This represents a major obstacle for quality assurance of expanded Tregs and raises significant safety concerns. Here, we describe a Treg activation signature that allows identification and sorting of epigenetically imprinted Tregs even after prolonged in vitro culture. We show that short-term reactivation resulted in expression of CD137 but not CD154 on stable FoxP3+ Tregs that displayed a demethylated Treg-specific demethylated region, high suppressive potential, and lack of inflammatory cytokine expression. We also applied this Treg activation signature for rapid testing of chimeric antigen receptor functionality in human Tregs and identified major differences in the signaling requirements regarding CD137 versus CD28 costimulation. Taken together, CD137+CD154- expression emerges as a universal Treg activation signature ex vivo and upon in vitro expansion allowing the identification and isolation of epigenetically stable antigen-activated Tregs and providing a means for their rapid functional testing in vitro .

Relocating the Active-Site Lysine in Rhodopsin: 2. Evolutionary Intermediates.

PubMed

Devine, Erin L; Theobald, Douglas L; Oprian, Daniel D

2016-08-30

The visual pigment rhodopsin is a G protein-coupled receptor that covalently binds its retinal chromophore via a Schiff base linkage to an active-site Lys residue in the seventh transmembrane helix. Although this residue is strictly conserved among all type II retinylidene proteins, we found previously that the active-site Lys in bovine rhodopsin (Lys296) can be moved to three other locations (G90K, T94K, S186K) while retaining the ability to form a pigment with retinal and to activate transducin in a light-dependent manner [ Devine et al. ( 2013 ) Proc. Natl. Acad. Sci. USA 110 , 13351 - 13355 ]. Because the active-site Lys is not functionally constrained to be in helix seven, it is possible that it could relocate within the protein, most likely via an evolutionary intermediate with two active-site Lys. Therefore, in this study we characterized potential evolutionary intermediates with two Lys in the active site. Four mutant rhodopsins were prepared in which the original Lys296 was left untouched and a second Lys residue was substituted for G90K, T94K, S186K, or F293K. All four constructs covalently bind 11-cis-retinal, form a pigment, and activate transducin in a light-dependent manner. These results demonstrate that rhodopsin can tolerate a second Lys in the retinal binding pocket and suggest that an evolutionary intermediate with two Lys could allow migration of the Schiff base Lys to a position other than the observed, highly conserved location in the seventh TM helix. From sequence-based searches, we identified two groups of natural opsins, insect UV cones and neuropsins, that contain Lys residues at two positions in their active sites and also have intriguing spectral similarities to the mutant rhodopsins studied here.

Acute exercise and physiological insulin induce distinct phosphorylation signatures on TBC1D1 and TBC1D4 proteins in human skeletal muscle

PubMed Central

Treebak, Jonas T; Pehmøller, Christian; Kristensen, Jonas M; Kjøbsted, Rasmus; Birk, Jesper B; Schjerling, Peter; Richter, Erik A; Goodyear, Laurie J; Wojtaszewski, Jørgen F P

2014-01-01

We investigated the phosphorylation signatures of two Rab-GTPase activating proteins TBC1D1 and TBC1D4 in human skeletal muscle in response to physical exercise and physiological insulin levels induced by a carbohydrate rich meal using a paired experimental design. Eight healthy male volunteers exercised in the fasted or fed state and muscle biopsies were taken before and immediately after exercise. We identified TBC1D1/4 phospho-sites that (1) did not respond to exercise or postprandial increase in insulin (TBC1D4: S666), (2) responded to insulin only (TBC1D4: S318), (3) responded to exercise only (TBC1D1: S237, S660, S700; TBC1D4: S588, S751), and (4) responded to both insulin and exercise (TBC1D1: T596; TBC1D4: S341, T642, S704). In the insulin-stimulated leg, Akt phosphorylation of both T308 and S473 correlated significantly with multiple sites on both TBC1D1 (T596) and TBC1D4 (S318, S341, S704). Interestingly, in the exercised leg in the fasted state TBC1D1 phosphorylation (S237, T596) correlated significantly with the activity of the α2/β2/γ3 AMPK trimer, whereas TBC1D4 phosphorylation (S341, S704) correlated with the activity of the α2/β2/γ1 AMPK trimer. Our data show differential phosphorylation of TBC1D1 and TBC1D4 in response to physiological stimuli in human skeletal muscle and support the idea that Akt and AMPK are upstream kinases. TBC1D1 phosphorylation signatures were comparable between in vitro contracted mouse skeletal muscle and exercised human muscle, and we show that AMPK regulated phosphorylation of these sites in mouse muscle. Contraction and exercise elicited a different phosphorylation pattern of TBC1D4 in mouse compared with human muscle, and although different circumstances in our experimental setup may contribute to this difference, the observation exemplifies that transferring findings between species is problematic. Key points Phosphorylation signature patterns on TBC1D1 and TBC1D4 proteins in the insulin–glucose pathway were

Signature Verification Based on Handwritten Text Recognition

NASA Astrophysics Data System (ADS)

Viriri, Serestina; Tapamo, Jules-R.

Signatures continue to be an important biometric trait because it remains widely used primarily for authenticating the identity of human beings. This paper presents an efficient text-based directional signature recognition algorithm which verifies signatures, even when they are composed of special unconstrained cursive characters which are superimposed and embellished. This algorithm extends the character-based signature verification technique. The experiments carried out on the GPDS signature database and an additional database created from signatures captured using the ePadInk tablet, show that the approach is effective and efficient, with a positive verification rate of 94.95%.

Allosteric site-mediated active site inhibition of PBP2a using Quercetin 3-O-rutinoside and its combination.

PubMed

Rani, Nidhi; Vijayakumar, Saravanan; P T V, Lakshmi; Arunachalam, Annamalai

2016-08-01

Recent crystallographic study revealed the involvement of allosteric site in active site inhibition of penicillin binding protein (PBP2a), where one molecule of Ceftaroline (Cef) binds to the allosteric site of PBP2a and paved way for the other molecule (Cef) to bind at the active site. Though Cef has the potency to inhibit the PBP2a, its adverse side effects are of major concern. Previous studies have reported the antibacterial property of Quercetin derivatives, a group of natural compounds. Hence, the present study aims to evaluate the effect of Quercetin 3-o-rutinoside (Rut) in allosteric site-mediated active site inhibition of PBP2a. The molecular docking studies between allosteric site and ligands (Rut, Que, and Cef) revealed a better binding efficiency (G-score) of Rut (-7.790318) and Cef (-6.194946) with respect to Que (-5.079284). Molecular dynamic (MD) simulation studies showed significant changes at the active site in the presence of ligands (Rut and Cef) at allosteric site. Four different combinations of Rut and Cef were docked and their G-scores ranged between -6.320 and -8.623. MD studies revealed the stability of the key residue (Ser403) with Rut being at both sites, compared to other complexes. Morphological analysis through electron microscopy confirmed that combination of Rut and Cefixime was able to disturb the bacterial cell membrane in a similar fashion to that of Rut and Cefixime alone. The results of this study indicate that the affinity of Rut at both sites were equally good, with further validations Rut could be considered as an alternative for inhibiting MRSA growth.

Influence of active site location on catalytic activity in de novo-designed zinc metalloenzymes.

PubMed

Zastrow, Melissa L; Pecoraro, Vincent L

2013-04-17

While metalloprotein design has now yielded a number of successful metal-bound and even catalytically active constructs, the question of where to put a metal site along a linear, repetitive sequence has not been thoroughly addressed. Often several possibilities in a given sequence may exist that would appear equivalent but may in fact differ for metal affinity, substrate access, or protein dynamics. We present a systematic variation of active site location for a hydrolytically active ZnHis3O site contained within a de novo-designed three-stranded coiled coil. We find that the maximal rate, substrate access, and metal-binding affinity are dependent on the selected position, while catalytic efficiency for p-nitrophenyl acetate hydrolysis can be retained regardless of the location of the active site. This achievement demonstrates how efficient, tailor-made enzymes which control rate, pKa, substrate and solvent access (and selectivity), and metal-binding affinity may be realized. These findings may be applied to the more advanced de novo design of constructs containing secondary interactions, such as hydrogen-bonding channels. We are now confident that changes to location for accommodating such channels can be achieved without location-dependent loss of catalytic efficiency. These findings bring us closer to our ultimate goal of incorporating the secondary interactions we believe will be necessary in order to improve both active site properties and the catalytic efficiency to be competitive with the native enzyme, carbonic anhydrase.

Real time gamma-ray signature identifier

DOEpatents

Rowland, Mark [Alamo, CA; Gosnell, Tom B [Moraga, CA; Ham, Cheryl [Livermore, CA; Perkins, Dwight [Livermore, CA; Wong, James [Dublin, CA

2012-05-15

A real time gamma-ray signature/source identification method and system using principal components analysis (PCA) for transforming and substantially reducing one or more comprehensive spectral libraries of nuclear materials types and configurations into a corresponding concise representation/signature(s) representing and indexing each individual predetermined spectrum in principal component (PC) space, wherein an unknown gamma-ray signature may be compared against the representative signature to find a match or at least characterize the unknown signature from among all the entries in the library with a single regression or simple projection into the PC space, so as to substantially reduce processing time and computing resources and enable real-time characterization and/or identification.

Spatial and temporal variability of hyperspectral signatures of terrain

NASA Astrophysics Data System (ADS)

Jones, K. F.; Perovich, D. K.; Koenig, G. G.

2008-04-01

Electromagnetic signatures of terrain exhibit significant spatial heterogeneity on a range of scales as well as considerable temporal variability. A statistical characterization of the spatial heterogeneity and spatial scaling algorithms of terrain electromagnetic signatures are required to extrapolate measurements to larger scales. Basic terrain elements including bare soil, grass, deciduous, and coniferous trees were studied in a quasi-laboratory setting using instrumented test sites in Hanover, NH and Yuma, AZ. Observations were made using a visible and near infrared spectroradiometer (350 - 2500 nm) and hyperspectral camera (400 - 1100 nm). Results are reported illustrating: i) several difference scenes; ii) a terrain scene time series sampled over an annual cycle; and iii) the detection of artifacts in scenes. A principal component analysis indicated that the first three principal components typically explained between 90 and 99% of the variance of the 30 to 40-channel hyperspectral images. Higher order principal components of hyperspectral images are useful for detecting artifacts in scenes.

Active Sites Environmental Monitoring Program: Mid-FY 1991 report

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

Ashwood, T.L.; Wickliff, D.S.; Morrissey, C.M.

1991-10-01

This report summarizes the activities of the Active Sites Environmental Monitoring Program (ASEMP) from October 1990 through March 1991. The ASEMP was established in 1989 by Solid Waste Operations and the Environmental Sciences Division to provide early detection and performance monitoring at active low-level radioactive waste (LLW) disposal sites in Solid Waste Storage Area (SWSA) 6 and transuranic (TRU) waste storage sites in SWSA 5 as required by chapters II and III of US Department of Energy Order 5820.2A. Monitoring results continue to demonstrate the no LLW is being leached from the storage vaults on the tumulus pads. Loading ofmore » vaults on Tumulus II began during this reporting period and 115 vaults had been loaded by the end of March 1991.« less

Provably secure identity-based identification and signature schemes from code assumptions

PubMed Central

Zhao, Yiming

2017-01-01

Code-based cryptography is one of few alternatives supposed to be secure in a post-quantum world. Meanwhile, identity-based identification and signature (IBI/IBS) schemes are two of the most fundamental cryptographic primitives, so several code-based IBI/IBS schemes have been proposed. However, with increasingly profound researches on coding theory, the security reduction and efficiency of such schemes have been invalidated and challenged. In this paper, we construct provably secure IBI/IBS schemes from code assumptions against impersonation under active and concurrent attacks through a provably secure code-based signature technique proposed by Preetha, Vasant and Rangan (PVR signature), and a security enhancement Or-proof technique. We also present the parallel-PVR technique to decrease parameter values while maintaining the standard security level. Compared to other code-based IBI/IBS schemes, our schemes achieve not only preferable public parameter size, private key size, communication cost and signature length due to better parameter choices, but also provably secure. PMID:28809940

Provably secure identity-based identification and signature schemes from code assumptions.

PubMed

Song, Bo; Zhao, Yiming

2017-01-01

Code-based cryptography is one of few alternatives supposed to be secure in a post-quantum world. Meanwhile, identity-based identification and signature (IBI/IBS) schemes are two of the most fundamental cryptographic primitives, so several code-based IBI/IBS schemes have been proposed. However, with increasingly profound researches on coding theory, the security reduction and efficiency of such schemes have been invalidated and challenged. In this paper, we construct provably secure IBI/IBS schemes from code assumptions against impersonation under active and concurrent attacks through a provably secure code-based signature technique proposed by Preetha, Vasant and Rangan (PVR signature), and a security enhancement Or-proof technique. We also present the parallel-PVR technique to decrease parameter values while maintaining the standard security level. Compared to other code-based IBI/IBS schemes, our schemes achieve not only preferable public parameter size, private key size, communication cost and signature length due to better parameter choices, but also provably secure.

Signatures of Slow Solar Wind Streams from Active Regions in the Inner Corona

NASA Astrophysics Data System (ADS)

Slemzin, V.; Harra, L.; Urnov, A.; Kuzin, S.; Goryaev, F.; Berghmans, D.

2013-08-01

The identification of solar-wind sources is an important question in solar physics. The existing solar-wind models ( e.g., the Wang-Sheeley-Arge model) provide the approximate locations of the solar wind sources based on magnetic field extrapolations. It has been suggested recently that plasma outflows observed at the edges of active regions may be a source of the slow solar wind. To explore this we analyze an isolated active region (AR) adjacent to small coronal hole (CH) in July/August 2009. On 1 August, Hinode/EUV Imaging Spectrometer observations showed two compact outflow regions in the corona. Coronal rays were observed above the active-region coronal hole (ARCH) region on the eastern limb on 31 July by STEREO-A/EUVI and at the western limb on 7 August by CORONAS- Photon/TESIS telescopes. In both cases the coronal rays were co-aligned with open magnetic-field lines given by the potential field source surface model, which expanded into the streamer. The solar-wind parameters measured by STEREO-B, ACE, Wind, and STEREO-A confirmed the identification of the ARCH as a source region of the slow solar wind. The results of the study support the suggestion that coronal rays can represent signatures of outflows from ARs propagating in the inner corona along open field lines into the heliosphere.

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.

CORONAL AND CHROMOSPHERIC SIGNATURES OF LARGE-SCALE DISTURBANCES ASSOCIATED WITH A MAJOR SOLAR ERUPTION

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

Zong, Weiguo; Dai, Yu, E-mail: ydai@nju.edu.cn

We present both coronal and chromospheric observations of large-scale disturbances associated with a major solar eruption on 2005 September 7. In the Geostationary Operational Environmental Satellites/Solar X-ray Imager (SXI), arclike coronal brightenings are recorded propagating in the southern hemisphere. The SXI front shows an initially constant speed of 730 km s{sup −1} and decelerates later on, and its center is near the central position angle of the associated coronal mass ejection (CME) but away from the flare site. Chromospheric signatures of the disturbances are observed in both Mauna Loa Solar Observatory (MLSO)/Polarimeter for Inner Coronal Studies Hα and MLSO/Chromospheric Helium Imore » Imaging Photometer He i λ10830 and can be divided into two parts. The southern signatures occur in regions where the SXI front sweeps over, with the Hα bright front coincident with the SXI front, while the He i dark front lags the SXI front but shows a similar kinematics. Ahead of the path of the southern signatures, oscillations of a filament are observed. The northern signatures occur near the equator, with the Hα and He i fronts coincident with each other. They first propagate westward and then deflect to the north at the boundary of an equatorial coronal hole. Based on these observational facts, we suggest that the global disturbances are associated with the CME lift-off and show a hybrid nature: a mainly non-wave CME flank nature for the SXI signatures and the corresponding southern chromospheric signatures, and a shocked fast-mode coronal MHD wave nature for the northern chromospheric signatures.« less

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;

MDD-carb: a combinatorial model for the identification of protein carbonylation sites with substrate motifs.

PubMed

Kao, Hui-Ju; Weng, Shun-Long; Huang, Kai-Yao; Kaunang, Fergie Joanda; Hsu, Justin Bo-Kai; Huang, Chien-Hsun; Lee, Tzong-Yi

2017-12-21

Carbonylation, which takes place through oxidation of reactive oxygen species (ROS) on specific residues, is an irreversibly oxidative modification of proteins. It has been reported that the carbonylation is related to a number of metabolic or aging diseases including diabetes, chronic lung disease, Parkinson's disease, and Alzheimer's disease. Due to the lack of computational methods dedicated to exploring motif signatures of protein carbonylation sites, we were motivated to exploit an iterative statistical method to characterize and identify carbonylated sites with motif signatures. By manually curating experimental data from research articles, we obtained 332, 144, 135, and 140 verified substrate sites for K (lysine), R (arginine), T (threonine), and P (proline) residues, respectively, from 241 carbonylated proteins. In order to examine the informative attributes for classifying between carbonylated and non-carbonylated sites, multifarious features including composition of twenty amino acids (AAC), composition of amino acid pairs (AAPC), position-specific scoring matrix (PSSM), and positional weighted matrix (PWM) were investigated in this study. Additionally, in an attempt to explore the motif signatures of carbonylation sites, an iterative statistical method was adopted to detect statistically significant dependencies of amino acid compositions between specific positions around substrate sites. Profile hidden Markov model (HMM) was then utilized to train a predictive model from each motif signature. Moreover, based on the method of support vector machine (SVM), we adopted it to construct an integrative model by combining the values of bit scores obtained from profile HMMs. The combinatorial model could provide an enhanced performance with evenly predictive sensitivity and specificity in the evaluation of cross-validation and independent testing. This study provides a new scheme for exploring potential motif signatures at substrate sites of protein

Corticosteroid receptors adopt distinct cyclical transcriptional signatures.

PubMed

Le Billan, Florian; Amazit, Larbi; Bleakley, Kevin; Xue, Qiong-Yao; Pussard, Eric; Lhadj, Christophe; Kolkhof, Peter; Viengchareun, Say; Fagart, Jérôme; Lombès, Marc

2018-05-07

Mineralocorticoid receptors (MRs) and glucocorticoid receptors (GRs) are two closely related hormone-activated transcription factors that regulate major pathophysiologic functions. High homology between these receptors accounts for the crossbinding of their corresponding ligands, MR being activated by both aldosterone and cortisol and GR essentially activated by cortisol. Their coexpression and ability to bind similar DNA motifs highlight the need to investigate their respective contributions to overall corticosteroid signaling. Here, we decipher the transcriptional regulatory mechanisms that underlie selective effects of MRs and GRs on shared genomic targets in a human renal cellular model. Kinetic, serial, and sequential chromatin immunoprecipitation approaches were performed on the period circadian protein 1 ( PER1) target gene, providing evidence that both receptors dynamically and cyclically interact at the same target promoter in a specific and distinct transcriptional signature. During this process, both receptors regulate PER1 gene by binding as homo- or heterodimers to the same promoter region. Our results suggest a novel level of MR-GR target gene regulation, which should be considered for a better and integrated understanding of corticosteroid-related pathophysiology.-Le Billan, F., Amazit, L., Bleakley, K., Xue, Q.-Y., Pussard, E., Lhadj, C., Kolkhof, P., Viengchareun, S., Fagart, J., Lombès, M. Corticosteroid receptors adopt distinct cyclical transcriptional signatures.

27 CFR 17.6 - Signature authority.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 27 Alcohol, Tobacco Products and Firearms 1 2010-04-01 2010-04-01 false Signature authority. 17.6... PRODUCTS General Provisions § 17.6 Signature authority. No claim, bond, tax return, or other required... other proper notification of signature authority has been filed with the TTB office where the required...

7 CFR 718.9 - Signature requirements.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 7 Agriculture 7 2010-01-01 2010-01-01 false Signature requirements. 718.9 Section 718.9... MULTIPLE PROGRAMS General Provisions § 718.9 Signature requirements. (a) When a program authorized by this chapter or Chapter XIV of this title requires the signature of a producer; landowner; landlord; or tenant...

Statistical analysis of the magnetization signatures of impact basins

NASA Astrophysics Data System (ADS)

Gabasova, L. R.; Wieczorek, M. A.

2017-09-01

We quantify the magnetic signatures of the largest lunar impact basins using recent mission data and robust statistical bounds, and obtain an early activity timeline for the lunar core dynamo which appears to peak earlier than indicated by Apollo paleointensity measurements.

Glove-based approach to online signature verification.

PubMed

Kamel, Nidal S; Sayeed, Shohel; Ellis, Grant A

2008-06-01

Utilizing the multiple degrees of freedom offered by the data glove for each finger and the hand, a novel on-line signature verification system using the Singular Value Decomposition (SVD) numerical tool for signature classification and verification is presented. The proposed technique is based on the Singular Value Decomposition in finding r singular vectors sensing the maximal energy of glove data matrix A, called principal subspace, so the effective dimensionality of A can be reduced. Having modeled the data glove signature through its r-principal subspace, signature authentication is performed by finding the angles between the different subspaces. A demonstration of the data glove is presented as an effective high-bandwidth data entry device for signature verification. This SVD-based signature verification technique is tested and its performance is shown to be able to recognize forgery signatures with a false acceptance rate of less than 1.2%.

48 CFR 804.101 - Contracting officer's signature.

Code of Federal Regulations, 2010 CFR

2010-10-01

... signature. 804.101 Section 804.101 Federal Acquisition Regulations System DEPARTMENT OF VETERANS AFFAIRS GENERAL ADMINISTRATIVE MATTERS Contract Execution 804.101 Contracting officer's signature. (a) If a... signature. ...

CD137+CD154− Expression As a Regulatory T Cell (Treg)-Specific Activation Signature for Identification and Sorting of Stable Human Tregs from In Vitro Expansion Cultures

PubMed Central

Nowak, Anna; Lock, Dominik; Bacher, Petra; Hohnstein, Thordis; Vogt, Katrin; Gottfreund, Judith; Giehr, Pascal; Polansky, Julia K.; Sawitzki, Birgit; Kaiser, Andrew; Walter, Jörn; Scheffold, Alexander

2018-01-01

Regulatory T cells (Tregs) are an attractive therapeutic tool for several different immune pathologies. Therapeutic Treg application often requires prolonged in vitro culture to generate sufficient Treg numbers or to optimize their functionality, e.g., via genetic engineering of their antigen receptors. However, purity of clinical Treg expansion cultures is highly variable, and currently, it is impossible to identify and separate stable Tregs from contaminating effector T cells, either ex vivo or after prior expansion. This represents a major obstacle for quality assurance of expanded Tregs and raises significant safety concerns. Here, we describe a Treg activation signature that allows identification and sorting of epigenetically imprinted Tregs even after prolonged in vitro culture. We show that short-term reactivation resulted in expression of CD137 but not CD154 on stable FoxP3+ Tregs that displayed a demethylated Treg-specific demethylated region, high suppressive potential, and lack of inflammatory cytokine expression. We also applied this Treg activation signature for rapid testing of chimeric antigen receptor functionality in human Tregs and identified major differences in the signaling requirements regarding CD137 versus CD28 costimulation. Taken together, CD137+CD154− expression emerges as a universal Treg activation signature ex vivo and upon in vitro expansion allowing the identification and isolation of epigenetically stable antigen-activated Tregs and providing a means for their rapid functional testing in vitro. PMID:29467769

AdaBoost-based on-line signature verifier

NASA Astrophysics Data System (ADS)

Hongo, Yasunori; Muramatsu, Daigo; Matsumoto, Takashi

2005-03-01

Authentication of individuals is rapidly becoming an important issue. The authors previously proposed a Pen-input online signature verification algorithm. The algorithm considers a writer"s signature as a trajectory of pen position, pen pressure, pen azimuth, and pen altitude that evolve over time, so that it is dynamic and biometric. Many algorithms have been proposed and reported to achieve accuracy for on-line signature verification, but setting the threshold value for these algorithms is a problem. In this paper, we introduce a user-generic model generated by AdaBoost, which resolves this problem. When user- specific models (one model for each user) are used for signature verification problems, we need to generate the models using only genuine signatures. Forged signatures are not available because imposters do not give forged signatures for training in advance. However, we can make use of another's forged signature in addition to the genuine signatures for learning by introducing a user generic model. And Adaboost is a well-known classification algorithm, making final decisions depending on the sign of the output value. Therefore, it is not necessary to set the threshold value. A preliminary experiment is performed on a database consisting of data from 50 individuals. This set consists of western-alphabet-based signatures provide by a European research group. In this experiment, our algorithm gives an FRR of 1.88% and an FAR of 1.60%. Since no fine-tuning was done, this preliminary result looks very promising.

A Measure of the Promiscuity of Proteins and Characteristics of Residues in the Vicinity of the Catalytic Site That Regulate Promiscuity

PubMed Central

Chakraborty, Sandeep; Rao, Basuthkar J.

2012-01-01

Promiscuity, the basis for the evolution of new functions through ‘tinkering’ of residues in the vicinity of the catalytic site, is yet to be quantitatively defined. We present a computational method Promiscuity Indices Estimator (PROMISE) - based on signatures derived from the spatial and electrostatic properties of the catalytic residues, to estimate the promiscuity (PromIndex) of proteins with known active site residues and 3D structure. PromIndex reflects the number of different active site signatures that have congruent matches in close proximity of its native catalytic site, the quality of the matches and difference in the enzymatic activity. Promiscuity in proteins is observed to follow a lognormal distribution (μ = 0.28, σ = 1.1 reduced chi-square = 3.0E-5). The PROMISE predicted promiscuous functions in any protein can serve as the starting point for directed evolution experiments. PROMISE ranks carboxypeptidase A and ribonuclease A amongst the more promiscuous proteins. We have also investigated the properties of the residues in the vicinity of the catalytic site that regulates its promiscuity. Linear regression establishes a weak correlation (R2∼0.1) between certain properties of the residues (charge, polar, etc) in the neighborhood of the catalytic residues and PromIndex. A stronger relationship states that most proteins with high promiscuity have high percentages of charged and polar residues within a radius of 3 Å of the catalytic site, which is validated using one-tailed hypothesis tests (P-values∼0.05). Since it is known that these characteristics are key factors in catalysis, their relationship with the promiscuity index cross validates the methodology of PROMISE. PMID:22359655

Stromal signatures in endometrioid endometrial carcinomas.

PubMed

Espinosa, Iñigo; Catasus, Lluis; D' Angelo, Emanuela; Mozos, Ana; Pedrola, Nuria; Bértolo, Cristina; Ferrer, Irene; Zannoni, Gian Franco; West, Robert B; van de Rijn, Matt; Matias-Guiu, Xavier; Prat, Jaime

2014-04-01

The pattern of myometrial invasion in endometrioid endometrial carcinomas varies considerably; ie, from widely scattered glands and cell nests, often associated with a fibromyxoid stromal reaction (desmoplasia) and/or a lymphocytic infiltrate, to invasive glands with little or no stromal response. Recently, two distinct stromal signatures derived from a macrophage response (colony-stimulating factor 1, CSF1) and a fibroblastic response (desmoid-type fibromatosis, DTF) were identified in breast carcinomas and correlated with clinicopathologic features including outcome. In this study, we explored whether these stromal signatures also apply to endometrioid carcinomas and how their expression patterns correlated with morphologic changes. We studied the stromal signatures both by immunohistochemistry and in situ hybridization in 98 primary endometrioid carcinomas with (87 cases) and without (11 cases) myometrial invasion as well as in the corresponding regional lymph nodes metatases of 9 myoinvasive tumors. Desmoplasia correlated positively with the DTF expression signature. Likewise, mononuclear infiltrates were found in the stroma of tumors expressing CSF1. Twenty-four out of eighty-seven (27%) myoinvasive endometrioid carcinomas were positive for the macrophage signature and thirteen out of eighty-seven (15%) expressed the fibroblast signature. Eleven additional cases were positive for both DTF and CSF1 signatures (11/87; 13%). However, over half of the cases (39/87; 45%) and the majority of the non-myoinvasive tumors (8/11; 73%) failed to express any of the two stromal signatures. The macrophage response (CSF1) was associated with higher tumor grade, lymphovascular invasion, and PIK3CA mutations (P<0.05). There was a concordance in the expression of the CSF1 signature in the primary tumors and their corresponding lymph node metastases. This study is the first characterization of stromal signatures in endometrioid carcinomas. Our findings shed new light on the

Environmental signatures and effects of an oil and gas wastewater spill in the Williston Basin, North Dakota.

PubMed

Cozzarelli, I M; Skalak, K J; Kent, D B; Engle, M A; Benthem, A; Mumford, A C; Haase, K; Farag, A; Harper, D; Nagel, S C; Iwanowicz, L R; Orem, W H; Akob, D M; Jaeschke, J B; Galloway, J; Kohler, M; Stoliker, D L; Jolly, G D

2017-02-01

Wastewaters from oil and gas development pose largely unknown risks to environmental resources. In January 2015, 11.4ML (million liters) of wastewater (300g/L TDS) from oil production in the Williston Basin was reported to have leaked from a pipeline, spilling into Blacktail Creek, North Dakota. Geochemical and biological samples were collected in February and June 2015 to identify geochemical signatures of spilled wastewaters as well as biological responses along a 44-km river reach. February water samples had elevated chloride (1030mg/L) and bromide (7.8mg/L) downstream from the spill, compared to upstream levels (11mg/L and <0.4mg/L, respectively). Lithium (0.25mg/L), boron (1.75mg/L) and strontium (7.1mg/L) were present downstream at 5-10 times upstream concentrations. Light hydrocarbon measurements indicated a persistent thermogenic source of methane in the stream. Semi-volatile hydrocarbons indicative of oil were not detected in filtered samples but low levels, including tetramethylbenzenes and di-methylnaphthalenes, were detected in unfiltered water samples downstream from the spill. Labile sediment-bound barium and strontium concentrations (June 2015) were higher downstream from the Spill Site. Radium activities in sediment downstream from the Spill Site were up to 15 times the upstream activities and, combined with Sr isotope ratios, suggest contributions from the pipeline fluid and support the conclusion that elevated concentrations in Blacktail Creek water are from the leaking pipeline. Results from June 2015 demonstrate the persistence of wastewater effects in Blacktail Creek several months after remediation efforts started. Aquatic health effects were observed in June 2015; fish bioassays showed only 2.5% survival at 7.1km downstream from the spill compared to 89% at the upstream reference site. Additional potential biological impacts were indicated by estrogenic inhibition in downstream waters. Our findings demonstrate that environmental signatures

Environmental signatures and effects of an oil and gas wastewater spill in the Williston Basin, North Dakota

USGS Publications Warehouse

Cozzarelli, Isabelle M.; Skalak, Katherine; Kent, D.B.; Engle, Mark A.; Benthem, Adam J.; Mumford, Adam; Haase, Karl B.; Farag, Aïda M.; Harper, David; Nagel, S. C.; Iwanowicz, Luke R.; Orem, William H.; Akob, Denise M.; Jaeschke, Jeanne B.; Galloway, Joel M.; Kohler, Matthias; Stoliker, Deborah L.; Jolly, Glenn D.

2017-01-01

Wastewaters from oil and gas development pose largely unknown risks to environmental resources. In January 2015, 11.4 M L (million liters) of wastewater (300 g/L TDS) from oil production in the Williston Basin was reported to have leaked from a pipeline, spilling into Blacktail Creek, North Dakota. Geochemical and biological samples were collected in February and June 2015 to identify geochemical signatures of spilled wastewaters as well as biological responses along a 44-km river reach. February water samples had elevated chloride (1030 mg/L) and bromide (7.8 mg/L) downstream from the spill, compared to upstream levels (11 mg/L and < 0.4 mg/L, respectively). Lithium (0.25 mg/L), boron (1.75 mg/L) and strontium (7.1 mg/L) were present downstream at 5–10 times upstream concentrations. Light hydrocarbon measurements indicated a persistent thermogenic source of methane in the stream. Semi-volatile hydrocarbons indicative of oil were not detected in filtered samples but low levels, including tetramethylbenzenes and di-methylnaphthalenes, were detected in unfiltered water samples downstream from the spill. Labile sediment-bound barium and strontium concentrations (June 2015) were higher downstream from the Spill Site. Radium activities in sediment downstream from the Spill Site were up to 15 times the upstream activities and, combined with Sr isotope ratios, suggest contributions from the pipeline fluid and support the conclusion that elevated concentrations in Blacktail Creek water are from the leaking pipeline. Results from June 2015 demonstrate the persistence of wastewater effects in Blacktail Creek several months after remediation efforts started. Aquatic health effects were observed in June 2015; fish bioassays showed only 2.5% survival at 7.1 km downstream from the spill compared to 89% at the upstream reference site. Additional potential biological impacts were indicated by estrogenic inhibition in downstream waters. Our findings demonstrate that

Combinational Circuit Obfuscation Through Power Signature Manipulation

DTIC Science & Technology

2011-06-01

Algorithm produced by SID . . . . . . . . . . . . . . . . . . . . . . 80 Appendix B . Power Signature Estimation Results 2 . . . . . . . . . . 85 B .1 Power...Signature for c264 Circuit Variant per Algorithm produced by SPICE Simulation . . . . . . . . . . . . . . 85 B .2 Power Signature for c5355 and c499...Smart SSR selecting rear level components and gates with 1000 iterations . . . . . . . . . 84 B .1. Power Signature for c264 By Random Sequence

Practical quantum digital signature

NASA Astrophysics Data System (ADS)

Yin, Hua-Lei; Fu, Yao; Chen, Zeng-Bing

2016-03-01

Guaranteeing nonrepudiation, unforgeability as well as transferability of a signature is one of the most vital safeguards in today's e-commerce era. Based on fundamental laws of quantum physics, quantum digital signature (QDS) aims to provide information-theoretic security for this cryptographic task. However, up to date, the previously proposed QDS protocols are impractical due to various challenging problems and most importantly, the requirement of authenticated (secure) quantum channels between participants. Here, we present the first quantum digital signature protocol that removes the assumption of authenticated quantum channels while remaining secure against the collective attacks. Besides, our QDS protocol can be practically implemented over more than 100 km under current mature technology as used in quantum key distribution.

25 CFR 213.10 - Lessor's signature.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 25 Indians 1 2010-04-01 2010-04-01 false Lessor's signature. 213.10 Section 213.10 Indians BUREAU... MEMBERS OF FIVE CIVILIZED TRIBES, OKLAHOMA, FOR MINING How to Acquire Leases § 213.10 Lessor's signature... thumbprint which shall be designated as “right” or “left” thumbmark. Such signatures must be witnessed by two...

Fracture Strength of Fused Silica From Photonic Signatures Around Collision Sites

NASA Technical Reports Server (NTRS)

Yost, William T.; Cramer, K Elliott

2015-01-01

Impact sites in glass affect its fracture strength. An analytical model that predicts fracture strength from grey-field polariscope (GFP) readings (photoelastic retardations) has been developed and reported in the literature. The model is suggestive that stress fields, resulting from impact damage, destablizes sites within the glass, which lead to pathways that cause strength degradation. Using data collected from fused silica specimens fabricated from outer window panes that were designed for the space shuttle, the model was tested against four categories of inflicted damage. The damage sites were cored from the window carcasses, examined with the GFP and broken using the ASTM Standard C1499-09 to measure the fracture strength. A correlation is made between the fracture strength and the photoelastic retardation measured at the damage site in each specimen. A least-squares fit is calculated. The results are compared with the predictions from the model. A plausible single-sided NDE damage site inspection method (a version of which is planned for glass inspection in the Orion Project) that relates photoelastic retardation in glass components to its fracture strength is presented.

All the catalytic active sites of MoS 2 for hydrogen evolution

DOE PAGES

Li, Guoqing; Zhang, Du; Qiao, Qiao; ...

2016-11-29

MoS 2 presents a promising low-cost catalyst for the hydrogen evolution reaction (HER), but the understanding about its active sites has remained limited. Here we present an unambiguous study of the catalytic activities of all possible reaction sites of MoS 2, including edge sites, sulfur vacancies, and grain boundaries. We demonstrate that, in addition to the well-known catalytically active edge sites, sulfur vacancies provide another major active site for the HER, while the catalytic activity of grain boundaries is much weaker. Here, the intrinsic turnover frequencies (Tafel slopes) of the edge sites, sulfur vacancies, and grain boundaries are estimated tomore » be 7.5 s –1 (65–75 mV/dec), 3.2 s –1 (65–85 mV/dec), and 0.1 s –1 (120–160 mV/dec), respectively. We also demonstrate that the catalytic activity of sulfur vacancies strongly depends on the density of the vacancies and the local crystalline structure in proximity to the vacancies. Unlike edge sites, whose catalytic activity linearly depends on the length, sulfur vacancies show optimal catalytic activities when the vacancy density is in the range of 7–10%, and the number of sulfur vacancies in high crystalline quality MoS 2 is higher than that in low crystalline quality MoS 2, which may be related with the proximity of different local crystalline structures to the vacancies.« less

Attack and improvements of fair quantum blind signature schemes

NASA Astrophysics Data System (ADS)

Zou, Xiangfu; Qiu, Daowen

2013-06-01

Blind signature schemes allow users to obtain the signature of a message while the signer learns neither the message nor the resulting signature. Therefore, blind signatures have been used to realize cryptographic protocols providing the anonymity of some participants, such as: secure electronic payment systems and electronic voting systems. A fair blind signature is a form of blind signature which the anonymity could be removed with the help of a trusted entity, when this is required for legal reasons. Recently, a fair quantum blind signature scheme was proposed and thought to be safe. In this paper, we first point out that there exists a new attack on fair quantum blind signature schemes. The attack shows that, if any sender has intercepted any valid signature, he (she) can counterfeit a valid signature for any message and can not be traced by the counterfeited blind signature. Then, we construct a fair quantum blind signature scheme by improved the existed one. The proposed fair quantum blind signature scheme can resist the preceding attack. Furthermore, we demonstrate the security of the proposed fair quantum blind signature scheme and compare it with the other one.

Identification of positive selection signatures in pigs by comparing linkage disequilibrium variances.

PubMed

Li, X; Yang, S; Dong, K; Tang, Z; Li, K; Fan, B; Wang, Z; Liu, B

2017-10-01

Selection affects the patterns of linkage disequilibrium (LD) around the site of a beneficial allele with an increase in LD among the hitchhiking alleles. Comparing the differences in regional LD between pig populations could help to identify putative genomic regions with potential adaptations for economic traits. In this study, using Illumina Porcine SNP60K BeadChip genotyping data from 207 Chinese indigenous, 117 South American village and 408 Large White pigs, we estimated the variation of genome-wide LD between populations using the varld program. The top 0.1% standardized VarLD scores were used as a criterion for all comparisons, and compared with LD blocks, a total of four selection signatures on Sus scrofa chromosome (SSC) 7, 9, 13 and 14 were identified in all populations. These signatures overlapped with quantitative trait loci for linoleic acid content, age at puberty, number of muscle fibers per unit area, hip structure and body weight traits in pigs. Among them, one of the signatures (56.5-56.6 Mb on SSC7) in Large White pigs harbored the ADAMTSL3 gene, which is known to affect body length. The findings of this study seem to point toward recent selection in different pig populations. Further investigations are encouraged to confirm the selection signatures detected by varld in the present study. © 2017 Stichting International Foundation for Animal Genetics.

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

Machine-Learning Methods Enable Exhaustive Searches for Active Bimetallic Facets and Reveal Active Site Motifs for CO 2 Reduction

DOE PAGES

Ulissi, Zachary W.; Tang, Michael T.; Xiao, Jianping; ...

2017-07-27

Bimetallic catalysts are promising for the most difficult thermal and electrochemical reactions, but modeling the many diverse active sites on polycrystalline samples is an open challenge. Here, we present a general framework for addressing this complexity in a systematic and predictive fashion. Active sites for every stable low-index facet of a bimetallic crystal are enumerated and cataloged, yielding hundreds of possible active sites. The activity of these sites is explored in parallel using a neural-network-based surrogate model to share information between the many density functional theory (DFT) relaxations, resulting in activity estimates with an order of magnitude fewer explicit DFTmore » calculations. Sites with interesting activity were found and provide targets for follow-up calculations. This process was applied to the electrochemical reduction of CO 2 on nickel gallium bimetallics and indicated that most facets had similar activity to Ni surfaces, but a few exposed Ni sites with a very favorable on-top CO configuration. This motif emerged naturally from the predictive modeling and represents a class of intermetallic CO 2 reduction catalysts. These sites rationalize recent experimental reports of nickel gallium activity and why previous materials screens missed this exciting material. Most importantly these methods suggest that bimetallic catalysts will be discovered by studying facet reactivity and diversity of active sites more systematically.« less

Machine-Learning Methods Enable Exhaustive Searches for Active Bimetallic Facets and Reveal Active Site Motifs for CO 2 Reduction

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

Ulissi, Zachary W.; Tang, Michael T.; Xiao, Jianping

Bimetallic catalysts are promising for the most difficult thermal and electrochemical reactions, but modeling the many diverse active sites on polycrystalline samples is an open challenge. Here, we present a general framework for addressing this complexity in a systematic and predictive fashion. Active sites for every stable low-index facet of a bimetallic crystal are enumerated and cataloged, yielding hundreds of possible active sites. The activity of these sites is explored in parallel using a neural-network-based surrogate model to share information between the many density functional theory (DFT) relaxations, resulting in activity estimates with an order of magnitude fewer explicit DFTmore » calculations. Sites with interesting activity were found and provide targets for follow-up calculations. This process was applied to the electrochemical reduction of CO 2 on nickel gallium bimetallics and indicated that most facets had similar activity to Ni surfaces, but a few exposed Ni sites with a very favorable on-top CO configuration. This motif emerged naturally from the predictive modeling and represents a class of intermetallic CO 2 reduction catalysts. These sites rationalize recent experimental reports of nickel gallium activity and why previous materials screens missed this exciting material. Most importantly these methods suggest that bimetallic catalysts will be discovered by studying facet reactivity and diversity of active sites more systematically.« less

Mutation at a strictly conserved, active site tyrosine in the copper amine oxidase leads to uncontrolled oxygenase activity.

PubMed

Chen, Zhi-Wei; Datta, Saumen; Dubois, Jennifer L; Klinman, Judith P; Mathews, F Scott

2010-08-31

The copper amine oxidases carry out two copper-dependent processes: production of their own redox-active cofactor (2,4,5-trihydroxyphenylalanine quinone, TPQ) and the subsequent oxidative deamination of substrate amines. Because the same active site pocket must facilitate both reactions, individual active site residues may serve multiple roles. We have examined the roles of a strictly conserved active site tyrosine Y305 in the copper amine oxidase from Hansenula polymorpha kinetically, spetroscopically (Dubois and Klinman (2006) Biochemistry 45, 3178), and, in the present work, structurally. While the Y305A enzyme is almost identical to the wild type, a novel, highly oxygenated species replaces TPQ in the Y305F active sites. This new structure not only provides the first direct detection of peroxy intermediates in cofactor biogenesis but also indicates the critical control of oxidation chemistry that can be conferred by a single active site residue.

Modeling calcification periods of Cytheridella ilosvayi from Florida based on isotopic signatures and hydrological data

NASA Astrophysics Data System (ADS)

Meyer, Juliane; Wrozyna, Claudia; Leis, Albrecht; Piller, Werner E.

2017-11-01

The isotopic signatures of ostracod shells are the result of the temperature and composition of their host water and the phenology and ecology of the target species. Investigations addressing the influence of site-specific environmental variations on the isotopic ranges of ostracod shells are still rare but can provide important information on habitat-dependent variations and may signify a seasonally restricted timing of calcification periods. Here we present isotopic signatures (δ18Oostr, δ13Costr) of living Cytheridella ilosvayi (Ostracoda) and physical, chemical, and isotopic (δD, δ18Owater, δ13CDIC) compositions of 14 freshwater habitats (rivers, lakes, canals, marshes, sinkholes) in South Florida from winter 2013 and summer 2014. We also present instrumental data of river temperatures and δ18O of precipitation (δ18Oprec) from this region. The physicochemical and isotopic compositions of the selected sites characterize the different habitats and show the influence of the source water, biological activity, and duration of exposure to the surface. Mean δ18Oostr and δ13Costr signatures of C. ilosvayi shells correlate well with the isotopic composition of their host waters. Within-sample variabilities in repeated isotopic measurements of single ostracod shells reflect habitat-dependent ranges. The similarly high range of ostracod δ18O in rivers and one marsh sample indicates that both temperature and δ18Oprec are responsible for their variation in the whole study area. Rivers and canals, which are predominantly influenced by the input and mixing of inorganic carbon from the catchment, show smaller δ13Costr ranges than the marsh dominated by local fluctuations in biological activities. Based on these observations, background data of water temperatures and δ18Oprec were used to calculate monthly δ18O variations in a theoretical calcite formed in rivers in Florida assuming a direct reaction on precipitation changes. The calculated values showed a high

Freshwater mussel shells as environmental chronicles: Geochemical and taphonomic signatures of mercury-related extirpations in the North Fork Holston River, Virginia

USGS Publications Warehouse

Brown, M.E.; Kowalewski, M.; Neves, R.J.; Cherry, D.S.; Schreiber, M.E.

2005-01-01

This study utilized freshwater mussel shells to assess mercury (Hg) contamination in the North Fork Holston River that extirpated (caused local extinctions of) a diverse mussel fauna. Shells (n = 366) were collected from five sites situated upstream (two sites), just below (one site), and downstream (two sites) of the town of Saltville, Virginia, where Hg was used to produce chlorine and caustic soda from 1950 to 1972. Shell samples were used to test the (1) utility of geochemical signatures of shells for assessing the spatial variation in Hg levels in the river relative to the contamination source and (2) value of taphonomy (postmortem shell alteration) for distinguishing sites that differ in extirpation histories. Geochemical signatures of 40 shells, analyzed using atomic absorption spectroscopy, indicated a strong longitudinal pattern. All shells from the two upstream sites had low Hg concentrations (<5-31 ??g/kg), shells directly below Saltville had variable, but dramatically higher concentrations (23-4637 ??g/kg), and shells from the two downstream sites displayed intermediate Hg levels (<5-115 ??g/kg) that declined with distance from Saltville. Two pre-industrial shells, collected at Saltville in 1917, yielded very low Hg estimates (5-6 ??g/kg). Hg signatures were consistent among mussel species, suggesting that Hg concentrations were invariant to species type; most likely, highly variable Hg levels, both across sites and through time, overwhelmed any interspecific differences in Hg acquisition. Also, a notable postmortem incorporation of Hg in mussel shells seemed unlikely, as the Hg content was not correlated with shell taphonomy (r = 0.18; p = 0.28). The taphonomic analysis (n = 366) showed that the degree of shell alteration reliably distinguished sites with different extirpation histories. At Saltville, where live mussels have been absent for at least 30 years, shells were most heavily altered and fragmented. Conversely, fresh-looking shells abounded

Functional Evolution of PLP-dependent Enzymes based on Active-Site Structural Similarities

PubMed Central

Catazaro, Jonathan; Caprez, Adam; Guru, Ashu; Swanson, David; Powers, Robert

2014-01-01

Families of distantly related proteins typically have very low sequence identity, which hinders evolutionary analysis and functional annotation. Slowly evolving features of proteins, such as an active site, are therefore valuable for annotating putative and distantly related proteins. To date, a complete evolutionary analysis of the functional relationship of an entire enzyme family based on active-site structural similarities has not yet been undertaken. Pyridoxal-5’-phosphate (PLP) dependent enzymes are primordial enzymes that diversified in the last universal ancestor. Using the Comparison of Protein Active Site Structures (CPASS) software and database, we show that the active site structures of PLP-dependent enzymes can be used to infer evolutionary relationships based on functional similarity. The enzymes successfully clustered together based on substrate specificity, function, and three-dimensional fold. This study demonstrates the value of using active site structures for functional evolutionary analysis and the effectiveness of CPASS. PMID:24920327

Chapter 12: Daily Patterns of Marbled Murrelet Activity at Inland Sites

Treesearch

Nancy L. Naslund; Brian P. O’Donnell

1995-01-01

Patterns in the daily activity of Marbled Murrelets (Brachyramphus marmoratus) at inland sites has been studied throughout their range from California to Alaska. Murrelets are most active at inland sites around dawn, and to a lesser degree, at dusk. Throughout their range, peak levels of activity (detections) occur in the hour around dawn, but...

An Active Site Water Network in the Plasminogen Activator Pla from Yersinia pestis

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

Eren, Elif; Murphy, Megan; Goguen, Jon

2010-08-13

The plasminogen activator Pla from Yersinia pestis is an outer membrane protease (omptin) that is important for the virulence of plague. Here, we present the high-resolution crystal structure of wild-type, enzymatically active Pla at 1.9 {angstrom}. The structure shows a water molecule located between active site residues D84 and H208, which likely corresponds to the nucleophilic water. A number of other water molecules are present in the active site, linking residues important for enzymatic activity. The R211 sidechain in loop L4 is close to the nucleophilic water and possibly involved in the stabilization of the oxyanion intermediate. Subtle conformational changesmore » of H208 result from the binding of lipopolysaccharide to the outside of the barrel, explaining the unusual dependence of omptins on lipopolysaccharide for activity. The Pla structure suggests a model for the interaction with plasminogen substrate and provides a more detailed understanding of the catalytic mechanism of omptin proteases.« less

Should fatty acid signature proportions sum to 1 for diet estimation?

USGS Publications Warehouse

Bromaghin, Jeffrey F.; Budge, Suzanne M.; Thiemann, Gregory W.

2016-01-01

Knowledge of predator diets, including how diets might change through time or differ among predators, provides essential insights into their ecology. Diet estimation therefore remains an active area of research within quantitative ecology. Quantitative fatty acid signature analysis (QFASA) is an increasingly common method of diet estimation. QFASA is based on a data library of prey signatures, which are vectors of proportions summarizing the fatty acid composition of lipids, and diet is estimated as the mixture of prey signatures that most closely approximates a predator’s signature. Diets are typically estimated using proportions from a subset of all fatty acids that are known to be solely or largely influenced by diet. Given the subset of fatty acids selected, the current practice is to scale their proportions to sum to 1.0. However, scaling signature proportions has the potential to distort the structural relationships within a prey library and between predators and prey. To investigate that possibility, we compared the practice of scaling proportions with two alternatives and found that the traditional scaling can meaningfully bias diet estimators under some conditions. Two aspects of the prey types that contributed to a predator’s diet influenced the magnitude of the bias: the degree to which the sums of unscaled proportions differed among prey types and the identifiability of prey types within the prey library. We caution investigators against the routine scaling of signature proportions in QFASA.

Icy Moon Absorption Signatures: Probes of Saturnian Magnetospheric Dynamics and Moon Activity

NASA Astrophysics Data System (ADS)

Roussos, E.; Krupp, N.; Jones, G. H.; Paranicas, C.; Mitchell, D. G.; Krimigis, S. M.; Motschmann, U.; Dougherty, M. K.; Lagg, A.; Woch, J.

2006-12-01

After the first flybys at the outer planets by the Pioneer and Voyager probes, it became evident that energetic charged particle absorption features in the radiation belts are important tracers of magnetospheric dynamical features and parameters. Absorption signatures are especially important for characterizing the Saturnian magnetosphere. Due to the spin and magnetic axes' near-alignment, losses of particles to the icy moon surfaces and rings are higher compared to the losses at other planetary magnetospheres. The refilling rate of these absorption features (termed "micorsignatures") can be associated with particle diffusion. In addition, as these microsignatures drift with the properties of the pre-depletion electrons, they provide us direct information on the drift shell structure in the radiation belts and the factors that influence their shape. The multiple icy moon L-shell crossings by the Cassini spacecraft during the first 2 years of the mission provided us with almost 100 electron absorption events by eight different moons, at various longitudinal separations from each one and at various electron energies. Their analysis seems to give a consistent picture of the electron diffusion source and puts aside a lot of inconsistencies that resulted from relevant Pioneer and Voyager studies. The presence of non-axisymmetric particle drift shells even down to the orbit of Enceladus (3.98 Rs), also revealed through this analysis, suggests either large ring current disturbances or the action of global or localized electric fields. Finally, despite these absorption signatures being observed far from the originating moons, they can give us hints on the nature of the local interaction between each moon and the magnetospheric plasma. It is, nevertheless, beyond any doubt that energetic charged particle absorption signatures are a very powerful tool that can be used to effectively probe a series of dynamical processes in the Saturnian magnetosphere.

A New Approach to Threshold Attribute Based Signatures

DTIC Science & Technology

2011-01-01

Inspired by developments in attribute based encryption and signatures, there has recently been a spurtof progress in the direction of threshold ...attribute based signatures (t-ABS). In this work we propose anovel approach to construct threshold attribute based signatures inspired by ring signatures...Thresholdattribute based signatures, dened by a (t; n) threshold predicate, ensure that the signer holds atleastt out of a specied set of n attributes

Observational Signatures Of Agn Feedback Across Cosmic Time

NASA Astrophysics Data System (ADS)

Wylezalek, Dominika

2017-06-01

While many compelling models of AGN feedback exist, there is no clear data-driven picture of how winds are launched, how they propagate through the galaxy and what impact they have on the galactic gas. Recent work suggests that AGN luminosity plays an important role. The following described projects focus on understanding the power, reach and impact of feedback processes exerted by AGN of different power. I first describe recent efforts in our group of relating feedback signatures in powerful quasars to the specific star formation rate in their host galaxies, where our results are consistent with the AGN having a `negative' impact through feedback on the galaxies' star formation history. Feedback signatures seem to be best observable in gas-rich galaxies where the coupling of the AGN-driven wind to the gas is strongest, in agreement with recent simulations. But how and where does this quenching happen? Is it accomplished through the mechanical action of jets or through nuclear winds driven by radiation pressure? Finally, I show that AGN signatures and AGN-driven winds can be easily hidden and not be apparent in the integrated spectrum of a galaxy hosting a low/intermediate-luminosity AGN. Using data from the new SDSS-IV MaNGA survey, we have developed a new AGN selection algorithm tailored to IFU data and we are uncovering a much more nuanced picture of AGN activity allowing us to discover AGN signatures at large distances from the galaxy center. This implies that large IFU surveys, such as the SDSS-IV MaNGA survey, might uncover many previously unknown AGN and feedback signatures related to them. Outflows and feedback from low- and intermediate-luminosity AGN might have been underestimated in the past but can potentially significantly contribute to the AGN/host-galaxy self-regulation.

General Conversion for Obtaining Strongly Existentially Unforgeable Signatures

NASA Astrophysics Data System (ADS)

Teranishi, Isamu; Oyama, Takuro; Ogata, Wakaha

We say that a signature scheme is strongly existentially unforgeable (SEU) if no adversary, given message/signature pairs adaptively, can generate a signature on a new message or a new signature on a previously signed message. We propose a general and efficient conversion in the standard model that transforms a secure signature scheme to SEU signature scheme. In order to construct that conversion, we use a chameleon commitment scheme. Here a chameleon commitment scheme is a variant of commitment scheme such that one can change the committed value after publishing the commitment if one knows the secret key. We define the chosen message security notion for the chameleon commitment scheme, and show that the signature scheme transformed by our proposed conversion satisfies the SEU property if the chameleon commitment scheme is chosen message secure. By modifying the proposed conversion, we also give a general and efficient conversion in the random oracle model, that transforms a secure signature scheme into a SEU signature scheme. This second conversion also uses a chameleon commitment scheme but only requires the key only attack security for it.

Anisotropic Covalency Contributions to Superexchange Pathways in Type One Copper Active Sites

PubMed Central

2015-01-01

Type one (T1) Cu sites deliver electrons to catalytic Cu active sites: the mononuclear type two (T2) Cu site in nitrite reductases (NiRs) and the trinuclear Cu cluster in the multicopper oxidases (MCOs). The T1 Cu and the remote catalytic sites are connected via a Cys-His intramolecular electron-transfer (ET) bridge, which contains two potential ET pathways: P1 through the protein backbone and P2 through the H-bond between the Cys and the His. The high covalency of the T1 Cu–S(Cys) bond is shown here to activate the T1 Cu site for hole superexchange via occupied valence orbitals of the bridge. This covalency-activated electronic coupling (HDA) facilitates long-range ET through both pathways. These pathways can be selectively activated depending on the geometric and electronic structure of the T1 Cu site and thus the anisotropic covalency of the T1 Cu–S(Cys) bond. In NiRs, blue (π-type) T1 sites utilize P1 and green (σ-type) T1 sites utilize P2, with P2 being more efficient. Comparing the MCOs to NiRs, the second-sphere environment changes the conformation of the Cys-His pathway, which selectively activates HDA for superexchange by blue π sites for efficient turnover in catalysis. These studies show that a given protein bridge, here Cys-His, provides different superexchange pathways and electronic couplings depending on the anisotropic covalencies of the donor and acceptor metal sites. PMID:25310460

Functional evolution of PLP-dependent enzymes based on active-site structural similarities.

PubMed

Catazaro, Jonathan; Caprez, Adam; Guru, Ashu; Swanson, David; Powers, Robert

2014-10-01

Families of distantly related proteins typically have very low sequence identity, which hinders evolutionary analysis and functional annotation. Slowly evolving features of proteins, such as an active site, are therefore valuable for annotating putative and distantly related proteins. To date, a complete evolutionary analysis of the functional relationship of an entire enzyme family based on active-site structural similarities has not yet been undertaken. Pyridoxal-5'-phosphate (PLP) dependent enzymes are primordial enzymes that diversified in the last universal ancestor. Using the comparison of protein active site structures (CPASS) software and database, we show that the active site structures of PLP-dependent enzymes can be used to infer evolutionary relationships based on functional similarity. The enzymes successfully clustered together based on substrate specificity, function, and three-dimensional-fold. This study demonstrates the value of using active site structures for functional evolutionary analysis and the effectiveness of CPASS. © 2014 Wiley Periodicals, Inc.

A Secure and Efficient Threshold Group Signature Scheme

NASA Astrophysics Data System (ADS)

Zhang, Yansheng; Wang, Xueming; Qiu, Gege

The paper presents a secure and efficient threshold group signature scheme aiming at two problems of current threshold group signature schemes: conspiracy attack and inefficiency. Scheme proposed in this paper takes strategy of separating designed clerk who is responsible for collecting and authenticating each individual signature from group, the designed clerk don't participate in distribution of group secret key and has his own public key and private key, designed clerk needs to sign part information of threshold group signature after collecting signatures. Thus verifier has to verify signature of the group after validating signature of the designed clerk. This scheme is proved to be secure against conspiracy attack at last and is more efficient by comparing with other schemes.

Exobiology and the search for biological signatures on Mars

NASA Technical Reports Server (NTRS)

Mancinelli, Rocco L.; Schwartz, Deborah E.

1988-01-01

In preparation for a Mars Rover/Sample return mission, the mission goals and objectives must be identified. One of the most important objectives must address exobiology and the question of the possibility of the origin and evolution of life on Mars. In particular, key signatures or bio-markers of a possible extinct Martian biota must be defined. To that end geographic locations (sites) that are likely to contain traces of past life must also be identified. Sites and experiments are being defined in support of a Mars rover sample return mission. In addition, analyses based on computer models of abiotic processes of CO2 loss from Mars suggest that the CO2 from the atmosphere may have precipitated as carbonates and be buried within the Martian regolith. The carbon cycle of perennially frozen lakes in the dry valley of Antarctica are currently being investigated. These lakes were purported to be a model system for the ancient Martian lakes. By understanding the dynamic balance between the abiotic vs. biotic cycling of carbon within this system, information is gathered which will enable the interpretation of data obtained by a Mars rover with respect to possible carbonate deposits and the processing of carbon by biological systems. These ancient carbonate deposits, and other sedimentary units would contain traces of biological signatures that would hold the key to understanding the origin and evolution of life on Mars, as well as Earth.

Post-analysis report on Chesapeake Bay data processing. [spectral analysis and recognition computer signature extension

NASA Technical Reports Server (NTRS)

Thomson, F.

1972-01-01

The additional processing performed on data collected over the Rhode River Test Site and Forestry Site in November 1970 is reported. The techniques and procedures used to obtain the processed results are described. Thermal data collected over three approximately parallel lines of the site were contoured, and the results color coded, for the purpose of delineating important scene constituents and to identify trees attacked by pine bark beetles. Contouring work and histogram preparation are reviewed and the important conclusions from the spectral analysis and recognition computer (SPARC) signature extension work are summarized. The SPARC setup and processing records are presented and recommendations are made for future data collection over the site.

Microwave remote sensing and radar polarization signatures of natural fields

NASA Technical Reports Server (NTRS)

Mo, Tsan

1989-01-01

Theoretical models developed for simulation of microwave remote sensing of the Earth surface from airborne/spaceborne sensors are described. Theoretical model calculations were performed and the results were compared with data of field measurements. Data studied included polarimetric images at the frequencies of P band, L band, and C band, acquired with airborne polarimeters over a agricultural field test site. Radar polarization signatures from bare soil surfaces and from tree covered fields were obtained from the data. The models developed in this report include: (1) Small perturbation model of wave scatterings from randomly rough surfaces, (2) Physical optics model, (3) Geometrical optics model, and (4) Electromagnetic wave scattering from dielectric cylinders of finite lengths, which replace the trees and branches in the modeling of tree covered field. Additionally, a three-layer emissivity model for passive sensing of a vegetation covered soil surface is also developed. The effects of surface roughness, soil moisture contents, and tree parameters on the polarization signatures were investigated.

47 CFR 54.680 - Validity of electronic signatures.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 47 Telecommunication 3 2013-10-01 2013-10-01 false Validity of electronic signatures. 54.680... Validity of electronic signatures. (a) For the purposes of this subpart, an electronic signature (defined by the Electronic Signatures in Global and National Commerce Act, as an electronic sound, symbol, or...

47 CFR 54.419 - Validity of electronic signatures.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 47 Telecommunication 3 2013-10-01 2013-10-01 false Validity of electronic signatures. 54.419... electronic signatures. (a) For the purposes of this subpart, an electronic signature, defined by the Electronic Signatures in Global and National Commerce Act, as an electronic sound, symbol, or process...

47 CFR 54.419 - Validity of electronic signatures.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 47 Telecommunication 3 2012-10-01 2012-10-01 false Validity of electronic signatures. 54.419... electronic signatures. (a) For the purposes of this subpart, an electronic signature, defined by the Electronic Signatures in Global and National Commerce Act, as an electronic sound, symbol, or process...

47 CFR 54.680 - Validity of electronic signatures.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 47 Telecommunication 3 2014-10-01 2014-10-01 false Validity of electronic signatures. 54.680... Validity of electronic signatures. (a) For the purposes of this subpart, an electronic signature (defined by the Electronic Signatures in Global and National Commerce Act, as an electronic sound, symbol, or...

47 CFR 54.419 - Validity of electronic signatures.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 47 Telecommunication 3 2014-10-01 2014-10-01 false Validity of electronic signatures. 54.419... electronic signatures. (a) For the purposes of this subpart, an electronic signature, defined by the Electronic Signatures in Global and National Commerce Act, as an electronic sound, symbol, or process...

HOX and TALE signatures specify human stromal stem cell populations from different sources.

PubMed

Picchi, Jacopo; Trombi, Luisa; Spugnesi, Laura; Barachini, Serena; Maroni, Giorgia; Brodano, Giovanni Barbanti; Boriani, Stefano; Valtieri, Mauro; Petrini, Mario; Magli, Maria Cristina

2013-04-01

Human stromal stem cell populations reside in different tissues and anatomical sites, however a critical question related to their efficient use in regenerative medicine is whether they exhibit equivalent biological properties. Here, we compared cellular and molecular characteristics of stromal stem cells derived from the bone marrow, at different body sites (iliac crest, sternum, and vertebrae) and other tissues (dental pulp and colon). In particular, we investigated whether homeobox genes of the HOX and TALE subfamilies might provide suitable markers to identify distinct stromal cell populations, as HOX proteins control cell positional identity and, together with their co-factors TALE, are involved in orchestrating differentiation of adult tissues. Our results show that stromal populations from different sources, although immunophenotypically similar, display distinct HOX and TALE signatures, as well as different growth and differentiation abilities. Stromal stem cells from different tissues are characterized by specific HOX profiles, differing in the number and type of active genes, as well as in their level of expression. Conversely, bone marrow-derived cell populations can be essentially distinguished for the expression levels of specific HOX members, strongly suggesting that quantitative differences in HOX activity may be crucial. Taken together, our data indicate that the HOX and TALE profiles provide positional, embryological and hierarchical identity of human stromal stem cells. Furthermore, our data suggest that cell populations derived from different body sites may not represent equivalent cell sources for cell-based therapeutical strategies for regeneration and repair of specific tissues. Copyright © 2012 Wiley Periodicals, Inc.

Active-site solvent replenishment observed during human carbonic anhydrase II catalysis.

PubMed

Kim, Jin Kyun; Lomelino, Carrie L; Avvaru, Balendu Sankara; Mahon, Brian P; McKenna, Robert; Park, SangYoun; Kim, Chae Un

2018-01-01

Human carbonic anhydrase II (hCA II) is a zinc metalloenzyme that catalyzes the reversible hydration/dehydration of CO 2 /HCO 3 - . Although hCA II has been extensively studied to investigate the proton-transfer process that occurs in the active site, its underlying mechanism is still not fully understood. Here, ultrahigh-resolution crystallographic structures of hCA II cryocooled under CO 2 pressures of 7.0 and 2.5 atm are presented. The structures reveal new intermediate solvent states of hCA II that provide crystallographic snapshots during the restoration of the proton-transfer water network in the active site. Specifically, a new intermediate water (W I ') is observed next to the previously observed intermediate water W I , and they are both stabilized by the five water molecules at the entrance to the active site (the entrance conduit). Based on these structures, a water network-restructuring mechanism is proposed, which takes place at the active site after the nucleophilic attack of OH - on CO 2 . This mechanism explains how the zinc-bound water (W Zn ) and W1 are replenished, which are directly responsible for the reconnection of the His64-mediated proton-transfer water network. This study provides the first 'physical' glimpse of how a water reservoir flows into the hCA II active site during its catalytic activity.

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.

40 CFR 263.25 - Electronic manifest signatures.

Code of Federal Regulations, 2014 CFR

2014-07-01

... 40 Protection of Environment 26 2014-07-01 2014-07-01 false Electronic manifest signatures. 263.25 Section 263.25 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) SOLID WASTES... Recordkeeping § 263.25 Electronic manifest signatures. (a) Electronic manifest signatures shall meet the...

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.

21 CFR 11.200 - Electronic signature components and controls.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 1 2010-04-01 2010-04-01 false Electronic signature components and controls. 11... SERVICES GENERAL ELECTRONIC RECORDS; ELECTRONIC SIGNATURES Electronic Signatures § 11.200 Electronic signature components and controls. (a) Electronic signatures that are not based upon biometrics shall: (1...

Seismic signature analysis for discrimination of people from animals

NASA Astrophysics Data System (ADS)

Damarla, Thyagaraju; Mehmood, Asif; Sabatier, James M.

2013-05-01

Cadence analysis has been the main focus for discriminating between the seismic signatures of people and animals. However, cadence analysis fails when multiple targets are generating the signatures. We analyze the mechanism of human walking and the signature generated by a human walker, and compare it with the signature generated by a quadruped. We develop Fourier-based analysis to differentiate the human signatures from the animal signatures. We extract a set of basis vectors to represent the human and animal signatures using non-negative matrix factorization, and use them to separate and classify both the targets. Grazing animals such as deer, cows, etc., often produce sporadic signals as they move around from patch to patch of grass and one must characterize them so as to differentiate their signatures from signatures generated by a horse steadily walking along a path. These differences in the signatures are used in developing a robust algorithm to distinguish the signatures of animals from humans. The algorithm is tested on real data collected in a remote area.

Radiocarbon and stable isotope investigations at the Central Rhineland sites of Gönnersdorf and Andernach-Martinsberg, Germany.

PubMed

Stevens, Rhiannon E; O'Connell, Tamsin C; Hedges, Robert E M; Street, Martin

2009-08-01

The late glacial open-air sites of Gönnersdorf and Andernach-Martinsberg in the German Central Rhineland are well known for their Magdalenian occupation and activities. The latter site also produced evidence for a younger, Final Palaeolithic occupation of the locality by people of the Federmessergruppen. Both sites are particularly well preserved, largely due to their burial beneath volcanic deposits of the late glacial Laacher See eruption. We conducted a program of AMS radiocarbon dating and stable isotope analyses with the aim of improving understanding of the chronological history and ecological setting of the two sites. Previously published radiocarbon dates appeared to indicate that the earliest Magdalenian occupation at Gönnersdorf fell around 12,900 uncalibrated (14)C yr BP, while the earliest occupation at Andernach may have been more than 500 radiocarbon years earlier. The AMS determinations presented here revise this impression and suggest that the onset of occupation at the two sites was in fact simultaneous and prior to the warming of Greenland Interstadial GI 1e. At Gönnersdorf, a chronological hiatus exists between the main Magdalenian faunal assemblage and mega-faunal remains interpreted as collected sub-fossil material. At Andernach-Martinsberg, there is a clear chronological hiatus between the Magdalenian occupation and subsequent Federmessergruppen activities at the site. However, an intermediate radiocarbon date on an atypically preserved horse bone is suggestive of ephemeral human visits to the site between these well demonstrated phases. A date of similar age on an elk bone from Gönnersdorf may indicate broadly contemporaneous human presence at Gönnersdorf too. Stable isotope analysis of faunal remains from Gönnersdorf and Andernach-Martinsberg was conducted with the aim of both reconstructing and comparing local environmental conditions at the two sites, and also potentially identifying subtle variations in the chronological development

Mutational Signatures in Cancer (MuSiCa): a web application to implement mutational signatures analysis in cancer samples.

PubMed

Díaz-Gay, Marcos; Vila-Casadesús, Maria; Franch-Expósito, Sebastià; Hernández-Illán, Eva; Lozano, Juan José; Castellví-Bel, Sergi

2018-06-14

Mutational signatures have been proved as a valuable pattern in somatic genomics, mainly regarding cancer, with a potential application as a biomarker in clinical practice. Up to now, several bioinformatic packages to address this topic have been developed in different languages/platforms. MutationalPatterns has arisen as the most efficient tool for the comparison with the signatures currently reported in the Catalogue of Somatic Mutations in Cancer (COSMIC) database. However, the analysis of mutational signatures is nowadays restricted to a small community of bioinformatic experts. In this work we present Mutational Signatures in Cancer (MuSiCa), a new web tool based on MutationalPatterns and built using the Shiny framework in R language. By means of a simple interface suited to non-specialized researchers, it provides a comprehensive analysis of the somatic mutational status of the supplied cancer samples. It permits characterizing the profile and burden of mutations, as well as quantifying COSMIC-reported mutational signatures. It also allows classifying samples according to the above signature contributions. MuSiCa is a helpful web application to characterize mutational signatures in cancer samples. It is accessible online at http://bioinfo.ciberehd.org/GPtoCRC/en/tools.html and source code is freely available at https://github.com/marcos-diazg/musica .

Mechanism and Catalytic Site Atlas (M-CSA): a database of enzyme reaction mechanisms and active sites.

PubMed

Ribeiro, António J M; Holliday, Gemma L; Furnham, Nicholas; Tyzack, Jonathan D; Ferris, Katherine; Thornton, Janet M

2018-01-04

M-CSA (Mechanism and Catalytic Site Atlas) is a database of enzyme active sites and reaction mechanisms that can be accessed at www.ebi.ac.uk/thornton-srv/m-csa. Our objectives with M-CSA are to provide an open data resource for the community to browse known enzyme reaction mechanisms and catalytic sites, and to use the dataset to understand enzyme function and evolution. M-CSA results from the merging of two existing databases, MACiE (Mechanism, Annotation and Classification in Enzymes), a database of enzyme mechanisms, and CSA (Catalytic Site Atlas), a database of catalytic sites of enzymes. We are releasing M-CSA as a new website and underlying database architecture. At the moment, M-CSA contains 961 entries, 423 of these with detailed mechanism information, and 538 with information on the catalytic site residues only. In total, these cover 81% (195/241) of third level EC numbers with a PDB structure, and 30% (840/2793) of fourth level EC numbers with a PDB structure, out of 6028 in total. By searching for close homologues, we are able to extend M-CSA coverage of PDB and UniProtKB to 51 993 structures and to over five million sequences, respectively, of which about 40% and 30% have a conserved active site. © The Author(s) 2017. Published by Oxford University Press on behalf of Nucleic Acids Research.

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

48 CFR 204.101 - Contracting officer's signature.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 48 Federal Acquisition Regulations System 3 2010-10-01 2010-10-01 false Contracting officer's signature. 204.101 Section 204.101 Federal Acquisition Regulations System DEFENSE ACQUISITION REGULATIONS... officer's signature. Follow the procedures at PGI 204.101 for signature of contract documents. [71 FR 9268...

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.

Can specific transcriptional regulators assemble a universal cancer signature?

NASA Astrophysics Data System (ADS)

Roy, Janine; Isik, Zerrin; Pilarsky, Christian; Schroeder, Michael

2013-10-01

Recently, there is a lot of interest in using biomarker signatures derived from gene expression data to predict cancer progression. We assembled signatures of 25 published datasets covering 13 types of cancers. How do these signatures compare with each other? On one hand signatures answering the same biological question should overlap, whereas signatures predicting different cancer types should differ. On the other hand, there could also be a Universal Cancer Signature that is predictive independently of the cancer type. Initially, we generate signatures for all datasets using classical approaches such as t-test and fold change and then, we explore signatures resulting from a network-based method, that applies the random surfer model of Google's PageRank algorithm. We show that the signatures as published by the authors and the signatures generated with classical methods do not overlap - not even for the same cancer type - whereas the network-based signatures strongly overlap. Selecting 10 out of 37 universal cancer genes gives the optimal prediction for all cancers thus taking a first step towards a Universal Cancer Signature. We furthermore analyze and discuss the involved genes in terms of the Hallmarks of cancer and in particular single out SP1, JUN/FOS and NFKB1 and examine their specific role in cancer progression.

25 CFR 82.7 - Notarization of petition signatures.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 25 Indians 1 2010-04-01 2010-04-01 false Notarization of petition signatures. 82.7 Section 82.7... signatures. (a) Signatures to a petition must be authenticated in one of the following ways: (1) Through having each signer subscribe or acknowledge his/her signature before a notary public; (2) Through having...

Active Site Gate Dynamics Modulate the Catalytic Activity of the Ubiquitination Enzyme E2-25K.

PubMed

Rout, Manoj K; Lee, Brian L; Lin, Aiyang; Xiao, Wei; Spyracopoulos, Leo

2018-05-03

The ubiquitin proteasome system (UPS) signals for degradation of proteins through attachment of K48-linked polyubiquitin chains, or alterations in protein-protein recognition through attachment of K63-linked chains. Target proteins are ubiquitinated in three sequential chemical steps by a three-component enzyme system. Ubiquitination, or E2 enzymes, catalyze the central step by facilitating reaction of a target protein lysine with the C-terminus of Ub that is attached to the active site cysteine of the E2 through a thioester bond. E2 reactivity is modulated by dynamics of an active site gate, whose central residue packs against the active site cysteine in a closed conformation. Interestingly, for the E2 Ubc13, which specifically catalyzes K63-linked ubiquitination, the central gate residue adopts an open conformation. We set out to determine if active site gate dynamics play a role in catalysis for E2-25K, which adopts the canonical, closed gate conformation, and which selectively synthesizes K48-linked ubiquitin chains. Gate dynamics were characterized using mutagenesis of key residues, combined with enzyme kinetics measurements, and main chain NMR relaxation. The experimental data were interpreted with all atom MD simulations. The data indicate that active site gate opening and closing rates for E2-25K are precisely balanced.

Hydrothermal activity lowers trophic diversity in Antarctic hydrothermal sediments

NASA Astrophysics Data System (ADS)

Bell, James B.; Reid, William D. K.; Pearce, David A.; Glover, Adrian G.; Sweeting, Christopher J.; Newton, Jason; Woulds, Clare

2017-12-01

Hydrothermal sediments are those in which hydrothermal fluid is discharged through sediments and are one of the least studied deep-sea ecosystems. We present a combination of microbial and biochemical data to assess trophodynamics between and within hydrothermal and background areas of the Bransfield Strait (1050-1647 m of depth). Microbial composition, biomass, and fatty acid signatures varied widely between and within hydrothermally active and background sites, providing evidence of diverse metabolic activity. Several species had different feeding strategies and trophic positions between hydrothermally active and inactive areas, and the stable isotope values of consumers were not consistent with feeding morphology. Niche area and the diversity of microbial fatty acids was lowest at the most hydrothermally active site, reflecting trends in species diversity. Faunal uptake of chemosynthetically produced organics was relatively limited but was detected at both hydrothermal and non-hydrothermal sites, potentially suggesting that hydrothermal activity can affect trophodynamics over a much wider area than previously thought.

Longitudinal Analysis of Whole Blood Transcriptomes to Explore Molecular Signatures Associated With Acute Renal Allograft Rejection

PubMed Central

Shin, Heesun; Günther, Oliver; Hollander, Zsuzsanna; Wilson-McManus, Janet E.; Ng, Raymond T.; Balshaw, Robert; Keown, Paul A.; McMaster, Robert; McManus, Bruce M.; Isbel, Nicole M.; Knoll, Greg; Tebbutt, Scott J.

2014-01-01

In this study, we explored a time course of peripheral whole blood transcriptomes from kidney transplantation patients who either experienced an acute rejection episode or did not in order to better delineate the immunological and biological processes measureable in blood leukocytes that are associated with acute renal allograft rejection. Using microarrays, we generated gene expression data from 24 acute rejectors and 24 nonrejectors. We filtered the data to obtain the most unambiguous and robustly expressing probe sets and selected a subset of patients with the clearest phenotype. We then performed a data-driven exploratory analysis using data reduction and differential gene expression analysis tools in order to reveal gene expression signatures associated with acute allograft rejection. Using a template-matching algorithm, we then expanded our analysis to include time course data, identifying genes whose expression is modulated leading up to acute rejection. We have identified molecular phenotypes associated with acute renal allograft rejection, including a significantly upregulated signature of neutrophil activation and accumulation following transplant surgery that is common to both acute rejectors and nonrejectors. Our analysis shows that this expression signature appears to stabilize over time in nonrejectors but persists in patients who go on to reject the transplanted organ. In addition, we describe an expression signature characteristic of lymphocyte activity and proliferation. This lymphocyte signature is significantly downregulated in both acute rejectors and nonrejectors following surgery; however, patients who go on to reject the organ show a persistent downregulation of this signature relative to the neutrophil signature. PMID:24526836

Built-in-test by signature inspection (bitsi)

DOEpatents

Bergeson, Gary C.; Morneau, Richard A.

1991-01-01

A system and method for fault detection for electronic circuits. A stimulus generator sends a signal to the input of the circuit under test. Signature inspection logic compares the resultant signal from test nodes on the circuit to an expected signal. If the signals do not match, the signature inspection logic sends a signal to the control logic for indication of fault detection in the circuit. A data input multiplexer between the test nodes of the circuit under test and the signature inspection logic can provide for identification of the specific node at fault by the signature inspection logic. Control logic responsive to the signature inspection logic conveys information about fault detection for use in determining the condition of the circuit. When used in conjunction with a system test controller, the built-in test by signature inspection system and method can be used to poll a plurality of circuits automatically and continuous for faults and record the results of such polling in the system test controller.

Intrusion detection using secure signatures

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

Nelson, Trent Darnel; Haile, Jedediah

A method and device for intrusion detection using secure signatures comprising capturing network data. A search hash value, value employing at least one one-way function, is generated from the captured network data using a first hash function. The presence of a search hash value match in a secure signature table comprising search hash values and an encrypted rule is determined. After determining a search hash value match, a decryption key is generated from the captured network data using a second hash function, a hash function different form the first hash function. One or more of the encrypted rules of themore » secure signatures table having a hash value equal to the generated search hash value are then decrypted using the generated decryption key. The one or more decrypted secure signature rules are then processed for a match and one or more user notifications are deployed if a match is identified.« less

SABER: A computational method for identifying active sites for new reactions

PubMed Central

Nosrati, Geoffrey R; Houk, K N

2012-01-01

A software suite, SABER (Selection of Active/Binding sites for Enzyme Redesign), has been developed for the analysis of atomic geometries in protein structures, using a geometric hashing algorithm (Barker and Thornton, Bioinformatics 2003;19:1644–1649). SABER is used to explore the Protein Data Bank (PDB) to locate proteins with a specific 3D arrangement of catalytic groups to identify active sites that might be redesigned to catalyze new reactions. As a proof-of-principle test, SABER was used to identify enzymes that have the same catalytic group arrangement present in o-succinyl benzoate synthase (OSBS). Among the highest-scoring scaffolds identified by the SABER search for enzymes with the same catalytic group arrangement as OSBS were l-Ala d/l-Glu epimerase (AEE) and muconate lactonizing enzyme II (MLE), both of which have been redesigned to become effective OSBS catalysts, demonstrated by experiments. Next, we used SABER to search for naturally existing active sites in the PDB with catalytic groups similar to those present in the designed Kemp elimination enzyme KE07. From over 2000 geometric matches to the KE07 active site, SABER identified 23 matches that corresponded to residues from known active sites. The best of these matches, with a 0.28 Å catalytic atom RMSD to KE07, was then redesigned to be compatible with the Kemp elimination using RosettaDesign. We also used SABER to search for potential Kemp eliminases using a theozyme predicted to provide a greater rate acceleration than the active site of KE07, and used Rosetta to create a design based on the proteins identified. PMID:22492397

SABER: a computational method for identifying active sites for new reactions.

PubMed

Nosrati, Geoffrey R; Houk, K N

2012-05-01

A software suite, SABER (Selection of Active/Binding sites for Enzyme Redesign), has been developed for the analysis of atomic geometries in protein structures, using a geometric hashing algorithm (Barker and Thornton, Bioinformatics 2003;19:1644-1649). SABER is used to explore the Protein Data Bank (PDB) to locate proteins with a specific 3D arrangement of catalytic groups to identify active sites that might be redesigned to catalyze new reactions. As a proof-of-principle test, SABER was used to identify enzymes that have the same catalytic group arrangement present in o-succinyl benzoate synthase (OSBS). Among the highest-scoring scaffolds identified by the SABER search for enzymes with the same catalytic group arrangement as OSBS were L-Ala D/L-Glu epimerase (AEE) and muconate lactonizing enzyme II (MLE), both of which have been redesigned to become effective OSBS catalysts, demonstrated by experiments. Next, we used SABER to search for naturally existing active sites in the PDB with catalytic groups similar to those present in the designed Kemp elimination enzyme KE07. From over 2000 geometric matches to the KE07 active site, SABER identified 23 matches that corresponded to residues from known active sites. The best of these matches, with a 0.28 Å catalytic atom RMSD to KE07, was then redesigned to be compatible with the Kemp elimination using RosettaDesign. We also used SABER to search for potential Kemp eliminases using a theozyme predicted to provide a greater rate acceleration than the active site of KE07, and used Rosetta to create a design based on the proteins identified. Copyright © 2012 The Protein Society.

Current signature sensor

NASA Technical Reports Server (NTRS)

Perotti, Jose M. (Inventor); Lucena, Angel (Inventor); Ihlefeld, Curtis (Inventor); Burns, Bradley (Inventor); Bassignani, Karin E. (Inventor)

2005-01-01

A solenoid health monitoring system uses a signal conditioner and controller assembly in one embodiment that includes analog circuitry and a DSP controller. The analog circuitry provides signal conditioning to the low-level raw signal coming from a signal acquisition assembly. Software running in a DSP analyzes the incoming data (recorded current signature) and determines the state of the solenoid whether it is energized, de-energized, or in a transitioning state. In one embodiment, the software identifies key features in the current signature during the transition phase and is able to determine the health of the solenoid.

17 CFR 230.471 - Signatures to amendments.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 17 Commodity and Securities Exchanges 2 2010-04-01 2010-04-01 false Signatures to amendments. 230... RULES AND REGULATIONS, SECURITIES ACT OF 1933 Amendments; Withdrawals § 230.471 Signatures to amendments... signed, such document shall be manually signed, or signed using either typed signatures or duplicated or...

31 CFR 321.19 - Certification of signatures.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 31 Money and Finance: Treasury 2 2010-07-01 2010-07-01 false Certification of signatures. 321.19... From Erroneous Payments § 321.19 Certification of signatures. The regulations in this subpart shall, to... signatures by an officer or designated employee of any financial institution authorized to certify requests...

40 CFR 262.25 - Electronic manifest signatures.

Code of Federal Regulations, 2014 CFR

2014-07-01

... 40 Protection of Environment 26 2014-07-01 2014-07-01 false Electronic manifest signatures. 262.25... (CONTINUED) STANDARDS APPLICABLE TO GENERATORS OF HAZARDOUS WASTE The Manifest § 262.25 Electronic manifest signatures. Electronic signature methods for the e-Manifest system shall: (a) Be a legally valid and...

17 CFR 201.65 - Identity and signature.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 17 Commodity and Securities Exchanges 2 2010-04-01 2010-04-01 false Identity and signature. 201.65... of 1934 § 201.65 Identity and signature. Applications pursuant to this subpart may omit the identity, mailing address, and signature of the applicant; provided, that such identity, mailing address and...

'Unconventional' coordination chemistry by metal chelating fragments in a metalloprotein active site.

PubMed

Martin, David P; Blachly, Patrick G; Marts, Amy R; Woodruff, Tessa M; de Oliveira, César A F; McCammon, J Andrew; Tierney, David L; Cohen, Seth M

2014-04-09

The binding of three closely related chelators: 5-hydroxy-2-methyl-4H-pyran-4-thione (allothiomaltol, ATM), 3-hydroxy-2-methyl-4H-pyran-4-thione (thiomaltol, TM), and 3-hydroxy-4H-pyran-4-thione (thiopyromeconic acid, TPMA) to the active site of human carbonic anhydrase II (hCAII) has been investigated. Two of these ligands display a monodentate mode of coordination to the active site Zn(2+) ion in hCAII that is not recapitulated in model complexes of the enzyme active site. This unprecedented binding mode in the hCAII-thiomaltol complex has been characterized by both X-ray crystallography and X-ray spectroscopy. In addition, the steric restrictions of the active site force the ligands into a 'flattened' mode of coordination compared with inorganic model complexes. This change in geometry has been shown by density functional computations to significantly decrease the strength of the metal-ligand binding. Collectively, these data demonstrate that the mode of binding by small metal-binding groups can be significantly influenced by the protein active site. Diminishing the strength of the metal-ligand bond results in unconventional modes of metal coordination not found in typical coordination compounds or even carefully engineered active site models, and understanding these effects is critical to the rational design of inhibitors that target clinically relevant metalloproteins.

Irma 5.2 multi-sensor signature prediction model

NASA Astrophysics Data System (ADS)

Savage, James; Coker, Charles; Thai, Bea; Aboutalib, Omar; Chow, Anthony; Yamaoka, Neil; Kim, Charles

2007-04-01

The Irma synthetic signature prediction code is being developed by the Munitions Directorate of the Air Force Research Laboratory (AFRL/MN) to facilitate the research and development of multi-sensor systems. There are over 130 users within the Department of Defense, NASA, Department of Transportation, academia, and industry. Irma began as a high-resolution, physics-based Infrared (IR) target and background signature model for tactical weapon applications and has grown to include: a laser (or active) channel (1990), improved scene generator to support correlated frame-to-frame imagery (1992), and passive IR/millimeter wave (MMW) channel for a co-registered active/passive IR/MMW model (1994). Irma version 5.0 was released in 2000 and encompassed several upgrades to both the physical models and software; host support was expanded to Windows, Linux, Solaris, and SGI Irix platforms. In 2005, version 5.1 was released after an extensive verification and validation of an upgraded and reengineered active channel. Since 2005, the reengineering effort has focused on the Irma passive channel. Field measurements for the validation effort include the unpolarized data collection. Irma 5.2 is scheduled for release in the summer of 2007. This paper will report the validation test results of the Irma passive models and discuss the new features in Irma 5.2.

Enhanced enzyme kinetic stability by increasing rigidity within the active site.

PubMed

Xie, Yuan; An, Jiao; Yang, Guangyu; Wu, Geng; Zhang, Yong; Cui, Li; Feng, Yan

2014-03-14

Enzyme stability is an important issue for protein engineers. Understanding how rigidity in the active site affects protein kinetic stability will provide new insight into enzyme stabilization. In this study, we demonstrated enhanced kinetic stability of Candida antarctica lipase B (CalB) by mutating the structurally flexible residues within the active site. Six residues within 10 Å of the catalytic Ser(105) residue with a high B factor were selected for iterative saturation mutagenesis. After screening 2200 colonies, we obtained the D223G/L278M mutant, which exhibited a 13-fold increase in half-life at 48 °C and a 12 °C higher T50(15), the temperature at which enzyme activity is reduced to 50% after a 15-min heat treatment. Further characterization showed that global unfolding resistance against both thermal and chemical denaturation also improved. Analysis of the crystal structures of wild-type CalB and the D223G/L278M mutant revealed that the latter formed an extra main chain hydrogen bond network with seven structurally coupled residues within the flexible α10 helix that are primarily involved in forming the active site. Further investigation of the relative B factor profile and molecular dynamics simulation confirmed that the enhanced rigidity decreased fluctuation of the active site residues at high temperature. These results indicate that enhancing the rigidity of the flexible segment within the active site may provide an efficient method for improving enzyme kinetic stability.

GASS-WEB: a web server for identifying enzyme active sites based on genetic algorithms.

PubMed

Moraes, João P A; Pappa, Gisele L; Pires, Douglas E V; Izidoro, Sandro C

2017-07-03

Enzyme active sites are important and conserved functional regions of proteins whose identification can be an invaluable step toward protein function prediction. Most of the existing methods for this task are based on active site similarity and present limitations including performing only exact matches on template residues, template size restraints, despite not being capable of finding inter-domain active sites. To fill this gap, we proposed GASS-WEB, a user-friendly web server that uses GASS (Genetic Active Site Search), a method based on an evolutionary algorithm to search for similar active sites in proteins. GASS-WEB can be used under two different scenarios: (i) given a protein of interest, to match a set of specific active site templates; or (ii) given an active site template, looking for it in a database of protein structures. The method has shown to be very effective on a range of experiments and was able to correctly identify >90% of the catalogued active sites from the Catalytic Site Atlas. It also managed to achieve a Matthew correlation coefficient of 0.63 using the Critical Assessment of protein Structure Prediction (CASP 10) dataset. In our analysis, GASS was ranking fourth among 18 methods. GASS-WEB is freely available at http://gass.unifei.edu.br/. © The Author(s) 2017. Published by Oxford University Press on behalf of Nucleic Acids Research.

Soil geochemical signature of urbanization and industrialization – Chicago, Illinois, USA

USGS Publications Warehouse

Cannon, W.F.; Horton, John D.

2009-01-01

The concentrations of 45 elements in ambient (not obviously disturbed) surface soils were determined for 57 sites distributed throughout the city of Chicago, Illinois in the upper Midwestern United States. These concentrations were compared to soils from 105 sites from a largely agricultural region within a 500-km radius surrounding the city and to soils collected from 90 sites across the state of Illinois. Although the bulk composition of the Chicago urban soils reflects largely natural sources, the soils are significantly enriched in many trace elements, apparently from anthropogenic sources. The median concentration of Pb in Chicago soils is 198 mg/kg, a 13-fold enrichment compared to regional concentrations. Zinc (median 235 mg/kg), Cu (59 mg/kg), and Ni (31 mg/kg) are also enriched from 2- to 4-fold in Chicago soils and all four elements show strong mutual correlations. These elevated concentrations are most likely related to vehicular and roadway sources and represent uneven distribution across the city as airborne material. Other airborne particulate material from a combination of fossil fuel combustion, waste incineration, and steel production may contribute to apparent elevated concentrations in Chicago soil of Fe (median 2.9%), Mo (5 mg/kg), V (82 mg/kg) and S (0.09%). Chicago soils are enriched from about 1.6- to 3-fold in these elements. Enrichments in P and Se may be caused by direct addition of phosphate fertilizer to parklands, lawns and gardens. The density of the sampling (1 site per 10 km2) is inadequate to define the distribution of the observed enrichments within the city or to predict soil compositions for most of the areas between sample sites, but does provide a statistically significant signature of the history of urban and industrial activity within the city in contrast to the surrounding agricultural lands.

Soft Shoulders Ahead: Spurious Signatures of Soft and Partial Selective Sweeps Result from Linked Hard Sweeps

PubMed Central

Schrider, Daniel R.; Mendes, Fábio K.; Hahn, Matthew W.; Kern, Andrew D.

2015-01-01

Characterizing the nature of the adaptive process at the genetic level is a central goal for population genetics. In particular, we know little about the sources of adaptive substitution or about the number of adaptive variants currently segregating in nature. Historically, population geneticists have focused attention on the hard-sweep model of adaptation in which a de novo beneficial mutation arises and rapidly fixes in a population. Recently more attention has been given to soft-sweep models, in which alleles that were previously neutral, or nearly so, drift until such a time as the environment shifts and their selection coefficient changes to become beneficial. It remains an active and difficult problem, however, to tease apart the telltale signatures of hard vs. soft sweeps in genomic polymorphism data. Through extensive simulations of hard- and soft-sweep models, here we show that indeed the two might not be separable through the use of simple summary statistics. In particular, it seems that recombination in regions linked to, but distant from, sites of hard sweeps can create patterns of polymorphism that closely mirror what is expected to be found near soft sweeps. We find that a very similar situation arises when using haplotype-based statistics that are aimed at detecting partial or ongoing selective sweeps, such that it is difficult to distinguish the shoulder of a hard sweep from the center of a partial sweep. While knowing the location of the selected site mitigates this problem slightly, we show that stochasticity in signatures of natural selection will frequently cause the signal to reach its zenith far from this site and that this effect is more severe for soft sweeps; thus inferences of the target as well as the mode of positive selection may be inaccurate. In addition, both the time since a sweep ends and biologically realistic levels of allelic gene conversion lead to errors in the classification and identification of selective sweeps. This

Soft shoulders ahead: spurious signatures of soft and partial selective sweeps result from linked hard sweeps.

PubMed

Schrider, Daniel R; Mendes, Fábio K; Hahn, Matthew W; Kern, Andrew D

2015-05-01

Characterizing the nature of the adaptive process at the genetic level is a central goal for population genetics. In particular, we know little about the sources of adaptive substitution or about the number of adaptive variants currently segregating in nature. Historically, population geneticists have focused attention on the hard-sweep model of adaptation in which a de novo beneficial mutation arises and rapidly fixes in a population. Recently more attention has been given to soft-sweep models, in which alleles that were previously neutral, or nearly so, drift until such a time as the environment shifts and their selection coefficient changes to become beneficial. It remains an active and difficult problem, however, to tease apart the telltale signatures of hard vs. soft sweeps in genomic polymorphism data. Through extensive simulations of hard- and soft-sweep models, here we show that indeed the two might not be separable through the use of simple summary statistics. In particular, it seems that recombination in regions linked to, but distant from, sites of hard sweeps can create patterns of polymorphism that closely mirror what is expected to be found near soft sweeps. We find that a very similar situation arises when using haplotype-based statistics that are aimed at detecting partial or ongoing selective sweeps, such that it is difficult to distinguish the shoulder of a hard sweep from the center of a partial sweep. While knowing the location of the selected site mitigates this problem slightly, we show that stochasticity in signatures of natural selection will frequently cause the signal to reach its zenith far from this site and that this effect is more severe for soft sweeps; thus inferences of the target as well as the mode of positive selection may be inaccurate. In addition, both the time since a sweep ends and biologically realistic levels of allelic gene conversion lead to errors in the classification and identification of selective sweeps. This

The SLE-key test serological signature: new insights into the course of lupus.

PubMed

Putterman, Chaim; Pisetsky, David S; Petri, Michelle; Caricchio, Roberto; Wu, Alan H B; Sanz, Ignacio; Oates, Jim C; Wallace, Steve; Sorek, Rachel; Gerwien, Robert; Safer, Pennina; Jakobi-Brook, Keren; Cohen, Irun R

2018-06-04

We previously described the multiplex autoantibody SLE-key Rule-Out test, which detects a signature of autoantibody reactivity that distinguishes healthy subjects from SLE patients with 94% sensitivity, 75% specificity and 93% negative predictive value; thus, an individual manifesting a positive Rule-Out test score is unlikely to have SLE (e.g. lupus is excluded). The objective of this current study was to evaluate the stability of the lupus-associated signature over time. We used banked serum samples from healthy subjects (n = 51) and lupus patients (n = 50 individual samples and n = 181 paired samples, for a total of n = 412 serum samples). The samples were drawn at different times after diagnosis to analyse the impact on the SLE-key Rule-Out test of time elapsed since diagnosis and any changes in disease activity (as reflected by the SLEDAI score). The SLE signature remains stable for the first 10 years after diagnosis; in this time frame, <10% of patients manifested a positive Rule-Out score and the SLE-key Rule-Out score was independent of the underlying disease activity as reflected by the SLEDAI score. After ⩾10 years, ∼30% of lupus subjects scored as SLE Ruled-Out; the proportion of patients manifesting this status was even greater in the subset of individuals with a SLEDAI score of 0. These findings raise the possibility that a significant number of SLE patients manifest a change in their serological signature over time, and that such a signature change may signify an evolution in the immunological features of their disease relevant to patient management.

29 CFR 102.116 - Signature of orders.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 29 Labor 2 2010-07-01 2010-07-01 false Signature of orders. 102.116 Section 102.116 Labor Regulations Relating to Labor NATIONAL LABOR RELATIONS BOARD RULES AND REGULATIONS, SERIES 8 Certification and Signature of Documents § 102.116 Signature of orders. The executive secretary or the associate executive...

Neural Signatures of Language Co-activation and Control in Bilingual Spoken Word Comprehension

PubMed Central

Chen, Peiyao; Bobb, Susan C.; Hoshino, Noriko; Marian, Viorica

2017-01-01

To examine the neural signatures of language co-activation and control during bilingual spoken word comprehension, Korean-English bilinguals and English monolinguals were asked to make overt or covert semantic relatedness judgments on auditorily-presented English word pairs. In two critical conditions, participants heard word pairs consisting of an English-Korean interlingual homophone (e.g., the sound /mu:n/ means “moon” in English and “door” in Korean) as the prime and an English word as the target. In the homophone-related condition, the target (e.g., “lock”) was related to the homophone’s Korean meaning, but not related to the homophone’s English meaning. In the homophone-unrelated condition, the target was unrelated to either the homophone’s Korean meaning or the homophone’s English meaning. In overtly responded situations, ERP results revealed that the reduced N400 effect in bilinguals for homophone-related word pairs correlated positively with the amount of their daily exposure to Korean. In covertly responded situations, ERP results showed a reduced late positive component for homophone-related word pairs in the right hemisphere, and this late positive effect was related to the neural efficiency of suppressing interference in a non-linguistic task. Together, these findings suggest 1) that the degree of language co-activation in bilingual spoken word comprehension is modulated by the amount of daily exposure to the non-target language; and 2) that bilinguals who are less influenced by cross-language activation may also have greater efficiency in suppressing interference in a non-linguistic task. PMID:28372943

Neural signatures of language co-activation and control in bilingual spoken word comprehension.

PubMed

Chen, Peiyao; Bobb, Susan C; Hoshino, Noriko; Marian, Viorica

2017-06-15

To examine the neural signatures of language co-activation and control during bilingual spoken word comprehension, Korean-English bilinguals and English monolinguals were asked to make overt or covert semantic relatedness judgments on auditorily-presented English word pairs. In two critical conditions, participants heard word pairs consisting of an English-Korean interlingual homophone (e.g., the sound /mu:n/ means "moon" in English and "door" in Korean) as the prime and an English word as the target. In the homophone-related condition, the target (e.g., "lock") was related to the homophone's Korean meaning, but not related to the homophone's English meaning. In the homophone-unrelated condition, the target was unrelated to either the homophone's Korean meaning or the homophone's English meaning. In overtly responded situations, ERP results revealed that the reduced N400 effect in bilinguals for homophone-related word pairs correlated positively with the amount of their daily exposure to Korean. In covertly responded situations, ERP results showed a reduced late positive component for homophone-related word pairs in the right hemisphere, and this late positive effect was related to the neural efficiency of suppressing interference in a non-linguistic task. Together, these findings suggest 1) that the degree of language co-activation in bilingual spoken word comprehension is modulated by the amount of daily exposure to the non-target language; and 2) that bilinguals who are less influenced by cross-language activation may also have greater efficiency in suppressing interference in a non-linguistic task. Copyright © 2017 Elsevier B.V. All rights reserved.

Facebook, Twitter Activities Sites, Location and Students' Interest in Learning

ERIC Educational Resources Information Center

Igbo, J. N.; Ezenwaji, Ifeyinwa; Ajuziogu, Christiana U.

2018-01-01

This study was carried out to ascertain the influence of social networking sites activities (twitter and Facebook) on secondary school students' interest in learning It also considered the impact of these social networking sites activities on location of the students. Two research questions and two null hypotheses guided the study. Mean and…

14 CFR 49.13 - Signatures and acknowledgements.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 14 Aeronautics and Space 1 2010-01-01 2010-01-01 false Signatures and acknowledgements. 49.13... RECORDING OF AIRCRAFT TITLES AND SECURITY DOCUMENTS General § 49.13 Signatures and acknowledgements. (a) Each signature on a conveyance must be in ink. (b) Paragraphs (b) through (f) of § 47.13 of this...

Numerical prediction of meteoric infrasound signatures

NASA Astrophysics Data System (ADS)

Nemec, Marian; Aftosmis, Michael J.; Brown, Peter G.

2017-06-01

We present a thorough validation of a computational approach to predict infrasonic signatures of centimeter-sized meteoroids. This is the first direct comparison of computational results with well-calibrated observations that include trajectories, optical masses and ground pressure signatures. We assume that the energy deposition along the meteor trail is dominated by atmospheric drag and simulate a steady, inviscid flow of air in thermochemical equilibrium to compute a near-body pressure signature of the meteoroid. This signature is then propagated through a stratified and windy atmosphere to the ground using a methodology from aircraft sonic-boom analysis. The results show that when the source of the signature is the cylindrical Mach-cone, the simulations closely match the observations. The prediction of the shock rise-time, the zero-peak amplitude of the waveform and the duration of the positive pressure phase are consistently within 10% of the measurements. Uncertainty in primarily the shape of the meteoroid results in a poorer prediction of the trailing part of the waveform. Overall, our results independently verify energy deposition estimates deduced from optical observations.

Investigation of Slow-wave Activity Saturation during Surgical Anesthesia Reveals a Signature of Neural Inertia in Humans.

PubMed

Warnaby, Catherine E; Sleigh, Jamie W; Hight, Darren; Jbabdi, Saad; Tracey, Irene

2017-10-01

Previously, we showed experimentally that saturation of slow-wave activity provides a potentially individualized neurophysiologic endpoint for perception loss during anesthesia. Furthermore, it is clear that induction and emergence from anesthesia are not symmetrically reversible processes. The observed hysteresis is potentially underpinned by a neural inertia mechanism as proposed in animal studies. In an advanced secondary analysis of 393 individual electroencephalographic data sets, we used slow-wave activity dose-response relationships to parameterize slow-wave activity saturation during induction and emergence from surgical anesthesia. We determined whether neural inertia exists in humans by comparing slow-wave activity dose responses on induction and emergence. Slow-wave activity saturation occurs for different anesthetics and when opioids and muscle relaxants are used during surgery. There was wide interpatient variability in the hypnotic concentrations required to achieve slow-wave activity saturation. Age negatively correlated with power at slow-wave activity saturation. On emergence, we observed abrupt decreases in slow-wave activity dose responses coincident with recovery of behavioral responsiveness in ~33% individuals. These patients are more likely to have lower power at slow-wave activity saturation, be older, and suffer from short-term confusion on emergence. Slow-wave activity saturation during surgical anesthesia implies that large variability in dosing is required to achieve a targeted potential loss of perception in individual patients. A signature for neural inertia in humans is the maintenance of slow-wave activity even in the presence of very-low hypnotic concentrations during emergence from anesthesia.

Modeling the Lexical Morphology of Western Handwritten Signatures

PubMed Central

Diaz-Cabrera, Moises; Ferrer, Miguel A.; Morales, Aythami

2015-01-01

A handwritten signature is the final response to a complex cognitive and neuromuscular process which is the result of the learning process. Because of the many factors involved in signing, it is possible to study the signature from many points of view: graphologists, forensic experts, neurologists and computer vision experts have all examined them. Researchers study written signatures for psychiatric, penal, health and automatic verification purposes. As a potentially useful, multi-purpose study, this paper is focused on the lexical morphology of handwritten signatures. This we understand to mean the identification, analysis, and description of the signature structures of a given signer. In this work we analyze different public datasets involving 1533 signers from different Western geographical areas. Some relevant characteristics of signature lexical morphology have been selected, examined in terms of their probability distribution functions and modeled through a General Extreme Value distribution. This study suggests some useful models for multi-disciplinary sciences which depend on handwriting signatures. PMID:25860942

Do biofilm communities respond to the chemical signatures of fracking? A test involving streams in North-central Arkansas.

PubMed

Johnson, Wilson H; Douglas, Marlis R; Lewis, Jeffrey A; Stuecker, Tara N; Carbonero, Franck G; Austin, Bradley J; Evans-White, Michelle A; Entrekin, Sally A; Douglas, Michael E

2017-02-03

Unconventional natural gas (UNG) extraction (fracking) is ongoing in 29 North American shale basins (20 states), with ~6000 wells found within the Fayetteville shale (north-central Arkansas). If the chemical signature of fracking is detectable in streams, it can be employed to bookmark potential impacts. We evaluated benthic biofilm community composition as a proxy for stream chemistry so as to segregate anthropogenic signatures in eight Arkansas River catchments. In doing so, we tested the hypothesis that fracking characteristics in study streams are statistically distinguishable from those produced by agriculture or urbanization. Four tributary catchments had UNG-wells significantly more dense and near to our sampling sites and were grouped as 'potentially-impacted catchment zones' (PICZ). Four others were characterized by significantly larger forested area with greater slope and elevation but reduced pasture, and were classified as 'minimally-impacted' (MICZ). Overall, 46 bacterial phyla/141 classes were identified, with 24 phyla (52%) and 54 classes (38%) across all samples. PICZ-sites were ecologically more variable than MICZ-sites, with significantly greater nutrient levels (total nitrogen, total phosphorous), and elevated Cyanobacteria as bioindicators that tracked these conditions. PICZ-sites also exhibited elevated conductance (a correlate of increased ion concentration) and depressed salt-intolerant Spartobacteria, suggesting the presence of brine as a fracking effect. Biofilm communities at PICZ-sites were significantly less variable than those at MICZ-sites. Study streams differed by Group according to morphology, land use, and water chemistry but not in biofilm community structure. Those at PICZ-sites covaried according to anthropogenic impact, and were qualitatively similar to communities found at sites disturbed by fracking. The hypothesis that fracking signatures in study streams are distinguishable from those produced by other anthropogenic effects

Active Site Hydrophobicity and the Convergent Evolution of Paraoxonase Activity in Structurally Divergent Enzymes: The Case of Serum Paraoxonase 1

PubMed Central

2016-01-01

Serum paraoxonase 1 (PON1) is a native lactonase capable of promiscuously hydrolyzing a broad range of substrates, including organophosphates, esters, and carbonates. Structurally, PON1 is a six-bladed β-propeller with a flexible loop (residues 70–81) covering the active site. This loop contains a functionally critical Tyr at position 71. We have performed detailed experimental and computational analyses of the role of selected Y71 variants in the active site stability and catalytic activity in order to probe the role of Y71 in PON1’s lactonase and organophosphatase activities. We demonstrate that the impact of Y71 substitutions on PON1’s lactonase activity is minimal, whereas the kcat for the paraoxonase activity is negatively perturbed by up to 100-fold, suggesting greater mutational robustness of the native activity. Additionally, while these substitutions modulate PON1’s active site shape, volume, and loop flexibility, their largest effect is in altering the solvent accessibility of the active site by expanding the active site volume, allowing additional water molecules to enter. This effect is markedly more pronounced in the organophosphatase activity than the lactonase activity. Finally, a detailed comparison of PON1 to other organophosphatases demonstrates that either a similar “gating loop” or a highly buried solvent-excluding active site is a common feature of these enzymes. We therefore posit that modulating the active site hydrophobicity is a key element in facilitating the evolution of organophosphatase activity. This provides a concrete feature that can be utilized in the rational design of next-generation organophosphate hydrolases that are capable of selecting a specific reaction from a pool of viable substrates. PMID:28026940

Active Site Hydrophobicity and the Convergent Evolution of Paraoxonase Activity in Structurally Divergent Enzymes: The Case of Serum Paraoxonase 1.

PubMed

Blaha-Nelson, David; Krüger, Dennis M; Szeler, Klaudia; Ben-David, Moshe; Kamerlin, Shina Caroline Lynn

2017-01-25

Serum paraoxonase 1 (PON1) is a native lactonase capable of promiscuously hydrolyzing a broad range of substrates, including organophosphates, esters, and carbonates. Structurally, PON1 is a six-bladed β-propeller with a flexible loop (residues 70-81) covering the active site. This loop contains a functionally critical Tyr at position 71. We have performed detailed experimental and computational analyses of the role of selected Y71 variants in the active site stability and catalytic activity in order to probe the role of Y71 in PON1's lactonase and organophosphatase activities. We demonstrate that the impact of Y71 substitutions on PON1's lactonase activity is minimal, whereas the k cat for the paraoxonase activity is negatively perturbed by up to 100-fold, suggesting greater mutational robustness of the native activity. Additionally, while these substitutions modulate PON1's active site shape, volume, and loop flexibility, their largest effect is in altering the solvent accessibility of the active site by expanding the active site volume, allowing additional water molecules to enter. This effect is markedly more pronounced in the organophosphatase activity than the lactonase activity. Finally, a detailed comparison of PON1 to other organophosphatases demonstrates that either a similar "gating loop" or a highly buried solvent-excluding active site is a common feature of these enzymes. We therefore posit that modulating the active site hydrophobicity is a key element in facilitating the evolution of organophosphatase activity. This provides a concrete feature that can be utilized in the rational design of next-generation organophosphate hydrolases that are capable of selecting a specific reaction from a pool of viable substrates.

Characterization of the active site properties of CYP4F12.

PubMed

Eksterowicz, John; Rock, Dan A; Rock, Brooke M; Wienkers, Larry C; Foti, Robert S

2014-10-01

Cytochrome P450 4F12 is a drug-metabolizing enzyme that is primarily expressed in the liver, kidney, colon, small intestine, and heart. The properties of CYP4F12 that may impart an increased catalytic selectivity (decreased promiscuity) were explored through in vitro metabolite elucidation, kinetic isotope effect experiments, and computational modeling of the CYP4F12 active site. By using astemizole as a probe substrate for CYP4F12 and CYP3A4, it was observed that although CYP4F12 favored astemizole O-demethylation as the primary route of metabolism, CYP3A4 was capable of metabolizing astemizole at multiple sites on the molecule. Deuteration of astemizole at the site of O-demethylation resulted in an isotope effect of 7.1 as well as an 8.3-fold decrease in the rate of clearance for astemizole by CYP4F12. Conversely, although an isotope effect of 3.8 was observed for the formation of the O-desmethyl metabolite when deuterated astemizole was metabolized by CYP3A4, there was no decrease in the clearance of astemizole. Development of a homology model of CYP4F12 based on the crystal structure of cytochrome P450 BM3 predicted an active site volume for CYP4F12 that was approximately 76% of the active site volume of CYP3A4. As predicted, multiple favorable binding orientations were available for astemizole docked into the active site of CYP3A4, but only a single binding orientation with the site of O-demethylation oriented toward the heme was identified for CYP4F12. Overall, it appears that although CYP4F12 may be capable of binding similar ligands to other cytochrome P450 enzymes such as CYP3A4, the ability to achieve catalytically favorable orientations may be inherently more difficult because of the increased steric constraints of the CYP4F12 active site. Copyright © 2014 by The American Society for Pharmacology and Experimental Therapeutics.

Geochemical signatures of tsunami deposits - what do they tell us?

NASA Astrophysics Data System (ADS)

Chague-Goff, Catherine; Goff, James R.

2010-05-01

In the last two and half decades, but even more since the 2004 Indian Ocean Tsunami (IOT), there has been a significant increase in the amount of literature dealing with recent, historical and palaeotsunamis. Much has been written and debated about the diagnostic criteria of historical and palaeotsunami deposits. Most of the diagnostic criteria or proxies used reflect the expertise of the researchers involved and thus tend to be biased towards sedimentology, stratigraphy and micropalaeontology, with some reference to geomorphology, archaeology, anthropology and palynology. It should however be noted that all criteria have never been reported from one site, and neither are they all found in one single deposit. Thus, the lack of one or more proxies should not be taken as unique evidence to refute the tsunamigenic origin of a specific deposit. Although geochemical signatures have long been used as indicators for palaeosalinity in sedimentary sequences, there appears to have been some reluctance to use them to help in the identification of historical and palaeotsunami deposits. Like other proxies, geochemistry alone may not provide a definite answer to the origin of a deposit. Furthermore, poor preservation due to environmental conditions or as a result of post-diagenetic processes, might complicate the interpretation of geochemical signatures left by tsunami inundation. Similar taphonomic problems are also faced for microfossil proxies. However, geochemistry provides another piece to the puzzle, and together with other proxies, it can help identify palaeotsunami deposits. Geochemical signatures can also provide clues about the landward limit of runup of a tsunami, beyond the area of sediment deposition. This was recently documented following the 2004 IOT and the 2009 South Pacific tsunami. A summary of examples of geochemical signatures recorded in interstitial water and sediment of recent, historical and palaeotsunami deposits is presented.

Seasonal variations in the stable carbon isotopic signature of biogenic methane in a coastal sediment

NASA Technical Reports Server (NTRS)

Martens, C. S.; Green, C. D.; Blair, N. E.; Des Marais, D. J.

1986-01-01

Systematic seasonal variations in the stable carbon isotopic signature of methane gas occur in the anoxic sediments of Cape Lookout Bight, a lagoonal basin on North Carolina's Outer Banks. Values for the carbon isotope ratio of methane range from -57.3 per mil during summer to -68.5 per mil during winter in gas bubbles with an average methane content of 95 percent. The variations are hypothesized to result from changes in the pathways of microbial methane production and cycling of key substrates including acetate and hydrogen. The use of stable isotopic signatures to investigate the global methane cycle through mass balance calculations, involving various sediment and soil biogenic sources, appears to require seasonally averaged data from individual sites.

Cell short circuit, preshort signature

NASA Technical Reports Server (NTRS)

Lurie, C.

1980-01-01

Short-circuit events observed in ground test simulations of DSCS-3 battery in-orbit operations are analyzed. Voltage signatures appearing in the data preceding the short-circuit event are evaluated. The ground test simulation is briefly described along with performance during reconditioning discharges. Results suggest that a characteristic signature develops prior to a shorting event.

Deletion of loop fragment adjacent to active site diminishes the stability and activity of exo-inulinase.

PubMed

Arjomand, Maryam Rezaei; Habibi-Rezaei, Mehran; Ahmadian, Gholamreza; Hassanzadeh, Malihe; Karkhane, Ali Asghar; Asadifar, Mandana; Amanlou, Massoud

2016-11-01

Inulinases are classified as hydrolases and widely used in the food and medical industries. Here, we report the deletion of a six-membered adjacent active site loop fragment ( 74 YGSDVT 79 sequence) from third Ω-loop of the exo-inulinase containing aspartate residue from Aspergillus niger to study its structural and functional importance. Site-directed mutagenesis was used to create the mutant of the exo-inulinase (Δ6SL). To investigate the stability of the region spanning this loop, MD simulations were performed 80ns for 20-85 residues. Molecular docking was performed to compare the interactions in the active sites of enzymes with fructose as a ligand. Accordingly, the functional thermostability of the exo-inulinase was significantly decreased upon loop fragment deletion. Evaluation of the kinetics parameters (V max , K m , k cat and, k cat /K m ) and activation energy (E a ) of the catalysis of enzymes indicated the importance of the deleted sequence on the catalytic performance of the enzyme. In conclusion, six-membered adjacent active site loop fragment not only plays a crucial role in the stability of the enzyme, but also it involves in the enzyme catalysis through lowering the activation energy of the catalysis and effective improving the catalytic performance. Copyright © 2016. Published by Elsevier B.V.

The Crystal Structure of a Quercetin 2,3-Dioxygenase from Bacillus subtilis Suggests Modulation of Enzyme Activity by a Change in the Metal Ion at the Active Site(s)

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

Gopal, B.; Madan, Lalima L.; Betz, Stephen F.

2010-11-10

Common structural motifs, such as the cupin domains, are found in enzymes performing different biochemical functions while retaining a similar active site configuration and structural scaffold. The soil bacterium Bacillus subtilis has 20 cupin genes (0.5% of the total genome) with up to 14% of its genes in the form of doublets, thus making it an attractive system for studying the effects of gene duplication. There are four bicupins in B. subtilis encoded by the genes yvrK, yoaN, yxaG, and ywfC. The gene products of yvrK and yoaN function as oxalate decarboxylases with a manganese ion at the active site(s),more » whereas YwfC is a bacitracin synthetase. Here we present the crystal structure of YxaG, a novel iron-containing quercetin 2,3-dioxygenase with one active site in each cupin domain. Yxag is a dimer, both in solution and in the crystal. The crystal structure shows that the coordination geometry of the Fe ion is different in the two active sites of YxaG. Replacement of the iron at the active site with other metal ions suggests modulation of enzymatic activity in accordance with the Irving-Williams observation on the stability of metal ion complexes. This observation, along with a comparison with the crystal structure of YvrK determined recently, has allowed for a detailed structure-function analysis of the active site, providing clues to the diversification of function in the bicupin family of proteins.« less

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.

Single Molecule Cluster Analysis Identifies Signature Dynamic Conformations along the Splicing Pathway

PubMed Central

Blanco, Mario R.; Martin, Joshua S.; Kahlscheuer, Matthew L.; Krishnan, Ramya; Abelson, John; Laederach, Alain; Walter, Nils G.

2016-01-01

The spliceosome is the dynamic RNA-protein machine responsible for faithfully splicing introns from precursor messenger RNAs (pre-mRNAs). Many of the dynamic processes required for the proper assembly, catalytic activation, and disassembly of the spliceosome as it acts on its pre-mRNA substrate remain poorly understood, a challenge that persists for many biomolecular machines. Here, we developed a fluorescence-based Single Molecule Cluster Analysis (SiMCAn) tool to dissect the manifold conformational dynamics of a pre-mRNA through the splicing cycle. By clustering common dynamic behaviors derived from selectively blocked splicing reactions, SiMCAn was able to identify signature conformations and dynamic behaviors of multiple ATP-dependent intermediates. In addition, it identified a conformation adopted late in splicing by a 3′ splice site mutant, invoking a mechanism for substrate proofreading. SiMCAn presents a novel framework for interpreting complex single molecule behaviors that should prove widely useful for the comprehensive analysis of a plethora of dynamic cellular machines. PMID:26414013

The microbial community structure in petroleum-contaminated sediments corresponds to geophysical signatures

USGS Publications Warehouse

Allen, J.P.; Atekwana, E.A.; Duris, J.W.; Werkema, D.D.; Rossbach, S.

2007-01-01

The interdependence between geoelectrical signatures at underground petroleum plumes and the structures of subsurface microbial communities was investigated. For sediments contaminated with light non-aqueousphase liquids, anomalous high conductivity values have been observed. Vertical changes in the geoelectrical properties of the sediments were concomitant with significant changes in the microbial community structures as determined by the construction and evaluation of 16S rRNA gene libraries. DNA sequencing of clones from four 16S rRNA gene libraries from different depths of a contaminated field site and two libraries from an uncontaminated background site revealed spatial heterogeneity in the microbial community structures. Correspondence analysis showed that the presence of distinct microbial populations, including the various hydrocarbon-degrading, syntrophic, sulfate-reducing, and dissimilatory-iron-reducing populations, was a contributing factor to the elevated geoelectrical measurements. Thus, through their growth and metabolic activities, microbial populations that have adapted to the use of petroleum as a carbon source can strongly influence their geophysical surroundings. Since changes in the geophysical properties of contaminated sediments parallel changes in the microbial community compositions, it is suggested that geoelectrical measurements can be a cost-efficient tool to guide microbiological sampling for microbial ecology studies during the monitoring of natural or engineered bioremediation processes. Copyright ?? 2007, American Society for Microbiology. All Rights Reserved.

In situ mineralogical-chemical analysis of Martian materials at landing/roving sites by active and passive remote sensing methods

NASA Technical Reports Server (NTRS)

Neukum, G.; Lehmann, F.; Regner, P.; Jaumann, R.

1988-01-01

Remote sensing of the Martian surface from the ground and from orbiting spacecraft has provided some first-order insight into the mineralogical-chemical composition and the weathering state of Martian surface materials. Much more detailed information can be gathered from performing such measurements in situ at the landing sites or from a rover in combination with analogous measurements from orbit. Measurements in the wavelength range of approximately 0.3 to 12.0 micrometers appear to be suitable to characterize much of the physical, mineralogical, petrological, and chemical properties of Martian surface materials and the weathering and other alteration processes that have acted on them. It is of particular importance to carry out measurements at the same time over a broad wavelength range since the reflectance signatures are caused by different effects and hence give different and complementing information. It appears particularly useful to employ a combination of active and passive methods because the use of active laser spectroscopy allows the obtaining of specific information on thermal infrared reflectance of surface materials. It seems to be evident that a spectrometric survey of Martian materials has to be focused on the analysis of altered and fresh mafic materials and rocks, water-bearing silicates, and possibly carbonates.

Inhibition of Super-Enhancer Activity in Autoinflammatory Site-Derived T Cells Reduces Disease-Associated Gene Expression.

PubMed

Peeters, Janneke G C; Vervoort, Stephin J; Tan, Sander C; Mijnheer, Gerdien; de Roock, Sytze; Vastert, Sebastiaan J; Nieuwenhuis, Edward E S; van Wijk, Femke; Prakken, Berent J; Creyghton, Menno P; Coffer, Paul J; Mokry, Michal; van Loosdregt, Jorg

2015-09-29

The underlying molecular mechanisms for many autoimmune diseases are poorly understood. Juvenile idiopathic arthritis (JIA) is an exceptionally well-suited model for studying autoimmune diseases due to its early onset and the possibility to analyze cells derived from the site of inflammation. Epigenetic profiling, utilizing primary JIA patient-derived cells, can contribute to the understanding of autoimmune diseases. With H3K27ac chromatin immunoprecipitation, we identified a disease-specific, inflammation-associated, typical enhancer and super-enhancer signature in JIA patient synovial-fluid-derived CD4(+) memory/effector T cells. RNA sequencing of autoinflammatory site-derived patient T cells revealed that BET inhibition, utilizing JQ1, inhibited immune-related super-enhancers and preferentially reduced disease-associated gene expression, including cytokine-related processes. Altogether, these results demonstrate the potential use of enhancer profiling to identify disease mediators and provide evidence for BET inhibition as a possible therapeutic approach for the treatment of autoimmune diseases. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

Metabolism dysregulation induces a specific lipid signature of nonalcoholic steatohepatitis in patients

PubMed Central

Chiappini, Franck; Coilly, Audrey; Kadar, Hanane; Gual, Philippe; Tran, Albert; Desterke, Christophe; Samuel, Didier; Duclos-Vallée, Jean-Charles; Touboul, David; Bertrand-Michel, Justine; Brunelle, Alain; Guettier, Catherine; Le Naour, François

2017-01-01

Nonalcoholic steatohepatitis (NASH) is a condition which can progress to cirrhosis and hepatocellular carcinoma. Markers for NASH diagnosis are still lacking. We performed a comprehensive lipidomic analysis on human liver biopsies including normal liver, nonalcoholic fatty liver and NASH. Random forests-based machine learning approach allowed characterizing a signature of 32 lipids discriminating NASH with 100% sensitivity and specificity. Furthermore, we validated this signature in an independent group of NASH patients. Then, metabolism dysregulations were investigated in both patients and murine models. Alterations of elongase and desaturase activities were observed along the fatty acid synthesis pathway. The decreased activity of the desaturase FADS1 appeared as a bottleneck, leading upstream to an accumulation of fatty acids and downstream to a deficiency of long-chain fatty acids resulting to impaired phospholipid synthesis. In NASH, mass spectrometry imaging on tissue section revealed the spreading into the hepatic parenchyma of selectively accumulated fatty acids. Such lipids constituted a highly toxic mixture to human hepatocytes. In conclusion, this study characterized a specific and sensitive lipid signature of NASH and positioned FADS1 as a significant player in accumulating toxic lipids during NASH progression. PMID:28436449

Identity-Based Verifiably Encrypted Signatures without Random Oracles

NASA Astrophysics Data System (ADS)

Zhang, Lei; Wu, Qianhong; Qin, Bo

Fair exchange protocol plays an important role in electronic commerce in the case of exchanging digital contracts. Verifiably encrypted signatures provide an optimistic solution to these scenarios with an off-line trusted third party. In this paper, we propose an identity-based verifiably encrypted signature scheme. The scheme is non-interactive to generate verifiably encrypted signatures and the resulting encrypted signature consists of only four group elements. Based on the computational Diffie-Hellman assumption, our scheme is proven secure without using random oracles. To the best of our knowledge, this is the first identity-based verifiably encrypted signature scheme provably secure in the standard model.

Radiation Gene-expression Signatures in Primary Breast Cancer Cells.

PubMed

Minafra, Luigi; Bravatà, Valentina; Cammarata, Francesco P; Russo, Giorgio; Gilardi, Maria C; Forte, Giusi I

2018-05-01

In breast cancer (BC) care, radiation therapy (RT) is an efficient treatment to control localized tumor. Radiobiological research is needed to understand molecular differences that affect radiosensitivity of different tumor subtypes and the response variability. The aim of this study was to analyze gene expression profiling (GEP) in primary BC cells following irradiation with doses of 9 Gy and 23 Gy delivered by intraoperative electron radiation therapy (IOERT) in order to define gene signatures of response to high doses of ionizing radiation. We performed GEP by cDNA microarrays and evaluated cell survival after IOERT treatment in primary BC cell cultures. Real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR) was performed to validate candidate genes. We showed, for the first time, a 4-gene and a 6-gene signature, as new molecular biomarkers, in two primary BC cell cultures after exposure at 9 Gy and 23 Gy respectively, for which we observed a significantly high survival rate. Gene signatures activated by different doses of ionizing radiation may predict response to RT and contribute to defining a personalized biological-driven treatment plan. Copyright© 2018, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

Glycosylation of Hemagglutinin and Neuraminidase of Influenza A Virus as Signature for Ecological Spillover and Adaptation among Influenza Reservoirs

PubMed Central

Kim, Paul; Jang, Yo Han; Kwon, Soon Bin; Lee, Chung Min; Han, Gyoonhee; Seong, Baik Lin

2018-01-01

Glycosylation of the hemagglutinin (HA) and neuraminidase (NA) of the influenza provides crucial means for immune evasion and viral fitness in a host population. However, the time-dependent dynamics of each glycosylation sites have not been addressed. We monitored the potential N-linked glycosylation (NLG) sites of over 10,000 HA and NA of H1N1 subtype isolated from human, avian, and swine species over the past century. The results show a shift in glycosylation sites as a hallmark of 1918 and 2009 pandemics, and also for the 1976 “abortive pandemic”. Co-segregation of particular glycosylation sites was identified as a characteristic of zoonotic transmission from animal reservoirs, and interestingly, of “reverse zoonosis” of human viruses into swine populations as well. After the 2009 pandemic, recent isolates accrued glycosylation at canonical sites in HA, reflecting gradual seasonal adaptation, and a novel glycosylation in NA as an independent signature for adaptation among humans. Structural predictions indicated a remarkably pleiotropic influence of glycans on multiple HA epitopes for immune evasion, without sacrificing the receptor binding of HA or the activity of NA. The results provided the rationale for establishing the ecological niche of influenza viruses among the reservoir and could be implemented for influenza surveillance and improving pandemic preparedness. PMID:29642453

A hybrid QM/MM simulation study of intramolecular proton transfer in the pyridoxal 5'-phosphate in the active site of transaminase: influence of active site interaction on proton transfer.

PubMed

Dutta Banik, Sindrila; Chandra, Amalendu

2014-09-25

Pyridoxal 5'-phosphate (PLP) Schiff base, a versatile cofactor, exhibits a tautomeric equilibrium that involves an intramolecular proton transfer between the N-protonated zwitterionic ketoenamine tautomer and the O-protonated covalent enolimine tautomer. It has been postulated that for the catalytic activity, the PLP has to be in the zwitterionic ketoenamine tautomeric form. However, the exact position of the tautomeric equilibrium of Schiff base in the active site of PLP-dependent enzyme is not known yet. In the present work, we investigated the tautomeric equilibrium for the external aldimine state of PLP aspartate (PLP-Asp) Schiff base in the active site of aspartate aminotransferase (AspAT) using combined quantum mechanical and molecular mechanical simulations. The main focus of the present study is to analyze the factors that control the tautomeric equilibrium in the active sites of various PLP-dependent enzymes. The results show that the ketoenamine tautomer is more preferred than the enolimine tautomer both in the gas and aqueous phases as well as in the active site of AspAT. Current simulations show that the active site of AspAT is more suitable for the ketoenamine tautomer compared to the enolimine tautomer. Interestingly, the Tyr225 acts as a proton donor to the phenolic oxygen in the ketoenamine tautomer, while in the covalent enolimine tautomer, it acts as a proton acceptor to the phenolic oxygen. Finally, the metadynamics study confirms this result. The calculated free energy barrier is about 7.5 kcal/mol. A comparative analysis of the microenvironment created by the active site residues of three different PLP-dependent enzymes (aspartate aminotransferase, Dopa decarboxylase, and Ala-racemase) has been carried out to understand the controlling factor(s) of the tautomeric equilibrium. The analysis shows that the intermolecular hydrogen bonding between active site residues and the phenolic oxygen of PLP shifts the tautomeric equilibrium toward the N

PCDD/F-isomers signature - Effect of metal chlorides and oxides.

PubMed

Zhang, Mengmei; Buekens, Alfons; Olie, Kees; Li, Xiaodong

2017-10-01

A recent paper presented the results from de novo tests, involving 11 distinct catalytic systems (oxides and chlorides of Cd, Cr, Cu, Ni, and Zn, as well as a blank sample). Their PCDD and PCDF formation activity was shown. This paper further assesses their isomer signature, with special emphasis on those congeners associated with chlorophenol precursor routes, and on 2,3,7,8- and 1,9-substituted congeners. Each metal catalyst generates a significantly different signature, also affected by the presence or absence of oxygen in the reaction atmosphere. Oxide and chloride catalysts supply distinctive signatures, suggesting singly weighted pathways. Quite a large number of data was handled, so that throughout this analysis special attention was given to testing and developing an appropriate methodology, allowing appropriate correlation analysis and statistical data treatment. The large tables resulting relate to the 11 catalytic systems, studied at 3 levels of oxygen concentration, with 94 PCDD/F-congeners considered individually. They constitute an extensive reference data bank for confronting novel experimental data with this vast data set. Copyright © 2017. Published by Elsevier Ltd.

A Sensitive and Specific Neural Signature for Picture-Induced Negative Affect

PubMed Central

Chang, Luke J.; Gianaros, Peter J.; Manuck, Stephen B.; Krishnan, Anjali; Wager, Tor D.

2015-01-01

Neuroimaging has identified many correlates of emotion but has not yet yielded brain representations predictive of the intensity of emotional experiences in individuals. We used machine learning to identify a sensitive and specific signature of emotional responses to aversive images. This signature predicted the intensity of negative emotion in individual participants in cross validation (n =121) and test (n = 61) samples (high–low emotion = 93.5% accuracy). It was unresponsive to physical pain (emotion–pain = 92% discriminative accuracy), demonstrating that it is not a representation of generalized arousal or salience. The signature was comprised of mesoscale patterns spanning multiple cortical and subcortical systems, with no single system necessary or sufficient for predicting experience. Furthermore, it was not reducible to activity in traditional “emotion-related” regions (e.g., amygdala, insula) or resting-state networks (e.g., “salience,” “default mode”). Overall, this work identifies differentiable neural components of negative emotion and pain, providing a basis for new, brain-based taxonomies of affective processes. PMID:26098873

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.

Signature-based store checking buffer

DOEpatents

Sridharan, Vilas; Gurumurthi, Sudhanva

2015-06-02

A system and method for optimizing redundant output verification, are provided. A hardware-based store fingerprint buffer receives multiple instances of output from multiple instances of computation. The store fingerprint buffer generates a signature from the content included in the multiple instances of output. When a barrier is reached, the store fingerprint buffer uses the signature to verify the content is error-free.

Community Update on Site Activities, July 19, 2013

EPA Pesticide Factsheets

In an effort to engage and inform community members interested in the New Bedford Harbor Superfund Site cleanup, EPA will be issuing periodic topic-based fact sheets that will provide background information and updates about ongoing activities.

Discovery and information-theoretic characterization of transcription factor binding sites that act cooperatively.

PubMed

Clifford, Jacob; Adami, Christoph

2015-09-02

Transcription factor binding to the surface of DNA regulatory regions is one of the primary causes of regulating gene expression levels. A probabilistic approach to model protein-DNA interactions at the sequence level is through position weight matrices (PWMs) that estimate the joint probability of a DNA binding site sequence by assuming positional independence within the DNA sequence. Here we construct conditional PWMs that depend on the motif signatures in the flanking DNA sequence, by conditioning known binding site loci on the presence or absence of additional binding sites in the flanking sequence of each site's locus. Pooling known sites with similar flanking sequence patterns allows for the estimation of the conditional distribution function over the binding site sequences. We apply our model to the Dorsal transcription factor binding sites active in patterning the Dorsal-Ventral axis of Drosophila development. We find that those binding sites that cooperate with nearby Twist sites on average contain about 0.5 bits of information about the presence of Twist transcription factor binding sites in the flanking sequence. We also find that Dorsal binding site detectors conditioned on flanking sequence information make better predictions about what is a Dorsal site relative to background DNA than detection without information about flanking sequence features.

Structural and Kinetic Analyses of Macrophage Migration Inhibitory Factor Active Site Interactions

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

Crichlow, G.; Lubetsky, J; Leng, L

Macrophage migration inhibitory factor (MIF) is a secreted protein expressed in numerous cell types that counters the antiinflammatory effects of glucocorticoids and has been implicated in sepsis, cancer, and certain autoimmune diseases. Interestingly, the structure of MIF contains a catalytic site resembling the tautomerase/isomerase sites of microbial enzymes. While bona fide physiological substrates remain unknown, model substrates have been identified. Selected compounds that bind in the tautomerase active site also inhibit biological functions of MIF. It had previously been shown that the acetaminophen metabolite, N-acetyl-p-benzoquinone imine (NAPQI), covalently binds to the active site of MIF. In this study, kinetic datamore » indicate that NAPQI inhibits MIF both covalently and noncovalently. The structure of MIF cocrystallized with NAPQI reveals that the NAPQI has undergone a chemical alteration forming an acetaminophen dimer (bi-APAP) and binds noncovalently to MIF at the mouth of the active site. We also find that the commonly used protease inhibitor, phenylmethylsulfonyl fluoride (PMSF), forms a covalent complex with MIF and inhibits the tautomerase activity. Crystallographic analysis reveals the formation of a stable, novel covalent bond for PMSF between the catalytic nitrogen of the N-terminal proline and the sulfur of PMSF with complete, well-defined electron density in all three active sites of the MIF homotrimer. Conclusions are drawn from the structures of these two MIF-inhibitor complexes regarding the design of novel compounds that may provide more potent reversible and irreversible inhibition of MIF.« less

Rac1 GTPase activates the WAVE regulatory complex through two distinct binding sites.

PubMed

Chen, Baoyu; Chou, Hui-Ting; Brautigam, Chad A; Xing, Wenmin; Yang, Sheng; Henry, Lisa; Doolittle, Lynda K; Walz, Thomas; Rosen, Michael K

2017-09-26

The Rho GTPase Rac1 activates the WAVE regulatory complex (WRC) to drive Arp2/3 complex-mediated actin polymerization, which underpins diverse cellular processes. Here we report the structure of a WRC-Rac1 complex determined by cryo-electron microscopy. Surprisingly, Rac1 is not located at the binding site on the Sra1 subunit of the WRC previously identified by mutagenesis and biochemical data. Rather, it binds to a distinct, conserved site on the opposite end of Sra1. Biophysical and biochemical data on WRC mutants confirm that Rac1 binds to both sites, with the newly identified site having higher affinity and both sites required for WRC activation. Our data reveal that the WRC is activated by simultaneous engagement of two Rac1 molecules, suggesting a mechanism by which cells may sense the density of active Rac1 at membranes to precisely control actin assembly.

Monocopper active site for partial methane oxidation in Cu-exchanged 8MR zeolites

DOE PAGES

Kulkarni, Ambarish R.; Zhao, Zhi -Jian; Siahrostami, Samira; ...

2016-08-17

Direct conversion of methane to methanol using oxygen is experiencing renewed interest owing to the availability of new natural gas resources. Copper-exchanged zeolites such as mordenite and ZSM-5 have shown encouraging results, and di- and tri-copper species have been suggested as active sites. Recently, small eight-membered ring (8MR) zeolites including SSZ-13, -16, and -39 have been shown to be active for methane oxidation, but the active sites and reaction mechanisms in these 8MR zeolites are not known. In this work, we use density functional theory (DFT) calculations to systematically evaluate monocopper species as active sites for the partial methane oxidationmore » reaction in Cu-exchanged SSZ-13. On the basis of kinetic and thermodynamic arguments, we suggest that [Cu IIOH] + species in the 8MR are responsible for the experimentally observed activity. Furthermore, our results successfully explain the available spectroscopic data and experimental observations including (i) the necessity of water for methanol extraction and (ii) the effect of Si/Al ratio on the catalyst activity. Monocopper species have not yet been suggested as an active site for the partial methane oxidation reaction, and our results suggest that [Cu IIOH] + active site may provide complementary routes for methane activation in zeolites in addition to the known [Cu–O–Cu] 2+ and Cu 3O 3 motifs.« less

Off-Site Supervision in Social Work Education: What Makes It Work?

ERIC Educational Resources Information Center

Maynard, Sarah P.; Mertz, Linda K. P.; Fortune, Anne E.

2015-01-01

The field practicum is the signature pedagogy of the social work profession, yet field directors struggle to find adequate field placements--both in quantity and quality. To accommodate more students with a dwindling pool of practicum sites, creative models of field supervision have emerged. This article considers off-site supervision and its…

48 CFR 4.102 - Contractor's signature.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 48 Federal Acquisition Regulations System 1 2010-10-01 2010-10-01 false Contractor's signature. 4.102 Section 4.102 Federal Acquisition Regulations System FEDERAL ACQUISITION REGULATION GENERAL ADMINISTRATIVE MATTERS Contract Execution 4.102 Contractor's signature. (a) Individuals. A contract with an...

Signature simulation of mixed materials

NASA Astrophysics Data System (ADS)

Carson, Tyler D.; Salvaggio, Carl

2015-05-01

Soil target signatures vary due to geometry, chemical composition, and scene radiometry. Although radiative transfer models and function-fit physical models may describe certain targets in limited depth, the ability to incorporate all three signature variables is difficult. This work describes a method to simulate the transient signatures of soil by first considering scene geometry synthetically created using 3D physics engines. Through the assignment of spectral data from the Nonconventional Exploitation Factors Data System (NEFDS), the synthetic scene is represented as a physical mixture of particles. Finally, first principles radiometry is modeled using the Digital Imaging and Remote Sensing Image Generation (DIRSIG) model. With DIRSIG, radiometric and sensing conditions were systematically manipulated to produce and record goniometric signatures. The implementation of this virtual goniometer allows users to examine how a target bidirectional reflectance distribution function (BRDF) will change with geometry, composition, and illumination direction. By using 3D computer graphics models, this process does not require geometric assumptions that are native to many radiative transfer models. It delivers a discrete method to circumnavigate the significant cost of time and treasure associated with hardware-based goniometric data collections.

Starry Messages - Searching for Signatures of Interstellar Archaeology

NASA Astrophysics Data System (ADS)

Carrigan, R. A., Jr.

Searching for signatures of cosmic-scale archaeological artefacts such as Dyson spheres or Kardashev civilizations is an interesting alternative to conventional SETI. Uncovering such an artifact does not require the intentional transmission of a signal on the part of the originating civilization. This type of search is called interstellar archaeology or sometimes cosmic archaeology . The detection of intelligence elsewhere in the Universe with interstellar archaeology or SETI would have broad implications for science. For example, the constraints of the anthropic principle would have to be loosened if a different type of intelligence was discovered elsewhere. A variety of interstellar archaeology signatures are discussed including non-natural planetary atmospheric constituents, stellar doping with isotopes of nuclear wastes, Dyson spheres, as well as signatures of stellar and galactic-scale engineering. The concept of a Fermi bubble due to interstellar migration is introduced in the discussion of galactic signatures. These potential interstellar archaeological signatures are classified using the Kardashev scale. A modified Drake equation is used to evaluate the relative challenges of finding various sources. With few exceptions interstellar archaeological signatures are clouded and beyond current technological capabilities. However SETI for so-called cultural transmissions and planetary atmosphere signatures are within reach.

BMI1 induces an invasive signature in melanoma that promotes metastasis and chemoresistance

PubMed Central

Ferretti, Roberta; Bhutkar, Arjun; McNamara, Molly C.; Lees, Jacqueline A.

2016-01-01

Melanoma can switch between proliferative and invasive states, which have identifying gene expression signatures that correlate with good and poor prognosis, respectively. However, the mechanisms controlling these signatures are poorly understood. In this study, we identify BMI1 as a key determinant of melanoma metastasis by which its overexpression enhanced and its deletion impaired dissemination. Remarkably, in this tumor type, BMI1 had no effect on proliferation or primary tumor growth but enhanced every step of the metastatic cascade. Consistent with the broad spectrum of effects, BMI1 activated widespread gene expression changes, which are characteristic of melanoma progression and also chemoresistance. Accordingly, we showed that up-regulation or down-regulation of BMI1 induced resistance or sensitivity to BRAF inhibitor treatment and that induction of noncanonical Wnt by BMI1 is required for this resistance. Finally, we showed that our BMI1-induced gene signature encompasses all of the hallmarks of the previously described melanoma invasive signature. Moreover, our signature is predictive of poor prognosis in human melanoma and is able to identify primary tumors that are likely to become metastatic. These data yield key insights into melanoma biology and establish BMI1 as a compelling drug target whose inhibition would suppress both metastasis and chemoresistance of melanoma. PMID:26679841

Signature Pedagogies in Support of Teachers' Professional Learning

ERIC Educational Resources Information Center

Parker, Melissa; Patton, Kevin; O'Sullivan, Mary

2016-01-01

Signature pedagogies [Shulman, L. 2005. "Signature pedagogies in the professions." "Daedalus" 134 (3): 52--59.] are a focus of teacher educators seeking to improve teaching and teacher education. The purpose of this paper is to present a preliminary common language of signature pedagogies for teacher professional development…

ErbB activation signatures as potential biomarkers for anti-ErbB3 treatment in HNSCC.

PubMed

Alvarado, Diego; Ligon, Gwenda F; Lillquist, Jay S; Seibel, Scott B; Wallweber, Gerald; Neumeister, Veronique M; Rimm, David L; McMahon, Gerald; LaVallee, Theresa M

2017-01-01

Head and neck squamous cell carcinoma (HNSCC) accounts for 3-5% of all tumor types and remains an unmet medical need with only two targeted therapies approved to date. ErbB3 (HER3), the kinase-impaired member of the EGFR/ErbB family, has been implicated as a disease driver in a number of solid tumors, including a subset of HNSCC. Here we show that the molecular components required for ErbB3 activation, including its ligand neuregulin-1 (NRG1), are highly prevalent in HNSCC and that HER2, but not EGFR, is the major activating ErbB3 kinase partner. We demonstrate that cetuximab treatment primarily inhibits the ERK signaling pathway and KTN3379, an anti-ErbB3 monoclonal antibody, inhibits the AKT signaling pathway, and that dual ErbB receptor inhibition results in enhanced anti-tumor activity in HNSCC models. Surprisingly, we found that while NRG1 is required for ErbB3 activation, it was not sufficient to fully predict for KTN3379 activity. An evaluation of HNSCC patient samples demonstrated that NRG1 expression was significantly associated with expression of the EGFR ligands amphiregulin (AREG) and transforming growth factor α (TGFα). Furthermore, NRG1-positive HNSCC cell lines that secreted high levels of AREG and TGFα or contained high levels of EGFR homodimers (H11D) demonstrated a better response to KTN3379. Although ErbB3 and EGFR activation are uncoupled at the receptor level, their respective signaling pathways are linked through co-expression of their respective ligands. We propose that NRG1 expression and EGFR activation signatures may enrich for improved efficacy of anti-ErbB3 therapeutic mAb approaches when combined with EGFR-targeting therapies in HNSCC.

What Motivates Young Adults to Talk About Physical Activity on Social Network Sites?

PubMed

Zhang, Ni; Campo, Shelly; Yang, Jingzhen; Eckler, Petya; Snetselaar, Linda; Janz, Kathleen; Leary, Emily

2017-06-22

Electronic word-of-mouth on social network sites has been used successfully in marketing. In social marketing, electronic word-of-mouth about products as health behaviors has the potential to be more effective and reach more young adults than health education through traditional mass media. However, little is known about what motivates people to actively initiate electronic word-of-mouth about health behaviors on their personal pages or profiles on social network sites, thus potentially reaching all their contacts on those sites. This study filled the gap by applying a marketing theoretical model to explore the factors associated with electronic word-of-mouth on social network sites about leisure-time physical activity. A Web survey link was sent to undergraduate students at one of the Midwestern universities and 439 of them completed the survey. The average age of the 439 participants was 19 years (SD=1 year, range: 18-24). Results suggested that emotional engagement with leisure-time physical activity (ie, affective involvement in leisure-time physical activity) predicted providing relevant opinions or information on social network sites. Social network site users who perceived stronger ties with all their contacts were more likely to provide and seek leisure-time physical activity opinions and information. People who provided leisure-time physical activity opinions and information were more likely to seek opinions and information, and people who forwarded information about leisure-time physical activity were more likely to chat about it. This study shed light on the application of the electronic word-of-mouth theoretical framework in promoting health behaviors. The findings can also guide the development of future social marketing interventions using social network sites to promote leisure-time physical activity. ©Ni Zhang, Shelly Campo, Jingzhen Yang, Petya Eckler, Linda Snetselaar, Kathleen Janz, Emily Leary. Originally published in the Journal of Medical

What Motivates Young Adults to Talk About Physical Activity on Social Network Sites?

PubMed Central

Campo, Shelly; Yang, Jingzhen; Eckler, Petya; Snetselaar, Linda; Janz, Kathleen; Leary, Emily

2017-01-01

Background Electronic word-of-mouth on social network sites has been used successfully in marketing. In social marketing, electronic word-of-mouth about products as health behaviors has the potential to be more effective and reach more young adults than health education through traditional mass media. However, little is known about what motivates people to actively initiate electronic word-of-mouth about health behaviors on their personal pages or profiles on social network sites, thus potentially reaching all their contacts on those sites. Objective This study filled the gap by applying a marketing theoretical model to explore the factors associated with electronic word-of-mouth on social network sites about leisure-time physical activity. Methods A Web survey link was sent to undergraduate students at one of the Midwestern universities and 439 of them completed the survey. Results The average age of the 439 participants was 19 years (SD=1 year, range: 18-24). Results suggested that emotional engagement with leisure-time physical activity (ie, affective involvement in leisure-time physical activity) predicted providing relevant opinions or information on social network sites. Social network site users who perceived stronger ties with all their contacts were more likely to provide and seek leisure-time physical activity opinions and information. People who provided leisure-time physical activity opinions and information were more likely to seek opinions and information, and people who forwarded information about leisure-time physical activity were more likely to chat about it. Conclusions This study shed light on the application of the electronic word-of-mouth theoretical framework in promoting health behaviors. The findings can also guide the development of future social marketing interventions using social network sites to promote leisure-time physical activity. PMID:28642215

Quantum blind dual-signature scheme without arbitrator

NASA Astrophysics Data System (ADS)

Li, Wei; Shi, Ronghua; Huang, Dazu; Shi, Jinjing; Guo, Ying

2016-03-01

Motivated by the elegant features of a bind signature, we suggest the design of a quantum blind dual-signature scheme with three phases, i.e., initial phase, signing phase and verification phase. Different from conventional schemes, legal messages are signed not only by the blind signatory but also by the sender in the signing phase. It does not rely much on an arbitrator in the verification phase as the previous quantum signature schemes usually do. The security is guaranteed by entanglement in quantum information processing. Security analysis demonstrates that the signature can be neither forged nor disavowed by illegal participants or attacker. It provides a potential application for e-commerce or e-payment systems with the current technology.

Corrosion Research And Web Site Activities

NASA Technical Reports Server (NTRS)

Heidersbach, Robert H.

2001-01-01

This report covers corrosion-related activities at the NASA Kennedy Space Center during the summer of 2000. The NASA Kennedy Space Center's corrosion web site, corrosion.ksc.nasa.gov, was updated with new information based on feedback over the past two years. The methodology for a two-year atmospheric exposure testing program to study the effectiveness of commercial chemicals sold for rinsing aircraft and other equipment was developed and some preliminary laboratory chemical analyses are presented.

Corrosion Research and Web Site Activities

NASA Technical Reports Server (NTRS)

Heidersbach, Robert H.

2002-01-01

This report covers corrosion-related activities at the NASA Kennedy Space Center during the summer of 2000. The NASA Kennedy Space Center's corrosion web site, corrosion.ksc.nasa.gov, was updated with new information based on feedback over the past two years. The methodology for a two-year atmospheric exposure testing program to study the effectiveness of commercial chemicals sold for rinsing aircraft and other equipment was developed and some preliminary laboratory chemical analyses are presented.

Newborn Urinary Metabolic Signatures of Prematurity and Other Disorders: A Case Control Study.

PubMed

Diaz, Sílvia O; Pinto, Joana; Barros, António S; Morais, Elisabete; Duarte, Daniela; Negrão, Fátima; Pita, Cristina; Almeida, Maria do Céu; Carreira, Isabel M; Spraul, Manfred; Gil, Ana M

2016-01-04

This work assesses the urinary metabolite signature of prematurity in newborns by nuclear magnetic resonance (NMR) spectroscopy, while establishing the role of possible confounders and signature specificity, through comparison to other disorders. Gender and delivery mode are shown to impact importantly on newborn urine composition, their analysis pointing out at specific metabolite variations requiring consideration in unmatched subject groups. Premature newborns are, however, characterized by a stronger signature of varying metabolites, suggestive of disturbances in nucleotide metabolism, lung surfactants biosynthesis and renal function, along with enhancement of tricarboxylic acid (TCA) cycle activity, fatty acids oxidation, and oxidative stress. Comparison with other abnormal conditions (respiratory depression episode, large for gestational age, malformations, jaundice and premature rupture of membranes) reveals that such signature seems to be largely specific of preterm newborns, showing that NMR metabolomics can retrieve particular disorder effects, as well as general stress effects. These results provide valuable novel information on the metabolic impact of prematurity, contributing to the better understanding of its effects on the newborn's state of health.

Transcriptional blood signatures distinguish pulmonary tuberculosis, pulmonary sarcoidosis, pneumonias and lung cancers.

PubMed

Bloom, Chloe I; Graham, Christine M; Berry, Matthew P R; Rozakeas, Fotini; Redford, Paul S; Wang, Yuanyuan; Xu, Zhaohui; Wilkinson, Katalin A; Wilkinson, Robert J; Kendrick, Yvonne; Devouassoux, Gilles; Ferry, Tristan; Miyara, Makoto; Bouvry, Diane; Valeyre, Dominique; Dominique, Valeyre; Gorochov, Guy; Blankenship, Derek; Saadatian, Mitra; Vanhems, Phillip; Beynon, Huw; Vancheeswaran, Rama; Wickremasinghe, Melissa; Chaussabel, Damien; Banchereau, Jacques; Pascual, Virginia; Ho, Ling-Pei; Lipman, Marc; O'Garra, Anne

2013-01-01

New approaches to define factors underlying the immunopathogenesis of pulmonary diseases including sarcoidosis and tuberculosis are needed to develop new treatments and biomarkers. Comparing the blood transcriptional response of tuberculosis to other similar pulmonary diseases will advance knowledge of disease pathways and help distinguish diseases with similar clinical presentations. To determine the factors underlying the immunopathogenesis of the granulomatous diseases, sarcoidosis and tuberculosis, by comparing the blood transcriptional responses in these and other pulmonary diseases. We compared whole blood genome-wide transcriptional profiles in pulmonary sarcoidosis, pulmonary tuberculosis, to community acquired pneumonia and primary lung cancer and healthy controls, before and after treatment, and in purified leucocyte populations. An Interferon-inducible neutrophil-driven blood transcriptional signature was present in both sarcoidosis and tuberculosis, with a higher abundance and expression in tuberculosis. Heterogeneity of the sarcoidosis signature correlated significantly with disease activity. Transcriptional profiles in pneumonia and lung cancer revealed an over-abundance of inflammatory transcripts. After successful treatment the transcriptional activity in tuberculosis and pneumonia patients was significantly reduced. However the glucocorticoid-responsive sarcoidosis patients showed a significant increase in transcriptional activity. 144-blood transcripts were able to distinguish tuberculosis from other lung diseases and controls. Tuberculosis and sarcoidosis revealed similar blood transcriptional profiles, dominated by interferon-inducible transcripts, while pneumonia and lung cancer showed distinct signatures, dominated by inflammatory genes. There were also significant differences between tuberculosis and sarcoidosis in the degree of their transcriptional activity, the heterogeneity of their profiles and their transcriptional response to treatment.

Transcriptional Blood Signatures Distinguish Pulmonary Tuberculosis, Pulmonary Sarcoidosis, Pneumonias and Lung Cancers

PubMed Central

Bloom, Chloe I.; Graham, Christine M.; Berry, Matthew P. R.; Rozakeas, Fotini; Redford, Paul S.; Wang, Yuanyuan; Xu, Zhaohui; Wilkinson, Katalin A.; Wilkinson, Robert J.; Kendrick, Yvonne; Devouassoux, Gilles; Ferry, Tristan; Miyara, Makoto; Bouvry, Diane; Dominique, Valeyre; Gorochov, Guy; Blankenship, Derek; Saadatian, Mitra; Vanhems, Phillip; Beynon, Huw; Vancheeswaran, Rama; Wickremasinghe, Melissa; Chaussabel, Damien; Banchereau, Jacques; Pascual, Virginia; Ho, Ling-pei; Lipman, Marc; O’Garra, Anne

2013-01-01

Rationale New approaches to define factors underlying the immunopathogenesis of pulmonary diseases including sarcoidosis and tuberculosis are needed to develop new treatments and biomarkers. Comparing the blood transcriptional response of tuberculosis to other similar pulmonary diseases will advance knowledge of disease pathways and help distinguish diseases with similar clinical presentations. Objectives To determine the factors underlying the immunopathogenesis of the granulomatous diseases, sarcoidosis and tuberculosis, by comparing the blood transcriptional responses in these and other pulmonary diseases. Methods We compared whole blood genome-wide transcriptional profiles in pulmonary sarcoidosis, pulmonary tuberculosis, to community acquired pneumonia and primary lung cancer and healthy controls, before and after treatment, and in purified leucocyte populations. Measurements and Main Results An Interferon-inducible neutrophil-driven blood transcriptional signature was present in both sarcoidosis and tuberculosis, with a higher abundance and expression in tuberculosis. Heterogeneity of the sarcoidosis signature correlated significantly with disease activity. Transcriptional profiles in pneumonia and lung cancer revealed an over-abundance of inflammatory transcripts. After successful treatment the transcriptional activity in tuberculosis and pneumonia patients was significantly reduced. However the glucocorticoid-responsive sarcoidosis patients showed a significant increase in transcriptional activity. 144-blood transcripts were able to distinguish tuberculosis from other lung diseases and controls. Conclusions Tuberculosis and sarcoidosis revealed similar blood transcriptional profiles, dominated by interferon-inducible transcripts, while pneumonia and lung cancer showed distinct signatures, dominated by inflammatory genes. There were also significant differences between tuberculosis and sarcoidosis in the degree of their transcriptional activity, the

Channeling by Proximity: The Catalytic Advantages of Active Site Colocalization Using Brownian Dynamics.

PubMed

Bauler, Patricia; Huber, Gary; Leyh, Thomas; McCammon, J Andrew

2010-05-06

Nature often colocalizes successive steps in a metabolic pathway. Such organization is predicted to increase the effective concentration of pathway intermediates near their recipient active sites and to enhance catalytic efficiency. Here, the pathway of a two-step reaction is modeled using a simple spherical approximation for the enzymes and substrate particles. Brownian dynamics are used to simulate the trajectory of a substrate particle as it diffuses between the active site zones of two different enzyme spheres. The results approximate distances for the most effective reaction pathways, indicating that the most effective reaction pathway is one in which the active sites are closely aligned. However, when the active sites are too close, the ability of the substrate to react with the first enzyme was hindered, suggesting that even the most efficient orientations can be improved for a system that is allowed to rotate or change orientation to optimize the likelihood of reaction at both sites.

Diurnal and Seasonal Cold Lands Signatures in SSM/I-scale Microwave Radiometry of the North Slope of Alaska

NASA Technical Reports Server (NTRS)

Kim, Edward J.; England, Anthony W.; Hildebrand, Peter H. (Technical Monitor)

2001-01-01

In this paper, we explore scaling and data assimilation-related issues associated with utilizing passive microwave satellite observations of Cold Lands-in this case, the climatologically and ecologically sensitive arctic tundra. Our approach expands on our earlier work using a one-year dataset from the Radiobrightness Energy Balance Experiment-3 (REBEX-3). REBEX-3 featured a tower-based SSM/I (Special Sensor Microwave/Imager) simulator deployed on the North Slope of Alaska in 1994-95. Two findings are significant here. First, a comparison of tower and satellite signatures at 19 and 37 GHz strongly suggested that the North Slope is radiometrically homogeneous for spatial scales up to SSM/I footprints (approximately 25 km), an unusual and valuable characteristic for monitoring and retrieving land surface conditions. And second, at the plot scale, signatures of snow/no-snow and freeze/thaw transitions were identifiable for tussock tundra land cover, so that even snow-free frozen tundra could be unambiguously distinguished from tundra covered with dry snow, another unusual and valuable characteristic. We present results from analyzing satellite brightness signatures of selected North Slope pixels corresponding to instrumented sites along a transect from the Brooks Range to the Arctic Ocean. A custom EASE (Equal Area Scalable Earth)-Grid processor was used to extract SSMJI data for every orbit with observations of this region during the 1994-95 year. The resulting high temporal-resolution (4-8 points/day), gridded data were then analyzed for evidence of the same diurnal and seasonal signatures seen at the plot scale (through micrometeorological and/or brightness data). Differences between satellite and tower brightness observations are quantified for various conditions at the REBEX-3 site. Such differences from the less-frequent and/or larger-scale satellite observations represent a form of input 'noise' in data assimilation applications. For the other sites, the

Polarimetric SAR calibration experiment using active radar calibrators

NASA Astrophysics Data System (ADS)

Freeman, Anthony; Shen, Yuhsyen; Werner, Charles L.

1990-03-01

Active radar calibrators are used to derive both the amplitude and phase characteristics of a multichannel polarimetric SAR from the complex image data. Results are presented from an experiment carried out using the NASA/JPL DC-8 aircraft SAR over a calibration site at Goldstone, California. As part of the experiment, polarimetric active radar calibrators (PARCs) with adjustable polarization signatures were deployed. Experimental results demonstrate that the PARCs can be used to calibrate polarimetric SAR images successfully. Restrictions on the application of the PARC calibration procedure are discussed.

Polarimetric SAR calibration experiment using active radar calibrators

NASA Technical Reports Server (NTRS)

Freeman, Anthony; Shen, Yuhsyen; Werner, Charles L.

1990-01-01

Active radar calibrators are used to derive both the amplitude and phase characteristics of a multichannel polarimetric SAR from the complex image data. Results are presented from an experiment carried out using the NASA/JPL DC-8 aircraft SAR over a calibration site at Goldstone, California. As part of the experiment, polarimetric active radar calibrators (PARCs) with adjustable polarization signatures were deployed. Experimental results demonstrate that the PARCs can be used to calibrate polarimetric SAR images successfully. Restrictions on the application of the PARC calibration procedure are discussed.

Cooperative activation of cardiac transcription through myocardin bridging of paired MEF2 sites

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

Anderson, Courtney M.; Hu, Jianxin; Thomas, Reuben

2017-03-28

Enhancers frequently contain multiple binding sites for the same transcription factor. These homotypic binding sites often exhibit synergy, whereby the transcriptional output from two or more binding sites is greater than the sum of the contributions of the individual binding sites alone. Although this phenomenon is frequently observed, the mechanistic basis for homotypic binding site synergy is poorly understood. Here in this paper, we identify a bona fide cardiac-specific Prkaa2 enhancer that is synergistically activated by homotypic MEF2 binding sites. We show that two MEF2 sites in the enhancer function cooperatively due to bridging of the MEF2C-bound sites by themore » SAP domain-containing co-activator protein myocardin, and we show that paired sites buffer the enhancer from integration site-dependent effects on transcription in vivo. Paired MEF2 sites are prevalent in cardiac enhancers, suggesting that this might be a common mechanism underlying synergy in the control of cardiac gene expression in vivo.« less

5 CFR 850.106 - Electronic signatures.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 5 Administrative Personnel 2 2011-01-01 2011-01-01 false Electronic signatures. 850.106 Section... (CONTINUED) RETIREMENT SYSTEMS MODERNIZATION General Provisions § 850.106 Electronic signatures. (a) Subject to any provisions prescribed by the Director under § 850.104— (1) An electronic communication may be...

5 CFR 850.106 - Electronic signatures.

Code of Federal Regulations, 2012 CFR

2012-01-01

... 5 Administrative Personnel 2 2012-01-01 2012-01-01 false Electronic signatures. 850.106 Section... (CONTINUED) RETIREMENT SYSTEMS MODERNIZATION General Provisions § 850.106 Electronic signatures. (a) Subject to any provisions prescribed by the Director under § 850.104— (1) An electronic communication may be...

5 CFR 850.106 - Electronic signatures.

Code of Federal Regulations, 2013 CFR

2013-01-01

... 5 Administrative Personnel 2 2013-01-01 2013-01-01 false Electronic signatures. 850.106 Section... (CONTINUED) RETIREMENT SYSTEMS MODERNIZATION General Provisions § 850.106 Electronic signatures. (a) Subject to any provisions prescribed by the Director under § 850.104— (1) An electronic communication may be...

5 CFR 850.106 - Electronic signatures.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 5 Administrative Personnel 2 2010-01-01 2010-01-01 false Electronic signatures. 850.106 Section... (CONTINUED) RETIREMENT SYSTEMS MODERNIZATION General Provisions § 850.106 Electronic signatures. (a) Subject to any provisions prescribed by the Director under § 850.104— (1) An electronic communication may be...

5 CFR 850.106 - Electronic signatures.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 5 Administrative Personnel 2 2014-01-01 2014-01-01 false Electronic signatures. 850.106 Section... (CONTINUED) ELECTRONIC RETIREMENT PROCESSING General Provisions § 850.106 Electronic signatures. (a) Subject to any provisions prescribed by the Director under § 850.104— (1) An electronic communication may be...

Detecting and visualizing weak signatures in hyperspectral data

NASA Astrophysics Data System (ADS)

MacPherson, Duncan James

This thesis evaluates existing techniques for detecting weak spectral signatures from remotely sensed hyperspectral data. Algorithms are presented that successfully detect hard-to-find 'mystery' signatures in unknown cluttered backgrounds. The term 'mystery' is used to describe a scenario where the spectral target and background endmembers are unknown. Sub-Pixel analysis and background suppression are used to find deeply embedded signatures which can be less than 10% of the total signal strength. Existing 'mystery target' detection algorithms are derived and compared. Several techniques are shown to be superior both visually and quantitatively. Detection performance is evaluated using confidence metrics that are developed. A multiple algorithm approach is shown to improve detection confidence significantly. Although the research focuses on remote sensing applications, the algorithms presented can be applied to a wide variety of diverse fields such as medicine, law enforcement, manufacturing, earth science, food production, and astrophysics. The algorithms are shown to be general and can be applied to both the reflective and emissive parts of the electromagnetic spectrum. The application scope is a broad one and the final results open new opportunities for many specific applications including: land mine detection, pollution and hazardous waste detection, crop abundance calculations, volcanic activity monitoring, detecting diseases in food, automobile or airplane target recognition, cancer detection, mining operations, extracting galactic gas emissions, etc.

21 CFR 1309.32 - Application forms; contents; signature.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 9 2010-04-01 2010-04-01 false Application forms; contents; signature. 1309.32... Application forms; contents; signature. (a) Any person who is required to be registered pursuant to § 1309.21... this paragraph and shall contain the signature of the individual being authorized to sign the...

17 CFR 1.4 - Use of electronic signatures.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 17 Commodity and Securities Exchanges 1 2011-04-01 2011-04-01 false Use of electronic signatures... REGULATIONS UNDER THE COMMODITY EXCHANGE ACT Definitions § 1.4 Use of electronic signatures. For purposes of... pool participant or a client of a commodity trading advisor, an electronic signature executed by the...

17 CFR 1.4 - Use of electronic signatures.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 17 Commodity and Securities Exchanges 1 2010-04-01 2010-04-01 false Use of electronic signatures... REGULATIONS UNDER THE COMMODITY EXCHANGE ACT Definitions § 1.4 Use of electronic signatures. For purposes of... broker, a pool participant or a client of a commodity trading advisor, an electronic signature executed...

17 CFR 1.4 - Use of electronic signatures.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 17 Commodity and Securities Exchanges 1 2012-04-01 2012-04-01 false Use of electronic signatures... REGULATIONS UNDER THE COMMODITY EXCHANGE ACT Definitions § 1.4 Use of electronic signatures. For purposes of... pool participant or a client of a commodity trading advisor, an electronic signature executed by the...

Momentum signatures of the Anderson transition

NASA Astrophysics Data System (ADS)

Sanjib, Ghosh

This thesis explores for possible signatures of Anderson localization and the Anderson metal-insulator transition (MIT) in momentum space. We find that an initial plane-wave propagating in a disordered medium exhibits a diffusive background and two interference peaks, the coherent backscattering (CBS) and the coherent forward scattering (CFS) peaks in the momentum distribution. We show, the signatures of Anderson localization and the Anderson transition are encoded in the dynamical properties of the two interference peaks, CBS and CFS. We develop finite-time scaling theory for the angular width of the CBS peak and in the height of the CFS peak. We demonstrate how to extract properties like critical exponent, the mobility edge and signatures of multifractality from this finite-time analysis. These momentum space signatures of the Anderson transition are novel and they promise to be experimental observables for wide range of systems, from cold atoms to classical waves or any wave systems where the momentum distribution is accessible.

Microbial network, phylogenetic diversity and community membership in the active layer across a permafrost thaw gradient.

PubMed

Mondav, Rhiannon; McCalley, Carmody K; Hodgkins, Suzanne B; Frolking, Steve; Saleska, Scott R; Rich, Virginia I; Chanton, Jeff P; Crill, Patrick M

2017-08-01

Biogenic production and release of methane (CH 4 ) from thawing permafrost has the potential to be a strong source of radiative forcing. We investigated changes in the active layer microbial community of three sites representative of distinct permafrost thaw stages at a palsa mire in northern Sweden. The palsa site (intact permafrost and low radiative forcing signature) had a phylogenetically clustered community dominated by Acidobacteria and Proteobacteria. The bog (thawing permafrost and low radiative forcing signature) had lower alpha diversity and midrange phylogenetic clustering, characteristic of ecosystem disturbance affecting habitat filtering. Hydrogenotrophic methanogens and Acidobacteria dominated the bog shifting from palsa-like to fen-like at the waterline. The fen (no underlying permafrost, high radiative forcing signature) had the highest alpha, beta and phylogenetic diversity, was dominated by Proteobacteria and Euryarchaeota and was significantly enriched in methanogens. The Mire microbial network was modular with module cores consisting of clusters of Acidobacteria, Euryarchaeota or Xanthomonodales. Loss of underlying permafrost with associated hydrological shifts correlated to changes in microbial composition, alpha, beta and phylogenetic diversity associated with a higher radiative forcing signature. These results support the complex role of microbial interactions in mediating carbon budget changes and climate feedback in response to climate forcing. © 2017 Society for Applied Microbiology and John Wiley & Sons Ltd.

Maturation of the [Ni-4Fe-4S] active site of carbon monoxide dehydrogenases.

PubMed

Merrouch, Mériem; Benvenuti, Martino; Lorenzi, Marco; Léger, Christophe; Fourmond, Vincent; Dementin, Sébastien

2018-02-14

Nickel-containing enzymes are diverse in terms of function and active site structure. In many cases, the biosynthesis of the active site depends on accessory proteins which transport and insert the Ni ion. We review and discuss the literature related to the maturation of carbon monoxide dehydrogenases (CODH) which bear a nickel-containing active site consisting of a [Ni-4Fe-4S] center called the C-cluster. The maturation of this center has been much less studied than that of other nickel-containing enzymes such as urease and NiFe hydrogenase. Several proteins present in certain CODH operons, including the nickel-binding proteins CooT and CooJ, still have unclear functions. We question the conception that the maturation of all CODH depends on the accessory protein CooC described as essential for nickel insertion into the active site. The available literature reveals biological variations in CODH active site biosynthesis.

CASPASE-9 CARD:CORE DOMAIN INTERACTIONS REQUIRE A PROPERLY-FORMED ACTIVE SITE

PubMed Central

Huber, Kristen L.; Serrano, Banyuhay P.; Hardy, Jeanne A.

2018-01-01

Caspase-9 is a critical factor in the initiation of apoptosis, and as a result is tightly regulated by a number of mechanisms. Caspase-9 contains a Caspase Activation and Recruitment Domain (CARD), which enables caspase-9 to form a tight interaction with the apoptosome, a heptameric activating platform. The caspase-9 CARD has been thought to be principally involved in recruitment to the apoptosome, but its roles outside this interaction have yet to be uncovered. In this work we show that the CARD is involved in physical interactions with the catalytic core of caspase-9 in the absence of the apoptosome; this interaction requires a properly formed caspase-9 active site. The active sites of caspases are composed of four extremely mobile loops. When the active-site loops are not properly ordered, the CARD and core domains of caspase-9 do not interact and behave independently, like loosely tethered beads. When the active-site loop bundle is properly ordered, the CARD domain interacts with the catalytic core, forming a single folding unit. Together these findings provide mechanistic insight into a new level of caspase-9 regulation, prompting speculation that the CARD may also play a role in the recruitment or recognition of substrate. PMID:29500231

Prediction of active sites of enzymes by maximum relevance minimum redundancy (mRMR) feature selection.

PubMed

Gao, Yu-Fei; Li, Bi-Qing; Cai, Yu-Dong; Feng, Kai-Yan; Li, Zhan-Dong; Jiang, Yang

2013-01-27

Identification of catalytic residues plays a key role in understanding how enzymes work. Although numerous computational methods have been developed to predict catalytic residues and active sites, the prediction accuracy remains relatively low with high false positives. In this work, we developed a novel predictor based on the Random Forest algorithm (RF) aided by the maximum relevance minimum redundancy (mRMR) method and incremental feature selection (IFS). We incorporated features of physicochemical/biochemical properties, sequence conservation, residual disorder, secondary structure and solvent accessibility to predict active sites of enzymes and achieved an overall accuracy of 0.885687 and MCC of 0.689226 on an independent test dataset. Feature analysis showed that every category of the features except disorder contributed to the identification of active sites. It was also shown via the site-specific feature analysis that the features derived from the active site itself contributed most to the active site determination. Our prediction method may become a useful tool for identifying the active sites and the key features identified by the paper may provide valuable insights into the mechanism of catalysis.

Application of signature-tagged mutagenesis to the study of virulence of Erwinia amylovora.

PubMed

Wang, Limei; Beer, Steven V

2006-12-01

To identify genes that contribute to the virulence of Erwinia amylovora in plants, 1892 mutants were created and screened in pools of < or =96 mutants using signature-tagged mutagenesis. Nineteen mutants were not recovered from apple shoots following inoculation, which suggested that the insertions in these mutants affected genes important for bacterial survival in planta. DNA flanking the Tn5 insertions in the 19 mutants was sequenced and analysed by blast. One mutant had a Tn5 insertion in amsE, a gene involved in the biosynthesis of exopolysaccaride (EPS). Fourteen mutants had insertions in loci that were implicated in biosynthesis or transport of particular amino acids or nucleotides, a site-specific recombinase active during cell division and several putative proteins of unknown function; the flanking DNA of the remaining four mutants lacked significant homology with any DNA in the database. When inoculated individually to hosts, 10 of the 19 mutants caused significantly less disease and multiplied less, as compared with the wild-type strain.

Assessment of Mars Exploration Rover Landing Site Predictions

NASA Technical Reports Server (NTRS)

Golombek, M. P.; Arvidson, R. E.; Bell, J. F., III; Christensen, P. R.; Crisp, J. A.; Ehlmann, B. L.; Fergason, R. L.; Grant, J. A.; Haldemann, A. F. C.; Parker, T. J.;

Active site densities, oxygen activation and adsorbed reactive oxygen in alcohol activation on npAu catalysts

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

Wang, Lu-Cun; Friend, C. M.; Fushimi, Rebecca

The activation of molecular O 2as well as the reactivity of adsorbed oxygen species is of central importance in aerobic selective oxidation chemistry on Au-based catalysts. Herein, we address the issue of O 2activation on unsupported nanoporous gold (npAu) catalysts by applying a transient pressure technique, a temporal analysis of products (TAP) reactor, to measure the saturation coverage of atomic oxygen, its collisional dissociation probability, the activation barrier for O 2dissociation, and the facility with which adsorbed O species activate methanol, the initial step in the catalytic cycle of esterification. The results from these experiments indicate that molecular O 2dissociationmore » is associated with surface silver, that the density of reactive sites is quite low, that adsorbed oxygen atoms do not spill over from the sites of activation onto the surrounding surface, and that methanol reacts quite facilely with the adsorbed oxygen atoms. In addition, the O species from O 2dissociation exhibits reactivity for the selective oxidation of methanol but not for CO. The TAP experiments also revealed that the surface of the npAu catalyst is saturated with adsorbed O under steady state reaction conditions, at least for the pulse reaction.« less

Active site densities, oxygen activation and adsorbed reactive oxygen in alcohol activation on npAu catalysts

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

Wang, Lu-Cun; Friend, C. M.; Fushimi, Rebecca

2016-01-01

The activation of molecular O 2as well as the reactivity of adsorbed oxygen species is of central importance in aerobic selective oxidation chemistry on Au-based catalysts. Herein, we address the issue of O 2activation on unsupported nanoporous gold (npAu) catalysts by applying a transient pressure technique, a temporal analysis of products (TAP) reactor, to measure the saturation coverage of atomic oxygen, its collisional dissociation probability, the activation barrier for O 2dissociation, and the facility with which adsorbed O species activate methanol, the initial step in the catalytic cycle of esterification. The results from these experiments indicate that molecular O 2dissociationmore » is associated with surface silver, that the density of reactive sites is quite low, that adsorbed oxygen atoms do not spill over from the sites of activation onto the surrounding surface, and that methanol reacts quite facilely with the adsorbed oxygen atoms. In addition, the O species from O 2dissociation exhibits reactivity for the selective oxidation of methanol but not for CO. The TAP experiments also revealed that the surface of the npAu catalyst is saturated with adsorbed O under steady state reaction conditions, at least for the pulse reaction.« less

Brownian aggregation rate of colloid particles with several active sites

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

Nekrasov, Vyacheslav M.; Yurkin, Maxim A.; Chernyshev, Andrei V., E-mail: chern@ns.kinetics.nsc.ru

2014-08-14

We theoretically analyze the aggregation kinetics of colloid particles with several active sites. Such particles (so-called “patchy particles”) are well known as chemically anisotropic reactants, but the corresponding rate constant of their aggregation has not yet been established in a convenient analytical form. Using kinematic approximation for the diffusion problem, we derived an analytical formula for the diffusion-controlled reaction rate constant between two colloid particles (or clusters) with several small active sites under the following assumptions: the relative translational motion is Brownian diffusion, and the isotropic stochastic reorientation of each particle is Markovian and arbitrarily correlated. This formula was shownmore » to produce accurate results in comparison with more sophisticated approaches. Also, to account for the case of a low number of active sites per particle we used Monte Carlo stochastic algorithm based on Gillespie method. Simulations showed that such discrete model is required when this number is less than 10. Finally, we applied the developed approach to the simulation of immunoagglutination, assuming that the formed clusters have fractal structure.« less

U.S. Army Research Laboratory (ARL) multimodal signatures database

NASA Astrophysics Data System (ADS)

Bennett, Kelly

2008-04-01

The U.S. Army Research Laboratory (ARL) Multimodal Signatures Database (MMSDB) is a centralized collection of sensor data of various modalities that are co-located and co-registered. The signatures include ground and air vehicles, personnel, mortar, artillery, small arms gunfire from potential sniper weapons, explosives, and many other high value targets. This data is made available to Department of Defense (DoD) and DoD contractors, Intel agencies, other government agencies (OGA), and academia for use in developing target detection, tracking, and classification algorithms and systems to protect our Soldiers. A platform independent Web interface disseminates the signatures to researchers and engineers within the scientific community. Hierarchical Data Format 5 (HDF5) signature models provide an excellent solution for the sharing of complex multimodal signature data for algorithmic development and database requirements. Many open source tools for viewing and plotting HDF5 signatures are available over the Web. Seamless integration of HDF5 signatures is possible in both proprietary computational environments, such as MATLAB, and Free and Open Source Software (FOSS) computational environments, such as Octave and Python, for performing signal processing, analysis, and algorithm development. Future developments include extending the Web interface into a portal system for accessing ARL algorithms and signatures, High Performance Computing (HPC) resources, and integrating existing database and signature architectures into sensor networking environments.

FIR signature verification system characterizing dynamics of handwriting features

NASA Astrophysics Data System (ADS)

Thumwarin, Pitak; Pernwong, Jitawat; Matsuura, Takenobu

2013-12-01

This paper proposes an online signature verification method based on the finite impulse response (FIR) system characterizing time-frequency characteristics of dynamic handwriting features. First, the barycenter determined from both the center point of signature and two adjacent pen-point positions in the signing process, instead of one pen-point position, is used to reduce the fluctuation of handwriting motion. In this paper, among the available dynamic handwriting features, motion pressure and area pressure are employed to investigate handwriting behavior. Thus, the stable dynamic handwriting features can be described by the relation of the time-frequency characteristics of the dynamic handwriting features. In this study, the aforesaid relation can be represented by the FIR system with the wavelet coefficients of the dynamic handwriting features as both input and output of the system. The impulse response of the FIR system is used as the individual feature for a particular signature. In short, the signature can be verified by evaluating the difference between the impulse responses of the FIR systems for a reference signature and the signature to be verified. The signature verification experiments in this paper were conducted using the SUBCORPUS MCYT-100 signature database consisting of 5,000 signatures from 100 signers. The proposed method yielded equal error rate (EER) of 3.21% on skilled forgeries.

Four-gene Pan-African Blood Signature Predicts Progression to Tuberculosis.

PubMed

Suliman, Sara; Thompson, Ethan; Sutherland, Jayne; Weiner Rd, January; Ota, Martin O C; Shankar, Smitha; Penn-Nicholson, Adam; Thiel, Bonnie; Erasmus, Mzwandile; Maertzdorf, Jeroen; Duffy, Fergal J; Hill, Philip C; Hughes, E Jane; Stanley, Kim; Downing, Katrina; Fisher, Michelle L; Valvo, Joe; Parida, Shreemanta K; van der Spuy, Gian; Tromp, Gerard; Adetifa, Ifedayo M O; Donkor, Simon; Howe, Rawleigh; Mayanja-Kizza, Harriet; Boom, W Henry; Dockrell, Hazel; Ottenhoff, Tom H M; Hatherill, Mark; Aderem, Alan; Hanekom, Willem A; Scriba, Thomas J; Kaufmann, Stefan He; Zak, Daniel E; Walzl, Gerhard

2018-04-06

Contacts of tuberculosis (TB) patients constitute an important target population for preventative measures as they are at high risk of infection with Mycobacterium tuberculosis and progression to disease. We investigated biosignatures with predictive ability for incident tuberculosis. In a case-control study nested within the Grand Challenges 6-74 longitudinal HIV-negative African cohort of exposed household contacts, we employed RNA sequencing, polymerase chain reaction (PCR) and the Pair Ratio algorithm in a training/test set approach. Overall, 79 progressors, who developed tuberculosis between 3 and 24 months following exposure, and 328 matched non-progressors, who remained healthy during 24 months of follow-up, were investigated. A four-transcript signature (RISK4), derived from samples in a South African and Gambian training set, predicted progression up to two years before onset of disease in blinded test set samples from South Africa, The Gambia and Ethiopia with little population-associated variability and also validated on an external cohort of South African adolescents with latent Mycobacterium tuberculosis infection. By contrast, published diagnostic or prognostic tuberculosis signatures predicted on samples from some but not all 3 countries, indicating site-specific variability. Post-hoc meta-analysis identified a single gene pair, C1QC/TRAV27, that would consistently predict TB progression in household contacts from multiple African sites but not in infected adolescents without known recent exposure events. Collectively, we developed a simple whole blood-based PCR test to predict tuberculosis in household contacts from diverse African populations, with potential for implementation in national TB contact investigation programs.

Stepwise Loop Insertion Strategy for Active Site Remodeling to Generate Novel Enzyme Functions.

PubMed

Hoque, Md Anarul; Zhang, Yong; Chen, Liuqing; Yang, Guangyu; Khatun, Mst Afroza; Chen, Haifeng; Hao, Liu; Feng, Yan

2017-05-19

The remodeling of active sites to generate novel biocatalysts is an attractive and challenging task. We developed a stepwise loop insertion strategy (StLois), in which randomized residue pairs are inserted into active site loops. The phosphotriesterase-like lactonase from Geobacillus kaustophilus (GkaP-PLL) was used to investigate StLois's potential for changing enzyme function. By inserting six residues into active site loop 7, the best variant ML7-B6 demonstrated a 16-fold further increase in catalytic efficiency toward ethyl-paraoxon compared with its initial template, that is a 609-fold higher, >10 7 fold substrate specificity shift relative to that of wild-type lactonase. The remodeled variants displayed 760-fold greater organophosphate hydrolysis activity toward the organophosphates parathion, diazinon, and chlorpyrifos. Structure and docking computations support the source of notably inverted enzyme specificity. Considering the fundamental importance of active site loops, the strategy has potential for the rapid generation of novel enzyme functions by loop remodeling.

Orthogonal use of a human tRNA synthetase active site to achieve multifunctionality.

PubMed

Zhou, Quansheng; Kapoor, Mili; Guo, Min; Belani, Rajesh; Xu, Xiaoling; Kiosses, William B; Hanan, Melanie; Park, Chulho; Armour, Eva; Do, Minh-Ha; Nangle, Leslie A; Schimmel, Paul; Yang, Xiang-Lei

2010-01-01

Protein multifunctionality is an emerging explanation for the complexity of higher organisms. In this regard, aminoacyl tRNA synthetases catalyze amino acid activation for protein synthesis, but some also act in pathways for inflammation, angiogenesis and apoptosis. It is unclear how these multiple functions evolved and how they relate to the active site. Here structural modeling analysis, mutagenesis and cell-based functional studies show that the potent angiostatic, natural fragment of human tryptophanyl-tRNA synthetase (TrpRS) associates via tryptophan side chains that protrude from its cognate cellular receptor vascular endothelial cadherin (VE-cadherin). VE-cadherin's tryptophan side chains fit into the tryptophan-specific active site of the synthetase. Thus, specific side chains of the receptor mimic amino acid substrates and expand the functionality of the active site of the synthetase. We propose that orthogonal use of the same active site may be a general way to develop multifunctionality of human tRNA synthetases and other proteins.

21 CFR 11.200 - Electronic signature components and controls.

Code of Federal Regulations, 2011 CFR

2011-04-01

... signature components and controls. (a) Electronic signatures that are not based upon biometrics shall: (1... signatures based upon biometrics shall be designed to ensure that they cannot be used by anyone other than...

21 CFR 11.200 - Electronic signature components and controls.

Code of Federal Regulations, 2013 CFR

2013-04-01

... signature components and controls. (a) Electronic signatures that are not based upon biometrics shall: (1... signatures based upon biometrics shall be designed to ensure that they cannot be used by anyone other than...

21 CFR 11.200 - Electronic signature components and controls.

Code of Federal Regulations, 2012 CFR

2012-04-01

... signature components and controls. (a) Electronic signatures that are not based upon biometrics shall: (1... signatures based upon biometrics shall be designed to ensure that they cannot be used by anyone other than...

21 CFR 11.200 - Electronic signature components and controls.

Code of Federal Regulations, 2014 CFR

2014-04-01

... signature components and controls. (a) Electronic signatures that are not based upon biometrics shall: (1... signatures based upon biometrics shall be designed to ensure that they cannot be used by anyone other than...

Static Signature Synthesis: A Neuromotor Inspired Approach for Biometrics.

PubMed

Ferrer, Miguel A; Diaz-Cabrera, Moises; Morales, Aythami

2015-03-01

In this paper we propose a new method for generating synthetic handwritten signature images for biometric applications. The procedures we introduce imitate the mechanism of motor equivalence which divides human handwriting into two steps: the working out of an effector independent action plan and its execution via the corresponding neuromuscular path. The action plan is represented as a trajectory on a spatial grid. This contains both the signature text and its flourish, if there is one. The neuromuscular path is simulated by applying a kinematic Kaiser filter to the trajectory plan. The length of the filter depends on the pen speed which is generated using a scalar version of the sigma lognormal model. An ink deposition model, applied pixel by pixel to the pen trajectory, provides realistic static signature images. The lexical and morphological properties of the synthesized signatures as well as the range of the synthesis parameters have been estimated from real databases of real signatures such as the MCYT Off-line and the GPDS960GraySignature corpuses. The performance experiments show that by tuning only four parameters it is possible to generate synthetic identities with different stability and forgers with different skills. Therefore it is possible to create datasets of synthetic signatures with a performance similar to databases of real signatures. Moreover, we can customize the created dataset to produce skilled forgeries or simple forgeries which are easier to detect, depending on what the researcher needs. Perceptual evaluation gives an average confusion of 44.06 percent between real and synthetic signatures which shows the realism of the synthetic ones. The utility of the synthesized signatures is demonstrated by studying the influence of the pen type and number of users on an automatic signature verifier.

In silico analysis of Pycnoporus cinnabarinus laccase active site with toxic industrial dyes.

PubMed

Prasad, Nirmal K; Vindal, Vaibhav; Narayana, Siva Lakshmi; Ramakrishna, V; Kunal, Swaraj Priyaranjan; Srinivas, M

2012-05-01

Laccases belong to multicopper oxidases, a widespread class of enzymes implicated in many oxidative functions in various industrial oxidative processes like production of fine chemicals to bioremediation of contaminated soil and water. In order to understand the mechanisms of substrate binding and interaction between substrates and Pycnoporus cinnabarinus laccase, a homology model was generated. The resulted model was further validated and used for docking studies with toxic industrial dyes- acid blue 74, reactive black 5 and reactive blue 19. Interactions of chemical mediators with the laccase was also examined. The docking analysis showed that the active site always cannot accommodate the dye molecules, due to constricted nature of the active site pocket and steric hindrance of the residues whereas mediators are relatively small and can easily be accommodated into the active site pocket, which, thereafter leads to the productive binding. The binding properties of these compounds along with identification of critical active site residues can be used for further site-directed mutagenesis experiments in order to identify their role in activity and substrate specificity, ultimately leading to improved mutants for degradation of these toxic compounds.

Neural Signatures of Stimulus Features in Visual Working Memory—A Spatiotemporal Approach

PubMed Central

Jackson, Margaret C.; Klein, Christoph; Mohr, Harald; Shapiro, Kimron L.; Linden, David E. J.

2010-01-01

We examined the neural signatures of stimulus features in visual working memory (WM) by integrating functional magnetic resonance imaging (fMRI) and event-related potential data recorded during mental manipulation of colors, rotation angles, and color–angle conjunctions. The N200, negative slow wave, and P3b were modulated by the information content of WM, and an fMRI-constrained source model revealed a progression in neural activity from posterior visual areas to higher order areas in the ventral and dorsal processing streams. Color processing was associated with activity in inferior frontal gyrus during encoding and retrieval, whereas angle processing involved right parietal regions during the delay interval. WM for color–angle conjunctions did not involve any additional neural processes. The finding that different patterns of brain activity underlie WM for color and spatial information is consistent with ideas that the ventral/dorsal “what/where” segregation of perceptual processing influences WM organization. The absence of characteristic signatures of conjunction-related brain activity, which was generally intermediate between the 2 single conditions, suggests that conjunction judgments are based on the coordinated activity of these 2 streams. PMID:19429863

Invisibly Sanitizable Digital Signature Scheme

NASA Astrophysics Data System (ADS)

Miyazaki, Kunihiko; Hanaoka, Goichiro; Imai, Hideki

A digital signature does not allow any alteration of the document to which it is attached. Appropriate alteration of some signed documents, however, should be allowed because there are security requirements other than the integrity of the document. In the disclosure of official information, for example, sensitive information such as personal information or national secrets is masked when an official document is sanitized so that its nonsensitive information can be disclosed when it is requested by a citizen. If this disclosure is done digitally by using the current digital signature schemes, the citizen cannot verify the disclosed information because it has been altered to prevent the leakage of sensitive information. The confidentiality of official information is thus incompatible with the integrity of that information, and this is called the digital document sanitizing problem. Conventional solutions such as content extraction signatures and digitally signed document sanitizing schemes with disclosure condition control can either let the sanitizer assign disclosure conditions or hide the number of sanitized portions. The digitally signed document sanitizing scheme we propose here is based on the aggregate signature derived from bilinear maps and can do both. Moreover, the proposed scheme can sanitize a signed document invisibly, that is, no one can distinguish whether the signed document has been sanitized or not.

Using a Stem Cell-Based Signature to Guide Therapeutic Selection in Cancer

PubMed Central

Shats, Igor; Gatza, Michael L.; Chang, Jeffrey T.; Mori, Seiichi; Wang, Jialiang; Rich, Jeremy; Nevins, Joseph R.

2010-01-01

Given the very substantial heterogeneity of most human cancers, it is likely that most cancer therapeutics will be active in only a small fraction of any population of patients. As such, the development of new therapeutics, coupled with methods to match a therapy with the individual patient, will be critical to achieving significant gains in disease outcome. One such opportunity is the use of expression signatures to identify key oncogenic phenotypes that can serve not only as biomarkers but also as a means of identifying therapeutic compounds that might specifically target these phenotypes. Given the potential importance of targeting tumors exhibiting a stem-like phenotype, we have developed an expression signature that reflects common biological aspects of various stem-like characteristics. The Consensus Stemness Ranking (CSR) signature is upregulated in cancer stem cell enriched samples, at advanced tumor stages and is associated with poor prognosis in multiple cancer types. Using two independent computational approaches we utilized the CSR signature to identify clinically useful compounds that could target the CSR phenotype. In vitro assays confirmed selectivity of several predicted compounds including topoisomerase inhibitors and resveratrol towards breast cancer cell lines that exhibit a high-CSR phenotype. Importantly, the CSR signature could predict clinical response of breast cancer patients to a neoadjuvant regimen that included a CSR-specific agent. Collectively, these results suggest therapeutic opportunities to target the CSR phenotype in a relevant cohort of cancer patients. PMID:21169407

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

Kinematics of Signature Writing in Healthy Aging*

PubMed Central

Caligiuri, Michael P.; Kim, Chi; Landy, Kelly M.

2014-01-01

Forensic document examiners (FDE) called upon to distinguish a genuine from a forged signature of an elderly person are often required to consider the question of age-related deterioration and whether the available exemplars reliably capture the natural effects of aging of the original writer. An understanding of the statistical relationship between advanced age and handwriting movements can reduce the uncertainty that may exist in an examiner’s approach to questioned signatures formed by elderly writers. The primary purpose of this study was to systematically examine age-related changes in signature kinematics in healthy writers. Forty-two healthy subjects between the ages of 60–91 years participated in this study. Signatures were recorded using a digitizing tablet and commercial software was used to examine the temporal and spatial stroke kinematics and pen pressure. Results indicated that vertical stroke duration and dysfluency increased with age, whereas vertical stroke amplitude and velocity decreased with age. Pen pressure decreased with age. We found that a linear model characterized the best-fit relationship between advanced age and handwriting movement parameters for signature formation. Male writers exhibited stronger age effects than female writers, especially for pen pressure and stroke dysfluency. The present study contributes to an understanding of how advanced age alters signature formation in otherwise healthy adults. PMID:24673648

Active-Site Hydration and Water Diffusion in Cytochrome P450cam: A Highly Dynamic Process

PubMed Central

Miao, Yinglong; Baudry, Jerome

2011-01-01

Long-timescale molecular dynamics simulations (300 ns) are performed on both the apo- (i.e., camphor-free) and camphor-bound cytochrome P450cam (CYP101). Water diffusion into and out of the protein active site is observed without biased sampling methods. During the course of the molecular dynamics simulation, an average of 6.4 water molecules is observed in the camphor-binding site of the apo form, compared to zero water molecules in the binding site of the substrate-bound form, in agreement with the number of water molecules observed in crystal structures of the same species. However, as many as 12 water molecules can be present at a given time in the camphor-binding region of the active site in the case of apo-P450cam, revealing a highly dynamic process for hydration of the protein active site, with water molecules exchanging rapidly with the bulk solvent. Water molecules are also found to exchange locations frequently inside the active site, preferentially clustering in regions surrounding the water molecules observed in the crystal structure. Potential-of-mean-force calculations identify thermodynamically favored trans-protein pathways for the diffusion of water molecules between the protein active site and the bulk solvent. Binding of camphor in the active site modifies the free-energy landscape of P450cam channels toward favoring the diffusion of water molecules out of the protein active site. PMID:21943431

Ballastic signature identification systems study

NASA Technical Reports Server (NTRS)

Reich, A.; Hine, T. L.

1976-01-01

The results are described of an attempt to establish a uniform procedure for documenting (recording) expended bullet signatures as effortlessly as possible and to build a comprehensive library of these signatures in a form that will permit the automated comparison of a new suspect bullet with the prestored library. The ultimate objective is to achieve a standardized format that will permit nationwide interaction between police departments, crime laboratories, and other interested law enforcement agencies.

Active Site Mutations Change the Cleavage Specificity of Neprilysin

PubMed Central

Sexton, Travis; Hitchcook, Lisa J.; Rodgers, David W.; Bradley, Luke H.; Hersh, Louis B.

2012-01-01

Neprilysin (NEP), a member of the M13 subgroup of the zinc-dependent endopeptidase family is a membrane bound peptidase capable of cleaving a variety of physiological peptides. We have generated a series of neprilysin variants containing mutations at either one of two active site residues, Phe563 and Ser546. Among the mutants studied in detail we observed changes in their activity towards leucine5-enkephalin, insulin B chain, and amyloid β1–40. For example, NEPF563I displayed an increase in preference towards cleaving leucine5-enkephalin relative to insulin B chain, while mutant NEPS546E was less discriminating than neprilysin. Mutants NEPF563L and NEPS546E exhibit different cleavage site preferences than neprilysin with insulin B chain and amyloid ß1–40 as substrates. These data indicate that it is possible to alter the cleavage site specificity of neprilysin opening the way for the development of substrate specific or substrate exclusive forms of the enzyme with enhanced therapeutic potential. PMID:22384224

Carbinolamine Formation and Dehydration in a DNA Repair Enzyme Active Site

PubMed Central

Dodson, M. L.; Walker, Ross C.; Lloyd, R. Stephen

2012-01-01

In order to suggest detailed mechanistic hypotheses for the formation and dehydration of a key carbinolamine intermediate in the T4 pyrimidine dimer glycosylase (T4PDG) reaction, we have investigated these reactions using steered molecular dynamics with a coupled quantum mechanics–molecular mechanics potential (QM/MM). We carried out simulations of DNA abasic site carbinolamine formation with and without a water molecule restrained to remain within the active site quantum region. We recovered potentials of mean force (PMF) from thirty replicate reaction trajectories using Jarzynski averaging. We demonstrated feasible pathways involving water, as well as those independent of water participation. The water–independent enzyme–catalyzed reaction had a bias–corrected Jarzynski–average barrier height of approximately for the carbinolamine formation reaction and ) for the reverse reaction at this level of representation. When the proton transfer was facilitated with an intrinsic quantum water, the barrier height was approximately in the forward (formation) reaction and for the reverse. In addition, two modes of unsteered (free dynamics) carbinolamine dehydration were observed: in one, the quantum water participated as an intermediate proton transfer species, and in the other, the active site protonated glutamate hydrogen was directly transferred to the carbinolamine oxygen. Water–independent unforced proton transfer from the protonated active site glutamate carboxyl to the unprotonated N–terminal amine was also observed. In summary, complex proton transfer events, some involving water intermediates, were studied in QM/MM simulations of T4PDG bound to a DNA abasic site. Imine carbinolamine formation was characterized using steered QM/MM molecular dynamics. Dehydration of the carbinolamine intermediate to form the final imine product was observed in free, unsteered, QM/MM dynamics simulations, as was unforced acid-base transfer between the active site

Stable Isotope Signatures Suggest Different Feeding Strategies for Atlantic and Gulf Menhaden

NASA Astrophysics Data System (ADS)

Perez-Perez, N.; Smith, S. L.; Gonsalves, L. C.; Lamb, M.

2016-02-01

Atlantic menhaden (Brevoortia tyrannus) is a keystone forage species that ranges on the Atlantic Coast from Nova Scotia to Florida. A related species, the Gulf menhaden (Brevoortia patronus) is found in the northern Gulf of Mexico from Florida to Texas. They each serve as prey for important recreational and commercial fish, such as blue fish, tuna and striped bass. Menhaden are filter feeders whose diets consist mostly of phytoplankton and zooplankton, and menhaden act as direct links between primary producers and larger valuable predators. In this study, we investigated and compared the isotopic signatures of water column nitrate (δ15N), bulk plankton and juvenile menhaden (δ 15N and δ 13C) collected from 5 sites in both the Choptank River, MD, and Apalachicola Bay, FL. We determined that menhaden inhabiting the temperate zone versus the sub-tropical region exhibited statistically different isotopic signatures, suggesting different feeding strategies. Choptank River menhaden were enriched 4‰ in δ 15N over Apalachicola Bay menhaden. Choptank River menhaden are mostly likely obtaining their diet from a higher trophic level (copepods, primary consumers) than Apalachicola Bay fish, who may consume more phytoplankton. The Choptank River menhaden also may be consuming more allochthonous material, and those from the Gulf area eat a more authochthonous diet. In addition, Atlantic menhaden collected from fresh water creeks versus those collected closer to the bay differed in their δ 13C compositions, depending on site collection, with creek fish being more depleted in the heavier carbon isotope. The δ 15N values of water column nitrate were similar at Choptank and Apalachicola sites.

Immobilization of alkaline phosphatase on solid surface through self-assembled monolayer and by active-site protection.

PubMed

Gao, En-Feng; Kang, Kyung Lhi; Kim, Jeong Hee

2014-06-01

Retaining biological activity of a protein after immobilization is an important issue and many studies reported to enhance the activity of proteins after immobilization. We recently developed a new immobilization method of enzyme using active-site protection and minimization of the cross-links between enzyme and surface with a DNA polymerase as a model system. In this study, we extended the new method to an enzyme with a small mono-substrate using alkaline phosphatase (AP) as another model system. A condition to apply the new method is that masking agents, in this case its own substrate needs to stay at the active-site of the enzyme to be immobilized in order to protect the active-site during the harsh immobilization process. This could be achieved by removal of essential divalent ion, Zn2+ that is required for full enzyme activity of AP from the masking solution while active-site of AP was protected with p-nitrophenyl phosphate (pNPP). Approximately 40% of the solution-phase activity was acquired with active-site protected immobilized AP. In addition to protection active-site of AP, the number of immobilization links was kinetically controlled. When the mole fraction of the activated carboxyl group of the linker molecule in self-assembled monolayer (SAM) of 12-mercaptododecanoic acid and 6-mercapto-1-ethanol was varied, 10% of 12-mercaptododecanoic acid gave the maximum enzyme activity. Approximately 51% increase in enzyme activity of the active-site protected AP was observed compared to that of the unprotected group. It was shown that the concept of active-site protection and kinetic control of the number of covalent immobilization bonds can be extended to enzymes with small mono-substrates. It opens the possibility of further extension of the new methods of active-site protection and kinetic control of immobilization bond to important enzymes used in research and industrial fields.

How to Assess the Signature of the Data: Catchments and Aquifers as Input Processing Systems

NASA Astrophysics Data System (ADS)

Lischeid, G.

2010-12-01

It has been argued recently that hydrological models should not only mimic observed data, but should reproduce the signatures of the data appropriately. However, there is no consent how these signatures could be assessed. In general, hydrological models aim at predicting groundwater head dynamics or hydrograph response to input signals (e.g., groundwater recharge, effective rain), based on information about structural properties of the system, like e.g., transmissivity fields, soil hydraulic conductivity, or size of the catchment water storage. That approach usually faces substantial spatial heterogeneities and nonlinear feedbacks. Here, an alternative approach is suggested for characterizing catchments or aquifers as input signal processing systems. The concept was developed for remote areas where direct anthropogenic effects (groundwater withdrawal, injection wells, etc.), plant water uptake and evaporation from groundwater and streams are negligible. Then, any increase of groundwater head or discharge is related to a corresponding input signal, i.e., groundwater recharge or effective rainfall. That signal propagates through the system and is increasingly attenuated and decelerated with increasing flowpath length. This attenuation differs from simple low-pass-filtering. E.g., different input signals propagate at different velocities, depending on rainfall intensity, antecedent soil moisture, etc. The new approach is based on a principal component analysis of time series of groundwater or lake water level, soil water content, or discharge at different sites. This information is used to for assessing the functional properties of the system rather than its structural heterogeneity at different measurement sites, and to assess first order controls on its spatial patterns. Thus, hydrologic measurements provide a mean to measure the functional properties of the system. It is suggested to use this as signatures of the data. In a next step, model structure can be

Polarization signatures of relativistic magnetohydrodynamic shocks in the blazar emission region. I. Force-free helical magnetic fields

DOE PAGES

Zhang, Haocheng; Deng, Wei; Li, Hui; ...

2016-01-20

The optical radiation and polarization signatures in blazars are known to be highly variable during flaring activities. It is frequently argued that shocks are the main driver of the flaring events. However, the spectral variability modelings generally lack detailed considerations of the self-consistent magnetic field evolution modeling; thus, so far the associated optical polarization signatures are poorly understood. We present the first simultaneous modeling of the optical radiation and polarization signatures based on 3D magnetohydrodynamic simulations of relativistic shocks in the blazar emission environment, with the simplest physical assumptions. By comparing the results with observations, we find that shocks inmore » a weakly magnetized environment will largely lead to significant changes in the optical polarization signatures, which are seldom seen in observations. Hence an emission region with relatively strong magnetization is preferred. In such an environment, slow shocks may produce minor flares with either erratic polarization fluctuations or considerable polarization variations, depending on the parameters; fast shocks can produce major flares with smooth polarization angle rotations. In addition, the magnetic fields in both cases are observed to actively revert to the original topology after the shocks. In addition, all these features are consistent with observations. Future observations of the radiation and polarization signatures will further constrain the flaring mechanism and the blazar emission environment.« less

Ultrafast Light-Driven Substrate Expulsion from the Active Site of a Photoswitchable Catalyst.

PubMed

Pescher, Manuel D; van Wilderen, Luuk J G W; Grützner, Susanne; Slavov, Chavdar; Wachtveitl, Josef; Hecht, Stefan; Bredenbeck, Jens

2017-09-25

The photoswitchable piperidine general base catalyst is a prototype structure for light control of catalysis. Its azobenzene moiety moves sterically shielding groups to either protect or expose the active site, thereby changing the basicity and hydrogen-bonding affinity of the compound. The reversible switching dynamics of the catalyst is probed in the infrared spectral range by monitoring hydrogen bond (HB) formation between its active site and methanol (MeOH) as HB donor. Steady-state infrared (IR) and ultrafast IR and UV/Vis spectroscopies are used to uncover ultrafast expulsion of MeOH from the active site within a few picoseconds. Thus, the force generated by the azobenzene moiety even in the final phase of its isomerization is sufficient to break a strong HB within 3 ps and to shut down access to the active site. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Dynamic Perturbation of the Active Site Determines Reversible Thermal Inactivation in Glycoside Hydrolase Family 12.

PubMed

Jiang, Xukai; Li, Wen; Chen, Guanjun; Wang, Lushan

2017-02-27

The temperature dependence of enzyme catalysis is highly debated. Specifically, how high temperatures induce enzyme inactivation has broad implications for both fundamental and applied science. Here, we explored the mechanism of the reversible thermal inactivation in glycoside hydrolase family 12 (GH12) using comparative molecular dynamics simulations. First, we investigated the distribution of structural flexibility over the enzyme and found that the active site was the general thermal-sensitive region in GH12 cellulases. The dynamic perturbation of the active site before enzyme denaturation was explored through principal-component analysis, which indicated that variations in the collective motion and conformational ensemble of the active site may precisely correspond to enzyme transition from its active form to the inactive form. Furthermore, the degree of dynamic perturbation of the active site was found to be negatively correlated with the melting temperatures of GH12 enzymes, further proving the importance of the dynamic stability of the active site. Additionally, analysis of the residue-interaction network revealed that the active site in thermophilic enzyme was capable of forming additional contacts with other amino acids than those observed in the mesophilic enzyme. These interactions are likely the key mechanisms underlying the differences in rigidity of the active site. These findings provide further biophysical insights into the reversible thermal inactivation of enzymes and potential applications in future protein engineering.

A General Quality Classification System for eIDs and e-Signatures

NASA Astrophysics Data System (ADS)

Ølnes, Jon; Buene, Leif; Andresen, Anette; Grindheim, Håvard; Apitzsch, Jörg; Rossi, Adriano

The PEPPOL (Pan-European Public Procurement On-Line) project is a large scale pilot under the CIP programme of the EU, exploring electronic public procurement in a unified European market. Interoperability of electronic signatures across borders is identified as a major obstacle to cross-border procurement. PEPPOL suggests specify-ing signature acceptance criteria in the form of signature policies that must be transparent and non-discriminatory. Validation solutions must then not only assess signature correctness but also signature policy adherence. This paper addresses perhaps the most important topic of a signature policy: Quality of eIDs and e-signatures. Discrete levels are suggested for: eID quality, assurance level for this quality, and for cryptographic quality of signatures.

12 CFR 269b.731 - Signature.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 12 Banks and Banking 3 2010-01-01 2010-01-01 false Signature. 269b.731 Section 269b.731 Banks and Banking FEDERAL RESERVE SYSTEM (CONTINUED) BOARD OF GOVERNORS OF THE FEDERAL RESERVE SYSTEM CHARGES OF UNFAIR LABOR PRACTICES General Rules § 269b.731 Signature. The original of each document filed shall be...

Non-active site mutation (Q123A) in New Delhi metallo-β-lactamase (NDM-1) enhanced its enzyme activity.

PubMed

Ali, Abid; Azam, Mohd W; Khan, Asad U

2018-06-01

New Delhi metallo β-lactamase-1 is one of the carbapenemases, causing hydrolysis of almost all β-lactamase antibiotics. Seventeen different NDM variants have been reported so far, they varied in their sequences either by single or multiple amino acid substitutions. Hence, it is important to understand its structural and functional relation. In the earlier studies role of active site residues has been studied but non-active site residues has not studied in detail. Therefore, we have initiated to further comprehend its structure and function relation by mutating some of its non-active site residues. A laboratory mutant of NDM-1 was generated by PCR-based site-directed mutagenesis, replacing Q to A at 123 position. The MICs of imipenem and meropenem for NDM-1 Q123A were found increased by 2 fold as compare to wild type and so the hydrolytic activity was enhanced (Kcat/Km) as compared to NDM-1 wild type. GOLD fitness scores were also found in favour of kinetics data. Secondary structure for α-helical content was determined by Far-UV circular dichroism (CD), which showed significant conformational changes. We conclude a noteworthy role of non-active-site amino acid residues in the catalytic activity of NDM-1. This study also provides an insight of emergence of new variants through natural evolution. Copyright © 2018 Elsevier B.V. All rights reserved.

DNA methylation analysis of paediatric low-grade astrocytomas identifies a tumour-specific hypomethylation signature in pilocytic astrocytomas.

PubMed

Jeyapalan, Jennie N; Doctor, Gabriel T; Jones, Tania A; Alberman, Samuel N; Tep, Alexander; Haria, Chirag M; Schwalbe, Edward C; Morley, Isabel C F; Hill, Alfred A; LeCain, Magdalena; Ottaviani, Diego; Clifford, Steven C; Qaddoumi, Ibrahim; Tatevossian, Ruth G; Ellison, David W; Sheer, Denise

2016-05-27

Low-grade gliomas (LGGs) account for about a third of all brain tumours in children. We conducted a detailed study of DNA methylation and gene expression to improve our understanding of the biology of pilocytic and diffuse astrocytomas. Pilocytic astrocytomas were found to have a distinctive signature at 315 CpG sites, of which 312 were hypomethylated and 3 were hypermethylated. Genomic analysis revealed that 182 of these sites are within annotated enhancers. The signature was not present in diffuse astrocytomas, or in published profiles of other brain tumours and normal brain tissue. The AP-1 transcription factor was predicted to bind within 200 bp of a subset of the 315 differentially methylated CpG sites; the AP-1 factors, FOS and FOSL1 were found to be up-regulated in pilocytic astrocytomas. We also analysed splice variants of the AP-1 target gene, CCND1, which encodes cell cycle regulator cyclin D1. CCND1a was found to be highly expressed in both pilocytic and diffuse astrocytomas, but diffuse astrocytomas have far higher expression of the oncogenic variant, CCND1b. These findings highlight novel genetic and epigenetic differences between pilocytic and diffuse astrocytoma, in addition to well-described alterations involving BRAF, MYB and FGFR1.

Observational signatures of self-destructive civilizations

NASA Astrophysics Data System (ADS)

Stevens, Adam; Forgan, Duncan; James, Jack O'malley

2016-10-01

We address the possibility that intelligent civilizations that destroy themselves could present signatures observable by humanity. Placing limits on the number of self-destroyed civilizations in the Milky Way has strong implications for the final three terms in Drake's Equation, and would allow us to identify which classes of solution to Fermi's Paradox fit with the evidence (or lack thereof). Using the Earth as an example, we consider a variety of scenarios in which humans could extinguish their own technological civilization. Each scenario presents some form of observable signature that could be probed by astronomical campaigns to detect and characterize extrasolar planetary systems. Some observables are unlikely to be detected at interstellar distances, but some scenarios are likely to produce significant changes in atmospheric composition that could be detected serendipitously with next-generation telescopes. In some cases, the timing of the observation would prove crucial to detection, as the decay of signatures is rapid compared with humanity's communication lifetime. In others, the signatures persist on far longer timescales.

Negative obstacle detection by thermal signature

NASA Technical Reports Server (NTRS)

Matthies, Larry; Rankin, A.

2003-01-01

Detecting negative obstacles (ditches, potholes, and other depressions) is one of the most difficult problems in perception for autonomous, off-road navigation. Past work has largely relied on range imagery, because that is based on the geometry of the obstacle, is largely insensitive to illumination variables, and because there have not been other reliable alternatives. However, the visible aspect of negative obstacles shrinks rapidly with range, making them impossible to detect in time to avoid them at high speed. To relive this problem, we show that the interiors of negative obstacles generally remain warmer than the surrounding terrain throughout the night, making thermal signature a stable property for night-time negative obstacle detection. Experimental results to date have achieved detection distances 45% greater by using thermal signature than by using range data alone. Thermal signature is the first known observable with potential to reveal a deep negative obstacle without actually seeing far into it. Modeling solar illumination has potential to extend the usefulness of thermal signature through daylight hours.

Multiple active site residues are important for photochemical efficiency in the light-activated enzyme protochlorophyllide oxidoreductase (POR).

PubMed

Menon, Binuraj R K; Hardman, Samantha J O; Scrutton, Nigel S; Heyes, Derren J

2016-08-01

Protochlorophyllide oxidoreductase (POR) catalyzes the light-driven reduction of protochlorophyllide (Pchlide), an essential, regulatory step in chlorophyll biosynthesis. The unique requirement of the enzyme for light has provided the opportunity to investigate how light energy can be harnessed to power biological catalysis and enzyme dynamics. Excited state interactions between the Pchlide molecule and the protein are known to drive the subsequent reaction chemistry. However, the structural features of POR and active site residues that are important for photochemistry and catalysis are currently unknown, because there is no crystal structure for POR. Here, we have used static and time-resolved spectroscopic measurements of a number of active site variants to study the role of a number of residues, which are located in the proposed NADPH/Pchlide binding site based on previous homology models, in the reaction mechanism of POR. Our findings, which are interpreted in the context of a new improved structural model, have identified several residues that are predicted to interact with the coenzyme or substrate. Several of the POR variants have a profound effect on the photochemistry, suggesting that multiple residues are important in stabilizing the excited state required for catalysis. Our work offers insight into how the POR active site geometry is finely tuned by multiple active site residues to support enzyme-mediated photochemistry and reduction of Pchlide, both of which are crucial to the existence of life on Earth. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

Heterogeneous Electrocatalyst with Molecular Cobalt Ions Serving as the Center of Active Sites.

PubMed

Wang, Jiong; Ge, Xiaoming; Liu, Zhaolin; Thia, Larissa; Yan, Ya; Xiao, Wei; Wang, Xin

2017-02-08

Molecular Co 2+ ions were grafted onto doped graphene in a coordination environment, resulting in the formation of molecularly well-defined, highly active electrocatalytic sites at a heterogeneous interface for the oxygen evolution reaction (OER). The S dopants of graphene are suggested to be one of the binding sites and to be responsible for improving the intrinsic activity of the Co sites. The turnover frequency of such Co sites is greater than that of many Co-based nanostructures and IrO 2 catalysts. Through a series of carefully designed experiments, the pathway for the evolution of the Co cation-based molecular catalyst for the OER was further demonstrated on such a single Co-ion site for the first time. The Co 2+ ions were successively oxidized to Co 3+ and Co 4+ states prior to the OER. The sequential oxidation was coupled with the transfer of different numbers of protons/hydroxides and generated an active Co 4+ ═O fragment. A side-on hydroperoxo ligand of the Co 4+ site is proposed as a key intermediate for the formation of dioxygen.

Criticality meets learning: Criticality signatures in a self-organizing recurrent neural network

PubMed Central

Del Papa, Bruno; Priesemann, Viola

2017-01-01

Many experiments have suggested that the brain operates close to a critical state, based on signatures of criticality such as power-law distributed neuronal avalanches. In neural network models, criticality is a dynamical state that maximizes information processing capacities, e.g. sensitivity to input, dynamical range and storage capacity, which makes it a favorable candidate state for brain function. Although models that self-organize towards a critical state have been proposed, the relation between criticality signatures and learning is still unclear. Here, we investigate signatures of criticality in a self-organizing recurrent neural network (SORN). Investigating criticality in the SORN is of particular interest because it has not been developed to show criticality. Instead, the SORN has been shown to exhibit spatio-temporal pattern learning through a combination of neural plasticity mechanisms and it reproduces a number of biological findings on neural variability and the statistics and fluctuations of synaptic efficacies. We show that, after a transient, the SORN spontaneously self-organizes into a dynamical state that shows criticality signatures comparable to those found in experiments. The plasticity mechanisms are necessary to attain that dynamical state, but not to maintain it. Furthermore, onset of external input transiently changes the slope of the avalanche distributions – matching recent experimental findings. Interestingly, the membrane noise level necessary for the occurrence of the criticality signatures reduces the model’s performance in simple learning tasks. Overall, our work shows that the biologically inspired plasticity and homeostasis mechanisms responsible for the SORN’s spatio-temporal learning abilities can give rise to criticality signatures in its activity when driven by random input, but these break down under the structured input of short repeating sequences. PMID:28552964

Does Twitter trigger bursts in signature collections?

PubMed

Yamaguchi, Rui; Imoto, Seiya; Kami, Masahiro; Watanabe, Kenji; Miyano, Satoru; Yuji, Koichiro

2013-01-01

The quantification of social media impacts on societal and political events is a difficult undertaking. The Japanese Society of Oriental Medicine started a signature-collecting campaign to oppose a medical policy of the Government Revitalization Unit to exclude a traditional Japanese medicine, "Kampo," from the public insurance system. The signature count showed a series of aberrant bursts from November 26 to 29, 2009. In the same interval, the number of messages on Twitter including the keywords "Signature" and "Kampo," increased abruptly. Moreover, the number of messages on an Internet forum that discussed the policy and called for signatures showed a train of spikes. In order to estimate the contributions of social media, we developed a statistical model with state-space modeling framework that distinguishes the contributions of multiple social media in time-series of collected public opinions. We applied the model to the time-series of signature counts of the campaign and quantified contributions of two social media, i.e., Twitter and an Internet forum, by the estimation. We found that a considerable portion (78%) of the signatures was affected from either of the social media throughout the campaign and the Twitter effect (26%) was smaller than the Forum effect (52%) in total, although Twitter probably triggered the initial two bursts of signatures. Comparisons of the estimated profiles of the both effects suggested distinctions between the social media in terms of sustainable impact of messages or tweets. Twitter shows messages on various topics on a time-line; newer messages push out older ones. Twitter may diminish the impact of messages that are tweeted intermittently. The quantification of social media impacts is beneficial to better understand people's tendency and may promote developing strategies to engage public opinions effectively. Our proposed method is a promising tool to explore information hidden in social phenomena.

Chemical and Physical Signatures for Microbial Forensics

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

Cliff, John B.; Kreuzer, Helen W.; Ehrhardt, Christopher J.

Chemical and physical signatures for microbial forensics John Cliff and Helen Kreuzer-Martin, eds. Humana Press Chapter 1. Introduction: Review of history and statement of need. Randy Murch, Virginia Tech Chapter 2. The Microbe: Structure, morphology, and physiology of the microbe as they relate to potential signatures of growth conditions. Joany Jackman, Johns Hopkins University Chapter 3. Science for Forensics: Special considerations for the forensic arena - quality control, sample integrity, etc. Mark Wilson (retired FBI): Western Carolina University Chapter 4. Physical signatures: Light and electron microscopy, atomic force microscopy, gravimetry etc. Joseph Michael, Sandia National Laboratory Chapter 5. Lipids: FAME,more » PLFA, steroids, LPS, etc. James Robertson, Federal Bureau of Investigation Chapter 6. Carbohydrates: Cell wall components, cytoplasm components, methods Alvin Fox, University of South Carolina School of Medicine David Wunschel, Pacific Northwest National Laboratory Chapter 7. Peptides: Peptides, proteins, lipoproteins David Wunschel, Pacific Northwest National Laboratory Chapter 8. Elemental content: CNOHPS (treated in passing), metals, prospective cell types John Cliff, International Atomic Energy Agency Chapter 9. Isotopic signatures: Stable isotopes C,N,H,O,S, 14C dating, potential for heavy elements. Helen Kreuzer-Martin, Pacific Northwest National Laboratory Michaele Kashgarian, Lawrence Livermore National Laboratory Chapter 10. Extracellular signatures: Cellular debris, heme, agar, headspace, spent media, etc Karen Wahl, Pacific Northwest National Laboratory Chapter 11. Data Reduction and Integrated Microbial Forensics: Statistical concepts, parametric and multivariate statistics, integrating signatures Kristin Jarman, Pacific Northwest National Laboratory« less

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.

Catalysis-dependent selenium incorporation and migration in the nitrogenase active site iron-molybdenum cofactor.

PubMed

Spatzal, Thomas; Perez, Kathryn A; Howard, James B; Rees, Douglas C

2015-12-16

Dinitrogen reduction in the biological nitrogen cycle is catalyzed by nitrogenase, a two-component metalloenzyme. Understanding of the transformation of the inert resting state of the active site FeMo-cofactor into an activated state capable of reducing dinitrogen remains elusive. Here we report the catalysis dependent, site-selective incorporation of selenium into the FeMo-cofactor from selenocyanate as a newly identified substrate and inhibitor. The 1.60 Å resolution structure reveals selenium occupying the S2B site of FeMo-cofactor in the Azotobacter vinelandii MoFe-protein, a position that was recently identified as the CO-binding site. The Se2B-labeled enzyme retains substrate reduction activity and marks the starting point for a crystallographic pulse-chase experiment of the active site during turnover. Through a series of crystal structures obtained at resolutions of 1.32-1.66 Å, including the CO-inhibited form of Av1-Se2B, the exchangeability of all three belt-sulfur sites is demonstrated, providing direct insights into unforeseen rearrangements of the metal center during catalysis.

Disaster relief through composite signatures

NASA Astrophysics Data System (ADS)

Hawley, Chadwick T.; Hyde, Brian; Carpenter, Tom; Nichols, Steve

2012-06-01

A composite signature is a group of signatures that are related in such a way to more completely or further define a target or operational endeavor at a higher fidelity. This paper builds on previous work developing innovative composite signatures associated with civil disasters, including physical, chemical and pattern/behavioral. For the composite signature approach to be successful it requires effective data fusion and visualization. This plays a key role in both preparedness and the response and recovery which are critical to saving lives. Visualization tools enhance the overall understanding of the crisis by pulling together and analyzing the data, and providing a clear and complete analysis of the information to the organizations/agencies dependant on it for a successful operation. An example of this, Freedom Web, is an easy-to-use data visualization and collaboration solution for use in homeland security, emergency preparedness, situational awareness, and event management. The solution provides a nationwide common operating picture for all levels of government through a web based, map interface. The tool was designed to be utilized by non-geospatial experts and is easily tailored to the specific needs of the users. Consisting of standard COTS and open source databases and a web server, users can view, edit, share, and highlight information easily and quickly through a standard internet browser.

17 CFR 230.402 - Number of copies; binding; signatures.

Code of Federal Regulations, 2010 CFR

2010-04-01

...; signatures. 230.402 Section 230.402 Commodity and Securities Exchanges SECURITIES AND EXCHANGE COMMISSION...; binding; signatures. (a) Three copies of the complete registration statement, including exhibits and all... bound and may contain facsimile versions of manual signatures in accordance with paragraph (e) of this...

Mutational signatures associated with tobacco smoking in human cancer

DOE PAGES

Alexandrov, Ludmil B.; Ju, Young Seok; Haase, Kerstin; ...

2016-11-04

Tobacco smoking increases the risk of at least 17 classes of cancer. Here, we analyzed somatic mutations and DNA methylation in 5,243 cancers of types for which tobacco smoking confers an elevated risk. Smoking is associated with increased mutation burdens of multiple distinct mutational signatures, which contribute to different extents in different cancers. One of these signatures, mainly found in cancers derived from tissues directly exposed to tobacco smoke, is attributable to misreplication of DNA damage caused by tobacco carcinogens. Others likely reflect indirect activation of DNA edi ting by APOBEC cytidine deaminases and of an endogenous clock-like mutational process.more » Smoking is associated with limited differences in methylation. The results are consistent with the proposition that smoking increases cancer risk by increasing the somatic mutation load, although direct evidence for this mechanism is lacking in some smoking-related cancer types.« less

Mutational signatures associated with tobacco smoking in human cancer

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

Alexandrov, Ludmil B.; Ju, Young Seok; Haase, Kerstin

Tobacco smoking increases the risk of at least 17 classes of cancer. Here, we analyzed somatic mutations and DNA methylation in 5,243 cancers of types for which tobacco smoking confers an elevated risk. Smoking is associated with increased mutation burdens of multiple distinct mutational signatures, which contribute to different extents in different cancers. One of these signatures, mainly found in cancers derived from tissues directly exposed to tobacco smoke, is attributable to misreplication of DNA damage caused by tobacco carcinogens. Others likely reflect indirect activation of DNA edi ting by APOBEC cytidine deaminases and of an endogenous clock-like mutational process.more » Smoking is associated with limited differences in methylation. The results are consistent with the proposition that smoking increases cancer risk by increasing the somatic mutation load, although direct evidence for this mechanism is lacking in some smoking-related cancer types.« less

A sense of embodiment is reflected in people's signature size.

PubMed

Rawal, Adhip; Harmer, Catherine J; Park, Rebecca J; O'Sullivan, Ursula D; Williams, J Mark G

2014-01-01

The size of a person's signature may reveal implicit information about how the self is perceived although this has not been closely examined. We conducted three experiments to test whether increases in signature size can be induced. Specifically, the aim of these experiments was to test whether changes in signature size reflect a person's current implicit sense of embodiment. Experiment 1 showed that an implicit affect task (positive subliminal evaluative conditioning) led to increases in signature size relative to an affectively neutral task, showing that implicit affective cues alter signature size. Experiments 2 and 3 demonstrated increases in signature size following experiential self-focus on sensory and affective stimuli relative to both conceptual self-focus and external (non-self-focus) in both healthy participants and patients with anorexia nervosa, a disorder associated with self-evaluation and a sense of disembodiment. In all three experiments, increases in signature size were unrelated to changes in self-reported mood and larger than manipulation unrelated variations. Together, these findings suggest that a person's sense of embodiment is reflected in their signature size.

Signature detection and matching for document image retrieval.

PubMed

Zhu, Guangyu; Zheng, Yefeng; Doermann, David; Jaeger, Stefan

2009-11-01

As one of the most pervasive methods of individual identification and document authentication, signatures present convincing evidence and provide an important form of indexing for effective document image processing and retrieval in a broad range of applications. However, detection and segmentation of free-form objects such as signatures from clustered background is currently an open document analysis problem. In this paper, we focus on two fundamental problems in signature-based document image retrieval. First, we propose a novel multiscale approach to jointly detecting and segmenting signatures from document images. Rather than focusing on local features that typically have large variations, our approach captures the structural saliency using a signature production model and computes the dynamic curvature of 2D contour fragments over multiple scales. This detection framework is general and computationally tractable. Second, we treat the problem of signature retrieval in the unconstrained setting of translation, scale, and rotation invariant nonrigid shape matching. We propose two novel measures of shape dissimilarity based on anisotropic scaling and registration residual error and present a supervised learning framework for combining complementary shape information from different dissimilarity metrics using LDA. We quantitatively study state-of-the-art shape representations, shape matching algorithms, measures of dissimilarity, and the use of multiple instances as query in document image retrieval. We further demonstrate our matching techniques in offline signature verification. Extensive experiments using large real-world collections of English and Arabic machine-printed and handwritten documents demonstrate the excellent performance of our approaches.

Infrared signature characteristic of a microturbine engine exhaust plume

NASA Astrophysics Data System (ADS)

Gu, Bonchan; Baek, Seung Wook; Jegal, Hyunwook; Choi, Seong Man; Kim, Won Cheol

2017-11-01

This research investigates the infrared signature of the exhaust plume ejected from a microturbine engine. Circular and square nozzles are designed and tested to study their effects on the resultant infrared signature of the plume. A microturbine engine is operated under steady conditions with a kerosene added lubricant oil as a fuel. The measurements of the infrared signature are conducted using a spectroradiometer. Blackbody radiance is also measured at an arbitrary temperature and compared to theoretical values to validate the reference and to calibrate the raw spectrum. The infrared signatures emitted from the plume are measured at three measurement locations along the plume for two nozzle configurations. The results are grouped into sub-bands to examine and discuss their specific spectral characteristics. The infrared signatures are shown to decrease as the distance from the nozzle exit increases, which is attributed to the hot exhaust plume mixing with ambient air. The degree to which the signature is reduced at the different the measurement locations was dependent on the sub-band. Comparison of the results shows that the infrared signature of the square nozzle is lower than that of the circular nozzle in specific bands.

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

Methylation of an alpha-foetoprotein gene intragenic site modulates gene activity.

PubMed Central

Opdecamp, K; Rivière, M; Molné, M; Szpirer, J; Szpirer, C

1992-01-01

By comparing the methylation pattern of Mspl/Hpall sites in the 5' region of the mouse alpha-foetoprotein (AFP) gene of different cells (hepatoma cells, foetal and adult liver, fibroblasts), we found a correlation between gene expression and unmethylation of a site located in the first intron of the gene. Other sites did not show this correlation. In transfection experiments of unmethylated and methylated AFP-CAT chimeric constructions, we then showed that methylation of the intronic site negatively modulates expression of CAT activity. We also found that a DNA segment centered on this site binds nuclear proteins; however methylation did not affect protein binding. Images PMID:1371343

Secure and Efficient Signature Scheme Based on NTRU for Mobile Payment

NASA Astrophysics Data System (ADS)

Xia, Yunhao; You, Lirong; Sun, Zhe; Sun, Zhixin

2017-10-01

Mobile payment becomes more and more popular, however the traditional public-key encryption algorithm has higher requirements for hardware which is not suitable for mobile terminals of limited computing resources. In addition, these public-key encryption algorithms do not have the ability of anti-quantum computing. This paper researches public-key encryption algorithm NTRU for quantum computation through analyzing the influence of parameter q and k on the probability of generating reasonable signature value. Two methods are proposed to improve the probability of generating reasonable signature value. Firstly, increase the value of parameter q. Secondly, add the authentication condition that meet the reasonable signature requirements during the signature phase. Experimental results show that the proposed signature scheme can realize the zero leakage of the private key information of the signature value, and increase the probability of generating the reasonable signature value. It also improve rate of the signature, and avoid the invalid signature propagation in the network, but the scheme for parameter selection has certain restrictions.

Non-contact multi-radar smart probing of body orientation based on micro-Doppler signatures.

PubMed

Li, Yiran; Pal, Ranadip; Li, Changzhi

2014-01-01

Micro-Doppler signatures carry useful information about body movements and have been widely applied to different applications such as human activity recognition and gait analysis. In this paper, micro-Doppler signatures are used to identify body orientation. Four AC-coupled continuous-wave (CW) smart radar sensors were used to form a multiple-radar network to carry out the experiments in this paper. 162 tests were performed in total. The experiment results showed a 100% accuracy in recognizing eight body orientations, i.e., facing north, northeast, east, southeast, south, southwest, west, and northwest.

Analysis of an Indirect Neutron Signature for Enhanced UF6 Cylinder Verification

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

Kulisek, Jonathan A.; McDonald, Benjamin S.; Smith, Leon E.

2017-02-21

The International Atomic Energy Agency (IAEA) currently uses handheld gamma-ray spectrometers combined with ultrasonic wall-thickness gauges to verify the declared enrichment of uranium hexafluoride (UF6) cylinders. The current method provides relatively low accuracy for the assay of 235U enrichment, especially for natural and depleted UF6. Furthermore, the current method provides no capability to assay the absolute mass of 235U in the cylinder due to the localized instrument geometry and limited penetration of the 186-keV gamma-ray signature from 235U. Also, the current verification process is a time-consuming component of on-site inspections at uranium enrichment plants. Toward the goal of a more-capablemore » cylinder assay method, the Pacific Northwest National Laboratory has developed the hybrid enrichment verification array (HEVA). HEVA measures both the traditional 186-keV direct signature and a non-traditional, high-energy neutron-induced signature (HEVANT). HEVANT enables full-volume assay of UF6 cylinders by exploiting the relatively larger mean free paths of the neutrons emitted from the UF6. In this work, Monte Carlo modeling is used as the basis for characterizing HEVANT in terms of the individual contributions to HEVANT from nuclides and hardware components. Monte Carlo modeling is also used to quantify the intrinsic efficiency of HEVA for neutron detection in a cylinder-assay geometry. Modeling predictions are validated against neutron-induced gamma-ray spectra from laboratory measurements and a relatively large population of Type 30B cylinders spanning a range of enrichments. Implications of the analysis and findings on the viability of HEVA for cylinder verification are discussed, such as the resistance of the HEVANT signature to manipulation by the nearby placement of neutron-conversion materials.« less

48 CFR 4.101 - Contracting officer's signature.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 48 Federal Acquisition Regulations System 1 2010-10-01 2010-10-01 false Contracting officer's signature. 4.101 Section 4.101 Federal Acquisition Regulations System FEDERAL ACQUISITION REGULATION GENERAL ADMINISTRATIVE MATTERS Contract Execution 4.101 Contracting officer's signature. Only contracting officers shall...

Distinct plasma immune signatures in ME/CFS are present early in the course of illness.

PubMed

Hornig, Mady; Montoya, José G; Klimas, Nancy G; Levine, Susan; Felsenstein, Donna; Bateman, Lucinda; Peterson, Daniel L; Gottschalk, C Gunnar; Schultz, Andrew F; Che, Xiaoyu; Eddy, Meredith L; Komaroff, Anthony L; Lipkin, W Ian

2015-02-01

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is an unexplained incapacitating illness that may affect up to 4 million people in the United States alone. There are no validated laboratory tests for diagnosis or management despite global efforts to find biomarkers of disease. We considered the possibility that inability to identify such biomarkers reflected variations in diagnostic criteria and laboratory methods as well as the timing of sample collection during the course of the illness. Accordingly, we leveraged two large, multicenter cohort studies of ME/CFS to assess the relationship of immune signatures with diagnosis, illness duration, and other clinical variables. Controls were frequency-matched on key variables known to affect immune status, including season of sampling and geographic site, in addition to age and sex. We report here distinct alterations in plasma immune signatures early in the course of ME/CFS ( n = 52) relative to healthy controls ( n = 348) that are not present in subjects with longer duration of illness ( n = 246). Analyses based on disease duration revealed that early ME/CFS cases had a prominent activation of both pro- and anti-inflammatory cytokines as well as dissociation of intercytokine regulatory networks. We found a stronger correlation of cytokine alterations with illness duration than with measures of illness severity, suggesting that the immunopathology of ME/CFS is not static. These findings have critical implications for discovery of interventional strategies and early diagnosis of ME/CFS.

Distinct plasma immune signatures in ME/CFS are present early in the course of illness

PubMed Central

Hornig, Mady; Montoya, José G.; Klimas, Nancy G.; Levine, Susan; Felsenstein, Donna; Bateman, Lucinda; Peterson, Daniel L.; Gottschalk, C. Gunnar; Schultz, Andrew F.; Che, Xiaoyu; Eddy, Meredith L.; Komaroff, Anthony L.; Lipkin, W. Ian

2015-01-01

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is an unexplained incapacitating illness that may affect up to 4 million people in the United States alone. There are no validated laboratory tests for diagnosis or management despite global efforts to find biomarkers of disease. We considered the possibility that inability to identify such biomarkers reflected variations in diagnostic criteria and laboratory methods as well as the timing of sample collection during the course of the illness. Accordingly, we leveraged two large, multicenter cohort studies of ME/CFS to assess the relationship of immune signatures with diagnosis, illness duration, and other clinical variables. Controls were frequency-matched on key variables known to affect immune status, including season of sampling and geographic site, in addition to age and sex. We report here distinct alterations in plasma immune signatures early in the course of ME/CFS (n = 52) relative to healthy controls (n = 348) that are not present in subjects with longer duration of illness (n = 246). Analyses based on disease duration revealed that early ME/CFS cases had a prominent activation of both pro- and anti-inflammatory cytokines as well as dissociation of intercytokine regulatory networks. We found a stronger correlation of cytokine alterations with illness duration than with measures of illness severity, suggesting that the immunopathology of ME/CFS is not static. These findings have critical implications for discovery of interventional strategies and early diagnosis of ME/CFS. PMID:26079000

Rapid comparison of protein binding site surfaces with Property Encoded Shape Distributions (PESD)

PubMed Central

Das, Sourav; Kokardekar, Arshad

2009-01-01

Patterns in shape and property distributions on the surface of binding sites are often conserved across functional proteins without significant conservation of the underlying amino-acid residues. To explore similarities of these sites from the viewpoint of a ligand, a sequence and fold-independent method was created to rapidly and accurately compare binding sites of proteins represented by property-mapped triangulated Gauss-Connolly surfaces. Within this paradigm, signatures for each binding site surface are produced by calculating their property-encoded shape distributions (PESD), a measure of the probability that a particular property will be at a specific distance to another on the molecular surface. Similarity between the signatures can then be treated as a measure of similarity between binding sites. As postulated, the PESD method rapidly detected high levels of similarity in binding site surface characteristics even in cases where there was very low similarity at the sequence level. In a screening experiment involving each member of the PDBBind 2005 dataset as a query against the rest of the set, PESD was able to retrieve a binding site with identical E.C. (Enzyme Commission) numbers as the top match in 79.5% of cases. The ability of the method in detecting similarity in binding sites with low sequence conservations were compared with state-of-the-art binding site comparison methods. PMID:19919089

37 CFR 2.74 - Form and signature of amendment.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 37 Patents, Trademarks, and Copyrights 1 2010-07-01 2010-07-01 false Form and signature of... signature of amendment. (a) Form of Amendment. Amendments should be set forth clearly and completely... record. (b) Signature. A request for amendment of an application must be signed by the applicant, someone...

Starry messages: Searching for signatures of interstellar archaeology

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