An Optimized Set of Fluorescence In Situ Hybridization Probes for Detection of Pancreatobiliary Tract Cancer in Cytology Brush Samples.

PubMed

Barr Fritcher, Emily G; Voss, Jesse S; Brankley, Shannon M; Campion, Michael B; Jenkins, Sarah M; Keeney, Matthew E; Henry, Michael R; Kerr, Sarah M; Chaiteerakij, Roongruedee; Pestova, Ekaterina V; Clayton, Amy C; Zhang, Jun; Roberts, Lewis R; Gores, Gregory J; Halling, Kevin C; Kipp, Benjamin R

2015-12-01

Pancreatobiliary cancer is detected by fluorescence in situ hybridization (FISH) of pancreatobiliary brush samples with UroVysion probes, originally designed to detect bladder cancer. We designed a set of new probes to detect pancreatobiliary cancer and compared its performance with that of UroVysion and routine cytology analysis. We tested a set of FISH probes on tumor tissues (cholangiocarcinoma or pancreatic carcinoma) and non-tumor tissues from 29 patients. We identified 4 probes that had high specificity for tumor vs non-tumor tissues; we called this set of probes pancreatobiliary FISH. We performed a retrospective analysis of brush samples from 272 patients who underwent endoscopic retrograde cholangiopancreatography for evaluation of malignancy at the Mayo Clinic; results were available from routine cytology and FISH with UroVysion probes. Archived residual specimens were retrieved and used to evaluate the pancreatobiliary FISH probes. Cutoff values for FISH with the pancreatobiliary probes were determined using 89 samples and validated in the remaining 183 samples. Clinical and pathologic evidence of malignancy in the pancreatobiliary tract within 2 years of brush sample collection was used as the standard; samples from patients without malignancies were used as negative controls. The validation cohort included 85 patients with malignancies (46.4%) and 114 patients with primary sclerosing cholangitis (62.3%). Samples containing cells above the cutoff for polysomy (copy number gain of ≥2 probes) were classified as positive in FISH with the UroVysion and pancreatobiliary probes. Multivariable logistic regression was used to estimate associations between clinical and pathology findings and results from FISH. The combination of FISH probes 1q21, 7p12, 8q24, and 9p21 identified cancer cells with 93% sensitivity and 100% specificity in pancreatobiliary tissue samples and were therefore included in the pancreatobiliary probe set. In the validation cohort of brush samples, pancreatobiliary FISH identified samples from patients with malignancy with a significantly higher level of sensitivity (64.7%) than the UroVysion probes (45.9%) (P < .001) or routine cytology analysis (18.8%) (P < .001), but similar specificity (92.9%, 90.8%, and 100.0% respectively). Factors significantly associated with detection of carcinoma, in adjusted analyses, included detection of polysomy by pancreatobiliary FISH (P < .001), a mass by cross-sectional imaging (P < .001), cancer cells by routine cytology (overall P = .003), as well as absence of primary sclerosing cholangitis (P = .011). We identified a set of FISH probes that detects cancer cells in pancreatobiliary brush samples from patients with and without primary sclerosing cholangitis with higher levels of sensitivity than UroVysion probes. Cytologic brushing test results and clinical features were independently associated with detection of cancer and might be used to identify patients with pancreatobiliary cancers. Copyright © 2015 AGA Institute. Published by Elsevier Inc. All rights reserved.

High-throughput flow alignment of barcoded hydrogel microparticles†

PubMed Central

Chapin, Stephen C.; Pregibon, Daniel C.

2010-01-01

Suspension (particle-based) arrays offer several advantages over conventional planar arrays in the detection and quantification of biomolecules, including the use of smaller sample volumes, more favorable probe-target binding kinetics, and rapid probe-set modification. We present a microfluidic system for the rapid alignment of multifunctional hydrogel microparticles designed to bear one or several biomolecule probe regions, as well as a graphical code to identify the embedded probes. Using high-speed imaging, we have developed and optimized a flow-through system that (1) allows for a high particle throughput, (2) ensures proper particle alignment for decoding and target quantification, and (3) can be reliably operated continuously without clogging. A tapered channel flanked by side focusing streams is used to orient the flexible, tablet-shaped particles into a well-ordered flow in the center of the channel. The effects of channel geometry, particle geometry, particle composition, particle loading density, and barcode design are explored to determine the best combination for eventual use in biological assays. Particles in the optimized system move at velocities of ~50 cm s−1 and with throughputs of ~40 particles s−1. Simple physical models and CFD simulations have been used to investigate flow behavior in the device. PMID:19823726

Evaluation of fluorophores for optimal performance in localization-based super-resolution imaging

PubMed Central

Dempsey, Graham T.; Vaughan, Joshua C.; Chen, Kok Hao; Bates, Mark; Zhuang, Xiaowei

2011-01-01

One approach to super-resolution fluorescence imaging uses sequential activation and localization of individual fluorophores to achieve high spatial resolution. Essential to this technique is the choice of fluorescent probes — the properties of the probes, including photons per switching event, on/off duty cycle, photostability, and number of switching cycles, largely dictate the quality of super-resolution images. While many probes have been reported, a systematic characterization of the properties of these probes and their impact on super-resolution image quality has been described in only a few cases. Here, we quantitatively characterized the switching properties of 26 organic dyes and directly related these properties to the quality of super-resolution images. This analysis provides a set of guidelines for characterization of super-resolution probes and a resource for selecting probes based on performance. Our evaluation identified several photoswitchable dyes with good to excellent performance in four independent spectral ranges, with which we demonstrated low crosstalk, four-color super-resolution imaging. PMID:22056676

Flow quality experiment in a tandem nozzle wind tunnel at Mach 3

NASA Astrophysics Data System (ADS)

Wu, Jie; Zamre, Pradip; Radespiel, Rolf

2015-01-01

In this study, the disturbance characterization and flow quality improvement of a newly designed Tandem Nozzle Mach 3 Wind Tunnel are presented. Firstly, a combined modal analysis is conducted to characterize the freestream disturbances with initial set-up of the settling chamber by using a Pitot probe and a hot-wire anemometry. Then, disturbance reduction in the supersonic wind tunnel is investigated by inserting various damping materials into the settling chamber, while a Pitot probe instrumented with Kulite sensor is employed to monitor the variation of the Pitot pressure fluctuation in the test section. Eventually, an optimized configuration of the settling chamber is determined by a combination of certain damping materials. Afterward, the freestream disturbances are re-characterized with the optimized set-up of the settling chamber, and the disturbance level is found to be significantly reduced. Through this study, valuable experience has been acquired for the disturbance reduction in tandem nozzle type supersonic wind tunnel for the first time, which enhances the feasibility of extending the operation range of conventional hypersonic Ludwieg tubes.

A Java-based tool for the design of classification microarrays.

PubMed

Meng, Da; Broschat, Shira L; Call, Douglas R

2008-08-04

Classification microarrays are used for purposes such as identifying strains of bacteria and determining genetic relationships to understand the epidemiology of an infectious disease. For these cases, mixed microarrays, which are composed of DNA from more than one organism, are more effective than conventional microarrays composed of DNA from a single organism. Selection of probes is a key factor in designing successful mixed microarrays because redundant sequences are inefficient and limited representation of diversity can restrict application of the microarray. We have developed a Java-based software tool, called PLASMID, for use in selecting the minimum set of probe sequences needed to classify different groups of plasmids or bacteria. The software program was successfully applied to several different sets of data. The utility of PLASMID was illustrated using existing mixed-plasmid microarray data as well as data from a virtual mixed-genome microarray constructed from different strains of Streptococcus. Moreover, use of data from expression microarray experiments demonstrated the generality of PLASMID. In this paper we describe a new software tool for selecting a set of probes for a classification microarray. While the tool was developed for the design of mixed microarrays-and mixed-plasmid microarrays in particular-it can also be used to design expression arrays. The user can choose from several clustering methods (including hierarchical, non-hierarchical, and a model-based genetic algorithm), several probe ranking methods, and several different display methods. A novel approach is used for probe redundancy reduction, and probe selection is accomplished via stepwise discriminant analysis. Data can be entered in different formats (including Excel and comma-delimited text), and dendrogram, heat map, and scatter plot images can be saved in several different formats (including jpeg and tiff). Weights generated using stepwise discriminant analysis can be stored for analysis of subsequent experimental data. Additionally, PLASMID can be used to construct virtual microarrays with genomes from public databases, which can then be used to identify an optimal set of probes.

Setting up a probe based, closed tube real-time PCR assay for focused detection of variable sequence alterations.

PubMed

Becságh, Péter; Szakács, Orsolya

2014-10-01

During diagnostic workflow when detecting sequence alterations, sometimes it is important to design an algorithm that includes screening and direct tests in combination. Normally the use of direct test, which is mainly sequencing, is limited. There is an increased need for effective screening tests, with "closed tube" during the whole process and therefore decreasing the risk of PCR product contamination. The aim of this study was to design such a closed tube, detection probe based screening assay to detect different kind of sequence alterations in the exon 11 of the human c-kit gene region. Inside this region there are variable possible deletions and single nucleotide changes. During assay setup, more probe chemistry formats were screened and tested. After some optimization steps the taqman probe format was selected.

Noise of a superconducting magnetic flux sensor based on a proximity Josephson junction.

PubMed

Jabdaraghi, R N; Golubev, D S; Pekola, J P; Peltonen, J T

2017-08-14

We demonstrate simultaneous measurements of DC transport properties and flux noise of a hybrid superconducting magnetometer based on the proximity effect (superconducting quantum interference proximity transistor, SQUIPT). The noise is probed by a cryogenic amplifier operating in the frequency range of a few MHz. In our non-optimized device, we achieve minimum flux noise ~4 μΦ 0 /Hz 1/2 , set by the shot noise of the probe tunnel junction. The flux noise performance can be improved by further optimization of the SQUIPT parameters, primarily minimization of the proximity junction length and cross section. Furthermore, the experiment demonstrates that the setup can be used to investigate shot noise in other nonlinear devices with high impedance. This technique opens the opportunity to measure sensitive magnetometers including SQUIPT devices with very low dissipation.

Entangling measurements for multiparameter estimation with two qubits

NASA Astrophysics Data System (ADS)

Roccia, Emanuele; Gianani, Ilaria; Mancino, Luca; Sbroscia, Marco; Somma, Fabrizia; Genoni, Marco G.; Barbieri, Marco

2018-01-01

Careful tailoring the quantum state of probes offers the capability of investigating matter at unprecedented precisions. Rarely, however, the interaction with the sample is fully encompassed by a single parameter, and the information contained in the probe needs to be partitioned on multiple parameters. There exist, then, practical bounds on the ultimate joint-estimation precision set by the unavailability of a single optimal measurement for all parameters. Here, we discuss how these considerations are modified for two-level quantum probes — qubits — by the use of two copies and entangling measurements. We find that the joint estimation of phase and phase diffusion benefits from such collective measurement, while for multiple phases no enhancement can be observed. We demonstrate this in a proof-of-principle photonics setup.

A magnetic nanobead-based bioassay provides sensitive detection of single- and biplex bacterial DNA using a portable AC susceptometer

PubMed Central

Strömberg, Mattias; Zardán Gómez de la Torre, Teresa; Nilsson, Mats; Svedlindh, Peter; Strømme, Maria

2014-01-01

Bioassays relying on magnetic read-out using probe-tagged magnetic nanobeads are potential platforms for low-cost biodiagnostic devices for pathogen detection. For optimal assay performance it is crucial to apply an easy, efficient and robust bead-probe conjugation protocol. In this paper, sensitive (1.5 pM) singleplex detection of bacterial DNA sequences is demonstrated in a portable AC susceptometer by a magnetic nanobead-based bioassay principle; the volume-amplified magnetic nanobead detection assay (VAM-NDA). Two bead sizes, 100 and 250 nm, are investigated along with a highly efficient, rapid, robust, and stable conjugation chemistry relying on the avidin–biotin interaction for bead-probe attachment. Avidin-biotin conjugation gives easy control of the number of detection probes per bead; thus allowing for systematic investigation of the impact of varying the detection probe surface coverage upon bead immobilization in rolling circle amplified DNA-coils. The existence of an optimal surface coverage is discussed. Biplex VAM-NDA detection is for the first time demonstrated in the susceptometer: Semi-quantitative results are obtained and it is concluded that the concentration of DNA-coils in the incubation volume is of crucial importance for target quantification. The present findings bring the development of commercial biodiagnostic devices relying on the VAM–NDA further towards implementation in point-of-care and outpatient settings. PMID:24174315

Thermodynamically optimal whole-genome tiling microarray design and validation.

PubMed

Cho, Hyejin; Chou, Hui-Hsien

2016-06-13

Microarray is an efficient apparatus to interrogate the whole transcriptome of species. Microarray can be designed according to annotated gene sets, but the resulted microarrays cannot be used to identify novel transcripts and this design method is not applicable to unannotated species. Alternatively, a whole-genome tiling microarray can be designed using only genomic sequences without gene annotations, and it can be used to detect novel RNA transcripts as well as known genes. The difficulty with tiling microarray design lies in the tradeoff between probe-specificity and coverage of the genome. Sequence comparison methods based on BLAST or similar software are commonly employed in microarray design, but they cannot precisely determine the subtle thermodynamic competition between probe targets and partially matched probe nontargets during hybridizations. Using the whole-genome thermodynamic analysis software PICKY to design tiling microarrays, we can achieve maximum whole-genome coverage allowable under the thermodynamic constraints of each target genome. The resulted tiling microarrays are thermodynamically optimal in the sense that all selected probes share the same melting temperature separation range between their targets and closest nontargets, and no additional probes can be added without violating the specificity of the microarray to the target genome. This new design method was used to create two whole-genome tiling microarrays for Escherichia coli MG1655 and Agrobacterium tumefaciens C58 and the experiment results validated the design.

Real-time PCR detection of Vibrio vulnificus in oysters: comparison of oligonucleotide primers and probes targeting vvhA.

PubMed

Panicker, Gitika; Bej, Asim K

2005-10-01

We compared three sets of oligonucleotide primers and two probes designed for Vibrio vulnificus hemolysin A gene (vvhA) for TaqMan-based real-time PCR method enabling specific detection of Vibrio vulnificus in oysters. Two of three sets of primers with a probe were specific for the detection of all 81 V. vulnificus isolates by TaqMan PCR. The 25 nonvibrio and 12 other vibrio isolates tested were negative. However, the third set of primers, F-vvh1059 and R-vvh1159, with the P-vvh1109 probe, although positive for all V. vulnificus isolates, also exhibited positive cycle threshold (C(T)) values for other Vibrio spp. Optimization of the TaqMan PCR assay using F-vvh785/R-vvh990 or F-vvh731/R-vvh1113 primers and the P-vvh874 probe detected 1 pg of purified DNA and 10(3) V. vulnificus CFU/ml in pure cultures. The enriched oyster tissue homogenate did not exhibit detectable inhibition to the TaqMan PCR amplification of vvhA. Detection of 3 x 10(3) CFU V. vulnificus, resulting from a 5-h enrichment of an initial inoculum of 1 CFU/g of oyster tissue homogenate, was achieved with F-vvh785/R-vvh990 or F-vvh731/R-vvh1113 primers and P-vvh875 probe. The application of the TaqMan PCR using these primers and probe, exhibited detection of V. vulnificus on 5-h-enriched natural oysters harvested from the Gulf of Mexico. Selection of appropriate primers and a probe on vvhA for TaqMan-PCR-based detection of V. vulnificus in post-harvest-treated oysters would help avoid false-positive results, thus ensuring a steady supply of safe oysters to consumers and reducing V. vulnificus-related illnesses and deaths.

Additive Manufacture (3D Printing) of Plasma Diagnostic Components and Assemblies for Fusion Experiments

NASA Astrophysics Data System (ADS)

Quinley, Morgan; Chun, Katherine; Melnik, Paul; Sieck, Paul; Smith, Trevor; Stuber, James; Woodruff, Simon; Romero-Talamas, Carlos; Rivera, William; Card, Alexander

2016-10-01

We are investigating the potential impact of additive manufacturing (3D printing) on the cost and complexity of plasma diagnostics. We present a survey of the current state-of-the-art in additive manufacture of metals, as well as the design of diagnostic components that have been optimized for and take advantage of these processes. Included among these is a set of retarding field analyzer probe heads that have been printed in tungsten with internal heat sinks and cooling channels. Finite element analysis of these probe heads shows the potential for a 750K reduction in peak temperature, allowing the probe to take data twice as often without melting. Results of the evaluation of these probe heads for mechanical strength and outgassing, as well as their use on Alcator C-Mod will be presented. Supported by DOE SBIR Grant DE-SC0011858.

Antenna Near-Field Probe Station Scanner

NASA Technical Reports Server (NTRS)

Darby, William G. (Inventor); Miranda, Felix A. (Inventor); Zaman, Afroz J. (Inventor); Lee, Richard Q. (Inventor); Barr, Philip J. (Inventor); Lambert, Kevin M (Inventor)

2011-01-01

A miniaturized antenna system is characterized non-destructively through the use of a scanner that measures its near-field radiated power performance. When taking measurements, the scanner can be moved linearly along the x, y and z axis, as well as rotationally relative to the antenna. The data obtained from the characterization are processed to determine the far-field properties of the system and to optimize the system. Each antenna is excited using a probe station system while a scanning probe scans the space above the antenna to measure the near field signals. Upon completion of the scan, the near-field patterns are transformed into far-field patterns. Along with taking data, this system also allows for extensive graphing and analysis of both the near-field and far-field data. The details of the probe station as well as the procedures for setting up a test, conducting a test, and analyzing the resulting data are also described.

Boronate-Based Fluorescent Probes: Imaging Hydrogen Peroxide in Living Systems

PubMed Central

Lin, Vivian S.; Dickinson, Bryan C.; Chang, Christopher J.

2014-01-01

Hydrogen peroxide, a reactive oxygen species with unique chemical properties, is produced endogenously in living systems as a destructive oxidant to ward off pathogens or as a finely tuned second messenger in dynamic cellular signaling pathways. In order to understand the complex roles that hydrogen peroxide can play in biological systems, new tools to monitor hydrogen peroxide in its native settings, with high selectivity and sensitivity, are needed. Knowledge of organic synthetic reactivity provides the foundation for the molecular design of selective, functional hydrogen peroxide probes. A palette of fluorescent and luminescent probes that react chemoselectively with hydrogen peroxide has been developed, utilizing a boronate oxidation trigger. These indicators offer a variety of colors and in cellulo characteristics and have been used to examine hydrogen peroxide in a number of experimental setups, including in vitro fluorometry, confocal fluorescence microscopy, and flow cytometry. In this chapter, we provide an overview of the chemical features of these probes and information on their behavior to help researchers select the optimal probe and application. PMID:23791092

Polarization-controlled optimal scatter suppression in transient absorption spectroscopy

PubMed Central

Malý, Pavel; Ravensbergen, Janneke; Kennis, John T. M.; van Grondelle, Rienk; Croce, Roberta; Mančal, Tomáš; van Oort, Bart

2017-01-01

Ultrafast transient absorption spectroscopy is a powerful technique to study fast photo-induced processes, such as electron, proton and energy transfer, isomerization and molecular dynamics, in a diverse range of samples, including solid state materials and proteins. Many such experiments suffer from signal distortion by scattered excitation light, in particular close to the excitation (pump) frequency. Scattered light can be effectively suppressed by a polarizer oriented perpendicular to the excitation polarization and positioned behind the sample in the optical path of the probe beam. However, this introduces anisotropic polarization contributions into the recorded signal. We present an approach based on setting specific polarizations of the pump and probe pulses, combined with a polarizer behind the sample. Together, this controls the signal-to-scatter ratio (SSR), while maintaining isotropic signal. We present SSR for the full range of polarizations and analytically derive the optimal configuration at angles of 40.5° between probe and pump and of 66.9° between polarizer and pump polarizations. This improves SSR by (or compared to polarizer parallel to probe). The calculations are validated by transient absorption experiments on the common fluorescent dye Rhodamine B. This approach provides a simple method to considerably improve the SSR in transient absorption spectroscopy. PMID:28262765

Evolutionary computation applied to the reconstruction of 3-D surface topography in the SEM.

PubMed

Kodama, Tetsuji; Li, Xiaoyuan; Nakahira, Kenji; Ito, Dai

2005-10-01

A genetic algorithm has been applied to the line profile reconstruction from the signals of the standard secondary electron (SE) and/or backscattered electron detectors in a scanning electron microscope. This method solves the topographical surface reconstruction problem as one of combinatorial optimization. To extend this optimization approach for three-dimensional (3-D) surface topography, this paper considers the use of a string coding where a 3-D surface topography is represented by a set of coordinates of vertices. We introduce the Delaunay triangulation, which attains the minimum roughness for any set of height data to capture the fundamental features of the surface being probed by an electron beam. With this coding, the strings are processed with a class of hybrid optimization algorithms that combine genetic algorithms and simulated annealing algorithms. Experimental results on SE images are presented.

Comparison of the Predictive Accuracy of DNA Array-Based Multigene Classifiers across cDNA Arrays and Affymetrix GeneChips

PubMed Central

Stec, James; Wang, Jing; Coombes, Kevin; Ayers, Mark; Hoersch, Sebastian; Gold, David L.; Ross, Jeffrey S; Hess, Kenneth R.; Tirrell, Stephen; Linette, Gerald; Hortobagyi, Gabriel N.; Symmans, W. Fraser; Pusztai, Lajos

2005-01-01

We examined how well differentially expressed genes and multigene outcome classifiers retain their class-discriminating values when tested on data generated by different transcriptional profiling platforms. RNA from 33 stage I-III breast cancers was hybridized to both Affymetrix GeneChip and Millennium Pharmaceuticals cDNA arrays. Only 30% of all corresponding gene expression measurements on the two platforms had Pearson correlation coefficient r ≥ 0.7 when UniGene was used to match probes. There was substantial variation in correlation between different Affymetrix probe sets matched to the same cDNA probe. When cDNA and Affymetrix probes were matched by basic local alignment tool (BLAST) sequence identity, the correlation increased substantially. We identified 182 genes in the Affymetrix and 45 in the cDNA data (including 17 common genes) that accurately separated 91% of cases in supervised hierarchical clustering in each data set. Cross-platform testing of these informative genes resulted in lower clustering accuracy of 45 and 79%, respectively. Several sets of accurate five-gene classifiers were developed on each platform using linear discriminant analysis. The best 100 classifiers showed average misclassification error rate of 2% on the original data that rose to 19.5% when tested on data from the other platform. Random five-gene classifiers showed misclassification error rate of 33%. We conclude that multigene predictors optimized for one platform lose accuracy when applied to data from another platform due to missing genes and sequence differences in probes that result in differing measurements for the same gene. PMID:16049308

Building versatile bipartite probes for quantum metrology

NASA Astrophysics Data System (ADS)

Farace, Alessandro; De Pasquale, Antonella; Adesso, Gerardo; Giovannetti, Vittorio

2016-01-01

We consider bipartite systems as versatile probes for the estimation of transformations acting locally on one of the subsystems. We investigate what resources are required for the probes to offer a guaranteed level of metrological performance, when the latter is averaged over specific sets of local transformations. We quantify such a performance via the average skew information (AvSk), a convex quantity which we compute in closed form for bipartite states of arbitrary dimensions, and which is shown to be strongly dependent on the degree of local purity of the probes. Our analysis contrasts and complements the recent series of studies focused on the minimum, rather than the average, performance of bipartite probes in local estimation tasks, which was instead determined by quantum correlations other than entanglement. We provide explicit prescriptions to characterize the most reliable states maximizing the AvSk, and elucidate the role of state purity, separability and correlations in the classification of optimal probes. Our results can help in the identification of useful resources for sensing, estimation and discrimination applications when complete knowledge of the interaction mechanism realizing the local transformation is unavailable, and access to pure entangled probes is technologically limited.

High quality-factor quartz tuning fork glass probe used in tapping mode atomic force microscopy for surface profile measurement

NASA Astrophysics Data System (ADS)

Chen, Yuan-Liu; Xu, Yanhao; Shimizu, Yuki; Matsukuma, Hiraku; Gao, Wei

2018-06-01

This paper presents a high quality-factor (Q-factor) quartz tuning fork (QTF) with a glass probe attached, used in frequency modulation tapping mode atomic force microscopy (AFM) for the surface profile metrology of micro and nanostructures. Unlike conventionally used QTFs, which have tungsten or platinum probes for tapping mode AFM, and suffer from a low Q-factor influenced by the relatively large mass of the probe, the glass probe, which has a lower density, increases the Q-factor of the QTF probe unit allowing it to obtain better measurement sensitivity. In addition, the process of attaching the probe to the QTF with epoxy resin, which is necessary for tapping mode AFM, is also optimized to further improve the Q-factor of the QTF glass probe. The Q-factor of the optimized QTF glass probe unit is demonstrated to be very close to that of a bare QTF without a probe attached. To verify the effectiveness and the advantages of the optimized QTF glass probe unit, the probe unit is integrated into a home-built tapping mode AFM for conducting surface profile measurements of micro and nanostructures. A blazed grating with fine tool marks of 100 nm, a microprism sheet with a vertical amplitude of 25 µm and a Fresnel lens with a steep slope of 90 degrees are used as measurement specimens. From the measurement results, it is demonstrated that the optimized QTF glass probe unit can achieve higher sensitivity as well as better stability than conventional probes in the measurement of micro and nanostructures.

Array of nucleic acid probes on biological chips for diagnosis of HIV and methods of using the same

DOEpatents

Chee, Mark; Gingeras, Thomas R.; Fodor, Stephen P. A.; Hubble, Earl A.; Morris, MacDonald S.

1999-01-19

The invention provides an array of oligonucleotide probes immobilized on a solid support for analysis of a target sequence from a human immunodeficiency virus. The array comprises at least four sets of oligonucleotide probes 9 to 21 nucleotides in length. A first probe set has a probe corresponding to each nucleotide in a reference sequence from a human immunodeficiency virus. A probe is related to its corresponding nucleotide by being exactly complementary to a subsequence of the reference sequence that includes the corresponding nucleotide. Thus, each probe has a position, designated an interrogation position, that is occupied by a complementary nucleotide to the corresponding nucleotide. The three additional probe sets each have a corresponding probe for each probe in the first probe set. Thus, for each nucleotide in the reference sequence, there are four corresponding probes, one from each of the probe sets. The three corresponding probes in the three additional probe sets are identical to the corresponding probe from the first probe or a subsequence thereof that includes the interrogation position, except that the interrogation position is occupied by a different nucleotide in each of the four corresponding probes.

Optimized Probe Masking for Comparative Transcriptomics of Closely Related Species

PubMed Central

Poeschl, Yvonne; Delker, Carolin; Trenner, Jana; Ullrich, Kristian Karsten; Quint, Marcel; Grosse, Ivo

2013-01-01

Microarrays are commonly applied to study the transcriptome of specific species. However, many available microarrays are restricted to model organisms, and the design of custom microarrays for other species is often not feasible. Hence, transcriptomics approaches of non-model organisms as well as comparative transcriptomics studies among two or more species often make use of cost-intensive RNAseq studies or, alternatively, by hybridizing transcripts of a query species to a microarray of a closely related species. When analyzing these cross-species microarray expression data, differences in the transcriptome of the query species can cause problems, such as the following: (i) lower hybridization accuracy of probes due to mismatches or deletions, (ii) probes binding multiple transcripts of different genes, and (iii) probes binding transcripts of non-orthologous genes. So far, methods for (i) exist, but these neglect (ii) and (iii). Here, we propose an approach for comparative transcriptomics addressing problems (i) to (iii), which retains only transcript-specific probes binding transcripts of orthologous genes. We apply this approach to an Arabidopsis lyrata expression data set measured on a microarray designed for Arabidopsis thaliana, and compare it to two alternative approaches, a sequence-based approach and a genomic DNA hybridization-based approach. We investigate the number of retained probe sets, and we validate the resulting expression responses by qRT-PCR. We find that the proposed approach combines the benefit of sequence-based stringency and accuracy while allowing the expression analysis of much more genes than the alternative sequence-based approach. As an added benefit, the proposed approach requires probes to detect transcripts of orthologous genes only, which provides a superior base for biological interpretation of the measured expression responses. PMID:24260119

Constrained Bayesian Active Learning of Interference Channels in Cognitive Radio Networks

NASA Astrophysics Data System (ADS)

Tsakmalis, Anestis; Chatzinotas, Symeon; Ottersten, Bjorn

2018-02-01

In this paper, a sequential probing method for interference constraint learning is proposed to allow a centralized Cognitive Radio Network (CRN) accessing the frequency band of a Primary User (PU) in an underlay cognitive scenario with a designed PU protection specification. The main idea is that the CRN probes the PU and subsequently eavesdrops the reverse PU link to acquire the binary ACK/NACK packet. This feedback indicates whether the probing-induced interference is harmful or not and can be used to learn the PU interference constraint. The cognitive part of this sequential probing process is the selection of the power levels of the Secondary Users (SUs) which aims to learn the PU interference constraint with a minimum number of probing attempts while setting a limit on the number of harmful probing-induced interference events or equivalently of NACK packet observations over a time window. This constrained design problem is studied within the Active Learning (AL) framework and an optimal solution is derived and implemented with a sophisticated, accurate and fast Bayesian Learning method, the Expectation Propagation (EP). The performance of this solution is also demonstrated through numerical simulations and compared with modified versions of AL techniques we developed in earlier work.

In vivo targeted peripheral nerve imaging with a nerve-specific nanoscale magnetic resonance probe.

PubMed

Zheng, Linfeng; Li, Kangan; Han, Yuedong; Wei, Wei; Zheng, Sujuan; Zhang, Guixiang

2014-11-01

Neuroimaging plays a pivotal role in clinical practice. Currently, computed tomography (CT), magnetic resonance imaging (MRI), ultrasonography, and positron emission tomography (PET) are applied in the clinical setting as neuroimaging modalities. There is no optimal imaging modality for clinical peripheral nerve imaging even though fluorescence/bioluminescence imaging has been used for preclinical studies on the nervous system. Some studies have shown that molecular and cellular MRI (MCMRI) can be used to visualize and image the cellular and molecular level of the nervous system. Other studies revealed that there are different pathological/molecular changes in the proximal and distal sites after peripheral nerve injury (PNI). Therefore, we hypothesized that in vivo peripheral nerve targets can be imaged using MCMRI with specific MRI probes. Specific probes should have higher penetrability for the blood-nerve barrier (BNB) in vivo. Here, a functional nanometre MRI probe that is based on nerve-specific proteins as targets, specifically, using a molecular antibody (mAb) fragment conjugated to iron nanoparticles as an MRI probe, was constructed for further study. The MRI probe allows for imaging the peripheral nerve targets in vivo. Copyright © 2014 Elsevier Ltd. All rights reserved.

Optimizing results of lithotripsy using robust electromagnetic probe.

PubMed

Keeley, F X; Pye, S D; Smith, G; Tolley, D A

1999-05-01

A significant impediment to the measurement of the pressures and forces created by lithotripter shockwaves has been their destructive properties, which have rendered most measuring devices impractical. We have developed and tested a robust electromagnetic probe to measure cavitational forces in vitro in the focal zones of extracorporeal lithotripters. The probe responds to the pressure gradient generated by the radial motion of cavitation bubbles. The effects of shockwaves from the Dornier MPL 9000 electrohydraulic lithotripter were measured over the lifetime of multiple electrodes. The pulse energy from the electrodes dropped off rapidly after approximately 50% of the lifetime quoted by the manufacturer. The electrodes were more efficient at higher power settings. As a result, we altered our protocol for the treatment of ureteral stones to use a higher kilovoltage and a second electrode whenever necessary. Stone-free rates after shockwave lithotripsy (SWL) in situ for stones < 11 mm have increased from 68.2% to 83.3%, and the retreatment rate has dropped from 23% to 15%. Despite significantly higher power settings (23.7 kV v 18.7 kV; P < 0.0001), the need for sedoanalgesia has remained relatively constant (26% v 31%). Measurement of cavitational forces from lithotripters using a robust electromagnetic probe is useful in planning treatment strategy. We have demonstrated a clinically measurable improvement since implementing our new treatment protocol. Because the probe responds directly to cavitational forces, it should also prove useful for the objective comparison of different SWL machines.

Frequency Optimization for Enhancement of Surface Defect Classification Using the Eddy Current Technique

PubMed Central

Fan, Mengbao; Wang, Qi; Cao, Binghua; Ye, Bo; Sunny, Ali Imam; Tian, Guiyun

2016-01-01

Eddy current testing is quite a popular non-contact and cost-effective method for nondestructive evaluation of product quality and structural integrity. Excitation frequency is one of the key performance factors for defect characterization. In the literature, there are many interesting papers dealing with wide spectral content and optimal frequency in terms of detection sensitivity. However, research activity on frequency optimization with respect to characterization performances is lacking. In this paper, an investigation into optimum excitation frequency has been conducted to enhance surface defect classification performance. The influences of excitation frequency for a group of defects were revealed in terms of detection sensitivity, contrast between defect features, and classification accuracy using kernel principal component analysis (KPCA) and a support vector machine (SVM). It is observed that probe signals are the most sensitive on the whole for a group of defects when excitation frequency is set near the frequency at which maximum probe signals are retrieved for the largest defect. After the use of KPCA, the margins between the defect features are optimum from the perspective of the SVM, which adopts optimal hyperplanes for structure risk minimization. As a result, the best classification accuracy is obtained. The main contribution is that the influences of excitation frequency on defect characterization are interpreted, and experiment-based procedures are proposed to determine the optimal excitation frequency for a group of defects rather than a single defect with respect to optimal characterization performances. PMID:27164112

Frequency Optimization for Enhancement of Surface Defect Classification Using the Eddy Current Technique.

PubMed

Fan, Mengbao; Wang, Qi; Cao, Binghua; Ye, Bo; Sunny, Ali Imam; Tian, Guiyun

2016-05-07

Eddy current testing is quite a popular non-contact and cost-effective method for nondestructive evaluation of product quality and structural integrity. Excitation frequency is one of the key performance factors for defect characterization. In the literature, there are many interesting papers dealing with wide spectral content and optimal frequency in terms of detection sensitivity. However, research activity on frequency optimization with respect to characterization performances is lacking. In this paper, an investigation into optimum excitation frequency has been conducted to enhance surface defect classification performance. The influences of excitation frequency for a group of defects were revealed in terms of detection sensitivity, contrast between defect features, and classification accuracy using kernel principal component analysis (KPCA) and a support vector machine (SVM). It is observed that probe signals are the most sensitive on the whole for a group of defects when excitation frequency is set near the frequency at which maximum probe signals are retrieved for the largest defect. After the use of KPCA, the margins between the defect features are optimum from the perspective of the SVM, which adopts optimal hyperplanes for structure risk minimization. As a result, the best classification accuracy is obtained. The main contribution is that the influences of excitation frequency on defect characterization are interpreted, and experiment-based procedures are proposed to determine the optimal excitation frequency for a group of defects rather than a single defect with respect to optimal characterization performances.

Q-PCR based bioburden assessment of drinking water throughout treatment and delivery to the International Space Station

NASA Technical Reports Server (NTRS)

Newcombe, David; Stuecker, Tara; La Duc, Myron; Venkateswaran, Kasthuri

2005-01-01

Previous studies indicated evidence of opportunistic pathogens samples obtained during missions to the International Space Station (ISS). This study utilized TaqMan quantitative PCR to determine specific gene abundance in potable and non-potable ISS waters. Probe and primer sets specific to the small subunit rRNA genes were used to elucidate overall bacterial rRNA gene numbers. while those specific for Burkholderia cepacia and Stenotrophomonas maltophilia were optimized and used to probe for the presence of these two opportunistic pathogens. This research builds upon previous microbial diversity studies of ISS water and demonstrates the utility of Q-PCR tool to examine water quality.

Coherent optimal control of photosynthetic molecules

NASA Astrophysics Data System (ADS)

Caruso, F.; Montangero, S.; Calarco, T.; Huelga, S. F.; Plenio, M. B.

2012-04-01

We demonstrate theoretically that open-loop quantum optimal control techniques can provide efficient tools for the verification of various quantum coherent transport mechanisms in natural and artificial light-harvesting complexes under realistic experimental conditions. To assess the feasibility of possible biocontrol experiments, we introduce the main settings and derive optimally shaped and robust laser pulses that allow for the faithful preparation of specified initial states (such as localized excitation or coherent superposition, i.e., propagating and nonpropagating states) of the photosystem and probe efficiently the subsequent dynamics. With these tools, different transport pathways can be discriminated, which should facilitate the elucidation of genuine quantum dynamical features of photosystems and therefore enhance our understanding of the role that coherent processes may play in actual biological complexes.

Optimization of chlorine fluxing process for magnesium removal from molten aluminum

NASA Astrophysics Data System (ADS)

Fu, Qian

High-throughput and low operational cost are the keys to a successful industrial process. Much aluminum is now recycled in the form of used beverage cans and this aluminum is of alloys that contain high levels of magnesium. It is common practice to "demag" the metal by injecting chlorine that preferentially reacts with the magnesium. In the conventional chlorine fluxing processes, low reaction efficiency results in excessive reactive gas emissions. In this study, through an experimental investigation of the reaction kinetics involved in this process, a mathematical model is set up for the purpose of process optimization. A feedback controlled chlorine reduction process strategy is suggested for demagging the molten aluminum to the desired magnesium level without significant gas emissions. This strategy also needs the least modification of the existing process facility. The suggested process time will only be slightly longer than conventional methods and chlorine usage and emissions will be reduced. In order to achieve process optimization through novel designs in any fluxing process, a system is necessary for measuring the bubble distribution in liquid metals. An electro-resistivity probe described in the literature has low accuracy and its capability to measure bubble distribution has not yet been fully demonstrated. A capacitance bubble probe was designed for bubble measurements in molten metals. The probe signal was collected and processed digitally. Higher accuracy was obtained by higher discrimination against corrupted signals. A single-size bubble experiment in Belmont metal was designed to reveal the characteristic response of the capacitance probe. This characteristic response fits well with a theoretical model. It is suggested that using a properly designed deconvolution process, the actual bubble size distribution can be calculated. The capacitance probe was used to study some practical bubble generation devices. Preliminary results on bubble distribution generated by a porous plug in Belmont metal showed bubbles much bigger than those in a water model. Preliminary results in molten aluminum showed that the probe was applicable in this harsh environment. An interesting bubble coalescence phenomenon was also observed in both Belmont metal and molten aluminum.

Entanglement-assisted quantum feedback control

NASA Astrophysics Data System (ADS)

Yamamoto, Naoki; Mikami, Tomoaki

2017-07-01

The main advantage of quantum metrology relies on the effective use of entanglement, which indeed allows us to achieve strictly better estimation performance over the standard quantum limit. In this paper, we propose an analogous method utilizing entanglement for the purpose of feedback control. The system considered is a general linear dynamical quantum system, where the control goal can be systematically formulated as a linear quadratic Gaussian control problem based on the quantum Kalman filtering method; in this setting, an entangled input probe field is effectively used to reduce the estimation error and accordingly the control cost function. In particular, we show that, in the problem of cooling an opto-mechanical oscillator, the entanglement-assisted feedback control can lower the stationary occupation number of the oscillator below the limit attainable by the controller with a coherent probe field and furthermore beats the controller with an optimized squeezed probe field.

Magnetostriction measurement by four probe method

NASA Astrophysics Data System (ADS)

Dange, S. N.; Radha, S.

2018-04-01

The present paper describes the design and setting up of an indigenouslydevelopedmagnetostriction(MS) measurement setup using four probe method atroom temperature.A standard strain gauge is pasted with a special glue on the sample and its change in resistance with applied magnetic field is measured using KeithleyNanovoltmeter and Current source. An electromagnet with field upto 1.2 tesla is used to source the magnetic field. The sample is placed between the magnet poles using self designed and developed wooden probe stand, capable of moving in three mutually perpendicular directions. The nanovoltmeter and current source are interfaced with PC using RS232 serial interface. A software has been developed in for logging and processing of data. Proper optimization of measurement has been done through software to reduce the noise due to thermal emf and electromagnetic induction. The data acquired for some standard magnetic samples are presented. The sensitivity of the setup is 1microstrain with an error in measurement upto 5%.

Estimating the similarity of alternative Affymetrix probe sets using transcriptional networks

PubMed Central

2013-01-01

Background The usefulness of the data from Affymetrix microarray analysis depends largely on the reliability of the files describing the correspondence between probe sets, genes and transcripts. Particularly, when a gene is targeted by several probe sets, these files should give information about the similarity of each alternative probe set pair. Transcriptional networks integrate the multiple correlations that exist between all probe sets and supply much more information than a simple correlation coefficient calculated for two series of signals. In this study, we used the PSAWN (Probe Set Assignment With Networks) programme we developed to investigate whether similarity of alternative probe sets resulted in some specific properties. Findings PSAWNpy delivered a full textual description of each probe set and information on the number and properties of secondary targets. PSAWNml calculated the similarity of each alternative probe set pair and allowed finding relationships between similarity and localisation of probes in common transcripts or exons. Similar alternative probe sets had very low negative correlation, high positive correlation and similar neighbourhood overlap. Using these properties, we devised a test that allowed grouping similar probe sets in a given network. By considering several networks, additional information concerning the similarity reproducibility was obtained, which allowed defining the actual similarity of alternative probe set pairs. In particular, we calculated the common localisation of probes in exons and in known transcripts and we showed that similarity was correctly correlated with them. The information collected on all pairs of alternative probe sets in the most popular 3’ IVT Affymetrix chips is available in tabular form at http://bns.crbm.cnrs.fr/download.html. Conclusions These processed data can be used to obtain a finer interpretation when comparing microarray data between biological conditions. They are particularly well adapted for searching 3’ alternative poly-adenylation events and can be also useful for studying the structure of transcriptional networks. The PSAWNpy, (in Python) and PSAWNml (in Matlab) programmes are freely available and can be downloaded at http://code.google.com/p/arraymatic. Tutorials and reference manuals are available at BMC Research Notes online (Additional file 1) or from http://bns.crbm.cnrs.fr/softwares.html. PMID:23517579

Optimization of Designs for Nanotube-based Scanning Probes

NASA Technical Reports Server (NTRS)

Harik, V. M.; Gates, T. S.; Bushnell, Dennis M. (Technical Monitor)

2002-01-01

Optimization of designs for nanotube-based scanning probes, which may be used for high-resolution characterization of nanostructured materials, is examined. Continuum models to analyze the nanotube deformations are proposed to help guide selection of the optimum probe. The limitations on the use of these models that must be accounted for before applying to any design problem are presented. These limitations stem from the underlying assumptions and the expected range of nanotube loading, end conditions, and geometry. Once the limitations are accounted for, the key model parameters along with the appropriate classification of nanotube structures may serve as a basis for the design optimization of nanotube-based probe tips.

An integrated fiber-optic probe combined with support vector regression for fast estimation of optical properties of turbid media.

PubMed

Zhou, Yang; Fu, Xiaping; Ying, Yibin; Fang, Zhenhuan

2015-06-23

A fiber-optic probe system was developed to estimate the optical properties of turbid media based on spatially resolved diffuse reflectance. Because of the limitations in numerical calculation of radiative transfer equation (RTE), diffusion approximation (DA) and Monte Carlo simulations (MC), support vector regression (SVR) was introduced to model the relationship between diffuse reflectance values and optical properties. The SVR models of four collection fibers were trained by phantoms in calibration set with a wide range of optical properties which represented products of different applications, then the optical properties of phantoms in prediction set were predicted after an optimal searching on SVR models. The results indicated that the SVR model was capable of describing the relationship with little deviation in forward validation. The correlation coefficient (R) of reduced scattering coefficient μ'(s) and absorption coefficient μ(a) in the prediction set were 0.9907 and 0.9980, respectively. The root mean square errors of prediction (RMSEP) of μ'(s) and μ(a) in inverse validation were 0.411 cm(-1) and 0.338 cm(-1), respectively. The results indicated that the integrated fiber-optic probe system combined with SVR model were suitable for fast and accurate estimation of optical properties of turbid media based on spatially resolved diffuse reflectance. Copyright © 2015 Elsevier B.V. All rights reserved.

Multi-probe-based resonance-frequency electrical impedance spectroscopy for detection of suspicious breast lesions: improving performance using partial ROC optimization

NASA Astrophysics Data System (ADS)

Lederman, Dror; Zheng, Bin; Wang, Xingwei; Wang, Xiao Hui; Gur, David

2011-03-01

We have developed a multi-probe resonance-frequency electrical impedance spectroscope (REIS) system to detect breast abnormalities. Based on assessing asymmetry in REIS signals acquired between left and right breasts, we developed several machine learning classifiers to classify younger women (i.e., under 50YO) into two groups of having high and low risk for developing breast cancer. In this study, we investigated a new method to optimize performance based on the area under a selected partial receiver operating characteristic (ROC) curve when optimizing an artificial neural network (ANN), and tested whether it could improve classification performance. From an ongoing prospective study, we selected a dataset of 174 cases for whom we have both REIS signals and diagnostic status verification. The dataset includes 66 "positive" cases recommended for biopsy due to detection of highly suspicious breast lesions and 108 "negative" cases determined by imaging based examinations. A set of REIS-based feature differences, extracted from the two breasts using a mirror-matched approach, was computed and constituted an initial feature pool. Using a leave-one-case-out cross-validation method, we applied a genetic algorithm (GA) to train the ANN with an optimal subset of features. Two optimization criteria were separately used in GA optimization, namely the area under the entire ROC curve (AUC) and the partial area under the ROC curve, up to a predetermined threshold (i.e., 90% specificity). The results showed that although the ANN optimized using the entire AUC yielded higher overall performance (AUC = 0.83 versus 0.76), the ANN optimized using the partial ROC area criterion achieved substantially higher operational performance (i.e., increasing sensitivity level from 28% to 48% at 95% specificity and/ or from 48% to 58% at 90% specificity).

Multiplex detection of agricultural pathogens

DOEpatents

Siezak, Thomas R.; Gardner, Shea; Torres, Clinton; Vitalis, Elizabeth; Lenhoff, Raymond J.

2013-01-15

Described are kits and methods useful for detection of agricultural pathogens in a sample. Genomic sequence information from agricultural pathogens was analyzed to identify signature sequences, e.g., polynucleotide sequences useful for confirming the presence or absence of a pathogen in a sample. Primer and probe sets were designed and optimized for use in a PCR based, multiplexed Luminex assay and/or an array assay to successfully identify the presence or absence of pathogens in a sample.

A Simple Method for Amplifying RNA Targets (SMART)

PubMed Central

McCalla, Stephanie E.; Ong, Carmichael; Sarma, Aartik; Opal, Steven M.; Artenstein, Andrew W.; Tripathi, Anubhav

2012-01-01

We present a novel and simple method for amplifying RNA targets (named by its acronym, SMART), and for detection, using engineered amplification probes that overcome existing limitations of current RNA-based technologies. This system amplifies and detects optimal engineered ssDNA probes that hybridize to target RNA. The amplifiable probe-target RNA complex is captured on magnetic beads using a sequence-specific capture probe and is separated from unbound probe using a novel microfluidic technique. Hybridization sequences are not constrained as they are in conventional target-amplification reactions such as nucleic acid sequence amplification (NASBA). Our engineered ssDNA probe was amplified both off-chip and in a microchip reservoir at the end of the separation microchannel using isothermal NASBA. Optimal solution conditions for ssDNA amplification were investigated. Although KCl and MgCl2 are typically found in NASBA reactions, replacing 70 mmol/L of the 82 mmol/L total chloride ions with acetate resulted in optimal reaction conditions, particularly for low but clinically relevant probe concentrations (≤100 fmol/L). With the optimal probe design and solution conditions, we also successfully removed the initial heating step of NASBA, thus achieving a true isothermal reaction. The SMART assay using a synthetic model influenza DNA target sequence served as a fundamental demonstration of the efficacy of the capture and microfluidic separation system, thus bridging our system to a clinically relevant detection problem. PMID:22691910

In situ magnetic compensation for potassium spin-exchange relaxation-free magnetometer considering probe beam pumping effect.

PubMed

Fang, Jiancheng; Wang, Tao; Quan, Wei; Yuan, Heng; Zhang, Hong; Li, Yang; Zou, Sheng

2014-06-01

A novel method to compensate the residual magnetic field for an atomic magnetometer consisting of two perpendicular beams of polarizations was demonstrated in this paper. The method can realize magnetic compensation in the case where the pumping rate of the probe beam cannot be ignored. In the experiment, the probe beam is always linearly polarized, whereas, the probe beam contains a residual circular component due to the imperfection of the polarizer, which leads to the pumping effect of the probe beam. A simulation of the probe beam's optical rotation and pumping rate was demonstrated. At the optimized points, the wavelength of the probe beam was optimized to achieve the largest optical rotation. Although, there is a small circular component in the linearly polarized probe beam, the pumping rate of the probe beam was non-negligible at the optimized wavelength which if ignored would lead to inaccuracies in the magnetic field compensation. Therefore, the dynamic equation of spin evolution was solved by considering the pumping effect of the probe beam. Based on the quasi-static solution, a novel magnetic compensation method was proposed, which contains two main steps: (1) the non-pumping compensation and (2) the sequence compensation with a very specific sequence. After these two main steps, a three-axis in situ magnetic compensation was achieved. The compensation method was suitable to design closed-loop spin-exchange relaxation-free magnetometer. By a combination of the magnetic compensation and the optimization, the magnetic field sensitivity was approximately 4 fT/Hz(1/2), which was mainly dominated by the noise of the magnetic shield.

Probing for quantum speedup in spin-glass problems with planted solutions

NASA Astrophysics Data System (ADS)

Hen, Itay; Job, Joshua; Albash, Tameem; Rønnow, Troels F.; Troyer, Matthias; Lidar, Daniel A.

2015-10-01

The availability of quantum annealing devices with hundreds of qubits has made the experimental demonstration of a quantum speedup for optimization problems a coveted, albeit elusive goal. Going beyond earlier studies of random Ising problems, here we introduce a method to construct a set of frustrated Ising-model optimization problems with tunable hardness. We study the performance of a D-Wave Two device (DW2) with up to 503 qubits on these problems and compare it to a suite of classical algorithms, including a highly optimized algorithm designed to compete directly with the DW2. The problems are generated around predetermined ground-state configurations, called planted solutions, which makes them particularly suitable for benchmarking purposes. The problem set exhibits properties familiar from constraint satisfaction (SAT) problems, such as a peak in the typical hardness of the problems, determined by a tunable clause density parameter. We bound the hardness regime where the DW2 device either does not or might exhibit a quantum speedup for our problem set. While we do not find evidence for a speedup for the hardest and most frustrated problems in our problem set, we cannot rule out that a speedup might exist for some of the easier, less frustrated problems. Our empirical findings pertain to the specific D-Wave processor and problem set we studied and leave open the possibility that future processors might exhibit a quantum speedup on the same problem set.

A magnetic nanobead-based bioassay provides sensitive detection of single- and biplex bacterial DNA using a portable AC susceptometer.

PubMed

Strömberg, Mattias; Zardán Gómez de la Torre, Teresa; Nilsson, Mats; Svedlindh, Peter; Strømme, Maria

2014-01-01

Bioassays relying on magnetic read-out using probe-tagged magnetic nanobeads are potential platforms for low-cost biodiagnostic devices for pathogen detection. For optimal assay performance it is crucial to apply an easy, efficient and robust bead-probe conjugation protocol. In this paper, sensitive (1.5 pM) singleplex detection of bacterial DNA sequences is demonstrated in a portable AC susceptometer by a magnetic nanobead-based bioassay principle; the volume-amplified magnetic nanobead detection assay (VAM-NDA). Two bead sizes, 100 and 250 nm, are investigated along with a highly efficient, rapid, robust, and stable conjugation chemistry relying on the avidin-biotin interaction for bead-probe attachment. Avidin-biotin conjugation gives easy control of the number of detection probes per bead; thus allowing for systematic investigation of the impact of varying the detection probe surface coverage upon bead immobilization in rolling circle amplified DNA-coils. The existence of an optimal surface coverage is discussed. Biplex VAM-NDA detection is for the first time demonstrated in the susceptometer: Semi-quantitative results are obtained and it is concluded that the concentration of DNA-coils in the incubation volume is of crucial importance for target quantification. The present findings bring the development of commercial biodiagnostic devices relying on the VAM-NDA further towards implementation in point-of-care and outpatient settings. © 2013 The Authors. Biotechnology Journal published by Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim. This is an open access article under the terms of the Creative Commons Attribution-License, which permits use and distribution in any medium, provided the original work is properly cited.

Study of probe-sample distance for biomedical spectra measurement.

PubMed

Wang, Bowen; Fan, Shuzhen; Li, Lei; Wang, Cong

2011-11-02

Fiber-based optical spectroscopy has been widely used for biomedical applications. However, the effect of probe-sample distance on the collection efficiency has not been well investigated. In this paper, we presented a theoretical model to maximize the illumination and collection efficiency in designing fiber optic probes for biomedical spectra measurement. This model was in general applicable to probes with single or multiple fibers at an arbitrary incident angle. In order to demonstrate the theory, a fluorescence spectrometer was used to measure the fluorescence of human finger skin at various probe-sample distances. The fluorescence spectrum and the total fluorescence intensity were recorded. The theoretical results show that for single fiber probes, contact measurement always provides the best results. While for multi-fiber probes, there is an optimal probe distance. When a 400- μm excitation fiber is used to deliver the light to the skin and another six 400- μm fibers surrounding the excitation fiber are used to collect the fluorescence signal, the experimental results show that human finger skin has very strong fluorescence between 475 nm and 700 nm under 450 nm excitation. The fluorescence intensity is heavily dependent on the probe-sample distance and there is an optimal probe distance. We investigated a number of probe-sample configurations and found that contact measurement could be the primary choice for single-fiber probes, but was very inefficient for multi-fiber probes. There was an optimal probe-sample distance for multi-fiber probes. By carefully choosing the probe-sample distance, the collection efficiency could be enhanced by 5-10 times. Our experiments demonstrated that the experimental results of the probe-sample distance dependence of collection efficiency in multi-fiber probes were in general agreement with our theory.

Vascular endothelial growth factor receptor-2 (VEGFR-2) inhibitors: development and validation of predictive 3-D QSAR models through extensive ligand- and structure-based approaches

NASA Astrophysics Data System (ADS)

Ragno, Rino; Ballante, Flavio; Pirolli, Adele; Wickersham, Richard B.; Patsilinakos, Alexandros; Hesse, Stéphanie; Perspicace, Enrico; Kirsch, Gilbert

2015-08-01

Vascular endothelial growth factor receptor-2, (VEGFR-2), is a key element in angiogenesis, the process by which new blood vessels are formed, and is thus an important pharmaceutical target. Here, 3-D quantitative structure-activity relationship (3-D QSAR) were used to build a quantitative screening and pharmacophore model of the VEGFR-2 receptors for design of inhibitors with improved activities. Most of available experimental data information has been used as training set to derive optimized and fully cross-validated eight mono-probe and a multi-probe quantitative models. Notable is the use of 262 molecules, aligned following both structure-based and ligand-based protocols, as external test set confirming the 3-D QSAR models' predictive capability and their usefulness in design new VEGFR-2 inhibitors. From a survey on literature, this is the first generation of a wide-ranging computational medicinal chemistry application on VEGFR2 inhibitors.

Einstein Inflationary Probe (EIP)

NASA Technical Reports Server (NTRS)

Hinshaw, Gary

2004-01-01

I will discuss plans to develop a concept for the Einstein Inflation Probe: a mission to detect gravity waves from inflation via the unique signature they impart to the cosmic microwave background (CMB) polarization. A sensitive CMB polarization satellite may be the only way to probe physics at the grand-unified theory (GUT) scale, exceeding by 12 orders of magnitude the energies studied at the Large Hadron Collider. A detection of gravity waves would represent a remarkable confirmation of the inflationary paradigm and set the energy scale at which inflation occurred when the universe was a fraction of a second old. Even a strong upper limit to the gravity wave amplitude would be significant, ruling out many common models of inflation, and pointing to inflation occurring at much lower energy, if at all. Measuring gravity waves via the CMB polarization will be challenging. We will undertake a comprehensive study to identify the critical scientific requirements for the mission and their derived instrumental performance requirements. At the core of the study will be an assessment of what is scientifically and experimentally optimal within the scope and purpose of the Einstein Inflation Probe.

On the improvement for charging large-scale flexible electrostatic actuators

NASA Astrophysics Data System (ADS)

Liao, Hsu-Ching; Chen, Han-Long; Su, Yu-Hao; Chen, Yu-Chi; Ko, Wen-Ching; Liou, Chang-Ho; Wu, Wen-Jong; Lee, Chih-Kung

2011-04-01

Recently, the development of flexible electret based electrostatic actuator has been widely discussed. The devices was shown to have high sound quality, energy saving, flexible structure and can be cut to any shape. However, achieving uniform charge on the electret diaphragm is one of the most critical processes needed to have the speaker ready for large-scale production. In this paper, corona discharge equipment contains multi-corona probes and grid bias was set up to inject spatial charges within the electret diaphragm. The optimal multi-corona probes system was adjusted to achieve uniform charge distribution of electret diaphragm. The processing conditions include the distance between the corona probes, the voltages of corona probe and grid bias, etc. We assembled the flexible electret loudspeakers first and then measured their sound pressure and beam pattern. The uniform charge distribution within the electret diaphragm based flexible electret loudspeaker provided us with the opportunity to shape the loudspeaker arbitrarily and to tailor the sound distribution per specifications request. Some of the potential futuristic applications for this device such as sound poster, smart clothes, and sound wallpaper, etc. were discussed as well.

Real-time PCR probe optimization using design of experiments approach.

PubMed

Wadle, S; Lehnert, M; Rubenwolf, S; Zengerle, R; von Stetten, F

2016-03-01

Primer and probe sequence designs are among the most critical input factors in real-time polymerase chain reaction (PCR) assay optimization. In this study, we present the use of statistical design of experiments (DOE) approach as a general guideline for probe optimization and more specifically focus on design optimization of label-free hydrolysis probes that are designated as mediator probes (MPs), which are used in reverse transcription MP PCR (RT-MP PCR). The effect of three input factors on assay performance was investigated: distance between primer and mediator probe cleavage site; dimer stability of MP and target sequence (influenza B virus); and dimer stability of the mediator and universal reporter (UR). The results indicated that the latter dimer stability had the greatest influence on assay performance, with RT-MP PCR efficiency increased by up to 10% with changes to this input factor. With an optimal design configuration, a detection limit of 3-14 target copies/10 μl reaction could be achieved. This improved detection limit was confirmed for another UR design and for a second target sequence, human metapneumovirus, with 7-11 copies/10 μl reaction detected in an optimum case. The DOE approach for improving oligonucleotide designs for real-time PCR not only produces excellent results but may also reduce the number of experiments that need to be performed, thus reducing costs and experimental times.

Mobile, Multimodal, Label-Free Imaging Probe Analysis of Choroidal Oximetry and Retinal Hypoxia

DTIC Science & Technology

2017-12-01

these same eye injuries. Primary blast-induced injury (PBI), which can occur in eyes that are not punctured or ruptured by the blast, is correlated ...optimization. (1A-F) The component of our PBI- devices, output pressure detection sensor, amplifier, and input pressure panel. (1G) Correlation between...by changing the setting of blast generator. (2A-B) Correlation between output pressure and blast time duration. (2C) After PBI- treatment, the eyes of

On the ground state of Yang-Mills theory

NASA Astrophysics Data System (ADS)

Bakry, Ahmed S.; Leinweber, Derek B.; Williams, Anthony G.

2011-08-01

We investigate the overlap of the ground state meson potential with sets of mesonic-trial wave functions corresponding to different gluonic distributions. We probe the transverse structure of the flux tube through the creation of non-uniform smearing profiles for the string of glue connecting two color sources in Wilson loop operator. The non-uniformly UV-regulated flux-tube operators are found to optimize the overlap with the ground state and display interesting features in the ground state overlap.

Multiplex detection of agricultural pathogens

DOEpatents

McBride, Mary Teresa; Slezak, Thomas Richard; Messenger, Sharon Lee

2010-09-14

Described are kits and methods useful for detection of seven agricultural pathogens (BPSV; BHV; BVD; FMDV; BTV; SVD; and VESV) in a sample. Genomic sequence information from 7 agricultural pathogens was analyzed to identify signature sequences, e.g., polynucleotide sequences useful for confirming the presence or absence of a pathogen in a sample. Primer and probe sets were designed and optimized for use in a PCR based, multiplexed Luminex assay to successfully identify the presence or absence of pathogens in a sample.

Development of a polymerase chain reaction assay for the rapid detection of the oral pathogenic bacterium, Selenomonas noxia.

PubMed

Cruz, Patricia; Mehretu, Arthuro M; Buttner, Mark P; Trice, Theresa; Howard, Katherine M

2015-08-14

In recent studies, periodontal health has been linked to being overweight and/or obese. Among common oral bacteria, Selenomonas noxia has been implicated in converting periodontal health to disease, and Selenomonas species have also been found in gastric ulcers. The objective of this study was to develop and validate a quantitative polymerase chain reaction (qPCR) assay for the specific and rapid detection of S. noxia. Two oligonucleotide primer pairs and one probe were designed and tested to determine optimal amplification signal with three strains of S. noxia. The PCR assay was tested against fourteen non-target organisms, including closely related oral Selenomonads, one phylogenetically closely related bacterium, and two commonly isolated oral bacteria. One of the primer sets was more sensitive at detecting the target organism and was selected for optimization and validation experiments. The designed primers and probe amplified the target organism with 100% specificity. PCR inhibition was observed with an internal positive control, and inhibition was resolved by diluting the DNA extract. The qPCR assay designed in this study can be used to specifically detect S. noxia in the clinical setting and in future research involving the enhanced detection of S. noxia. The assay can also be used in epidemiological studies for understanding the role of S. noxia in disease processes including, but not limited to, oral health and obesity of infectious origin.

In situ magnetic compensation for potassium spin-exchange relaxation-free magnetometer considering probe beam pumping effect

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

Fang, Jiancheng; Wang, Tao, E-mail: wangtaowt@aspe.buaa.edu.cn; Quan, Wei

2014-06-15

A novel method to compensate the residual magnetic field for an atomic magnetometer consisting of two perpendicular beams of polarizations was demonstrated in this paper. The method can realize magnetic compensation in the case where the pumping rate of the probe beam cannot be ignored. In the experiment, the probe beam is always linearly polarized, whereas, the probe beam contains a residual circular component due to the imperfection of the polarizer, which leads to the pumping effect of the probe beam. A simulation of the probe beam's optical rotation and pumping rate was demonstrated. At the optimized points, the wavelengthmore » of the probe beam was optimized to achieve the largest optical rotation. Although, there is a small circular component in the linearly polarized probe beam, the pumping rate of the probe beam was non-negligible at the optimized wavelength which if ignored would lead to inaccuracies in the magnetic field compensation. Therefore, the dynamic equation of spin evolution was solved by considering the pumping effect of the probe beam. Based on the quasi-static solution, a novel magnetic compensation method was proposed, which contains two main steps: (1) the non-pumping compensation and (2) the sequence compensation with a very specific sequence. After these two main steps, a three-axis in situ magnetic compensation was achieved. The compensation method was suitable to design closed-loop spin-exchange relaxation-free magnetometer. By a combination of the magnetic compensation and the optimization, the magnetic field sensitivity was approximately 4 fT/Hz{sup 1/2}, which was mainly dominated by the noise of the magnetic shield.« less

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

Heredia-Langner, Alejandro; Amidan, Brett G.; Matzner, Shari

We present results from the optimization of a re-identification process using two sets of biometric data obtained from the Civilian American and European Surface Anthropometry Resource Project (CAESAR) database. The datasets contain real measurements of features for 2378 individuals in a standing (43 features) and seated (16 features) position. A genetic algorithm (GA) was used to search a large combinatorial space where different features are available between the probe (seated) and gallery (standing) datasets. Results show that optimized model predictions obtained using less than half of the 43 gallery features and data from roughly 16% of the individuals available producemore » better re-identification rates than two other approaches that use all the information available.« less

Simplified Numerical Analysis of ECT Probe - Eddy Current Benchmark Problem 3

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

Sikora, R.; Chady, T.; Gratkowski, S.

2005-04-09

In this paper a third eddy current benchmark problem is considered. The objective of the benchmark is to determine optimal operating frequency and size of the pancake coil designated for testing tubes made of Inconel. It can be achieved by maximization of the change in impedance of the coil due to a flaw. Approximation functions of the probe (coil) characteristic were developed and used in order to reduce number of required calculations. It results in significant speed up of the optimization process. An optimal testing frequency and size of the probe were achieved as a final result of the calculation.

Optimization of the imaging response of scanning microwave microscopy measurements

NASA Astrophysics Data System (ADS)

Sardi, G. M.; Lucibello, A.; Kasper, M.; Gramse, G.; Proietti, E.; Kienberger, F.; Marcelli, R.

2015-07-01

In this work, we present the analytical modeling and preliminary experimental results for the choice of the optimal frequencies when performing amplitude and phase measurements with a scanning microwave microscope. In particular, the analysis is related to the reflection mode operation of the instrument, i.e., the acquisition of the complex reflection coefficient data, usually referred as S11. The studied configuration is composed of an atomic force microscope with a microwave matched nanometric cantilever probe tip, connected by a λ/2 coaxial cable resonator to a vector network analyzer. The set-up is provided by Keysight Technologies. As a peculiar result, the optimal frequencies, where the maximum sensitivity is achieved, are different for the amplitude and for the phase signals. The analysis is focused on measurements of dielectric samples, like semiconductor devices, textile pieces, and biological specimens.

Preentry communications study. Outer planets atmospheric entry probe

NASA Technical Reports Server (NTRS)

Hinrichs, C. A.

1976-01-01

A pre-entry communications study is presented for a relay link between a Jupiter entry probe and a spacecraft in hyperbolic orbit. Two generic communications links of interest are described: a pre-entry link to a spun spacecraft antenna, and a pre-entry link to a despun spacecraft antenna. The propagation environment of Jupiter is defined. Although this is one of the least well known features of Jupiter, enough information exists to reasonably establish bounds on the performance of a communications link. Within these bounds, optimal carrier frequencies are defined. The next step is to identify optimal relative geometries between the probe and the spacecraft. Optimal trajectories are established for both spun and despun spacecraft antennas. Given the optimal carrier frequencies, and the optimal trajectories, the data carrying capacities of the pre-entry links are defined. The impact of incorporating pre-entry communications into a basic post entry probe is then assessed. This assessment covers the disciplines of thermal control, power source, mass properties and design layout. A conceptual design is developed of an electronically despun antenna for use on a Pioneer class of spacecraft.

Hands-Free Transcranial Color Doppler Probe

NASA Technical Reports Server (NTRS)

Chin, Robert; Madala, Srihdar; Sattler, Graham

2012-01-01

Current transcranial color Doppler (TCD) transducer probes are bulky and difficult to move in tiny increments to search and optimize TCD signals. This invention provides miniature motions of a TCD transducer probe to optimize TCD signals. The mechanical probe uses a spherical bearing in guiding and locating the tilting crystal face. The lateral motion of the crystal face as it tilts across the full range of motion was achieved by minimizing the distance between the pivot location and the crystal face. The smallest commonly available metal spherical bearing was used with an outer diameter of 12 mm, a 3-mm tall retaining ring, and 5-mm overall height. Small geared motors were used that would provide sufficient power in a very compact package. After confirming the validity of the basic positioning concept, optimization design loops were completed to yield the final design. A parallel motor configuration was used to minimize the amount of space wasted inside the probe case while minimizing the overall case dimensions. The distance from the front edge of the crystal to the edge of the case was also minimized to allow positioning of the probe very close to the ear on the temporal lobe. The mechanical probe is able to achieve a +/-20deg tip and tilt with smooth repeatable action in a very compact package. The enclosed probe is about 7 cm long, 4 cm wide, and 1.8 cm tall. The device is compact, hands-free, and can be adjusted via an innovative touchscreen. Positioning of the probe to the head is performed via conventional transducer gels and pillows. This device is amendable to having advanced software, which could intelligently focus and optimize the TCD signal.

Simplified Real-Time Multiplex Detection of Loop-Mediated Isothermal Amplification Using Novel Mediator Displacement Probes with Universal Reporters.

PubMed

Becherer, Lisa; Bakheit, Mohammed; Frischmann, Sieghard; Stinco, Silvina; Borst, Nadine; Zengerle, Roland; von Stetten, Felix

2018-04-03

A variety of real-time detection techniques for loop-mediated isothermal amplification (LAMP) based on the change in fluorescence intensity during DNA amplification enable simultaneous detection of multiple targets. However, these techniques depend on fluorogenic probes containing target-specific sequences. That complicates the adaption to different targets leading to time-consuming assay optimization. Here, we present the first universal real-time detection technique for multiplex LAMP. The novel approach allows simple assay design and is easy to implement for various targets. The innovation features a mediator displacement probe and a universal reporter. During amplification of target DNA the mediator is displaced from the mediator displacement probe. Then it hybridizes to the reporter generating a fluorescence signal. The novel mediator displacement (MD) detection was validated against state-of-the-art molecular beacon (MB) detection by means of a HIV-1 RT-LAMP: MD surpassed MB detection by accelerated probe design (MD: 10 min, MB: 3-4 h), shorter times to positive (MD 4.1 ± 0.1 min shorter than MB, n = 36), improved signal-to-noise fluorescence ratio (MD: 5.9 ± 0.4, MB: 2.7 ± 0.4; n = 15), and showed equally good or better analytical performance parameters. The usability of one universal mediator-reporter set in different multiplex assays was successfully demonstrated for a biplex RT-LAMP of HIV-1 and HTLV-1 and a biplex LAMP of Haemophilus ducreyi and Treponema pallidum, both showing good correlation between target concentration and time to positive. Due to its simple implementation it is suggested to extend the use of the universal mediator-reporter sets to the detection of various other diagnostic panels.

Development and validation of a numerical model for cross-section optimization of a multi-part probe for soft tissue intervention.

PubMed

Frasson, L; Neubert, J; Reina, S; Oldfield, M; Davies, B L; Rodriguez Y Baena, F

2010-01-01

The popularity of minimally invasive surgical procedures is driving the development of novel, safer and more accurate surgical tools. In this context a multi-part probe for soft tissue surgery is being developed in the Mechatronics in Medicine Laboratory at Imperial College, London. This study reports an optimization procedure using finite element methods, for the identification of an interlock geometry able to limit the separation of the segments composing the multi-part probe. An optimal geometry was obtained and the corresponding three-dimensional finite element model validated experimentally. Simulation results are shown to be consistent with the physical experiments. The outcome of this study is an important step in the provision of a novel miniature steerable probe for surgery.

Single-Cell Resolution Imaging of Retinal Ganglion Cell Apoptosis In Vivo Using a Cell-Penetrating Caspase-Activatable Peptide Probe

PubMed Central

Qiu, Xudong; Johnson, James R.; Wilson, Bradley S.; Gammon, Seth T.; Piwnica-Worms, David; Barnett, Edward M.

2014-01-01

Peptide probes for imaging retinal ganglion cell (RGC) apoptosis consist of a cell-penetrating peptide targeting moiety and a fluorophore-quencher pair flanking an effector caspase consensus sequence. Using ex vivo fluorescence imaging, we previously validated the capacity of these probes to identify apoptotic RGCs in cell culture and in an in vivo rat model of N-methyl- D-aspartate (NMDA)-induced neurotoxicity. Herein, using TcapQ488, a new probe designed and synthesized for compatibility with clinically-relevant imaging instruments, and real time imaging of a live rat RGC degeneration model, we fully characterized time- and dose-dependent probe activation, signal-to-noise ratios, and probe safety profiles in vivo. Adult rats received intravitreal injections of four NMDA concentrations followed by varying TcapQ488 doses. Fluorescence fundus imaging was performed sequentially in vivo using a confocal scanning laser ophthalmoscope and individual RGCs displaying activated probe were counted and analyzed. Rats also underwent electroretinography following intravitreal injection of probe. In vivo fluorescence fundus imaging revealed distinct single-cell probe activation as an indicator of RGC apoptosis induced by intravitreal NMDA injection that corresponded to the identical cells observed in retinal flat mounts of the same eye. Peak activation of probe in vivo was detected 12 hours post probe injection. Detectable fluorescent RGCs increased with increasing NMDA concentration; sensitivity of detection generally increased with increasing TcapQ488 dose until saturating at 0.387 nmol. Electroretinography following intravitreal injections of TcapQ488 showed no significant difference compared with control injections. We optimized the signal-to-noise ratio of a caspase-activatable cell penetrating peptide probe for quantitative non-invasive detection of RGC apoptosis in vivo. Full characterization of probe performance in this setting creates an important in vivo imaging standard for functional evaluation of future probe analogues and provides a basis for extending this strategy into glaucoma-specific animal models. PMID:24586415

Cost-Effective NEO Characterization Using Solar Electric Propulsion (SEP)

NASA Astrophysics Data System (ADS)

Dissly, R. W.; Reinert, R.; Mitchell, S.

2003-05-01

We present a cost-effective multiple NEO rendezvous mission design optimized around the capabilities of Ball's 200-kg NEOX Solar Electric Propelled microsatellite. The NEOX spacecraft is 3-axis stabilized with better-than 1 milliradian pointing accuracy to serve as an excellent imaging platform; its DSN compatible telecommunications subsystem can support a 6.4-kbps downlink rate at 3 AU earth range. The spacecraft mass is <200kg at launch to allow launch as a cost-effective secondary payload. It uses proven SEP technology to provide 12km/s of Delta-V, which enables multiple rendezvous' in a single mission. Cost-effectiveness is optimized by launch as a secondary payload (e.g., Ariane-5 ASAP) or as a multiple manifest on a single dedicated launch vehicle (e.g., 4 on a Delta-II 2925). Following separation from the LV, we describe a candidate mission profile that minimizes cost by using the spacecraft's 12km/s of SEP Delta-V to allow orbiting up to 4 separate NEO's. Orbiting as opposed to flying by augments the mission's science return by providing the NEO mass and by allowing multiple phase angle imaging. The NEOX Spacecraft has the capability to support a 20kg payload drawing 100W average during SEP cruise, with >1kW available during the NEO orbital phase when the SEP thrusters are not powered. We will present a candidate payload suite that includes a visible/NIR imager, a laser altimeter, and a set of small, self-righting surface probes that can be used to assess the geophysical state of the object surface and near-surface environments. The surface probe payload notionally includes a set of cameras for imaging the body surface at mm-scale resolution, an accelerometer package to measure surface mechanical properties upon probe impact, a Langmuir probe to measure the electrostatic gradient immediately above the object surface, and an explosive charge that can be remotely detonated at the end of the surface mission to excavate an artificial crater that can be remotely observed from the orbiting spacecraft.

Comprehensive performance comparison of high-resolution array platforms for genome-wide Copy Number Variation (CNV) analysis in humans.

PubMed

Haraksingh, Rajini R; Abyzov, Alexej; Urban, Alexander Eckehart

2017-04-24

High-resolution microarray technology is routinely used in basic research and clinical practice to efficiently detect copy number variants (CNVs) across the entire human genome. A new generation of arrays combining high probe densities with optimized designs will comprise essential tools for genome analysis in the coming years. We systematically compared the genome-wide CNV detection power of all 17 available array designs from the Affymetrix, Agilent, and Illumina platforms by hybridizing the well-characterized genome of 1000 Genomes Project subject NA12878 to all arrays, and performing data analysis using both manufacturer-recommended and platform-independent software. We benchmarked the resulting CNV call sets from each array using a gold standard set of CNVs for this genome derived from 1000 Genomes Project whole genome sequencing data. The arrays tested comprise both SNP and aCGH platforms with varying designs and contain between ~0.5 to ~4.6 million probes. Across the arrays CNV detection varied widely in number of CNV calls (4-489), CNV size range (~40 bp to ~8 Mbp), and percentage of non-validated CNVs (0-86%). We discovered strikingly strong effects of specific array design principles on performance. For example, some SNP array designs with the largest numbers of probes and extensive exonic coverage produced a considerable number of CNV calls that could not be validated, compared to designs with probe numbers that are sometimes an order of magnitude smaller. This effect was only partially ameliorated using different analysis software and optimizing data analysis parameters. High-resolution microarrays will continue to be used as reliable, cost- and time-efficient tools for CNV analysis. However, different applications tolerate different limitations in CNV detection. Our study quantified how these arrays differ in total number and size range of detected CNVs as well as sensitivity, and determined how each array balances these attributes. This analysis will inform appropriate array selection for future CNV studies, and allow better assessment of the CNV-analytical power of both published and ongoing array-based genomics studies. Furthermore, our findings emphasize the importance of concurrent use of multiple analysis algorithms and independent experimental validation in array-based CNV detection studies.

Characterization of Biofilm Community Structure by Ribosomal RNA sequences

DTIC Science & Technology

1989-12-01

for strains of Fibrobacter, 2) Desulfobacter genus-specific probe, 3) Desulfosarcina genus-specific probe, 4) archaebacterial kingdom -specific probes...and 5) eubacterial kingdom -specific probes 5) eukaryote kingdom -specific probe and 6) a general probe encompassing all characterized sulfate-reducing...sets have been fabricated. The group-specific primer sets selectively amplify either sulfate-reducing bacteria or archaebacteria . The SRB-specific

Hands-Free Transcranial Color Doppler Probe

NASA Technical Reports Server (NTRS)

Chin, Robert; Madala, Srihdar; Sattler, Graham

2012-01-01

Current transcranial color Doppler (TCD) transducer probes are bulky and difficult to move in tiny increments to search and optimize TCD signals. This invention provides miniature motions of a TCD transducer probe to optimize TCD signals. The mechanical probe uses spherical bearing in guiding and locating the tilting crystal face. The lateral motion of the crystal face as it tilts across the full range of motion was achieved by minimizing the distance between the pivot location and the crystal face. The smallest commonly available metal spherical bearing was used with an outer diameter of 12 mm, a 3-mm tall retaining ring, and 5-mm overall height. Small geared motors were used that would provide sufficient power in a very compact package. After confirming the validity of the basic positioning concept, optimization design loops were completed to yield the final design.

PET-Probe: Evaluation of Technical Performance and Clinical Utility of a Handheld High-Energy Gamma Probe in Oncologic Surgery.

PubMed

Gulec, Seza A; Daghighian, Farhad; Essner, Richard

2016-12-01

Positron emission tomography (PET) has become an invaluable part of patient evaluation in surgical oncology. PET is less than optimal for detecting lesions <1 cm, and the intraoperative localization of small PET-positive lesions can be challenging as a result of difficulties in surgical exposure. We undertook this investigation to assess the utility of a handheld high-energy gamma probe (PET-Probe) for intraoperative identification of 18 F-deoxyglucose (FDG)-avid tumors. Forty patients underwent a diagnostic whole-body FDG-PET scan for consideration for surgical exploration and resection. Before surgery, all patients received an intravenous injection of 7 to 10 mCi of FDG. At surgery, the PET-Probe was used to determine absolute counts per second at the known tumor site(s) demonstrated by whole-body PET and at adjacent normal tissue (at least 4 cm away from tumor-bearing sites). Tumor-to-background ratios were calculated. Thirty-two patients (80%) underwent PET-Probe-guided surgery with therapeutic intent in a recurrent or metastatic disease setting. Eight patients underwent surgery for diagnostic exploration. Anatomical locations of the PET-identified lesions were neck and supraclavicular (n = 8), axilla (n = 5), groin and deep iliac (n = 4), trunk and extremity soft tissue (n = 3), abdominal and retroperitoneal (n = 19), and lung (n = 2). PET-Probe detected all PET-positive lesions. The PET-Probe was instrumental in localization of lesions in 15 patients that were not immediately apparent by surgical exploration. The PET-Probe identified all lesions demonstrated by PET scanning and, in selected cases, was useful in localizing FDG-avid disease not seen with conventional PET scanning.

Asymmetric rotor-like probes to polarized fluorescence study of the macroscopically oriented uniaxial media: Model parameters recognition

NASA Astrophysics Data System (ADS)

Buczkowski, M.; Fisz, J. J.

2008-07-01

In this paper the possibility of the numerical data modelling in the case of angle- and time-resolved fluorescence spectroscopy is investigated. The asymmetric fluorescence probes are assumed to undergo the restricted rotational diffusion in a hosting medium. This process is described quantitatively by the diffusion tensor and the aligning potential. The evolution of the system is expressed in terms of the Smoluchowski equation with an appropriate time-developing operator. A matrix representation of this operator is calculated, then symmetrized and diagonalized. The resulting propagator is used to generate the synthetic noisy data set that imitates results of experimental measurements. The data set serves as a groundwork to the χ2 optimization, performed by the genetic algorithm followed by the gradient search, in order to recover model parameters, which are diagonal elements of the diffusion tensor, aligning potential expansion coefficients and directions of the electronic dipole moments. This whole procedure properly identifies model parameters, showing that the outlined formalism should be taken in the account in the case of analysing real experimental data.

Interplay of magnetism and superconductivity in EuFe2(As1-xPx)2 single crystals probed by muon spin rotation and 57Fe Mössbauer spectroscopy

NASA Astrophysics Data System (ADS)

Goltz, T.; Kamusella, S.; Jeevan, H. S.; Gegenwart, P.; Luetkens, H.; Materne, P.; Spehling, J.; Sarkar, R.; Klauss, H.-H.

2014-12-01

We present our results of a local probe study on EuFe2(As1-xPx)2 single crystals with x=0.13, 0.19 and 0.28 by means of muon spin rotation and 57Fe Mössbauer spectroscopy. We focus our discussion on the sample with x=0.19 viz. at the optimal substitution level, where bulk superconductivity (TSC = 28 K) sets in above static europium order (TEu = 20 K) but well below the onset of the iron antiferromagnetic (AFM) transition (~100 K). We find enhanced spin dynamics in the Fe sublattice closely above TSC and propose that these are related to enhanced Eu fluctuations due to the evident coupling of both sublattices observed in our experiments.

Smart detection of microRNAs through fluorescence enhancement on a photonic crystal.

PubMed

Pasquardini, L; Potrich, C; Vaghi, V; Lunelli, L; Frascella, F; Descrovi, E; Pirri, C F; Pederzolli, C

2016-04-01

The detection of low abundant biomarkers, such as circulating microRNAs, demands innovative detection methods with increased resolution, sensitivity and specificity. Here, a biofunctional surface was implemented for the selective capture of microRNAs, which were detected through fluorescence enhancement directly on a photonic crystal. To set up the optimal biofunctional surface, epoxy-coated commercially available microscope slides were spotted with specific anti-microRNA probes. The optimal concentration of probe as well as of passivating agent were selected and employed for titrating the microRNA hybridization. Cross-hybridization of different microRNAs was also tested, resulting negligible. Once optimized, the protocol was adapted to the photonic crystal surface, where fluorescent synthetic miR-16 was hybridized and imaged with a dedicated equipment. The photonic crystal consists of a dielectric multilayer patterned with a grating structure. In this way, it is possible to take advantage from both a resonant excitation of fluorophores and an angularly redirection of the emitted radiation. As a result, a significant fluorescence enhancement due to the resonant structure is collected from the patterned photonic crystal with respect to the outer non-structured surface. The dedicated read-out system is compact and based on a wide-field imaging detection, with little or no optical alignment issues, which makes this approach particularly interesting for further development such as for example in microarray-type bioassays. Copyright © 2016 Elsevier B.V. All rights reserved.

A multimodal spectroscopy system for real-time disease diagnosis

NASA Astrophysics Data System (ADS)

Šćepanović, Obrad R.; Volynskaya, Zoya; Kong, Chae-Ryon; Galindo, Luis H.; Dasari, Ramachandra R.; Feld, Michael S.

2009-04-01

The combination of reflectance, fluorescence, and Raman spectroscopy—termed multimodal spectroscopy (MMS)—provides complementary and depth-sensitive information about tissue composition. As such, MMS is a promising tool for disease diagnosis, particularly in atherosclerosis and breast cancer. We have developed an integrated MMS instrument and optical fiber spectral probe for simultaneous collection of all three modalities in a clinical setting. The MMS instrument multiplexes three excitation sources, a xenon flash lamp (370-740 nm), a nitrogen laser (337 nm), and a diode laser (830 nm), through the MMS probe to excite tissue and collect the spectra. The spectra are recorded on two spectrograph/charge-coupled device modules, one optimized for visible wavelengths (reflectance and fluorescence) and the other for the near-infrared (Raman), and processed to provide diagnostic parameters. We also describe the design and calibration of a unitary MMS optical fiber probe 2 mm in outer diameter, containing a single appropriately filtered excitation fiber and a ring of 15 collection fibers, with separate groups of appropriately filtered fibers for efficiently collecting reflectance, fluorescence, and Raman spectra from the same tissue location. A probe with this excitation/collection geometry has not been used previously to collect reflectance and fluorescence spectra, and thus physical tissue models ("phantoms") are used to characterize the probe's spectroscopic response. This calibration provides probe-specific modeling parameters that enable accurate extraction of spectral parameters. This clinical MMS system has been used recently to analyze artery and breast tissue in vivo and ex vivo.

Optimal stimulus scheduling for active estimation of evoked brain networks.

PubMed

Kafashan, MohammadMehdi; Ching, ShiNung

2015-12-01

We consider the problem of optimal probing to learn connections in an evoked dynamic network. Such a network, in which each edge measures an input-output relationship between sites in sensor/actuator-space, is relevant to emerging applications in neural mapping and neural connectivity estimation. We show that the problem of scheduling nodes to a probe (i.e., stimulate) amounts to a problem of optimal sensor scheduling. By formulating the evoked network in state-space, we show that the solution to the greedy probing strategy has a convenient form and, under certain conditions, is optimal over a finite horizon. We adopt an expectation maximization technique to update the state-space parameters in an online fashion and demonstrate the efficacy of the overall approach in a series of detailed numerical examples. The proposed method provides a principled means to actively probe time-varying connections in neuronal networks. The overall method can be implemented in real time and is particularly well-suited to applications in stimulation-based cortical mapping in which the underlying network dynamics are changing over time.

Optimal stimulus scheduling for active estimation of evoked brain networks

NASA Astrophysics Data System (ADS)

Kafashan, MohammadMehdi; Ching, ShiNung

2015-12-01

Objective. We consider the problem of optimal probing to learn connections in an evoked dynamic network. Such a network, in which each edge measures an input-output relationship between sites in sensor/actuator-space, is relevant to emerging applications in neural mapping and neural connectivity estimation. Approach. We show that the problem of scheduling nodes to a probe (i.e., stimulate) amounts to a problem of optimal sensor scheduling. Main results. By formulating the evoked network in state-space, we show that the solution to the greedy probing strategy has a convenient form and, under certain conditions, is optimal over a finite horizon. We adopt an expectation maximization technique to update the state-space parameters in an online fashion and demonstrate the efficacy of the overall approach in a series of detailed numerical examples. Significance. The proposed method provides a principled means to actively probe time-varying connections in neuronal networks. The overall method can be implemented in real time and is particularly well-suited to applications in stimulation-based cortical mapping in which the underlying network dynamics are changing over time.

Barriers to ART adherence & follow ups among patients attending ART centres in Maharashtra, India.

PubMed

Joglekar, N; Paranjape, R; Jain, R; Rahane, G; Potdar, R; Reddy, K S; Sahay, S

2011-12-01

Adherence to ART is a patient specific issue influenced by a variety of situations that a patient may encounter, especially in resource-limited settings. A study was conducted to understand factors and influencers of adherence to ART and their follow ups among patients attending ART centres in Maharashtra, India. Between January and March 2009, barriers to ART adherence among 32 patients at three selected ART centres functioning under national ART roll-out programme in Maharashtra, India, were studied using qualitative methods. Consenting patients were interviewed to assess barriers to ART adherence. Constant comparison method was used to identify grounded codes. Patients reported multiple barriers to ART adherence and follow up as (i) Financial barriers where the contributing factors were unemployment, economic dependency, and debt, (ii) social norm of attending family rituals, and fulfilling social obligations emerged as socio-cultural barriers, (iii) patients' belief, attitude and behaviour towards medication and self-perceived stigma were the reasons for sub-optimal adherence, and (iv) long waiting period, doctor-patient relationship and less time devoted in counselling at the center contributed to missed visits. Mainstreaming ART can facilitate access and address 'missed doses' due to travel and migration. A 'morning' and 'evening' ART centre/s hours may reduce work absenteeism and help in time management. Proactive 'adherence probing' and probing on internalized stigma might optimize adherence. Adherence probing to prevent transitioning to suboptimal adherence among patients stable on ART is recommended.

SigReannot-mart: a query environment for expression microarray probe re-annotations.

PubMed

Moreews, François; Rauffet, Gaelle; Dehais, Patrice; Klopp, Christophe

2011-01-01

Expression microarrays are commonly used to study transcriptomes. Most of the arrays are now based on oligo-nucleotide probes. Probe design being a tedious task, it often takes place once at the beginning of the project. The oligo set is then used for several years. During this time period, the knowledge gathered by the community on the genome and the transcriptome increases and gets more precise. Therefore re-annotating the set is essential to supply the biologists with up-to-date annotations. SigReannot-mart is a query environment populated with regularly updated annotations for different oligo sets. It stores the results of the SigReannot pipeline that has mainly been used on farm and aquaculture species. It permits easy extraction in different formats using filters. It is used to compare probe sets on different criteria, to choose the set for a given experiment to mix probe sets in order to create a new one.

Synthetic oligonucleotide probes deduced from amino acid sequence data. Theoretical and practical considerations.

PubMed

Lathe, R

1985-05-05

Synthetic probes deduced from amino acid sequence data are widely used to detect cognate coding sequences in libraries of cloned DNA segments. The redundancy of the genetic code dictates that a choice must be made between (1) a mixture of probes reflecting all codon combinations, and (2) a single longer "optimal" probe. The second strategy is examined in detail. The frequency of sequences matching a given probe by chance alone can be determined and also the frequency of sequences closely resembling the probe and contributing to the hybridization background. Gene banks cannot be treated as random associations of the four nucleotides, and probe sequences deduced from amino acid sequence data occur more often than predicted by chance alone. Probe lengths must be increased to confer the necessary specificity. Examination of hybrids formed between unique homologous probes and their cognate targets reveals that short stretches of perfect homology occurring by chance make a significant contribution to the hybridization background. Statistical methods for improving homology are examined, taking human coding sequences as an example, and considerations of codon utilization and dinucleotide frequencies yield an overall homology of greater than 82%. Recommendations for probe design and hybridization are presented, and the choice between using multiple probes reflecting all codon possibilities and a unique optimal probe is discussed.

Continuous-variable quantum probes for structured environments

NASA Astrophysics Data System (ADS)

Bina, Matteo; Grasselli, Federico; Paris, Matteo G. A.

2018-01-01

We address parameter estimation for structured environments and suggest an effective estimation scheme based on continuous-variables quantum probes. In particular, we investigate the use of a single bosonic mode as a probe for Ohmic reservoirs, and obtain the ultimate quantum limits to the precise estimation of their cutoff frequency. We assume the probe prepared in a Gaussian state and determine the optimal working regime, i.e., the conditions for the maximization of the quantum Fisher information in terms of the initial preparation, the reservoir temperature, and the interaction time. Upon investigating the Fisher information of feasible measurements, we arrive at a remarkable simple result: homodyne detection of canonical variables allows one to achieve the ultimate quantum limit to precision under suitable, mild, conditions. Finally, upon exploiting a perturbative approach, we find the invariant sweet spots of the (tunable) characteristic frequency of the probe, able to drive the probe towards the optimal working regime.

Performance Comparison of High-Speed Dual-Pneumatic Vitrectomy Cutters during Simulated Vitrectomy with Balanced Salt Solution.

PubMed

Abulon, Dina Joy K; Buboltz, David C

2015-02-01

To measure flow rate of balanced salt solution and IOP during simulated vitrectomy using two sets of high-speed dual-pneumatic probes. A closed-model eye system measured IOP and flow rate of a balanced salt solution through infusion cannula. The Constellation Vision System was tested with two sets of high-speed dual-pneumatic probes (UltraVit 23-gauge and enhanced 25+-gauge 5000-cpm probes; UltraVit 23-gauge and enhanced 25+-gauge 7500-cpm probes; n = 6 each) under different vacuum levels and cut rates in three duty cycle modes. In both probe sets, flow rates were dependent on cut rate with the biased open and biased closed duty cycles. Flow rates were highest with the biased open duty cycle, lower with the 50/50 duty cycle, and lowest with the biased closed duty cycle. IOP, as expected, was inversely associated with flow rate using both probe sets. The 7500-cpm probes offer greater control and customization compared with 5000-cpm probes under certain experimental conditions. At maximum cut rates, performance of 7500-cpm probes was similar to that of 5000-cpm probes, suggesting that 7500-cpm probes may be used without sacrifice of flow rate and IOP stability. Customization of vitrectomy parameters allows greater surgeon control during vitrectomy and may expand the usefulness of vitrectomy probes.

Where do pulse oximeter probes break?

PubMed

Crede, S; Van der Merwe, G; Hutchinson, J; Woods, D; Karlen, W; Lawn, J

2014-06-01

Pulse oximetry, a non-invasive method for accurate assessment of blood oxygen saturation (SPO2), is an important monitoring tool in health care facilities. However, it is often not available in many low-resource settings, due to expense, overly sophisticated design, a lack of organised procurement systems and inadequate medical device management and maintenance structures. Furthermore medical devices are often fragile and not designed to withstand the conditions of low-resource settings. In order to design a probe, better suited to the needs of health care facilities in low-resource settings this study aimed to document the site and nature of pulse oximeter probe breakages in a range of different probe designs in a low to middle income country. A retrospective review of job cards relating to the assessment and repair of damaged or faulty pulse oximeter probes was conducted at a medical device repair company based in Cape Town, South Africa, specializing in pulse oximeter probe repairs. 1,840 job cards relating to the assessment and repair of pulse oximeter probes were reviewed. 60.2 % of probes sent for assessment were finger-clip probes. For all probes, excluding the neonatal wrap probes, the most common point of failure was the probe wiring (>50 %). The neonatal wrap most commonly failed at the strap (51.5 %). The total cost for quoting on the broken pulse oximeter probes and for the subsequent repair of devices, excluding replacement components, amounted to an estimated ZAR 738,810 (USD $98,508). Improving the probe wiring would increase the life span of pulse oximeter probes. Increasing the life span of probes will make pulse oximetry more affordable and accessible. This is of high priority in low-resource settings where frequent repair or replacement of probes is unaffordable or impossible.

OCaPPI-Db: an oligonucleotide probe database for pathogen identification through hybridization capture.

PubMed

Gasc, Cyrielle; Constantin, Antony; Jaziri, Faouzi; Peyret, Pierre

2017-01-01

The detection and identification of bacterial pathogens involved in acts of bio- and agroterrorism are essential to avoid pathogen dispersal in the environment and propagation within the population. Conventional molecular methods, such as PCR amplification, DNA microarrays or shotgun sequencing, are subject to various limitations when assessing environmental samples, which can lead to inaccurate findings. We developed a hybridization capture strategy that uses a set of oligonucleotide probes to target and enrich biomarkers of interest in environmental samples. Here, we present Oligonucleotide Capture Probes for Pathogen Identification Database (OCaPPI-Db), an online capture probe database containing a set of 1,685 oligonucleotide probes allowing for the detection and identification of 30 biothreat agents up to the species level. This probe set can be used in its entirety as a comprehensive diagnostic tool or can be restricted to a set of probes targeting a specific pathogen or virulence factor according to the user's needs. : http://ocappidb.uca.works. © The Author(s) 2017. Published by Oxford University Press.

Radiolabeled inorganic nanoparticles for positron emission tomography imaging of cancer: an overview

PubMed Central

CHAKRAVARTY, Rubel; GOEL, Shreya; DASH, Ashutosh; CAI, Weibo

2017-01-01

Over the last few years, a plethora of radiolabeled inorganic nanoparticles have been developed and evaluated for their potential use as probes in positron emission tomography (PET) imaging of a wide variety of cancers. Inorganic nanoparticles represent an emerging paradigm in molecular imaging probe design, allowing the incorporation of various imaging modalities, targeting ligands, and therapeutic payloads into a single vector. A major challenge in this endeavor is to develop disease-specific nanoparticles with facile and robust radiolabeling strategies. Also, the radiolabeled nanoparticles should demonstrate adequate in vitro and in vivo stability, enhanced sensitivity for detection of disease at an early stage, optimized in vivo pharmacokinetics for reduced non-specific organ uptake, and improved targeting for achieving high efficacy. Owing to these challenges and other technological and regulatory issues, only a single radiolabeled nanoparticle formulation, namely “C-dots” (Cornell dots), has found its way into clinical trials thus far. This review describes the available options for radiolabeling of nanoparticles and summarizes the recent developments in PET imaging of cancer in preclinical and clinical settings using radiolabeled nanoparticles as probes. The key considerations toward clinical translation of these novel PET imaging probes are discussed, which will be beneficial for advancement of the field. PMID:28124549

Probing phenylalanine/adenine pi-stacking interactions in protein complexes with explicitly correlated and CCSD(T) computations.

PubMed

Copeland, Kari L; Anderson, Julie A; Farley, Adam R; Cox, James R; Tschumper, Gregory S

2008-11-13

To examine the effects of pi-stacking interactions between aromatic amino acid side chains and adenine bearing ligands in crystalline protein structures, 26 toluene/(N9-methyl)adenine model configurations have been constructed from protein/ligand crystal structures. Full geometry optimizations with the MP2 method cause the 26 crystal structures to collapse to six unique structures. The complete basis set (CBS) limit of the CCSD(T) interaction energies has been determined for all 32 structures by combining explicitly correlated MP2-R12 computations with a correction for higher-order correlation effects from CCSD(T) calculations. The CCSD(T) CBS limit interaction energies of the 26 crystal structures range from -3.19 to -6.77 kcal mol (-1) and average -5.01 kcal mol (-1). The CCSD(T) CBS limit interaction energies of the optimized complexes increase by roughly 1.5 kcal mol (-1) on average to -6.54 kcal mol (-1) (ranging from -5.93 to -7.05 kcal mol (-1)). Corrections for higher-order correlation effects are extremely important for both sets of structures and are responsible for the modest increase in the interaction energy after optimization. The MP2 method overbinds the crystal structures by 2.31 kcal mol (-1) on average compared to 4.50 kcal mol (-1) for the optimized structures.

Probe interface design consideration. [for interplanetary spacecraft missions

NASA Technical Reports Server (NTRS)

Casani, E. K.

1974-01-01

Interface design between a probe and a spacecraft requires not only technical considerations but also management planning and mission analysis interactions. Two further aspects of importance are the flyby versus the probe trade-off, and the relay link design and data handling optimization.

EvOligo: A Novel Software to Design and Group Libraries of Oligonucleotides Applicable for Nucleic Acid-Based Experiments.

PubMed

Milewski, Marek C; Kamel, Karol; Kurzynska-Kokorniak, Anna; Chmielewski, Marcin K; Figlerowicz, Marek

2017-10-01

Experimental methods based on DNA and RNA hybridization, such as multiplex polymerase chain reaction, multiplex ligation-dependent probe amplification, or microarray analysis, require the use of mixtures of multiple oligonucleotides (primers or probes) in a single test tube. To provide an optimal reaction environment, minimal self- and cross-hybridization must be achieved among these oligonucleotides. To address this problem, we developed EvOligo, which is a software package that provides the means to design and group DNA and RNA molecules with defined lengths. EvOligo combines two modules. The first module performs oligonucleotide design, and the second module performs oligonucleotide grouping. The software applies a nearest-neighbor model of nucleic acid interactions coupled with a parallel evolutionary algorithm to construct individual oligonucleotides, and to group the molecules that are characterized by the weakest possible cross-interactions. To provide optimal solutions, the evolutionary algorithm sorts oligonucleotides into sets, preserves preselected parts of the oligonucleotides, and shapes their remaining parts. In addition, the oligonucleotide sets can be designed and grouped based on their melting temperatures. For the user's convenience, EvOligo is provided with a user-friendly graphical interface. EvOligo was used to design individual oligonucleotides, oligonucleotide pairs, and groups of oligonucleotide pairs that are characterized by the following parameters: (1) weaker cross-interactions between the non-complementary oligonucleotides and (2) more uniform ranges of the oligonucleotide pair melting temperatures than other available software products. In addition, in contrast to other grouping algorithms, EvOligo offers time-efficient sorting of paired and unpaired oligonucleotides based on various parameters defined by the user.

Optimising probe holder design for sentinel lymph node imaging using clinical photoacoustic system with Monte Carlo simulation

NASA Astrophysics Data System (ADS)

Sivasubramanian, Kathyayini; Periyasamy, Vijitha; Wen, Kew Kok; Pramanik, Manojit

2017-03-01

Photoacoustic tomography is a hybrid imaging modality that combines optical and ultrasound imaging. It is rapidly gaining attention in the field of medical imaging. The challenge is to translate it into a clinical setup. In this work, we report the development of a handheld clinical photoacoustic imaging system. A clinical ultrasound imaging system is modified to integrate photoacoustic imaging with the ultrasound imaging. Hence, light delivery has been integrated with the ultrasound probe. The angle of light delivery is optimized in this work with respect to the depth of imaging. Optimization was performed based on Monte Carlo simulation for light transport in tissues. Based on the simulation results, the probe holders were fabricated using 3D printing. Similar results were obtained experimentally using phantoms. Phantoms were developed to mimic sentinel lymph node imaging scenario. Also, in vivo sentinel lymph node imaging was done using the same system with contrast agent methylene blue up to a depth of 1.5 cm. The results validate that one can use Monte Carlo simulation as a tool to optimize the probe holder design depending on the imaging needs. This eliminates a trial and error approach generally used for designing a probe holder.

Dimensionality of Data Matrices with Applications to Gene Expression Profiles

ERIC Educational Resources Information Center

Feng, Xingdong

2009-01-01

Probe-level microarray data are usually stored in matrices. Take a given probe set (gene), for example, each row of the matrix corresponds to an array, and each column corresponds to a probe. Often, people summarize each array by the gene expression level. Is one number sufficient to summarize a whole probe set for a specific gene in an array?…

A support vector machine designed to identify breasts at high risk using multi-probe generated REIS signals: a preliminary assessment

NASA Astrophysics Data System (ADS)

Gur, David; Zheng, Bin; Lederman, Dror; Dhurjaty, Sreeram; Sumkin, Jules; Zuley, Margarita

2010-02-01

A new resonance-frequency based electronic impedance spectroscopy (REIS) system with multi-probes, including one central probe and six external probes that are designed to contact the breast skin in a circular form with a radius of 60 millimeters to the central ("nipple") probe, has been assembled and installed in our breast imaging facility. We are conducting a prospective clinical study to test the performance of this REIS system in identifying younger women (< 50 years old) at higher risk for having or developing breast cancer. In this preliminary analysis, we selected a subset of 100 examinations. Among these, 50 examinations were recommended for a biopsy due to detection of a highly suspicious breast lesion and 50 were determined negative during mammography screening. REIS output signal sweeps that we used to compute an initial feature included both amplitude and phase information representing differences between corresponding (matched) EIS signal values acquired from the left and right breasts. A genetic algorithm was applied to reduce the feature set and optimize a support vector machine (SVM) to classify the REIS examinations into "biopsy recommended" and "non-biopsy" recommended groups. Using the leave-one-case-out testing method, the classification performance as measured by the area under the receiver operating characteristic (ROC) curve was 0.816 +/- 0.042. This pilot analysis suggests that the new multi-probe-based REIS system could potentially be used as a risk stratification tool to identify pre-screened young women who are at higher risk of having or developing breast cancer.

How I do it-optimizing radiofrequency ablation in spinal metastases using iCT and navigation.

PubMed

Kavakebi, Pujan; Freyschlag, C F; Thomé, C

2017-10-01

Exact positioning of the radiofrequency ablation (RFA) probe for tumor treatment under fluoroscopic guidance can be difficult because of potentially small inaccessible lesions and the radiation dose to the medical staff in RFA. In addition, vertebroplasty (VP) can be significantly high. Description and workflow of RFA in spinal metastasis using iCT (intraoperative computed tomography) and 3D-navigation-based probe placement followed by VP. RFA and VP can be successfully combined with iCT-based navigation, which leads to a reduction of radiation to the staff and optimal probe positioning due to 3D navigation.

Characterizing the Diversity and Biological Relevance of the MLPCN Assay Manifold and Screening Set

PubMed Central

Zhang, Jintao; Lushington, Gerald H.; Huan, Jun

2011-01-01

The NIH Molecular Libraries Initiative (MLI), launched in 2004 with initial goals of identifying chemical probes for characterizing gene function and druggability, has produced PubChem, a chemical genomics knowledgebase for fostering translation of basic research into new therapeutic strategies. This paper assesses progress toward these goals by evaluating MLI target novelty and propensity for undergoing biochemically or therapeutically relevant modulations and the degree of chemical diversity and biogenic bias inherent in the MLI screening set. Our analyses suggest that while MLI target selection has not yet been fully optimized for biochemical diversity, it covers biologically interesting pathway space that complements established drug targets. We find the MLI screening set to be chemically diverse and to have greater biogenic bias than comparable collections of commercially available compounds. Biogenic enhancements such as incorporation of more metabolite-like chemotypes are suggested. PMID:21568288

Identifying members of the domain Archaea with rRNA-targeted oligonucleotide probes.

PubMed

Burggraf, S; Mayer, T; Amann, R; Schadhauser, S; Woese, C R; Stetter, K O

1994-09-01

Two 16S rRNA-targeted oligonucleotide probes were designed for the archaeal kingdoms Euryachaeota and Crenarchaeota. Probe specificities were evaluated by nonradioactive dot blot hybridization against selected reference organisms. The successful application of fluorescent-probe derivatives for whole-cell hybridization required organism-specific optimizations of fixation and hybridization conditions to assure probe penetration and morphological integrity of the cells. The probes allowed preliminary grouping of three new hyperthermophilic isolates. Together with other group-specific rRNA-targeted oligonucleotide probes, these probes will facilitate rapid in situ monitoring of the populations present in hydrothermal systems and support cultivation attempts.

Which electrode? A comparison of four endoscopic methods of electrocoagulation in experimental bleeding ulcers.

PubMed Central

Swain, C P; Mills, T N; Shemesh, E; Dark, J M; Lewin, M R; Clifton, J S; Northfield, T C; Cotton, P B; Salmon, P R

1984-01-01

Several inexpensive endoscopic methods of electrocoagulation have been advocated for treatment of gastrointestinal haemorrhage. We compared four types of electrode: dry monopolar - Cameron Miller (M), liquid monopolar - Storz (L), bipolar - Bicap ACMI (B), and heater probe - Seattle (H). The electrical and thermal properties of these probes were studied using computerised monitoring of energy deposition and their efficacy and safety was tested in a randomised study in 140 experimental canine gastric ulcers. At optimal pulse settings 20J (M), 70J (L), 17J (B), 15J (H), effective haemostasis was achieved in all ulcers, the mean number of pulses being M5, L6, H6 and B11, the first three requiring significantly (p less than 0.01) less pulse than B. Relative safety of the electrodes was assessed by comparing the incidence of full thickness damage at histology: B24%, H20%, L58% and M69%; B and H proving significantly (p less than 0.01) safer than L and M. Sticking was assessed as H greater than B greater than M much greater than L. Insensitivity to extreme angulation and force of application was assessed as L greater than B greater than M (H is preset). Of the two safer electrodes the heater probe was more effective than the bipolar probe. Despite its greater tendency to stick than the other devices, the heater probe appeared the most promising of the endoscopic electrodes tested. Images Fig. 1 Fig. 2 PMID:6510772

Diagnostics of the ITER neutral beam test facility.

PubMed

Pasqualotto, R; Serianni, G; Sonato, P; Agostini, M; Brombin, M; Croci, G; Dalla Palma, M; De Muri, M; Gazza, E; Gorini, G; Pomaro, N; Rizzolo, A; Spolaore, M; Zaniol, B

2012-02-01

The ITER heating neutral beam (HNB) injector, based on negative ions accelerated at 1 MV, will be tested and optimized in the SPIDER source and MITICA full injector prototypes, using a set of diagnostics not available on the ITER HNB. The RF source, where the H(-)∕D(-) production is enhanced by cesium evaporation, will be monitored with thermocouples, electrostatic probes, optical emission spectroscopy, cavity ring down, and laser absorption spectroscopy. The beam is analyzed by cooling water calorimetry, a short pulse instrumented calorimeter, beam emission spectroscopy, visible tomography, and neutron imaging. Design of the diagnostic systems is presented.

Multiplex detection of respiratory pathogens

DOEpatents

McBride, Mary [Brentwood, CA; Slezak, Thomas [Livermore, CA; Birch, James M [Albany, CA

2012-07-31

Described are kits and methods useful for detection of respiratory pathogens (influenza A (including subtyping capability for H1, H3, H5 and H7 subtypes) influenza B, parainfluenza (type 2), respiratory syncytial virus, and adenovirus) in a sample. Genomic sequence information from the respiratory pathogens was analyzed to identify signature sequences, e.g., polynucleotide sequences useful for confirming the presence or absence of a pathogen in a sample. Primer and probe sets were designed and optimized for use in a PCR based, multiplexed Luminex assay to successfully identify the presence or absence of pathogens in a sample.

PROBING THE EXPANSION HISTORY OF THE UNIVERSE BY MODEL-INDEPENDENT RECONSTRUCTION FROM SUPERNOVAE AND GAMMA-RAY BURST MEASUREMENTS

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

Feng, Chao-Jun; Li, Xin-Zhou, E-mail: fengcj@shnu.edu.cn, E-mail: kychz@shnu.edu.cn

To probe the late evolution history of the universe, we adopt two kinds of optimal basis systems. One of them is constructed by performing the principle component analysis, and the other is built by taking the multidimensional scaling approach. Cosmological observables such as the luminosity distance can be decomposed into these basis systems. These basis systems are optimized for different kinds of cosmological models that are based on different physical assumptions, even for a mixture model of them. Therefore, the so-called feature space that is projected from the basis systems is cosmological model independent, and it provides a parameterization for studying and reconstructing themore » Hubble expansion rate from the supernova luminosity distance and even gamma-ray burst (GRB) data with self-calibration. The circular problem when using GRBs as cosmological candles is naturally eliminated in this procedure. By using the Levenberg–Marquardt technique and the Markov Chain Monte Carlo method, we perform an observational constraint on this kind of parameterization. The data we used include the “joint light-curve analysis” data set that consists of 740 Type Ia supernovae and 109 long GRBs with the well-known Amati relation.« less

Validating a new methodology for optical probe design and image registration in fNIRS studies

PubMed Central

Wijeakumar, Sobanawartiny; Spencer, John P.; Bohache, Kevin; Boas, David A.; Magnotta, Vincent A.

2015-01-01

Functional near-infrared spectroscopy (fNIRS) is an imaging technique that relies on the principle of shining near-infrared light through tissue to detect changes in hemodynamic activation. An important methodological issue encountered is the creation of optimized probe geometry for fNIRS recordings. Here, across three experiments, we describe and validate a processing pipeline designed to create an optimized, yet scalable probe geometry based on selected regions of interest (ROIs) from the functional magnetic resonance imaging (fMRI) literature. In experiment 1, we created a probe geometry optimized to record changes in activation from target ROIs important for visual working memory. Positions of the sources and detectors of the probe geometry on an adult head were digitized using a motion sensor and projected onto a generic adult atlas and a segmented head obtained from the subject's MRI scan. In experiment 2, the same probe geometry was scaled down to fit a child's head and later digitized and projected onto the generic adult atlas and a segmented volume obtained from the child's MRI scan. Using visualization tools and by quantifying the amount of intersection between target ROIs and channels, we show that out of 21 ROIs, 17 and 19 ROIs intersected with fNIRS channels from the adult and child probe geometries, respectively. Further, both the adult atlas and adult subject-specific MRI approaches yielded similar results and can be used interchangeably. However, results suggest that segmented heads obtained from MRI scans be used for registering children's data. Finally, in experiment 3, we further validated our processing pipeline by creating a different probe geometry designed to record from target ROIs involved in language and motor processing. PMID:25705757

Are mind wandering rates an artifact of the probe-caught method? Using self-caught mind wandering in the classroom to test, and reject, this possibility.

PubMed

Varao-Sousa, Trish L; Kingstone, Alan

2018-06-26

Mind wandering (MW) reports often rely on individuals responding to specific external thought probes. Researchers have used this probe-caught method almost exclusively, due to its reliability across a wide range of testing situations. However, it remains an open question whether the probe-caught MW rates in more complex settings converge with those for simpler tasks, because of the rather artificial and controlled nature of the probe-caught methodology itself, which is shared across the different settings. To address this issue, we measured MW in a real-world lecture, during which students indicated whether they were mind wandering by simply catching themselves (as one would normally do in real life) or by catching themselves and responding to thought probes. Across three separate lectures, self-caught MW reports were stable and unaffected by the inclusion of MW probes. That the probe rates were similar to those found in prior classroom research and did not affect the self-caught MW rates strongly suggests that the past consistency of probe-caught MW rates across a range of different settings is not an artifact of the thought-probe method. Our study also indicates that the self-caught MW methodology is a reliable way to acquire MW data. The extension of measurement techniques to include students' self-caught reports provides valuable information about how to successfully and naturalistically monitor MW in lecture settings, outside the laboratory.

[Research progress of probe design software of oligonucleotide microarrays].

PubMed

Chen, Xi; Wu, Zaoquan; Liu, Zhengchun

2014-02-01

DNA microarray has become an essential medical genetic diagnostic tool for its high-throughput, miniaturization and automation. The design and selection of oligonucleotide probes are critical for preparing gene chips with high quality. Several sets of probe design software have been developed and are available to perform this work now. Every set of the software aims to different target sequences and shows different advantages and limitations. In this article, the research and development of these sets of software are reviewed in line with three main criteria, including specificity, sensitivity and melting temperature (Tm). In addition, based on the experimental results from literatures, these sets of software are classified according to their applications. This review will be helpful for users to choose an appropriate probe-design software. It will also reduce the costs of microarrays, improve the application efficiency of microarrays, and promote both the research and development (R&D) and commercialization of high-performance probe design software.

An evanescent wave biosensor--Part I: Fluorescent signal acquisition from step-etched fiber optic probes.

PubMed

Anderson, G P; Golden, J P; Ligler, F S

1994-06-01

A fiber-optic biosensor capable of remote continuous monitoring has recently been designed. To permit sensing at locations separate from the optoelectronic instrumentation, long optical fibers are utilized. An evanescent wave immuno-probe is prepared by removing the cladding near the distal end of the fiber and covalently attaching antibodies to the core. Probes with a radius unaltered from that of the original core inefficiently returned the signal produced upon binding the fluorescent-labelled antigen. To elucidate the limiting factors in signal acquisition, a series of fibers with increasingly reduced probe core radius was examined. The results were consistent with the V-number mismatch, the difference in mode carrying capacity between the clad and unclad fiber, being a critical factor in limiting signal coupling from the fiber probe. However, it was also delineated that conditions which conserve excitation power, such that power in the evanescent wave is optimized, must also be met to obtain a maximal signal. The threshold sensitivity for the optimal step-etched fiber probe was improved by over 20-fold in an immunoassay, although, it was demonstrated that signal acquisition decreased along the probe length, suggesting that a sensor region of uniform radius is not ideal.

Optimal approaches for inline sampling of organisms in ballast water: L-shaped vs. Straight sample probes

NASA Astrophysics Data System (ADS)

Wier, Timothy P.; Moser, Cameron S.; Grant, Jonathan F.; Riley, Scott C.; Robbins-Wamsley, Stephanie H.; First, Matthew R.; Drake, Lisa A.

2017-10-01

Both L-shaped ("L") and straight ("Straight") sample probes have been used to collect water samples from a main ballast line in land-based or shipboard verification testing of ballast water management systems (BWMS). A series of experiments was conducted to quantify and compare the sampling efficiencies of L and Straight sample probes. The findings from this research-that both L and Straight probes sample organisms with similar efficiencies-permit increased flexibility for positioning sample probes aboard ships.

Development of a 3-wire probe for the simultaneous measurement of turbulent velocity, concentration and temperature fields

NASA Astrophysics Data System (ADS)

Hewes, Alaïs; Mydlarski, Laurent

2015-11-01

The present work focuses on the design and optimization of a probe used to simultaneously measure the velocity, concentration and temperature fields in a turbulent jet. The underlying principles of this sensor are based in thermal-anemometry techniques, and the design of this 3-wire probe builds off the previous work of Sirivat and Warhaft, J. Fluid Mech., 1982. In the first part of this study, the effect of different overheat ratios in the first two wires (called the ``interference'' or ``Way-Libby'' probe - used to infer velocity and concentration) are investigated. Of particular interest is their effect on the quality of the resulting calibration, as well as the measured velocity and concentration data. Four different overheat ratio pairs for the two wires comprising the interference probe are studied. In the second part of this work, a third wire, capable of detecting temperature fluctuations, is added to the 3-wire probe. The optimal configuration of this probe, including wire type and overheat ratio for the third wire, is studied and the simultaneously-measured velocity, concentration, and temperature data (e.g. spectra, PDFs) for different probe configurations are presented. Supported by the Natural Sciences and Engineering Research Council of Canada (Grant 217184).

Optimizing multi-step B-side charge separation in photosynthetic reaction centers from Rhodobacter capsulatus

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

Faries, Kaitlyn M.; Kressel, Lucas L.; Dylla, Nicholas P.

Using high-throughput methods for mutagenesis, protein isolation and charge-separation functionality, we have assayed 40 Rhodobacter capsulatus reaction center (RC) mutants for their P+ QB- yield (P is a dimer of bacteriochlorophylls and Q is a ubiquinone) as produced using the normally inactive B-side cofactors BB and HB (where B is a bacteriochlorophyll and H is a bacteriopheophytin). Two sets of mutants explore all possible residues at M131 (M polypeptide, native residue Val near HB) in tandem with either a fixed His or a fixed Asn at L181 (L polypeptide, native residue Phe near BB). A third set of mutants exploresmore » all possible residues at L181 with a fixed Glu at M131 that can form a hydrogen bond to HB. For each set of mutants, the results of a rapid millisecond screening assay that probes the yield of P+ QB- are compared among that set and to the other mutants reported here or previously. For a subset of eight mutants, the rate constants and yields of the individual B-side electron transfer processes are determined via transient absorption measurements spanning 100 fs to 50 μs. The resulting ranking of mutants for their yield of P+ QB- from ultrafast experiments is in good agreement with that obtained from the millisecond screening assay, further validating the efficient, high-throughput screen for B-side transmembrane charge separation. Results from mutants that individually show progress toward optimization of P+ HB- → P+ QB- electron transfer or initial P* → P+ HB- conversion highlight unmet challenges of optimizing both processes simultaneously.« less

An exemplar-familiarity model predicts short-term and long-term probe recognition across diverse forms of memory search.

PubMed

Nosofsky, Robert M; Cox, Gregory E; Cao, Rui; Shiffrin, Richard M

2014-11-01

Experiments were conducted to test a modern exemplar-familiarity model on its ability to account for both short-term and long-term probe recognition within the same memory-search paradigm. Also, making connections to the literature on attention and visual search, the model was used to interpret differences in probe-recognition performance across diverse conditions that manipulated relations between targets and foils across trials. Subjects saw lists of from 1 to 16 items followed by a single item recognition probe. In a varied-mapping condition, targets and foils could switch roles across trials; in a consistent-mapping condition, targets and foils never switched roles; and in an all-new condition, on each trial a completely new set of items formed the memory set. In the varied-mapping and all-new conditions, mean correct response times (RTs) and error proportions were curvilinear increasing functions of memory set size, with the RT results closely resembling ones from hybrid visual-memory search experiments reported by Wolfe (2012). In the consistent-mapping condition, new-probe RTs were invariant with set size, whereas old-probe RTs increased slightly with increasing study-test lag. With appropriate choice of psychologically interpretable free parameters, the model accounted well for the complete set of results. The work provides support for the hypothesis that a common set of processes involving exemplar-based familiarity may govern long-term and short-term probe recognition across wide varieties of memory- search conditions. PsycINFO Database Record (c) 2014 APA, all rights reserved.

Analyzing Planck and low redshift data sets with advanced statistical methods

NASA Astrophysics Data System (ADS)

Eifler, Tim

The recent ESA/NASA Planck mission has provided a key data set to constrain cosmology that is most sensitive to physics of the early Universe, such as inflation and primordial NonGaussianity (Planck 2015 results XIII). In combination with cosmological probes of the LargeScale Structure (LSS), the Planck data set is a powerful source of information to investigate late time phenomena (Planck 2015 results XIV), e.g. the accelerated expansion of the Universe, the impact of baryonic physics on the growth of structure, and the alignment of galaxies in their dark matter halos. It is the main objective of this proposal to re-analyze the archival Planck data, 1) with different, more recently developed statistical methods for cosmological parameter inference, and 2) to combine Planck and ground-based observations in an innovative way. We will make the corresponding analysis framework publicly available and believe that it will set a new standard for future CMB-LSS analyses. Advanced statistical methods, such as the Gibbs sampler (Jewell et al 2004, Wandelt et al 2004) have been critical in the analysis of Planck data. More recently, Approximate Bayesian Computation (ABC, see Weyant et al 2012, Akeret et al 2015, Ishida et al 2015, for cosmological applications) has matured to an interesting tool in cosmological likelihood analyses. It circumvents several assumptions that enter the standard Planck (and most LSS) likelihood analyses, most importantly, the assumption that the functional form of the likelihood of the CMB observables is a multivariate Gaussian. Beyond applying new statistical methods to Planck data in order to cross-check and validate existing constraints, we plan to combine Planck and DES data in a new and innovative way and run multi-probe likelihood analyses of CMB and LSS observables. The complexity of multiprobe likelihood analyses scale (non-linearly) with the level of correlations amongst the individual probes that are included. For the multi-probe analysis proposed here we will use the existing CosmoLike software, a computationally efficient analysis framework that is unique in its integrated ansatz of jointly analyzing probes of large-scale structure (LSS) of the Universe. We plan to combine CosmoLike with publicly available CMB analysis software (Camb, CLASS) to include modeling capabilities of CMB temperature, polarization, and lensing measurements. The resulting analysis framework will be capable to independently and jointly analyze data from the CMB and from various probes of the LSS of the Universe. After completion we will utilize this framework to check for consistency amongst the individual probes and subsequently run a joint likelihood analysis of probes that are not in tension. The inclusion of Planck information in a joint likelihood analysis substantially reduces DES uncertainties in cosmological parameters, and allows for unprecedented constraints on parameters that describe astrophysics. In their recent review Observational Probes of Cosmic Acceleration (Weinberg et al 2013) the authors emphasize the value of a balanced program that employs several of the most powerful methods in combination, both to cross-check systematic uncertainties and to take advantage of complementary information. The work we propose follows exactly this idea: 1) cross-checking existing Planck results with alternative methods in the data analysis, 2) checking for consistency of Planck and DES data, and 3) running a joint analysis to constrain cosmology and astrophysics. It is now expedient to develop and refine multi-probe analysis strategies that allow the comparison and inclusion of information from disparate probes to optimally obtain cosmology and astrophysics. Analyzing Planck and DES data poses an ideal opportunity for this purpose and corresponding lessons will be of great value for the science preparation of Euclid and WFIRST.

System Design under Uncertainty: Evolutionary Optimization of the Gravity Probe-B Spacecraft

NASA Technical Reports Server (NTRS)

Pullen, Samuel P.; Parkinson, Bradford W.

1994-01-01

This paper discusses the application of evolutionary random-search algorithms (Simulated Annealing and Genetic Algorithms) to the problem of spacecraft design under performance uncertainty. Traditionally, spacecraft performance uncertainty has been measured by reliability. Published algorithms for reliability optimization are seldom used in practice because they oversimplify reality. The algorithm developed here uses random-search optimization to allow us to model the problem more realistically. Monte Carlo simulations are used to evaluate the objective function for each trial design solution. These methods have been applied to the Gravity Probe-B (GP-B) spacecraft being developed at Stanford University for launch in 1999, Results of the algorithm developed here for GP-13 are shown, and their implications for design optimization by evolutionary algorithms are discussed.

Less is more: Patient-level meta-analysis reveals paradoxical dose-response effects of a computer-based social anxiety intervention targeting attentional bias.

PubMed

Price, Rebecca B; Kuckertz, Jennie M; Amir, Nader; Bar-Haim, Yair; Carlbring, Per; Wallace, Meredith L

2017-12-01

The past decade of research has seen considerable interest in computer-based approaches designed to directly target cognitive mechanisms of anxiety, such as attention bias modification (ABM). By pooling patient-level datasets from randomized controlled trials of ABM that utilized a dot-probe training procedure, we assessed the impact of training "dose" on relevant outcomes among a pooled sample of 693 socially anxious adults. A paradoxical effect of the number of training trials administered was observed for both posttraining social anxiety symptoms and behavioral attentional bias (AB) toward threat (the target mechanism of ABM). Studies administering a large (>1,280) number of training trials showed no benefit of ABM over control conditions, while those administering fewer training trials showed significant benefit for ABM in reducing social anxiety (P = .02). These moderating effects of dose were not better explained by other examined variables and previously identified moderators, including patient age, training setting (laboratory vs. home), or type of anxiety assessment (clinician vs. self-report). Findings inform the optimal dosing for future dot-probe style ABM applications in both research and clinical settings, and suggest several novel avenues for further research. © 2017 Wiley Periodicals, Inc.

Measurement of cytoplasmic Ca2+ concentration in Saccharomyces cerevisiae induced by air cold plasma

NASA Astrophysics Data System (ADS)

Xiaoyu, DONG

2018-03-01

In this study, a novel approach to measure the absolute cytoplasmic Ca2+ concentration ([Ca2+]cyt) using the Ca2+ indicator fluo-3 AM was established. The parameters associated with the probe fluo-3 AM were optimized to accurately determine fluorescence intensity from the Ca2+-bound probe. Using three optimized parameters (final concentration of 6 mM probe, incubation time of 135 min, loading probe before plasma treatment), the maximum fluorescence intensity (F max = 527.8 a.u.) and the minimum fluorescence intensity (F min = 63.8 a.u.) were obtained in a saturated Ca2+ solution or a solution of lacking Ca2+. Correspondingly, the maximum [Ca2+]cyt induced by cold plasma was 1232.5 nM. Therefore, the Ca2+ indicator fluo-3 AM was successfully applied to measure the absolute [Ca2+]cyt in Saccharomyces cerevisiae stimulated by cold plasma at atmospheric air pressure.

Optimizing the specificity of nucleic acid hybridization.

PubMed

Zhang, David Yu; Chen, Sherry Xi; Yin, Peng

2012-01-22

The specific hybridization of complementary sequences is an essential property of nucleic acids, enabling diverse biological and biotechnological reactions and functions. However, the specificity of nucleic acid hybridization is compromised for long strands, except near the melting temperature. Here, we analytically derived the thermodynamic properties of a hybridization probe that would enable near-optimal single-base discrimination and perform robustly across diverse temperature, salt and concentration conditions. We rationally designed 'toehold exchange' probes that approximate these properties, and comprehensively tested them against five different DNA targets and 55 spurious analogues with energetically representative single-base changes (replacements, deletions and insertions). These probes produced discrimination factors between 3 and 100+ (median, 26). Without retuning, our probes function robustly from 10 °C to 37 °C, from 1 mM Mg(2+) to 47 mM Mg(2+), and with nucleic acid concentrations from 1 nM to 5 µM. Experiments with RNA also showed effective single-base change discrimination.

Design of a Selective Substrate and Activity Based Probe for Human Neutrophil Serine Protease 4

PubMed Central

Kasperkiewicz, Paulina; Poreba, Marcin; Snipas, Scott J.; Lin, S. Jack; Kirchhofer, Daniel; Salvesen, Guy S.; Drag, Marcin

2015-01-01

Human neutrophil serine protease 4 (NSP4), also known as PRSS57, is a recently discovered fourth member of the neutrophil serine proteases family. Although its biological function is not precisely defined, it is suggested to regulate neutrophil response and innate immune reactions. To create optimal substrates and visualization probes for NSP4 that distinguish it from other NSPs we have employed a Hybrid Combinatorial Substrate Library approach that utilizes natural and unnatural amino acids to explore protease subsite preferences. Library results were validated by synthesizing individual substrates, leading to the identification of an optimal substrate peptide. This substrate was converted to a covalent diphenyl phosphonate probe with an embedded biotin tag. This probe demonstrated high inhibitory activity and stringent specificity and may be suitable for visualizing NSP4 in the background of other NSPs. PMID:26172376

Optimizing the choice of spin-squeezed states for detecting and characterizing quantum processes

DOE PAGES

Rozema, Lee A.; Mahler, Dylan H.; Blume-Kohout, Robin; ...

2014-11-07

Quantum metrology uses quantum states with no classical counterpart to measure a physical quantity with extraordinary sensitivity or precision. Most such schemes characterize a dynamical process by probing it with a specially designed quantum state. The success of such a scheme usually relies on the process belonging to a particular one-parameter family. If this assumption is violated, or if the goal is to measure more than one parameter, a different quantum state may perform better. In the most extreme case, we know nothing about the process and wish to learn everything. This requires quantum process tomography, which demands an informationallymore » complete set of probe states. It is very convenient if this set is group covariant—i.e., each element is generated by applying an element of the quantum system’s natural symmetry group to a single fixed fiducial state. In this paper, we consider metrology with 2-photon (“biphoton”) states and report experimental studies of different states’ sensitivity to small, unknown collective SU( 2) rotations [“ SU( 2) jitter”]. Maximally entangled N00 N states are the most sensitive detectors of such a rotation, yet they are also among the worst at fully characterizing an a priori unknown process. We identify (and confirm experimentally) the best SU( 2)-covariant set for process tomography; these states are all less entangled than the N00 N state, and are characterized by the fact that they form a 2-design.« less

Pulsed-voltage atom probe tomography of low conductivity and insulator materials by application of ultrathin metallic coating on nanoscale specimen geometry.

PubMed

Adineh, Vahid R; Marceau, Ross K W; Chen, Yu; Si, Kae J; Velkov, Tony; Cheng, Wenlong; Li, Jian; Fu, Jing

2017-10-01

We present a novel approach for analysis of low-conductivity and insulating materials with conventional pulsed-voltage atom probe tomography (APT), by incorporating an ultrathin metallic coating on focused ion beam prepared needle-shaped specimens. Finite element electrostatic simulations of coated atom probe specimens were performed, which suggest remarkable improvement in uniform voltage distribution and subsequent field evaporation of the insulated samples with a metallic coating of approximately 10nm thickness. Using design of experiment technique, an experimental investigation was performed to study physical vapor deposition coating of needle specimens with end tip radii less than 100nm. The final geometries of the coated APT specimens were characterized with high-resolution scanning electron microscopy and transmission electron microscopy, and an empirical model was proposed to determine the optimal coating thickness for a given specimen size. The optimal coating strategy was applied to APT specimens of resin embedded Au nanospheres. Results demonstrate that the optimal coating strategy allows unique pulsed-voltage atom probe analysis and 3D imaging of biological and insulated samples. Copyright © 2017 Elsevier B.V. All rights reserved.

Dual representation of item positions in verbal short-term memory: Evidence for two access modes.

PubMed

Lange, Elke B; Verhaeghen, Paul; Cerella, John

Memory sets of N = 1~5 digits were exposed sequentially from left-to-right across the screen, followed by N recognition probes. Probes had to be compared to memory list items on identity only (Sternberg task) or conditional on list position. Positions were probed randomly or in left-to-right order. Search functions related probe response times to set size. Random probing led to ramped, "Sternbergian" functions whose intercepts were elevated by the location requirement. Sequential probing led to flat search functions-fast responses unaffected by set size. These results suggested that items in STM could be accessed either by a slow search-on-identity followed by recovery of an associated location tag, or in a single step by following item-to-item links in study order. It is argued that this dual coding of location information occurs spontaneously at study, and that either code can be utilised at retrieval depending on test demands.

Non-invasive diagnostic system and its opto-mechanical probe for combining confocal Raman spectroscopy and optical coherence tomography.

PubMed

Klemes, Jan; Kotzianova, Adela; Pokorny, Marek; Mojzes, Peter; Novak, Jindrich; Sukova, Lada; Demuth, Jaroslav; Vesely, Jaroslav; Sasek, Ladislav; Velebny, Vladimir

2017-11-01

Non-invasive optical diagnostic methods allow important information about studied systems to be obtained in a non-destructive way. Complete diagnosis requires information about the chemical composition as well as the morphological structure of a sample. We report on the development of an opto-mechanical probe that combines Raman spectroscopy (RS) and optical coherence tomography (OCT), two methods that provide all the crucial information needed for a non-invasive diagnosis. The aim of this paper is to introduce the technical design, construction and optimization of a dual opto-mechanical probe combining two in-house developed devices for confocal RS and OCT. The unique benefit of the probe is a gradual acquisition of OCT and RS data, which allows to use the acquired OCT images to pinpoint locations of interest for RS measurements. The parameters and the correct functioning of the probe were verified by RS scanning of various samples (silicon wafer and ex vivo tissue) based on their OCT images - lateral as well as depth scanning was performed. Both the OCT and RS systems were developed, optimized and tested with the ultimate aim of verifying the functionality of the probe. Picture: Schematic illustration and visualization of the developed RS-OCT probe. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Reliability design and assessment of a micro-probe using the results of a tensile test of a beryllium-copper alloy thin film

NASA Astrophysics Data System (ADS)

Park, Jun-Hyub; Shin, Myung-Soo

2011-09-01

This paper describes the results of tensile tests for a beryllium-copper (BeCu) alloy thin film and the application of the results to the design of a probe. The copper alloy films were fabricated by electroplating. To obtain the tensile characteristics of the film, the dog-bone type specimen was fabricated by the etching method. The tensile tests were performed with the specimen using a test machine developed by the authors. The BeCu alloy has an elastic modulus of 119 GPa and the 0.2% offset yield and ultimate tensile strengths of 1078 MPa and 1108 MPa, respectively. The design and manufacture of a smaller probe require higher pad density and smaller pad-pitch chips. It should be effective in high-frequency testing. For the design of a new micro-probe, we investigated several design parameters that may cause problems, such as the contact force and life, using the tensile properties and the design of experiment method in conjunction with finite element analysis. The optimal dimensions of the probe were found using the response surface method. The probe with optimal dimensions was manufactured by a precision press process. It was verified that the manufactured probe satisfied the life, the contact force and the over drive through the compression tests and the life tests of the probes.

[Optimization and assessment of a reverse hybridization system for the detection of HBV drug-resistant mutations].

PubMed

Liu, Yan-chen; Huang, Ai-long; Hu, Yuan; Hu, Jie-li; Lai, Guo-qi; Zhang, Wen-lu

2011-12-01

To establish a detection method for HBV drug-resistant mutations related to lamivudine, adefovir and entecavir by optimization and assessment of reverse hybridization system. 26 degenerated probes covering 10 drug-resistant hotspots of 3 drugs were synthesized and immobilized on the same positively charged nylon membrane. PCR products labeled with digoxigenin were hybridized with corresponding probes. To improve the sensitivity and specificity, 4 reaction steps of reverse hybridization were optimized including the number of labeled digoxigenin, the energy intensity of UV cross-linking, hybridization and stringency wash conditions. To prove the feasibility, the specificity, sensitivity and accuracy of this system were assessed respectively. Sensitive and specific results are obtained by the optimization of the following 4 reaction steps: the primers labeled with 3 digoxigenin, energy intensity of UV cross-linking for 1500 x 0.1 mJ/cm², hybridization at 42 degrees C and stringency wash with 0.5 x SSC and 0.1% SDS solution at 44 degrees C for 30 min. In the assessment of system, the majority of probes have high specificity. The quantity of PCR product with a concentration of 10 ng/μl or above can be detected by this method. The concordant rate between reverse hybridization and direct sequencing is 93.9% in the clinical sample test. Though the specificity of several probes needs to be improved further, it is a simple, rapid and sensitive method which can detect HBV resistant mutations related to lamivudine, adefovir and entecavir simultaneously. Due to the short distance between 180 and 181, likewise 202 and 204, the sequence of the same probe covers two codon positions, and hybridization will be interfered by each other. To avoid such interference, the possible solution is that probes are designed by arranging and combining various forms of two near codons.

Minimum-variance Brownian motion control of an optically trapped probe.

PubMed

Huang, Yanan; Zhang, Zhipeng; Menq, Chia-Hsiang

2009-10-20

This paper presents a theoretical and experimental investigation of the Brownian motion control of an optically trapped probe. The Langevin equation is employed to describe the motion of the probe experiencing random thermal force and optical trapping force. Since active feedback control is applied to suppress the probe's Brownian motion, actuator dynamics and measurement delay are included in the equation. The equation of motion is simplified to a first-order linear differential equation and transformed to a discrete model for the purpose of controller design and data analysis. The derived model is experimentally verified by comparing the model prediction to the measured response of a 1.87 microm trapped probe subject to proportional control. It is then employed to design the optimal controller that minimizes the variance of the probe's Brownian motion. Theoretical analysis is derived to evaluate the control performance of a specific optical trap. Both experiment and simulation are used to validate the design as well as theoretical analysis, and to illustrate the performance envelope of the active control. Moreover, adaptive minimum variance control is implemented to maintain the optimal performance in the case in which the system is time varying when operating the actively controlled optical trap in a complex environment.

Femtosecond pump/supercontinuum-probe spectroscopy: optimized setup and signal analysis for single-shot spectral referencing.

PubMed

Dobryakov, A L; Kovalenko, S A; Weigel, A; Pérez-Lustres, J L; Lange, J; Müller, A; Ernsting, N P

2010-11-01

A setup for pump/supercontinuum-probe spectroscopy is described which (i) is optimized to cancel fluctuations of the probe light by single-shot referencing, and (ii) extends the probe range into the near-uv (1000-270 nm). Reflective optics allow 50 μm spot size in the sample and upon entry into two separate spectrographs. The correlation γ(same) between sample and reference readings of probe light level at every pixel exceeds 0.99, compared to γ(consec)<0.92 reported for consecutive referencing. Statistical analysis provides the confidence interval of the induced optical density, ΔOD. For demonstration we first examine a dye (Hoechst 33258) bound in the minor groove of double-stranded DNA. A weak 1.1 ps spectral oscillation in the fluorescence region, assigned to DNA breathing, is shown to be significant. A second example concerns the weak vibrational structure around t=0 which reflects stimulated Raman processes. With 1% fluctuations of probe power, baseline noise for a transient absorption spectrum becomes 25 μOD rms in 1 s at 1 kHz, allowing to record resonance Raman spectra of flavine adenine dinucleotide in the S(0) and S(1) state.

SU-F-J-182: Investigation of Systems for Improved Accuracy in Clinical Y-90 Percent Delivered Calculations

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

McBeth, R; Elder, D; Kesner, A

2016-06-15

Purpose: Y-90 Selective Internal Radiation Therapy (SIRT) is used to treat liver tumors, and by nature has variability in the percent of the intended dose that is actually delivered. To determine the quality of the administration, pre and post activity measurements are taken, and used to infer percent delivered. Vendor specifications indicate the use of an ion chamber to take these measurements. In our work, we investigated the accuracy of ion chambers, and compared them to other detector systems. Methods: We have built phantoms, phantom holders, and protocols, which allow us to measure our Y90 doses with varying apparatuses: amore » dose calibrator, a Geiger-counter, an ion chamber, a crystal based thyroid probe, and a gamma camera. We have set up a system that has enabled us to gather data by measuring clinical Y90 doses as they are used in the clinic using all of the instrumental methods. Five initial doses (25 measurements/acquisitions) have been taken at the time of this abstract submission. Results: Our initial results show that measurements acquired using scintillation based detectors (thyroid probe and gamma camera) correlate better with the gold standard (i.e. the dose calibrator). Pearson correlations between the dose calibrator measurements and the GM counter, Ion chamber, thyroid probe, and gamma camera were found to be 0.88, 0.83, 0.98, 0.99, respectively. More acquisitions and analysis are planned to determine the precision of the systems, as well as optimal energy window settings. Conclusion: It is likely that current standard practice can be improved using scintillation crystal based detectors. Such systems are more sensitive, can integrate signal, and can use energy discrimination. Furthermore, phantoms can be built to integrate with probe and gamma camera systems that are robust and provide reproducibility. Future work will include expanded acquisition and analysis.« less

Convergence in parameters and predictions using computational experimental design.

PubMed

Hagen, David R; White, Jacob K; Tidor, Bruce

2013-08-06

Typically, biological models fitted to experimental data suffer from significant parameter uncertainty, which can lead to inaccurate or uncertain predictions. One school of thought holds that accurate estimation of the true parameters of a biological system is inherently problematic. Recent work, however, suggests that optimal experimental design techniques can select sets of experiments whose members probe complementary aspects of a biochemical network that together can account for its full behaviour. Here, we implemented an experimental design approach for selecting sets of experiments that constrain parameter uncertainty. We demonstrated with a model of the epidermal growth factor-nerve growth factor pathway that, after synthetically performing a handful of optimal experiments, the uncertainty in all 48 parameters converged below 10 per cent. Furthermore, the fitted parameters converged to their true values with a small error consistent with the residual uncertainty. When untested experimental conditions were simulated with the fitted models, the predicted species concentrations converged to their true values with errors that were consistent with the residual uncertainty. This paper suggests that accurate parameter estimation is achievable with complementary experiments specifically designed for the task, and that the resulting parametrized models are capable of accurate predictions.

Development of endovascular vibrating polymer actuator probe for mechanical thrombolysis: a phantom study.

PubMed

Choi, Seung Hong; Yoon, Bye-Ri; Oh, Jin Sun; Han, Moon Hee; Lee, Jang Yeol; Cho, Hye Rim; Kim, Moon June; Rhee, Kyehan; Jho, Jae Young

2011-01-01

In this study, we propose a new method for enhancement of intraarterial thrombolysis using an ionic polymer-metal composite (IPMC) actuator. The purpose of this study was to test the mechanical thrombolysis efficiency of IPMC actuators and evaluate the endovascular vibrating polymer actuator probe for mechanical thrombolysis in a phantom model; 2 × 1 × 15 mm (2 mm in width, 1 mm in thickness, and 15 mm in length) and 0.8 × 0.8 × 10 mm (0.8 mm in width, 0.8 mm in thickness, and 10 mm in length) IPMC actuators were fabricated by stacking five and four Nafion-117 films, respectively. We manufactured the endovascular vibrating polymer actuator probe, for which thrombolysis efficiency was tested in a vascular phantom. The phantom study using 2 × 1 × 15 mm IPMC actuators showed that 5 Hz actuation is the optimal frequency for thrombolysis under both 2 and 3 V, when blood clot was not treated with rtPA, and when exposed to rtPA, IPMC actuators under the optimized condition (3 V, 5 Hz, and 5 min) significantly increased the thrombolysis degree compared with control and other experimental groups (p < 0.05). In addition, 0.8 × 0.8 × 10 mm IPMC actuators also revealed a significantly higher thrombolysis degree under the optimized condition than the control and rtPA only groups (p < 0.05). Finally, the fabricated probe using 0.8 × 0.8 × 10 mm IPMC actuators also incurred higher thrombolysis degree under the optimized condition than the control and rtPA only groups (p < 0.05). A vibrating polymer actuator probe is a feasible device for intravascular thrombolysis, and further study in an animal model is warranted.

Electromechanical characterization of individual micron-sized metal coated polymer particles

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

Bazilchuk, Molly; Kristiansen, Helge; Conpart AS, Skjetten 2013

Micron-sized polymer particles with nanoscale metal coatings are essential in conductive adhesives for electronics assembly. The particles function in a compressed state in the adhesives. The link between mechanical properties and electrical conductivity is thus of the utmost importance in the formation of good electrical contact. A custom flat punch set-up based on nanoindentation has been developed to simultaneously deform and electrically probe individual particles. The set-up has a sufficiently low internal resistance to allow the measurement of sub-Ohm contact resistances. Additionally, the set-up can capture mechanical failure of the particles. Combining this data yields a fundamental understanding of contactmore » behavior. We demonstrate that this method can clearly distinguish between particles of different sizes, with different thicknesses of metal coating, and different metallization schemes. The technique provides good repeatability and physical insight into the behavior of these particles that can guide adhesive design and the optimization of bonding processes.« less

Method and apparatus for in-situ drying investigation and optimization of slurry drying methodology

DOEpatents

Armstrong, Beth L.; Daniel, Claus; Howe, Jane Y.; Kiggans, Jr, James O.; Sabau, Adrian S.; Wood, III, David L.; Kalnaus, Sergiy

2016-05-10

A method of drying casted slurries that includes calculating drying conditions from an experimental model for a cast slurry and forming a cast film. An infrared heating probe is positioned on one side of the casted slurry and a thermal probe is positioned on an opposing side of the casted slurry. The infrared heating probe may control the temperature of the casted slurry during drying. The casted slurry may be observed with an optical microscope, while applying the drying conditions from the experimental model. Observing the casted slurry includes detecting the incidence of micro-structural changes in the casted slurry during drying to determine if the drying conditions from the experimental model are optimal.

Optimized Design and Synthesis of Cell Permeable Biarsenical Cyanine Probe for Imaging Tagged Cytosolic Bacterial Proteins

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

Fu, Na; Xiong, Yijia; Squier, Thomas C.

2013-01-21

To optimize cellular delivery and specific labeling of tagged cytosolic proteins by biarsenical fluorescent probes build around a cyanine dye scaffold, we have systematically varied the polarity of the hydrophobic tails (i.e., 4-5 methylene groups appended by a sulfonate or methoxy ester moiety) and arsenic capping reagent (ethanedithiol versus benzenedithiol). Targeted labeling of the cytosolic proteins SlyD and the alpha subunit of RNA polymerase engineered with a tetracysteine tagging sequences demonstrate the utility of the newly synthesized probes for live-cell visualization, albeit with varying efficiencies and background intensities. Optimal routine labeling and visualization is apparent using the ethanedithiol capping reagentmore » with the uncharged methoxy ester functionalized acyl chains. These measurements demonstrate the general utility of this class of photostable and highly fluorescent biarsenical reagents based on the cyanine scaffold for in vivo targeting of tagged cellular proteins for live cell measurements of protein dynamics.« less

Measuring reactive oxygen and nitrogen species with fluorescent probes: challenges and limitations

PubMed Central

Kalyanaraman, Balaraman; Darley-Usmar, Victor; Davies, Kelvin J.A.; Dennery, Phyllis A.; Forman, Henry Jay; Grisham, Matthew B.; Mann, Giovanni E.; Moore, Kevin; Roberts, L. Jackson; Ischiropoulos, Harry

2013-01-01

The purpose of this position paper is to present a critical analysis of the challenges and limitations of the most widely used fluorescent probes for detecting and measuring reactive oxygen and nitrogen species. Where feasible, we have made recommendations for the use of alternate probes and appropriate analytical techniques that measure the specific products formed from the reactions between fluorescent probes and reactive oxygen and nitrogen species. We have proposed guidelines that will help present and future researchers with regard to the optimal use of selected fluorescent probes and interpretation of results. PMID:22027063

Technical Parameters Modeling of a Gas Probe Foaming Using an Active Experimental Type Research

NASA Astrophysics Data System (ADS)

Tîtu, A. M.; Sandu, A. V.; Pop, A. B.; Ceocea, C.; Tîtu, S.

2018-06-01

The present paper deals with a current and complex topic, namely - a technical problem solving regarding the modeling and then optimization of some technical parameters related to the natural gas extraction process. The study subject is to optimize the gas probe sputtering using experimental research methods and data processing by regular probe intervention with different sputtering agents. This procedure makes that the hydrostatic pressure to be reduced by the foam formation from the water deposit and the scrubbing agent which can be removed from the surface by the produced gas flow. The probe production data was analyzed and the so-called candidate for the research itself emerged. This is an extremely complex study and it was carried out on the field works, finding that due to the severe gas field depletion the wells flow decreases and the start of their loading with deposit water, was registered. It was required the regular wells foaming, to optimize the daily production flow and the disposal of the wellbore accumulated water. In order to analyze the process of natural gas production, the factorial experiment and other methods were used. The reason of this choice is that the method can offer very good research results with a small number of experimental data. Finally, through this study the extraction process problems were identified by analyzing and optimizing the technical parameters, which led to a quality improvement of the extraction process.

Comparing Cognitive Interviewing and Online Probing: Do They Find Similar Results?

ERIC Educational Resources Information Center

Meitinger, Katharina; Behr, Dorothée

2016-01-01

This study compares the application of probing techniques in cognitive interviewing (CI) and online probing (OP). Even though the probing is similar, the methods differ regarding typical mode setting, sample size, level of interactivity, and goals. We analyzed probing answers to the International Social Survey Programme item battery on specific…

Clinical utility of multiplex ligation-dependent probe amplification technique in identification of aetiology of unexplained mental retardation: a study in 203 Indian patients.

PubMed

Boggula, Vijay R; Shukla, Anju; Danda, Sumita; Hariharan, Sankar V; Nampoothiri, Sheela; Kumar, Rashmi; Phadke, Shubha R

2014-01-01

Developmental delay (DD)/mental retardation also described as intellectual disability (ID), is seen in 1-3 per cent of general population. Diagnosis continues to be a challenge at clinical level. With the advancement of new molecular cytogenetic techniques such as cytogenetic microarray (CMA), multiplex ligation-dependent probe amplification (MLPA) techniques, many microdeletion/microduplication syndromes with DD/ID are now delineated. MLPA technique can probe 40-50 genomic regions in a single reaction and is being used for evaluation of cases with DD/ID. In this study we evaluated the clinical utility of MLPA techniques with different probe sets to identify the aetiology of unexplained mental retardation in patients with ID/DD. A total of 203 randomly selected DD/ID cases with/without malformations were studied. MLPA probe sets for subtelomeric regions (P070/P036) and common microdeletions/microduplications (P245-A2) and X-chromosome (P106) were used. Positive cases with MLPA technique were confirmed using either fluorescence in situ hybridization (FISH) or follow up confirmatory MLPA probe sets. The overall detection rate was found to be 9.3 per cent (19 out of 203). The detection rates were 6.9 and 7.4 per cent for common microdeletion/microduplication and subtelomeric probe sets, respectively. No abnormality was detected with probe set for X-linked ID. The subtelomeric abnormalities detected included deletions of 1p36.33, 4p, 5p, 9p, 9q, 13q telomeric regions and duplication of 9pter. The deletions/duplications detected in non telomeric regions include regions for Prader Willi/Angelman regions, Williams syndrome, Smith Magenis syndrome and Velocardiofacial syndrome. Our results show that the use of P245-A2 and P070/P036-E1 probes gives good diagnostic yield. Though MLPA cannot probe the whole genome like cytogenetic microarray, due to its ease and relative low cost it is an important technique for evaluation of cases with DD/ID.

Optimization of a reusable, DNA pseudoknot-based electrochemical sensor for sequence-specific DNA detection in blood serum.

PubMed

Cash, Kevin J; Heeger, Alan J; Plaxco, Kevin W; Xiao, Yi

2009-01-15

We describe in detail a new electrochemical DNA (E-DNA) sensing platform based on target-induced conformation changes in an electrode-bound DNA pseudoknot. The pseudoknot, a DNA structure containing two stem-loops in which the first stem's loop forms part of the second stem, is modified with a methylene blue redox tag at its 3' terminus and covalently attached to a gold electrode via the 5' terminus. In the absence of a target, the structure of the pseudoknot probe minimizes collisions between the redox tag and the electrode, thus reducing faradaic current. Target binding disrupts the pseudoknot structure, liberating a flexible, single-stranded element that can strike the electrode and efficiently transfer electrons. In this article we report further characterization and optimization of this new E-DNA architecture. We find that optimal signaling is obtained at an intermediate probe density ( approximately 1.8 x 10(13) molecules/cm(2) apparent density), which presumably represents a balance between steric and electrostatic blocking at high probe densities and increased background currents arising from transfer from the pseudoknot probe at lower densities. We also find that optimal 3' stem length, which appears to be 7 base pairs, represents a balance between pseudoknot structural stability and target affinity. Finally, a 3' loop comprised of poly(A) exhibits better mismatch discrimination than the equivalent poly(T) loop, but at the cost of decreased gain. Optimization over this parameter space significantly improves the signaling of the pseudoknot-based E-DNA architecture, leading to the ability to sensitively and specifically detect DNA targets even when challenged in complex, multicomponent samples such as blood serum.

Optimization of a Reusable, DNA Pseudoknot-Based Electrochemical Sensor for Sequence-Specific DNA Detection in Blood Serum

PubMed Central

Cash, Kevin J.; Heeger, Alan J.; Plaxco, Kevin W.; Xiao, Yi

2010-01-01

We describe in detail a new electrochemical DNA (E-DNA) sensing platform based on target-induced conformation changes in an electrode-bound DNA pseudoknot. The pseudoknot, a DNA structure containing two stem-loops in which the first stem’s loop forms part of the second stem, is modified with a methylene blue redox tag at its 3′ terminus and covalently attached to a gold electrode via the 5′ terminus. In the absence of a target, the structure of the pseudoknot probe minimizes collisions between the redox tag and the electrode, thus reducing faradaic current. Target binding disrupts the pseudoknot structure, liberating a flexible, single-stranded element that can strike the electrode and efficiently transfer electrons. In this article we report further characterization and optimization of this new E-DNA architecture. We find that optimal signaling is obtained at an intermediate probe density (~1.8 × 1013 molecules/cm2 apparent density), which presumably represents a balance between steric and electrostatic blocking at high probe densities and increased background currents arising from transfer from the pseudoknot probe at lower densities. We also find that optimal 3′ stem length, which appears to be 7 base pairs, represents a balance between pseudoknot structural stability and target affinity. Finally, a 3′ loop comprised of poly(A) exhibits better mismatch discrimination than the equivalent poly(T) loop, but at the cost of decreased gain. Optimization over this parameter space significantly improves the signaling of the pseudoknot-based E-DNA architecture, leading to the ability to sensitively and specifically detect DNA targets even when challenged in complex, multicomponent samples such as blood serum. PMID:19093760

Design of 240,000 orthogonal 25mer DNA barcode probes.

PubMed

Xu, Qikai; Schlabach, Michael R; Hannon, Gregory J; Elledge, Stephen J

2009-02-17

DNA barcodes linked to genetic features greatly facilitate screening these features in pooled formats using microarray hybridization, and new tools are needed to design large sets of barcodes to allow construction of large barcoded mammalian libraries such as shRNA libraries. Here we report a framework for designing large sets of orthogonal barcode probes. We demonstrate the utility of this framework by designing 240,000 barcode probes and testing their performance by hybridization. From the test hybridizations, we also discovered new probe design rules that significantly reduce cross-hybridization after their introduction into the framework of the algorithm. These rules should improve the performance of DNA microarray probe designs for many applications.

Design of 240,000 orthogonal 25mer DNA barcode probes

PubMed Central

Xu, Qikai; Schlabach, Michael R.; Hannon, Gregory J.; Elledge, Stephen J.

2009-01-01

DNA barcodes linked to genetic features greatly facilitate screening these features in pooled formats using microarray hybridization, and new tools are needed to design large sets of barcodes to allow construction of large barcoded mammalian libraries such as shRNA libraries. Here we report a framework for designing large sets of orthogonal barcode probes. We demonstrate the utility of this framework by designing 240,000 barcode probes and testing their performance by hybridization. From the test hybridizations, we also discovered new probe design rules that significantly reduce cross-hybridization after their introduction into the framework of the algorithm. These rules should improve the performance of DNA microarray probe designs for many applications. PMID:19171886

Development and construction of a comprehensive set of research diagnostics for the FLARE user facility

NASA Astrophysics Data System (ADS)

Yoo, Jongsoo; Jara-Almonte, J.; Majeski, S.; Frank, S.; Ji, H.; Yamada, M.

2016-10-01

FLARE (Facility for Laboratory Reconnection Experiments) will be operated as a flexible user facility, and so a complete set of research diagnostics is under development, including magnetic probe arrays, Langmuir probes, Mach probes, spectroscopic probes, and a laser interferometer. In order to accommodate the various requirements of users, large-scale (1 m), variable resolution (0.5-4 cm) magnetic probes have been designed, and are currently being prototyped. Moreover, a fully fiber-coupled laser interferometer has been designed to measure the line-integrated electron density. This fiber-coupled interferometer system will reduce the complexity of alignment processes and minimize maintenance of the system. Finally, improvements to the electrostatic probes and spectroscopic probes currently used in the Magnetic Reconnection Experiment (MRX) are discussed. The specifications of other subsystems, such as integrators and digitizers, are also presented. This work is supported by DoE Contract No. DE-AC0209CH11466.

Construction of a novel peptide nucleic acid piezoelectric gene sensor microarray detection system.

PubMed

Chen, Ming; Liu, Minghua; Yu, Lili; Cai, Guoru; Chen, Qinghai; Wu, Rong; Wang, Feng; Zhang, Bo; Jiang, Tianlun; Fu, Welling

2005-08-01

A novel 2 x 5 clamped style piezoelectric gene sensor microarray has been successfully constructed. Every crystal unit of the fabricated gene sensor can oscillate independently without interfering with each other. The bis-peptide nucleic acid (bis-PNA) probe, which can combine with target DNA or RNA sequences more effectively and specifically than a DNA probe, was designed and immobilized on the surface of the gene sensor microarray to substitute the conventional DNA probe for direct detection of the hepatitis B virus (HBV) genomic DNA. Detection conditions were then explored and optimized. Results showed that PBS buffer of pH 6.8, an ion concentration of 20 mmol/liter, and a probe concentration of 1.5 micromol/liter were optimal for the detection system. Under such optimized experimental conditions, the specificity of bis-PNA was proved much higher than that of DNA probe. The relationship between quantity of target and decrease of frequency showed a typical saturation curve when concentrations of target HBV DNA varied from 10 pg/liter to 100 microg/liter, and 10 microg/liter was the watershed, with a statistic linear regression equation of I gC = -2.7455 + 0.0691 deltaF and the correlating coefficient of 0.9923. Fortunately, this is exactly the most ordinary variant range of the HBV virus concentration in clinical hepatitis samples. So, a good technical platform is successfully constructed and it will be applied to detect HBV quantitatively in clinical samples.

Virtual Impactor for Sub-micron Aerosol Particles

NASA Astrophysics Data System (ADS)

Bolshakov, A. A.; Strawa, A. W.; Hallar, A. G.

2005-12-01

The objective of a virtual impactor is to separate out the larger particles in a flow from the smaller particles in such a way that both sizes of particles are available for sampling. A jet of particle-laden air is accelerated toward a collection probe so that a small gap exists between the acceleration nozzle and the probe. A vacuum is applied to deflect a major portion of the airstream away form the collection probe. Particles larger than a certain size have sufficient momentum so that they cross the deflected streamlines and enter the collection probe, whereas smaller particles follow the deflected streamlines. The result is that the collection probe will contain a higher concentration of larger particles than is in the initial airstream. Typically, virtual impactors are high-flow devices used to separate out particles greater than several microns in diameter. We have developed a special virtual impactor to concentrate aerosol particles of diameters between 0.5 to 1 micron for the purpose of calibrating the optical cavity ring-down instrument [1]. No similar virtual impactors are commercially available. In our design, we have exploited considerations described earlier [2-4]. Performance of our virtual impactor was evaluated in an experimental set-up using TSI 3076 nebulizer and TSI 3936 scanning mobility particle size spectrometer. Under experimental conditions optimized for the best performance of the virtual impactor, we were able to concentrate the 700-nm polystyrene particles no less than 15-fold. However, under experimental conditions optimized for calibrating our cavity ring-down instrument, a concentration factor attainable was from 4 to 5. During calibration experiments, maximum realized particle number densities were 190, 300 and 1600 cm-3 for the 900-nm, 700-nm and 500-nm spheres, respectively. This paper discusses the design of the impactor and laboratory studies verifying its performance. References: 1. A.W. Strawa, R. Castaneda, T. Owano, D.S. Baer, B.A. Paldus, J. Atm. Ocean. Technol., 20, 454-465 (2003). 2. V.A. Marple, K.L. Rubow, B.A. Olson, Aerosol Sci. Technol., 22, 140-150 (1995). 3. B.T. Chen, H.C. Yeh, Y.S. Cheng, J. Aerosol Sci., 16, 343-354 (1985). 4. V.A. Marple, C.M. Chien, Environ. Sci. Technol., 14, 976-985 (1980).

Infrared laser sealing of porcine vascular tissues using a 1,470 nm diode laser: Preliminary in vivo studies.

PubMed

Cilip, Christopher M; Kerr, Duane; Latimer, Cassandra A; Rosenbury, Sarah B; Giglio, Nicholas C; Hutchens, Thomas C; Nau, William H; Fried, Nathaniel M

2017-04-01

Infrared (IR) lasers are being explored as an alternative to radiofrequency (RF) and ultrasonic (US) devices for rapid hemostasis with minimal collateral zones of thermal damage and tissue necrosis. Previously, a 1,470 nm IR laser sealed and cut ex vivo porcine renal arteries of 1-8 mm diameter in 2 seconds, yielding burst pressures greater than 1,200 mmHg and thermal coagulation zones less than 3 mm. This preliminary study describes in vivo testing of a handheld laser probe in a porcine model. A handheld prototype with vessel/tissue clasping mechanism was tested on 73 blood vessels less than 6 mm diameter using 1,470 nm laser power of 35 W for 1-5 seconds. Device power settings, irradiation time, tissue type, vessel diameter, and histology sample number were recorded for each procedure. The probe was evaluated for hemostasis after sealing isolated and bundled arteriole/venous (A/V) vasculature of porcine abdomen and hind leg. Sealed vessel samples were collected for histological analysis of lateral thermal damage. Hemostasis was achieved in 57 of 73 seals (78%). The probe consistently sealed vasculature in small bowel mesentery, mesometrium, and gastrosplenic and epiploic regions. Seal performance was less consistent on hind leg vasculature including saphenous arteries/bundles and femoral and iliac arteries. Collagen denaturation averaged 1.6 ± 0.9 mm in eight samples excised for histologic examination. A handheld laser probe sealed porcine vessels, in vivo. Further probe development and laser parameter optimization is necessary before infrared lasers may be evaluated as an alternative to RF and US vessel sealing devices. Lasers Surg. Med. 49:366-371, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Design Optimization for Interferometric Space-Based 21-cm Power Spectrum Measurements

NASA Astrophysics Data System (ADS)

Pober, Jonathan

2018-06-01

Observations of the highly-redshifted 21 cm hyperfine line of neutral hydrogen (HI) are one of the most promising probes for the future of cosmology. At redshifts z > 30, the HI signal is likely the only measurable emission, as luminous objects have yet to form. At these very low radio frequencies, however, the earth’s ionosphere becomes opaque — necessitating observations from space. The major challenge to neutral hydrogen cosmology (at all redshifts) lies in the presence of bright foreground emission, which can dominate the HI signal by as much as eight orders of magnitude at the highest redshifts. The only method for extracting the cosmological signal relies on the spectral smoothness of the foregrounds; since each frequency of the HI signal probes a different redshift, the cosmological emission is essentially uncorrelated from frequency to frequency. The key challenge for designing an experiment lies in maintaining the spectral smoothness of the foregrounds. If the frequency response of the instrument introduces spectral structure (or at least, a residual that cannot be calibrated out at the necessary precision), it quickly becomes impossible to distinguish the cosmological signal from the foregrounds. This principle has guided the design of ground-based experiments like the Precision Array for Probing the Epoch of Reionization (PAPER) and the Hydrogen Epoch of Reionization Array (HERA). However, there still exists no unifying framework for turning this design "philosophy" into a robust, quantitative set of performance metrics and specifications. In this talk, I will present updates on the efforts of my research group to translate lessons learned from ground-based experiments into a fully traceable set of mission requirements for Cosmic Dawn Mapper or other space-based 21 cm interferometer.

Fusion of classifiers for REIS-based detection of suspicious breast lesions

NASA Astrophysics Data System (ADS)

Lederman, Dror; Wang, Xingwei; Zheng, Bin; Sumkin, Jules H.; Tublin, Mitchell; Gur, David

2011-03-01

After developing a multi-probe resonance-frequency electrical impedance spectroscopy (REIS) system aimed at detecting women with breast abnormalities that may indicate a developing breast cancer, we have been conducting a prospective clinical study to explore the feasibility of applying this REIS system to classify younger women (< 50 years old) into two groups of "higher-than-average risk" and "average risk" of having or developing breast cancer. The system comprises one central probe placed in contact with the nipple, and six additional probes uniformly distributed along an outside circle to be placed in contact with six points on the outer breast skin surface. In this preliminary study, we selected an initial set of 174 examinations on participants that have completed REIS examinations and have clinical status verification. Among these, 66 examinations were recommended for biopsy due to findings of a highly suspicious breast lesion ("positives"), and 108 were determined as negative during imaging based procedures ("negatives"). A set of REIS-based features, extracted using a mirror-matched approach, was computed and fed into five machine learning classifiers. A genetic algorithm was used to select an optimal subset of features for each of the five classifiers. Three fusion rules, namely sum rule, weighted sum rule and weighted median rule, were used to combine the results of the classifiers. Performance evaluation was performed using a leave-one-case-out cross-validation method. The results indicated that REIS may provide a new technology to identify younger women with higher than average risk of having or developing breast cancer. Furthermore, it was shown that fusion rule, such as a weighted median fusion rule and a weighted sum fusion rule may improve performance as compared with the highest performing single classifier.

Analysis of Eddy Current Capabilities for the Detection of Outer Diameter Stress Corrosion Cracking in Small Bore Metallic Structures

NASA Technical Reports Server (NTRS)

Wincheski, Buzz; Williams, Phillip; Simpson, John

2007-01-01

The use of eddy current techniques for the detection of outer diameter damage in tubing and many complex aerospace structures often requires the use of an inner diameter probe due to a lack of access to the outside of the part. In small bore structures the probe size and orientation are constrained by the inner diameter of the part, complicating the optimization of the inspection technique. Detection of flaws through a significant remaining wall thickness becomes limited not only by the standard depth of penetration, but also geometrical aspects of the probe. Recently, an orthogonal eddy current probe was developed for detection of such flaws in Space Shuttle Primary Reaction Control System (PRCS) Thrusters. In this case, the detection of deeply buried stress corrosion cracking by an inner diameter eddy current probe was sought. Probe optimization was performed based upon the limiting spatial dimensions, flaw orientation, and required detection sensitivity. Analysis of the probe/flaw interaction was performed through the use of finite and boundary element modeling techniques. Experimental data for the flaw detection capabilities, including a probability of detection study, will be presented along with the simulation data. The results of this work have led to the successful deployment of an inspection system for the detection of stress corrosion cracking in Space Shuttle Primary Reaction Control System (PRCS) Thrusters.

Selection of optimal oligonucleotide probes for microarrays usingmultiple criteria, global alignment and parameter estimation.

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

Li, Xingyuan; He, Zhili; Zhou, Jizhong

2005-10-30

The oligonucleotide specificity for microarray hybridizationcan be predicted by its sequence identity to non-targets, continuousstretch to non-targets, and/or binding free energy to non-targets. Mostcurrently available programs only use one or two of these criteria, whichmay choose 'false' specific oligonucleotides or miss 'true' optimalprobes in a considerable proportion. We have developed a software tool,called CommOligo using new algorithms and all three criteria forselection of optimal oligonucleotide probes. A series of filters,including sequence identity, free energy, continuous stretch, GC content,self-annealing, distance to the 3'-untranslated region (3'-UTR) andmelting temperature (Tm), are used to check each possibleoligonucleotide. A sequence identity is calculated based onmore » gapped globalalignments. A traversal algorithm is used to generate alignments for freeenergy calculation. The optimal Tm interval is determined based on probecandidates that have passed all other filters. Final probes are pickedusing a combination of user-configurable piece-wise linear functions andan iterative process. The thresholds for identity, stretch and freeenergy filters are automatically determined from experimental data by anaccessory software tool, CommOligo_PE (CommOligo Parameter Estimator).The program was used to design probes for both whole-genome and highlyhomologous sequence data. CommOligo and CommOligo_PE are freely availableto academic users upon request.« less

The Three-Dimensional Point Spread Function of Aberration-Corrected Scanning Transmission Electron Microscopy

PubMed Central

Lupini, A.R.; de Jonge, N.

2012-01-01

Aberration-correction reduces the depth of field in scanning transmission electron microscopy (STEM) and thus allows three-dimensional imaging by depth-sectioning. This imaging mode offers the potential for sub-Ångstrom lateral resolution and nanometer-scale depth sensitivity. For biological samples, which may be many microns across and where high lateral resolution may not always be needed, optimizing the depth resolution even at the expense of lateral resolution may be desired, aiming to image through thick specimens. Although there has been extensive work examining and optimizing the probe formation in two-dimensions, there is less known about the probe shape along the optical axis. Here the probe shape is examined in three-dimensions in an attempt to better understand the depth-resolution in this mode. Examples are presented of how aberrations change the probe shape in three-dimensions, and it is found that off-axial aberrations may need to be considered for focal series of large areas. It is shown that oversized or annular apertures theoretically improve the vertical resolution for 3D imaging of nanoparticles. When imaging nanoparticles of several nanometer size, regular STEM can thereby be optimized such that the vertical full width at half maximum approaches that of the aberration corrected STEM with a standard aperture. PMID:21878149

Dynamic transfer applied to secondary ion imaging over large scanned fields with the nanoSIMS 50 at high mass resolution

NASA Astrophysics Data System (ADS)

Slodzian, Georges; Wu, Ting-Di; Duprat, Jean; Engrand, Cécile; Guerquin-Kern, Jean-Luc

2017-12-01

Dynamic transfer is an adaptive optical approach used for coupling a scanning ion probe with the mass spectrometer designed for analyzing sputtered ions emanating from the probe impact. Its tuning is of crucial importance for getting uniform signal collection over large scanning fields and therefore scanning images free of vignetting in a context of high mass resolution. Revisiting the optical design of the NanoSIMS 50 instrument, where the same set of lenses focuses the primary ion probe on the sample and collects secondary ions from the sample, led us to develop novel experimental procedures to achieve dynamic transfer tuning and overcome instrumental imperfections. It is the case for scanning distortion that may be induced by the octopole used for correcting probe astigmatism and may cause irreducible vignetting on scanning images. We show that it is possible to develop complete tuning procedures by compromising temporarily on the sharpness of the probe focus. Most importantly, we show that, in a context of high mass resolution, the transfer does not significantly disturb isotopic ratios over large scanned fields provided external coils are properly adjusted to compensate ambient magnetic fields. Deepening the procedures led us to demonstrate that the scanning center of the probe may not coincide with the imaging center of COOL, Coaxial Objective Lenses forming the probe and extracting secondary ions. We have checked that bringing those two centers into coincidence resulted in a better image quality over large fields. In the present work, we show how to handle the secondary beam in order to position it before it enters the spectrometer. That capability is essential for optimizing transmission at high mass resolution by aligning the secondary beam axis on a given entrance axis of the spectrometer. These results led us to propose several instrumental improvements including the crucial interest of an additional octopole upstream in the primary ion probe column to prevent scanning distortion when performing astigmatism correction and the possibility of offsetting primary beam deviating plates to bring scanning and imaging centers in coincidence.

Structure-Based Design of Highly Selective Inhibitors of the CREB Binding Protein Bromodomain.

PubMed

Denny, R Aldrin; Flick, Andrew C; Coe, Jotham; Langille, Jonathan; Basak, Arindrajit; Liu, Shenping; Stock, Ingrid; Sahasrabudhe, Parag; Bonin, Paul; Hay, Duncan A; Brennan, Paul E; Pletcher, Mathew; Jones, Lyn H; Chekler, Eugene L Piatnitski

2017-07-13

Chemical probes are required for preclinical target validation to interrogate novel biological targets and pathways. Selective inhibitors of the CREB binding protein (CREBBP)/EP300 bromodomains are required to facilitate the elucidation of biology associated with these important epigenetic targets. Medicinal chemistry optimization that paid particular attention to physiochemical properties delivered chemical probes with desirable potency, selectivity, and permeability attributes. An important feature of the optimization process was the successful application of rational structure-based drug design to address bromodomain selectivity issues (particularly against the structurally related BRD4 protein).

Dichroic beamsplitter for high energy laser diagnostics

DOEpatents

LaFortune, Kai N [Livermore, CA; Hurd, Randall [Tracy, CA; Fochs, Scott N [Livermore, CA; Rotter, Mark D [San Ramon, CA; Hackel, Lloyd [Livermore, CA

2011-08-30

Wavefront control techniques are provided for the alignment and performance optimization of optical devices. A Shack-Hartmann wavefront sensor can be used to measure the wavefront distortion and a control system generates feedback error signal to optics inside the device to correct the wavefront. The system can be calibrated with a low-average-power probe laser. An optical element is provided to couple the optical device to a diagnostic/control package in a way that optimizes both the output power of the optical device and the coupling of the probe light into the diagnostics.

Comparison of chirped-probe-pulse and hybrid femtosecond/picosecond coherent anti-Stokes Raman scattering for combustion thermometry.

PubMed

Richardson, Daniel R; Stauffer, Hans U; Roy, Sukesh; Gord, James R

2017-04-10

A comparison is made between two ultrashort-pulse coherent anti-Stokes Raman scattering (CARS) thermometry techniques-hybrid femtosecond/picosecond (fs/ps) CARS and chirped-probe-pulse (CPP) fs-CARS-that have become standards for high-repetition-rate thermometry in the combustion diagnostics community. These two variants of fs-CARS differ only in the characteristics of the ps-duration probe pulse; in hybrid fs/ps CARS a spectrally narrow, time-asymmetric probe pulse is used, whereas a highly chirped, spectrally broad probe pulse is used in CPP fs-CARS. Temperature measurements were performed using both techniques in near-adiabatic flames in the temperature range 1600-2400 K and for probe time delays of 0-30 ps. Under these conditions, both techniques are shown to exhibit similar temperature measurement accuracies and precisions to previously reported values and to each other. However, it is observed that initial calibration fits to the spectrally broad CPP results require more fitting parameters and a more robust optimization algorithm and therefore significantly increased computational cost and complexity compared to the fitting of hybrid fs/ps CARS data. The optimized model parameters varied more for the CPP measurements than for the hybrid fs/ps measurements for different experimental conditions.

Probe-pulse optimization for nonresonant suppression in hybrid fs/ps coherent anti-Stokes Raman scattering at high temperature.

PubMed

Miller, Joseph D; Slipchenko, Mikhail N; Meyer, Terrence R

2011-07-04

Hybrid femtosecond/picosecond coherent anti-Stokes Raman scattering (fs/ps CARS) offers accurate thermometry at kHz rates for combustion diagnostics. In high-temperature flames, selection of probe-pulse characteristics is key to simultaneously optimizing signal-to-nonresonant-background ratio, signal strength, and spectral resolution. We demonstrate a simple method for enhancing signal-to-nonresonant-background ratio by using a narrowband Lorentzian filter to generate a time-asymmetric probe pulse with full-width-half-maximum (FWHM) pulse width of only 240 fs. This allows detection within just 310 fs after the Raman excitation for eliminating nonresonant background while retaining 45% of the resonant signal at 2000 K. The narrow linewidth is comparable to that of a time-symmetric sinc2 probe pulse with a pulse width of ~2.4 ps generated with a conventional 4-f pulse shaper. This allows nonresonant-background-free, frequency-domain vibrational spectroscopy at high temperature, as verified using comparisons to a time-dependent theoretical fs/ps CARS model.

Optimizing the specificity of nucleic acid hybridization

PubMed Central

Zhang, David Yu; Chen, Sherry Xi; Yin, Peng

2014-01-01

The specific hybridization of complementary sequences is an essential property of nucleic acids, enabling diverse biological and biotechnological reactions and functions. However, the specificity of nucleic acid hybridization is compromised for long strands, except near the melting temperature. Here, we analytically derived the thermodynamic properties of a hybridization probe that would enable near-optimal single-base discrimination and perform robustly across diverse temperature, salt and concentration conditions. We rationally designed ‘toehold exchange’ probes that approximate these properties, and comprehensively tested them against five different DNA targets and 55 spurious analogues with energetically representative single-base changes (replacements, deletions and insertions). These probes produced discrimination factors between 3 and 100+ (median, 26). Without retuning, our probes function robustly from 10 °C to 37 °C, from 1 mM Mg2+ to 47 mM Mg2+, and with nucleic acid concentrations from 1 nM to 5 μM. Experiments with RNA also showed effective single-base change discrimination. PMID:22354435

Precision thermometry and the quantum speed limit

NASA Astrophysics Data System (ADS)

Campbell, Steve; Genoni, Marco G.; Deffner, Sebastian

2018-04-01

We assess precision thermometry for an arbitrary single quantum system. For a d-dimensional harmonic system we show that the gap sets a single temperature that can be optimally estimated. Furthermore, we establish a simple linear relationship between the gap and this temperature, and show that the precision exhibits a quadratic relationship. We extend our analysis to explore systems with arbitrary spectra, showing that exploiting anharmonicity and degeneracy can greatly enhance the precision of thermometry. Finally, we critically assess the dynamical features of two thermometry protocols for a two level system. By calculating the quantum speed limit we find that, despite the gap fixing a preferred temperature to probe, there is no evidence of this emerging in the dynamical features.

Signal enhancement in protein NMR using the spin-noise tuning optimum

PubMed Central

Nausner, Martin; Goger, Michael; Bendet-Taicher, Eli; Schlagnitweit, Judith

2010-01-01

We have assessed the potential of an alternative probe tuning strategy based on the spin-noise response for application in common high-resolution multi-dimensional biomolecular NMR experiments with water signal suppression on aqueous and salty samples. The method requires the adjustment of the optimal tuning condition, which may be offset by several 100 kHz from the conventional tuning settings using the noise response of the water protons as an indicator. Although the radio frequency-pulse durations are typically longer under such conditions, signal-to-noise gains of up to 22% were achieved. At salt concentrations up to 100 mM a substantial sensitivity gain was observed. PMID:20924647

The Challenges and Opportunities for International Cooperative Radio Science; Experience with Mars Express and Venus Express Missions

NASA Technical Reports Server (NTRS)

Holmes, Dwight P.; Thompson, Tommy; Simpson, Richard; Tyler, G. Leonard; Dehant, Veronique; Rosenblatt, Pascal; Hausler, Bernd; Patzold, Martin; Goltz, Gene; Kahan, Daniel;

Performance Characteristics and Utilization of Rapid Antigen Test, DNA Probe, and Culture for Detection of Group A Streptococci in an Acute Care Clinic

PubMed Central

Chapin, Kimberle C.; Blake, Patricia; Wilson, Claire D.

2002-01-01

Group A streptococcus (GAS) antigen testing has become a routine point-of-care (POC) test in acute care settings. Concern about performance parameters (PP) of these tests as well as inappropriate antibiotic use has resulted in various recommendations regarding diagnosis of GAS. There were two objectives in this study. The first was to evaluate the rapid GAS antigen test presently in use (Thermo BioStar, Boulder, Colo.) and the GAS Direct probe test (Gen-Probe, San Diego, Calif.) compared to culture. The second was to define the optimal use of these technologies in a large acute care pediatric clinic. A total of 520 consecutive pediatric patients presenting with symptoms of pharyngitis at any of three Lahey Clinic acute care facilities were evaluated. Pharyngeal specimens were collected using a double-swab collection device (Copan, Corona, Calif.). One swab was used for the antigen test, the second was used for the probe test, and the pledget was placed in the collection device for culture on 5% sheep blood agar, incubated for 48 h anaerobically, and subsequently placed in Todd-Hewitt broth. After discrepant analysis, sensitivity, specificity, and positive and negative predictive values were as follows: 94.8, 100, 100, and 96.9% for the probe test and 86.1, 97.1, 93.7, and 93.4% for the antigen test, respectively. Sensitivity using an enhanced culture technique was 99.4% (163 of 164). False-positive (FP) antigen results were often seen from patients previously diagnosed and/or treated for GAS. No FP results were seen with the probe test. Colony counts for the false-negative (FN) antigen tests were higher than those for the FN probe tests. Compared to culture and DNA probe, the rapid antigen test (RAT) offered a result at the time of the patient's visit, with acceptable PP when prevalence of disease is high. Follow-up testing with the RAT of GAS patients who previously tested as positive should be avoided due to increased FP results. The probe test was comparable to culture in performance. Results indicate the probe test can be used as the primary test or as a backup to negative antigen tests. The probe test offers the advantage over culture of same-day reporting of a final result but, in contrast to a POC test, necessitates follow-up communication to the patient. Preliminary data show the specificity of the probe test to be greater than that of the RAT for patients previously diagnosed with GAS. PMID:12409399

Public Data Set: Radially Scanning Magnetic Probes to Study Local Helicity Injection Dynamics

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

Richner, Nathan J; Bongard, Michael W; Fonck, Raymond J

This data set contains openly-documented, machine readable digital research data corresponding to figures published in N.J. Richner et al., 'Radially Scanning Magnetic Probes to Study Local Helicity Injection Dynamics,' accepted for publication in Rev. Sci. Instrum (2018).

Structured decomposition design of partial Mueller matrix polarimeters.

PubMed

Alenin, Andrey S; Scott Tyo, J

2015-07-01

Partial Mueller matrix polarimeters (pMMPs) are active sensing instruments that probe a scattering process with a set of polarization states and analyze the scattered light with a second set of polarization states. Unlike conventional Mueller matrix polarimeters, pMMPs do not attempt to reconstruct the entire Mueller matrix. With proper choice of generator and analyzer states, a subset of the Mueller matrix space can be reconstructed with fewer measurements than that of the full Mueller matrix polarimeter. In this paper we consider the structure of the Mueller matrix and our ability to probe it using a reduced number of measurements. We develop analysis tools that allow us to relate the particular choice of generator and analyzer polarization states to the portion of Mueller matrix space that the instrument measures, as well as develop an optimization method that is based on balancing the signal-to-noise ratio of the resulting instrument with the ability of that instrument to accurately measure a particular set of desired polarization components with as few measurements as possible. In the process, we identify 10 classes of pMMP systems, for which the space coverage is immediately known. We demonstrate the theory with a numerical example that designs partial polarimeters for the task of monitoring the damage state of a material as presented earlier by Hoover and Tyo [Appl. Opt.46, 8364 (2007)10.1364/AO.46.008364APOPAI1559-128X]. We show that we can reduce the polarimeter to making eight measurements while still covering the Mueller matrix subspace spanned by the objects.

Probing optimal measurement configuration for optical scatterometry by the multi-objective genetic algorithm

NASA Astrophysics Data System (ADS)

Chen, Xiuguo; Gu, Honggang; Jiang, Hao; Zhang, Chuanwei; Liu, Shiyuan

2018-04-01

Measurement configuration optimization (MCO) is a ubiquitous and important issue in optical scatterometry, whose aim is to probe the optimal combination of measurement conditions, such as wavelength, incidence angle, azimuthal angle, and/or polarization directions, to achieve a higher measurement precision for a given measuring instrument. In this paper, the MCO problem is investigated and formulated as a multi-objective optimization problem, which is then solved by the multi-objective genetic algorithm (MOGA). The case study on the Mueller matrix scatterometry for the measurement of a Si grating verifies the feasibility of the MOGA in handling the MCO problem in optical scatterometry by making a comparison with the Monte Carlo simulations. Experiments performed at the achieved optimal measurement configuration also show good agreement between the measured and calculated best-fit Mueller matrix spectra. The proposed MCO method based on MOGA is expected to provide a more general and practical means to solve the MCO problem in the state-of-the-art optical scatterometry.

Attentional bias to threat in the general population is contingent on target competition, not on attentional control settings.

PubMed

Wirth, Benedikt Emanuel; Wentura, Dirk

2018-04-01

Dot-probe studies usually find an attentional bias towards threatening stimuli only in anxious participants. Here, we investigated under what conditions such a bias occurs in unselected samples. According to contingent-capture theory, an irrelevant cue only captures attention if it matches an attentional control setting. Therefore, we first tested the hypothesis that an attentional control setting tuned to threat must be activated in (non-anxious) individuals. In Experiment 1, we used a dot-probe task with a manipulation of attentional control settings ('threat' - set vs. control set). Surprisingly, we found an (anxiety-independent) attentional bias to angry faces that was not moderated by attentional control settings. Since we presented two stimuli (i.e., a target and a distractor) on the target screen in Experiment 1 (a necessity to realise the test of contingent capture), but most dot-probe studies only employ a single target, we conducted Experiment 2 to test the hypothesis that attentional bias in the general population is contingent on target competition. Participants performed a dot-probe task, involving presentation of a stand-alone target or a target competing with a distractor. We found an (anxiety-independent) attentional bias towards angry faces in the latter but not the former condition. This suggests that attentional bias towards angry faces in unselected samples is not contingent on attentional control settings but on target competition.

Aberrated electron probes for magnetic spectroscopy with atomic resolution: Theory and practical aspects

DOE PAGES

Rusz, Ján; Idrobo, Juan Carlos

2016-03-24

It was recently proposed that electron magnetic circular dichroism (EMCD) can be measured in scanning transmission electron microscopy (STEM) with atomic resolution by tuning the phase distribution of a electron beam. Here, we describe the theoretical and practical aspects for the detection of out-of-plane and in-plane magnetization utilizing atomic size electron probes. Here we present the calculated optimized astigmatic probes and discuss how to achieve them experimentally.

Measurement of stray EC radiation on W7-AS

NASA Astrophysics Data System (ADS)

Gandini, F.; Hirsch, M.; Cirant, S.; Erckmann, V.; Granucci, G.; Kasparek, W.; Laqua, H. P.; Muzzini, V.; Nowak, S.; Radau, S.

2001-10-01

In the framework of a collaboration between IFP-CNR Milano, IPP Garching/Greifswald and IPF Stuttgart, a set of four millimeterwave probes has been installed in W7-AS stellarator at selected positions of the inner vessel wall. Their purpose is to observe RF stray radiation during operation in presence of strong level of Electron Cyclotron (EC) waves, used for plasma start-up, heating and current drive. The aim of these measurements is to benchmark two complementary theoretical models for the distribution of the stray radiation in the vessel. From these codes, quantitative predictions are expected for the spatial distribution of the RF wall load and the RF-impact on in-vessel components in large future devices such as W7-X and, possibly, ITER. This input is important to optimize the wall armour and select rf-compatible in-vessel materials. We present first measurements from different heating and startup scenarios, with up to 800 kW of injected power at 140 GHz and different launching geometries. An analysis of measurements performed on FTU using a previous version of sniffer probe is also presented.

A versatile optical profilometer based on conoscopic holography sensors for acquisition of specular and diffusive surfaces in artworks

NASA Astrophysics Data System (ADS)

Gaburro, Nicola; Marchioro, Giacomo; Daffara, Claudia

2017-07-01

Surface metrology of artworks requires the design of suitable devices for in-situ non-destructive measurement together with reliable procedures for an effective analysis of such non-engineered variegate objects. To advance the state-of-the-art it has been implemented a versatile optical micro-profilometry taking advantage of the adapt- ability of conoscopic holography sensors, able to operate with irregular shapes and composite materials (diffusive, specular, and polychrome) of artworks. The scanning technique is used to obtain wide field and high spatially resolved areal profilometry. The prototype has a modular scheme based on a set of conoscopic sensors, extending the typical design based on a scanning stage and a single probe with a limited bandwidth, thus allowing the collection of heights data from surface with different scales and materials with variegate optical response. The system was optimized by characterizing the quality of the measurement with the probes triggered in continuous scanning modality. The results obtained on examples of cultural heritage objects (2D paintings, 3D height-relief) and materials (pictorial, metallic) demonstrate the versatility of the implemented device.

Discovery of a novel calcium-sensitive fluorescent probe for α-ketoglutarate.

PubMed

Gan, Lin-Lin; Chen, Lin-Hai; Nan, Fa-Jun

2017-12-01

α-Ketoglutarate (α-KG), a pivotal metabolite in energy metabolism, has been implicated in nonalcoholic fatty liver disease (NAFLD) and several cancers. It is recently proposed that plasma α-KG is a surrogate biomarker of NAFLD. Here, we report the development of a novel "turn-on" chemosensor for α-KG that contains a coumarin moiety as a fluorophore. Using benzothiazole-coumarin (BTC) as inspiration, we designed a probe for calcium ion recognition that possesses a unique fluorophore compared with previously reported probes for α-KG measurement. This chemosensor is based on the specific Schiff base reaction and the calcium ion recognition property of the widely used calcium indicator BTC. The probe was synthesized, and a series of parallel experiments were conducted to optimize the chemical recognition process. Compared to the initial weak fluorescence, a remarkable 7.6-fold enhancement in fluorescence intensity (I/I 0 at 495 nm) was observed for the conditions in which the probe (1 μmol/L), α-KG (50 μmol/L), and Ca 2+ (100 μmol/L) were incubated at 30 °C in EtOH. The probe displayed good selectivity for α-KG even in an environment with an abundance of amino acids and other interfering species such as glutaric acid. We determined that the quantitative detection range of α-KG in EtOH was between 5 and 50 μmol/L. Finally, probe in serum loaded with α-KG (10 mmol/L) showed a 7.4-fold fluorescence enhancement. In summary, a novel probe for detecting the biomarker α-KG through a typical Schiff base reaction has been discovered. With further optimization, this probe may be a good alternative for detecting the physiological metabolite α-KG.

Optimal control theory with continuously distributed target states: An application to NaK

NASA Astrophysics Data System (ADS)

Kaiser, Andreas; May, Volkhard

2006-01-01

Laser pulse control of molecular dynamics is studied theoretically by using optimal control theory. The control theory is extended to target states which are distributed in time as well as in a space of parameters which are responsible for a change of individual molecular properties. This generalized treatment of a control task is first applied to wave packet formation in randomly oriented diatomic systems. Concentrating on an ensemble of NaK molecules which are not aligned the control yield decreases drastically when compared with an aligned ensemble. Second, we demonstrate for NaK the maximization of the probe pulse transient absorption in a pump-probe scheme with an optimized pump pulse. These computations suggest an overall optical control scheme, whereby a flexible technique is suggested to form particular wave packets in the excited state potential energy surface. In particular, it is shown that considerable wave packet localization at the turning points of the first-excited Σ-state potential energy surfaces of NaK may be achieved. The dependency of the control yield on the probe pulse parameters is also discussed.

An Eddy Current Testing Platform System for Pipe Defect Inspection Based on an Optimized Eddy Current Technique Probe Design.

PubMed

Rifai, Damhuji; Abdalla, Ahmed N; Razali, Ramdan; Ali, Kharudin; Faraj, Moneer A

2017-03-13

The use of the eddy current technique (ECT) for the non-destructive testing of conducting materials has become increasingly important in the past few years. The use of the non-destructive ECT plays a key role in the ensuring the safety and integrity of the large industrial structures such as oil and gas pipelines. This paper introduce a novel ECT probe design integrated with the distributed ECT inspection system (DSECT) use for crack inspection on inner ferromagnetic pipes. The system consists of an array of giant magneto-resistive (GMR) sensors, a pneumatic system, a rotating magnetic field excitation source and a host PC acting as the data analysis center. Probe design parameters, namely probe diameter, an excitation coil and the number of GMR sensors in the array sensor is optimized using numerical optimization based on the desirability approach. The main benefits of DSECT can be seen in terms of its modularity and flexibility for the use of different types of magnetic transducers/sensors, and signals of a different nature with either digital or analog outputs, making it suited for the ECT probe design using an array of GMR magnetic sensors. A real-time application of the DSECT distributed system for ECT inspection can be exploited for the inspection of 70 mm carbon steel pipe. In order to predict the axial and circumference defect detection, a mathematical model is developed based on the technique known as response surface methodology (RSM). The inspection results of a carbon steel pipe sample with artificial defects indicate that the system design is highly efficient.

Universal Oligonucleotide Microarray for Sub-Typing of Influenza A Virus

PubMed Central

Ryabinin, Vladimir A.; Kostina, Elena V.; Maksakova, Galiya A.; Neverov, Alexander A.; Chumakov, Konstantin M.; Sinyakov, Alexander N.

2011-01-01

A universal microchip was developed for genotyping Influenza A viruses. It contains two sets of oligonucleotide probes allowing viruses to be classified by the subtypes of hemagglutinin (H1–H13, H15, H16) and neuraminidase (N1–N9). Additional sets of probes are used to detect H1N1 swine influenza viruses. Selection of probes was done in two steps. Initially, amino acid sequences specific to each subtype were identified, and then the most specific and representative oligonucleotide probes were selected. Overall, between 19 and 24 probes were used to identify each subtype of hemagglutinin (HA) and neuraminidase (NA). Genotyping included preparation of fluorescently labeled PCR amplicons of influenza virus cDNA and their hybridization to microarrays of specific oligonucleotide probes. Out of 40 samples tested, 36 unambiguously identified HA and NA subtypes of Influenza A virus. PMID:21559081

Novel Multisensor Probe for Monitoring Bladder Temperature During Locoregional Chemohyperthermia for Nonmuscle-Invasive Bladder Cancer: Technical Feasibility Study

PubMed Central

Geijsen, Debby E.; Zum Vörde Sive Vörding, Paul J.; Schooneveldt, Gerben; Sijbrands, Jan; Hulshof, Maarten C.; de la Rosette, Jean; de Reijke, Theo M.; Crezee, Hans

2013-01-01

Abstract Background and Purpose: The effectiveness of locoregional hyperthermia combined with intravesical instillation of mitomycin C to reduce the risk of recurrence and progression of intermediate- and high-risk nonmuscle-invasive bladder cancer is currently investigated in clinical trials. Clinically effective locoregional hyperthermia delivery necessitates adequate thermal dosimetry; thus, optimal thermometry methods are needed to monitor accurately the temperature distribution throughout the bladder wall. The aim of the study was to evaluate the technical feasibility of a novel intravesical device (multi-sensor probe) developed to monitor the local bladder wall temperatures during loco-regional C-HT. Materials and Methods: A multisensor thermocouple probe was designed for deployment in the human bladder, using special sensors to cover the bladder wall in different directions. The deployment of the thermocouples against the bladder wall was evaluated with visual, endoscopic, and CT imaging in bladder phantoms, porcine models, and human bladders obtained from obduction for bladder volumes and different deployment sizes of the probe. Finally, porcine bladders were embedded in a phantom and subjected to locoregional heating to compare probe temperatures with additional thermometry inside and outside the bladder wall. Results: The 7.5 cm thermocouple probe yielded optimal bladder wall contact, adapting to different bladder volumes. Temperature monitoring was shown to be accurate and representative for the actual bladder wall temperature. Conclusions: Use of this novel multisensor probe could yield a more accurate monitoring of the bladder wall temperature during locoregional chemohyperthermia. PMID:24112045

Optimal design of a touch trigger probe

NASA Astrophysics Data System (ADS)

Li, Rui-Jun; Xiang, Meng; Fan, Kuang-Chao; Zhou, Hao; Feng, Jian

2015-02-01

A tungsten stylus with a ruby ball tip was screwed into a floating plate, which was supported by four leaf springs. The displacement of the tip caused by the contact force in 3D could be transferred into the tilt or vertical displacement of a plane mirror mounted on the floating plate. A quadrant photo detector (QPD) based two dimensional angle sensor was used to detect the tilt or the vertical displacement of the plane mirror. The structural parameters of the probe are optimized for equal sensitivity and equal stiffness in a displacement range of +/-5 μm, and a restricted horizontal size of less than 40 mm. Simulation results indicated that the stiffness was less than 0.6 mN/μm and equal in 3D. Experimental results indicated that the probe could be used to achieve a resolution of 1 nm.

High-sensitivity detection and monitoring of microcirculation using cutaneous and catheter probes for Doppler optical coherence tomography

NASA Astrophysics Data System (ADS)

Yang, Victor X.; Gordon, M. L.; Qi, B.; Yue, E. Seng; Tang, S.; Bisland, Stuart K.; Pekar, J.; Lo, S.; Marcon, Norman E.; Wilson, B.; Vitkin, Alex

2003-07-01

Background: Currently clinical Doppler ultrasound cannot detect microvascular blood flow and it is difficult to provide depth discrimination using laser Doppler flowmetry. Doppler optical coherence tomography (DOCT) is a novel technique for noninvasive subsurface imaging of microcirculation and tissue structure. Aims: To design handheld and catheter-based DOCT probes for clinical cutaneous and endoscopic imaging. To develop signal processing techniques for real-time detection and quantification of microvascular blood flow. Methods: A DOCT system, with interchangeable cutaneous and catheter probes, was developed. The axial spatial resolution was 10 μm, and the velocity resolution was 20 μm/s, using a 1300 nm broadband infrared light. The system achieved real-time imaging with frame rates up to 32 Hz at 512 x 256 pixels per frame. We used the system to detect microcirculation in human skin and rat esophagus, and to monitor microvascular responses to photodynamic therapy (PDT) in a rat tumor model. Results: We present experimental results from in vivo DOCT imaging of microcirculation in human skin arterio-venous malformations (AVM), normal rat esophagus, and a rat gliosarcoma PDT model. In the PDT model, we followed microvascular responses to PDT and observed differences in the microcirculation during and after therapy, which can have important implications for PDT dosimetry and treatment optimization. Conclusions: To our knowledge, this is the first demonstration of endoscopic catheter-based DOCT detection of microcirculation in vivo. In addition, AVM can be detected using handheld cutaneous DOCT probes under clinical settings. DOCT may serve as a real-time monitoring tool for PDT dosimetry, especially for vascular targeting photosensitizers.

Difference in thermodynamics between two types of esophageal temperature probes: Insights from an experimental study.

PubMed

Gianni, Carola; Atoui, Moustapha; Mohanty, Sanghamitra; Trivedi, Chintan; Bai, Rong; Al-Ahmad, Amin; Burkhardt, J David; Gallinghouse, G Joseph; Hranitzky, Patrick M; Horton, Rodney P; Sanchez, Javier E; Di Biase, Luigi; Lakkireddy, Dhanunjaya R; Natale, Andrea

2016-11-01

Luminal esophageal temperature monitoring is performed with a variety of temperature probes, but little is known about the relationship between the structure of a given probe and its thermodynamic characteristics. The purpose of this study was to evaluate the difference in thermodynamics between a 9Fr standard esophageal probe and an 18Fr esophageal stethoscope. In the experimental setting, each probe was submerged in a constant temperature water bath maintained at 42°C; in the patient setting, we monitored the temperature with both probes at the same time. The time constant of the stethoscope was higher than that of the probe (33.5 vs 8.3 s). Compared to the probe, the mean temperature measured by the stethoscope at 10 seconds was significantly lower (22.5°C ± 0.4°C vs 33.5°C ± 0.3°C, P<.0001), whereas the time to reach the peak temperature was significantly longer (132.6 ± 5.9 s vs 38.8 ± 1.0 s, P<.0001). Even in the ablation cases we observed that when the esophageal probe reached a peak temperature of 39.6°C ± 0.3°C, the esophageal stethoscope still displayed a temperature of 37.3°C ± 0.2°C (a mean of 2.39°C ± 0.3°C lower, P<.0001), showing a <0.5°C increase in temperature half of the times. The 18Fr esophageal stethoscope has a significantly slower time response compared to the 9Fr esophageal probe. In the clinical setting, this might result in a considerable underestimation of the luminal esophageal temperature with potentially fatal consequences. Copyright © 2016 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.

Non-aqueous Electrode Processing and Construction of Lithium-ion Coin Cells.

PubMed

Stein, Malcolm; Chen, Chien-Fan; Robles, Daniel J; Rhodes, Christopher; Mukherjee, Partha P

2016-02-01

Research into new and improved materials to be utilized in lithium-ion batteries (LIB) necessitates an experimental counterpart to any computational analysis. Testing of lithium-ion batteries in an academic setting has taken on several forms, but at the most basic level lies the coin cell construction. In traditional LIB electrode preparation, a multi-phase slurry composed of active material, binder, and conductive additive is cast out onto a substrate. An electrode disc can then be punched from the dried sheet and used in the construction of a coin cell for electrochemical evaluation. Utilization of the potential of the active material in a battery is critically dependent on the microstructure of the electrode, as an appropriate distribution of the primary components are crucial to ensuring optimal electrical conductivity, porosity, and tortuosity, such that electrochemical and transport interaction is optimized. Processing steps ranging from the combination of dry powder, wet mixing, and drying can all critically affect multi-phase interactions that influence the microstructure formation. Electrochemical probing necessitates the construction of electrodes and coin cells with the utmost care and precision. This paper aims at providing a step-by-step guide of non-aqueous electrode processing and coin cell construction for lithium-ion batteries within an academic setting and with emphasis on deciphering the influence of drying and calendaring.

Non-aqueous Electrode Processing and Construction of Lithium-ion Coin Cells

PubMed Central

Stein, Malcolm; Chen, Chien-Fan; Robles, Daniel J.; Rhodes, Christopher; Mukherjee, Partha P.

2016-01-01

Research into new and improved materials to be utilized in lithium-ion batteries (LIB) necessitates an experimental counterpart to any computational analysis. Testing of lithium-ion batteries in an academic setting has taken on several forms, but at the most basic level lies the coin cell construction. In traditional LIB electrode preparation, a multi-phase slurry composed of active material, binder, and conductive additive is cast out onto a substrate. An electrode disc can then be punched from the dried sheet and used in the construction of a coin cell for electrochemical evaluation. Utilization of the potential of the active material in a battery is critically dependent on the microstructure of the electrode, as an appropriate distribution of the primary components are crucial to ensuring optimal electrical conductivity, porosity, and tortuosity, such that electrochemical and transport interaction is optimized. Processing steps ranging from the combination of dry powder, wet mixing, and drying can all critically affect multi-phase interactions that influence the microstructure formation. Electrochemical probing necessitates the construction of electrodes and coin cells with the utmost care and precision. This paper aims at providing a step-by-step guide of non-aqueous electrode processing and coin cell construction for lithium-ion batteries within an academic setting and with emphasis on deciphering the influence of drying and calendaring. PMID:26863503

Developing a bright 17 keV x-ray source for probing high-energy-density states of matter at high spatial resolution

NASA Astrophysics Data System (ADS)

Huntington, C. M.; Park, H.-S.; Maddox, B. R.; Barrios, M. A.; Benedetti, R.; Braun, D. G.; Hohenberger, M.; Landen, O. L.; Regan, S. P.; Wehrenberg, C. E.; Remington, B. A.

2015-04-01

A set of experiments were performed on the National Ignition Facility (NIF) to develop and optimize a bright, 17 keV x-ray backlighter probe using laser-irradiated Nb foils. High-resolution one-dimensional imaging was achieved using a 15 μm wide slit in a Ta substrate to aperture the Nb Heα x-rays onto an open-aperture, time integrated camera. To optimize the x-ray source for imaging applications, the effect of laser pulse shape and spatial profile on the target was investigated. Two laser pulse shapes were used—a "prepulse" shape that included a 3 ns, low-intensity laser foot preceding the high-energy 2 ns square main laser drive, and a pulse without the laser foot. The laser spatial profile was varied by the use of continuous phase plates (CPPs) on a pair of shots compared to beams at best focus, without CPPs. A comprehensive set of common diagnostics allowed for a direct comparison of imaging resolution, total x-ray conversion efficiency, and x-ray spectrum between shots. The use of CPPs was seen to reduce the high-energy tail of the x-ray spectrum, whereas the laser pulse shape had little effect on the high-energy tail. The measured imaging resolution was comparably high for all combinations of laser parameters, but a higher x-ray flux was achieved without phase plates. This increased flux was the result of smaller laser spot sizes, which allowed us to arrange the laser focal spots from multiple beams and produce an x-ray source which was more localized behind the slit aperture. Our experiments are a first demonstration of point-projection geometry imaging at NIF at the energies (>10 keV) necessary for imaging denser, higher-Z targets than have previously been investigated.

Persistence of Microbial Contamination on Transvaginal Ultrasound Probes despite Low-Level Disinfection Procedure

PubMed Central

M'Zali, Fatima; Bounizra, Carole; Leroy, Sandrine; Mekki, Yahia; Quentin-Noury, Claudine; Kann, Michael

2014-01-01

Aim of the Study In many countries, Low Level Disinfection (LLD) of covered transvaginal ultrasound probes is recommended between patients' examinations. The aim of this study was to evaluate the antimicrobial efficacy of LLD under routine conditions on a range of microorganisms. Materials and Methods Samples were taken over a six month period in a private French Radiology Center. 300 specimens derived from endovaginal ultrasound probes were analyzed after disinfection of the probe with wipes impregnated with a quaternary ammonium compound and chlorhexidine. Human papillomavirus (HPV) was sought in the first set of s100 samples, Chlamydia trachomatis and mycoplasmas were searched in the second set of 100 samples, bacteria and fungi in the third 100 set samples. HPV, C. trachomatis and mycoplasmas were detected by PCR amplification. PCR positive samples were subjected to a nuclease treatment before an additional PCR assay to assess the likely viable microorganisms. Bacteria and fungi were investigated by conventional methods. Results A substantial persistence of microorganisms was observed on the disinfected probes: HPV DNA was found on 13% of the samples and 7% in nuclease-resistant form. C. trachomatis DNA was detected on 20% of the probes by primary PCR but only 2% after nuclease treatment, while mycoplasma DNA was amplified in 8% and 4%, respectively. Commensal and/or environmental bacterial flora was present on 86% of the probes, occasionally in mixed culture, and at various levels (10->3000 CFU/probe); Staphylococcus aureus was cultured from 4% of the probes (10-560 CFU/probe). No fungi were isolated. Conclusion Our findings raise concerns about the efficacy of impregnated towels as a sole mean for disinfection of ultrasound probes. Although the ultrasound probes are used with disposable covers, our results highlight the potential risk of cross contamination between patients during ultrasound examination and emphasize the need for reviewing the disinfection procedure. PMID:24695371

probeBase—an online resource for rRNA-targeted oligonucleotide probes and primers: new features 2016

PubMed Central

Greuter, Daniel; Loy, Alexander; Horn, Matthias; Rattei, Thomas

2016-01-01

probeBase http://www.probebase.net is a manually maintained and curated database of rRNA-targeted oligonucleotide probes and primers. Contextual information and multiple options for evaluating in silico hybridization performance against the most recent rRNA sequence databases are provided for each oligonucleotide entry, which makes probeBase an important and frequently used resource for microbiology research and diagnostics. Here we present a major update of probeBase, which was last featured in the NAR Database Issue 2007. This update describes a complete remodeling of the database architecture and environment to accommodate computationally efficient access. Improved search functions, sequence match tools and data output now extend the opportunities for finding suitable hierarchical probe sets that target an organism or taxon at different taxonomic levels. To facilitate the identification of complementary probe sets for organisms represented by short rRNA sequence reads generated by amplicon sequencing or metagenomic analysis with next generation sequencing technologies such as Illumina and IonTorrent, we introduce a novel tool that recovers surrogate near full-length rRNA sequences for short query sequences and finds matching oligonucleotides in probeBase. PMID:26586809

Recent Development of Inorganic Nanoparticles for Biomedical Imaging

PubMed Central

2018-01-01

Inorganic nanoparticle-based biomedical imaging probes have been studied extensively as a potential alternative to conventional molecular imaging probes. Not only can they provide better imaging performance but they can also offer greater versatility of multimodal, stimuli-responsive, and targeted imaging. However, inorganic nanoparticle-based probes are still far from practical use in clinics due to safety concerns and less-optimized efficiency. In this context, it would be valuable to look over the underlying issues. This outlook highlights the recent advances in the development of inorganic nanoparticle-based probes for MRI, CT, and anti-Stokes shift-based optical imaging. Various issues and possibilities regarding the construction of imaging probes are discussed, and future research directions are suggested. PMID:29632878

Kagome fiber based ultrafast laser microsurgery probe delivering micro-Joule pulse energies.

PubMed

Subramanian, Kaushik; Gabay, Ilan; Ferhanoğlu, Onur; Shadfan, Adam; Pawlowski, Michal; Wang, Ye; Tkaczyk, Tomasz; Ben-Yakar, Adela

2016-11-01

We present the development of a 5 mm, piezo-actuated, ultrafast laser scalpel for fast tissue microsurgery. Delivery of micro-Joules level energies to the tissue was made possible by a large, 31 μm, air-cored inhibited-coupling Kagome fiber. We overcome the fiber's low NA by using lenses made of high refractive index ZnS, which produced an optimal focusing condition with 0.23 NA objective. The optical design achieved a focused laser spot size of 4.5 μm diameter covering a 75 × 75 μm 2 scan area in a miniaturized setting. The probe could deliver the maximum available laser power, achieving an average fluence of 7.8 J/cm 2 on the tissue surface at 62% transmission efficiency. Such fluences could produce uninterrupted, 40 μm deep cuts at translational speeds of up to 5 mm/s along the tissue. We predicted that the best combination of speed and coverage exists at 8 mm/s for our conditions. The onset of nonlinear absorption in ZnS, however, limited the probe's energy delivery capabilities to 1.4 μJ for linear operation at 1.5 picosecond pulse-widths of our fiber laser. Alternatives like broadband CaF 2 crystals should mitigate such nonlinear limiting behavior. Improved opto-mechanical design and appropriate material selection should allow substantially higher fluence delivery and propel such Kagome fiber-based scalpels towards clinical translation.

Analysis and Optimization of the Recovered ESA Huygens Mission

NASA Astrophysics Data System (ADS)

Kazeminejad, Bobby

2002-06-01

The Huygens Probe is the ESA-provided element of the joint NASA/ESA Cassini - Huygens mission to Saturn and Titan. A recently discovered design flaw in the Huygens radio receiver onboard Cassini led to a significantly different mission geometry, redesigned and implemented by both the ESA Huygens and NASA Cassini project teams. A numerical integration of the Orbiter trajectory and the Huygens descent profile with simplified assumptions for Probe attitude and correlated aerodynamic aspects offered the opportunity to re-calculate key mission parameters, which depend on the relative geometry and motion of the bodies. This was a crucial step to assess whether science-imposed constraints were not violated. A review of existing Titan wind and atmosphere models and their physical background led to a subsequent parametric study of their impact on the supersonic entry phase, the parachute descent and finally the bodyfixed landing coordinates of the Probe. In addition to the deterministic (nominal) Probe trajectory, it is important to quantify the influence of various uncertainties that enter into the equations of motion on the results (e.g., state vectors, physical parameters of the environment and the Probe itself). This was done by propagating the system covariance matrix together with the nominal state vectors. A sophisticated Monte Carlo technique developed to save up computation time was then used to determine statistical percentiles of the key parameters. The Probe Orbiter link geometry was characterized by evaluating the link budget and received frequency at receiver level. In this calculation the spin of the Probe and the asymmetric gain pattern of the transmitting antennas was taken into account. The results were then used in a mathematical model that describes the tracking capability of the receiver symbol synchronizer. This allowed the loss of data during the mission to be quantified. A subsequent parametric study of different sets of mission parameters with the goal of minimizing the data losses and maximizing the overall mission robustness resulted in the recommendation to change the flyby altitude of the Orbiter from 65,000 km down to 60,000 km.

Use of molecular techniques to evaluate the survival of a microorganism injected into an aquifer

USGS Publications Warehouse

Thiem, S.M.; Krumme, M.L.; Smith, R.L.; Tiedje, J.M.

1994-01-01

A PCR primer set and an internal probe that are specific for Pseudomonas sp. strain B13, a 3-chlorobenzoate-metabolizing strain, were developed. Using this primer set and probe, we were able to detect Pseudomonas sp. strain B13 DNA sequences in DNA extracted from aquifer samples 14.5 months after Pseudomonas sp. strain B13 had been injected into a sand and gravel aquifer. This primer set and probe were also used to analyze isolates from 3-chlorobenzoate enrichments of the aquifer samples by Southern blot analysis. Hybridization of Southern blots with the Pseudomonas sp. strain B13-specific probe and a catabolic probe in conjunction with restriction fragment length polymorphism (RFLP) analysis of ribosome genes was used to determine that viable Pseudomonas sp. strain B13 persisted in this environment. We isolated a new 3-chlorobenzoate-degrading strain from one of these enrichment cultures. The B13-specific probe does not hybridize to DNA from this isolate. The new strain could be the result of gene exchange between Pseudomonas sp. strain B13 and an indigenous bacterium. This speculation is based on an RFLP pattern of ribosome genes that differs from that of Pseudomonas sp. strain B13, the fact that identically sized restriction fragments hybridized to the catabolic gene probe, and the absence of any enrichable 3-chlorobenzoate-degrading strains in the aquifer prior to inoculation.

Mechanism-based biomarker gene sets for glutathione depletion-related hepatotoxicity in rats

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

Gao Weihua; Mizukawa, Yumiko; Nakatsu, Noriyuki

Chemical-induced glutathione depletion is thought to be caused by two types of toxicological mechanisms: PHO-type glutathione depletion [glutathione conjugated with chemicals such as phorone (PHO) or diethyl maleate (DEM)], and BSO-type glutathione depletion [i.e., glutathione synthesis inhibited by chemicals such as L-buthionine-sulfoximine (BSO)]. In order to identify mechanism-based biomarker gene sets for glutathione depletion in rat liver, male SD rats were treated with various chemicals including PHO (40, 120 and 400 mg/kg), DEM (80, 240 and 800 mg/kg), BSO (150, 450 and 1500 mg/kg), and bromobenzene (BBZ, 10, 100 and 300 mg/kg). Liver samples were taken 3, 6, 9 andmore » 24 h after administration and examined for hepatic glutathione content, physiological and pathological changes, and gene expression changes using Affymetrix GeneChip Arrays. To identify differentially expressed probe sets in response to glutathione depletion, we focused on the following two courses of events for the two types of mechanisms of glutathione depletion: a) gene expression changes occurring simultaneously in response to glutathione depletion, and b) gene expression changes after glutathione was depleted. The gene expression profiles of the identified probe sets for the two types of glutathione depletion differed markedly at times during and after glutathione depletion, whereas Srxn1 was markedly increased for both types as glutathione was depleted, suggesting that Srxn1 is a key molecule in oxidative stress related to glutathione. The extracted probe sets were refined and verified using various compounds including 13 additional positive or negative compounds, and they established two useful marker sets. One contained three probe sets (Akr7a3, Trib3 and Gstp1) that could detect conjugation-type glutathione depletors any time within 24 h after dosing, and the other contained 14 probe sets that could detect glutathione depletors by any mechanism. These two sets, with appropriate scoring systems, could be promising biomarkers for preclinical examination of hepatotoxicity.« less

"Gap hunting" to characterize clustered probe signals in Illumina methylation array data.

PubMed

Andrews, Shan V; Ladd-Acosta, Christine; Feinberg, Andrew P; Hansen, Kasper D; Fallin, M Daniele

2016-01-01

The Illumina 450k array has been widely used in epigenetic association studies. Current quality-control (QC) pipelines typically remove certain sets of probes, such as those containing a SNP or with multiple mapping locations. An additional set of potentially problematic probes are those with DNA methylation distributions characterized by two or more distinct clusters separated by gaps. Data-driven identification of such probes may offer additional insights for downstream analyses. We developed a procedure, termed "gap hunting," to identify probes showing clustered distributions. Among 590 peripheral blood samples from the Study to Explore Early Development, we identified 11,007 "gap probes." The vast majority (9199) are likely attributed to an underlying SNP(s) or other variant in the probe, although SNP-affected probes exist that do not produce a gap signals. Specific factors predict which SNPs lead to gap signals, including type of nucleotide change, probe type, DNA strand, and overall methylation state. These expected effects are demonstrated in paired genotype and 450k data on the same samples. Gap probes can also serve as a surrogate for the local genetic sequence on a haplotype scale and can be used to adjust for population stratification. The characteristics of gap probes reflect potentially informative biology. QC pipelines may benefit from an efficient data-driven approach that "flags" gap probes, rather than filtering such probes, followed by careful interpretation of downstream association analyses. Our results should translate directly to the recently released Illumina EPIC array given the similar chemistry and content design.

Nonpeptide-Based Small-Molecule Probe for Fluorogenic and Chromogenic Detection of Chymotrypsin.

PubMed

Wu, Lei; Yang, Shu-Hou; Xiong, Hao; Yang, Jia-Qian; Guo, Jun; Yang, Wen-Chao; Yang, Guang-Fu

2017-03-21

We report herein a nonpeptide-based small-molecule probe for fluorogenic and chromogenic detection of chymotrypsin, as well as the primary application for this probe. This probe was rationally designed by mimicking the peptide substrate and optimized by adjusting the recognition group. The refined probe 2 exhibits good specificity toward chymotrypsin, producing about 25-fold higher enhancement in both the fluorescence intensity and absorbance upon the catalysis by chymotrypsin. Compared with the most widely used peptide substrate (AMC-FPAA-Suc) of chymotrypsin, probe 2 shows about 5-fold higher binding affinity and comparable catalytical efficiency against chymotrypsin. Furthermore, it was successfully applied for the inhibitor characterization. To the best of our knowledge, probe 2 is the first nonpeptide-based small-molecule probe for chymotrypsin, with the advantages of simple structure and high sensitivity compared to the widely used peptide-based substrates. This small-molecule probe is expected to be a useful molecular tool for drug discovery and chymotrypsin-related disease diagnosis.

Long-Term Implanted cOFM Probe Causes Minimal Tissue Reaction in the Brain

PubMed Central

Hochmeister, Sonja; Asslaber, Martin; Kroath, Thomas; Pieber, Thomas R.; Sinner, Frank

2014-01-01

This study investigated the histological tissue reaction to long-term implanted cerebral open flow microperfusion (cOFM) probes in the frontal lobe of the rat brain. Most probe-based cerebral fluid sampling techniques are limited in application time due to the formation of a glial scar that hinders substance exchange between brain tissue and the probe. A glial scar not only functions as a diffusion barrier but also alters metabolism and signaling in extracellular brain fluid. cOFM is a recently developed probe-based technique to continuously sample extracellular brain fluid with an intact blood-brain barrier. After probe implantation, a 2 week healing period is needed for blood-brain barrier reestablishment. Therefore, cOFM probes need to stay in place and functional for at least 15 days after implantation to ensure functionality. Probe design and probe materials are optimized to evoke minimal tissue reaction even after a long implantation period. Qualitative and quantitative histological tissue analysis revealed no continuous glial scar formation around the cOFM probe 30 days after implantation and only a minor tissue reaction regardless of perfusion of the probe. PMID:24621608

Multiplex real-time PCR assays for the identification of the potato cyst and tobacco cyst nematodes

USDA-ARS?s Scientific Manuscript database

TaqMan primer-probe sets were developed for the detection and identification of potato cyst nematodes (PCN) Globodera pallida and G. rostochiensis using two-tube, multiplex real-time PCR. One tube contained a primer-probe set specific for G. pallida (pale cyst nematode) multiplexed with another prim...

Stochastic Simulation of Dopamine Neuromodulation for Implementation of Fluorescent Neurochemical Probes in the Striatal Extracellular Space.

PubMed

Beyene, Abraham G; McFarlane, Ian R; Pinals, Rebecca L; Landry, Markita P

2017-10-18

Imaging the dynamic behavior of neuromodulatory neurotransmitters in the extracelluar space that arise from individual quantal release events would constitute a major advance in neurochemical imaging. Spatial and temporal resolution of these highly stochastic neuromodulatory events requires concurrent advances in the chemical development of optical nanosensors selective for neuromodulators in concert with advances in imaging methodologies to capture millisecond neurotransmitter release. Herein, we develop and implement a stochastic model to describe dopamine dynamics in the extracellular space (ECS) of the brain dorsal striatum to guide the design and implementation of fluorescent neurochemical probes that record neurotransmitter dynamics in the ECS. Our model is developed from first-principles and simulates release, diffusion, and reuptake of dopamine in a 3D simulation volume of striatal tissue. We find that in vivo imaging of neuromodulation requires simultaneous optimization of dopamine nanosensor reversibility and sensitivity: dopamine imaging in the striatum or nucleus accumbens requires nanosensors with an optimal dopamine dissociation constant (K d ) of 1 μM, whereas K d s above 10 μM are required for dopamine imaging in the prefrontal cortex. Furthermore, as a result of the probabilistic nature of dopamine terminal activity in the striatum, our model reveals that imaging frame rates of 20 Hz are optimal for recording temporally resolved dopamine release events. Our work provides a modeling platform to probe how complex neuromodulatory processes can be studied with fluorescent nanosensors and enables direct evaluation of nanosensor chemistry and imaging hardware parameters. Our stochastic model is generic for evaluating fluorescent neurotransmission probes, and is broadly applicable to the design of other neurotransmitter fluorophores and their optimization for implementation in vivo.

AIE active multianalyte fluorescent probe for the detection of Cu2+, Ni2+ and Hg2+ ions.

PubMed

Pannipara, Mehboobali; Al-Sehemi, Abdullah G; Irfan, Ahmad; Assiri, Mohammed; Kalam, Abul; Al-Ammari, Yahya S

2018-08-05

A novel pyrazolyl chromene derivative (Probe 1) displaying aggregation induced emission (AIE) properties that capable of sensing of multiple metal ions has been designed and synthesized. The multi analyte probe exhibits selective sensing for Cu 2+ and Ni 2+ ions via fluorescence turn-off mechanism and ratiometric selectivity for Hg 2+ ions in aqueous media. The extent of binding of the probe with sensitive metal ions has been demonstrated. The experimental results were further investigated by computational means by optimizing the ground state geometries of Probe 1 and its various metal complexes for Probe 1-Ni, Probe 1-Hg and Probe 1-Cu using density functional theory (DFT) at B3LYP/6-31+g(d,p) (LANL2DZ) level. On the basis of binding energies, the stability of metal complexes has been studied. In Probe 1-Ni and Probe 1-Cu complexes, charge transfer has been observed from Probe 1 to metal ions revealing ligand to metal charge transfer (LMCT) while in Probe1-Hg complex LMCT as well as intra-molecular charge tranfer (ICT) within Probe 1. Copyright © 2018 Elsevier B.V. All rights reserved.

Rapid Bacterial Testing for Spacecraft Water

NASA Technical Reports Server (NTRS)

Lisle, John T.; Pyle, Barry H.; McFeters, Gordon A.

1996-01-01

Evaluations of the fluorogenic stains and probes will continue. E. coli 0157:H7 will be used as the reference strain for optimizing protocols. We anticipate the continued use of the fluorescent antibodies (TRITC and FITC labeled) in conjunction with CTC, Rhl23, DiBAC4(3), DAPI and acridine orange. Chemunex, the manufacturer of the ChemScan analyzer system, also makes a fluorogenic probe, Chemchrome B, which will be incorporated into the suite of probes to evaluate once their system is on site. Regardless of the combination of stains and probes all will be evaluated on membrane filters. Development of a FISH protocol that will be applicable to our conditions will be continued. Complimentary 16s rRNA probes to Ps. aeruginosa and currently in our laboratory will be evaluated first. Once this protocol has been adequately optimized other probes will be ordered for u a select number of other species. Currently, protocols to evaluate the effects of disinfection and the resulting lethality, injury on stain and/or probe specificity and reliability are being developed. E. coli 0157:H7 is the reference strain and chlorine the disinfectant the reference protocol is being developed around. Upon completion of this work, the resulting protocol will be extended to other species and disinfectants (e.g., iodine). Similar disinfectant experiments will then be conducted on the same species after starvation to evaluate the effects of starvation on disinfection resistance and the applicability of the stains and probes. Development of the immunomagnetic separation system will continue. Combined with the rapid methods described above, with enumeration by the ChemScan, we anticipate that this will provide a highly sensitive technique for the detection of specific, active bacteria.

Coupling Molecular Beacons to Barcoded Metal Nanowires for Multiplexed, Sealed Chamber DNA Bioassays

PubMed Central

Stoermer, Rebecca L.; Cederquist, Kristin B.; McFarland, Sean K.; Sha, Michael Y.; Penn, Sharron G.

2010-01-01

We have combined molecular beacon (MB) probes with barcoded metal nanowires to enable no-wash, sealed chamber, multiplexed detection of nucleic acids. Probe design and experimental parameters important in nanowire-based MB assays are discussed. Loop regions of 24 bases and 5 base pair stem regions in the beacon probes gave optimal performance. Our results suggest that thermodynamic predictions for secondary structure stability of solution-phase MB can guide probe design for nanowire-based assays. Dengue virus-specific probes with predicted solution-phase ΔG of folding in 500 mM buffered NaCl of approximately −4 kcal/mol performed better than those with ΔG > −2 or < −6 kcal/mol. Buffered 300–500 mM NaCl was selected after comparison of several buffers previously reported for similar types of assays, and 200–500 mM NaCl was found to be the optimal ionic strength for the hybridization temperatures (25 and 50 °C) and probe designs used here. Target binding to the surface as a function of solution concentration fit a Sips isotherm with Kd = 1.7 ± 0.3 nM. The detection limit was ∼100 pM, limited by incomplete quenching. Single base mismatches could be discriminated from fully complementary targets. Oligonucleotide target sequences specific for human immunodeficiency, hepatitis C, and severe acute respiratory viruses were assayed simultaneously in a no-wash, sealed chamber, multiplexed experiment in which each of three probe sequences was attached to a different pattern of encoded nanowires. Finally, we demonstrated that probe-coated nanowires retain their selectivity and sensitivity in a triplexed assay after storage for over 3 months. PMID:17177440

PROBES FOR THE SPECIFIC DETECTION OF CRYPTOSPORIDIUM PARVUM

EPA Science Inventory

A probe set, consisting of two synthetic oligonucleotides each tagged with a fluorescent reporter molecule, has been developed for specific detection of Cryptosporidium parvum.Each probe strand detects ribosomal RNA from a range of isolates of this species, and the combination is...

Optimization of digital droplet polymerase chain reaction for quantification of genetically modified organisms

PubMed Central

Gerdes, Lars; Iwobi, Azuka; Busch, Ulrich; Pecoraro, Sven

2016-01-01

Digital PCR in droplets (ddPCR) is an emerging method for more and more applications in DNA (and RNA) analysis. Special requirements when establishing ddPCR for analysis of genetically modified organisms (GMO) in a laboratory include the choice between validated official qPCR methods and the optimization of these assays for a ddPCR format. Differentiation between droplets with positive reaction and negative droplets, that is setting of an appropriate threshold, can be crucial for a correct measurement. This holds true in particular when independent transgene and plant-specific reference gene copy numbers have to be combined to determine the content of GM material in a sample. Droplets which show fluorescent units ranging between those of explicit positive and negative droplets are called ‘rain’. Signals of such droplets can hinder analysis and the correct setting of a threshold. In this manuscript, a computer-based algorithm has been carefully designed to evaluate assay performance and facilitate objective criteria for assay optimization. Optimized assays in return minimize the impact of rain on ddPCR analysis. We developed an Excel based ‘experience matrix’ that reflects the assay parameters of GMO ddPCR tests performed in our laboratory. Parameters considered include singleplex/duplex ddPCR, assay volume, thermal cycler, probe manufacturer, oligonucleotide concentration, annealing/elongation temperature, and a droplet separation evaluation. We additionally propose an objective droplet separation value which is based on both absolute fluorescence signal distance of positive and negative droplet populations and the variation within these droplet populations. The proposed performance classification in the experience matrix can be used for a rating of different assays for the same GMO target, thus enabling employment of the best suited assay parameters. Main optimization parameters include annealing/extension temperature and oligonucleotide concentrations. The droplet separation value allows for easy and reproducible assay performance evaluation. The combination of separation value with the experience matrix simplifies the choice of adequate assay parameters for a given GMO event. PMID:27077048

Optimization of digital droplet polymerase chain reaction for quantification of genetically modified organisms.

PubMed

Gerdes, Lars; Iwobi, Azuka; Busch, Ulrich; Pecoraro, Sven

2016-03-01

Digital PCR in droplets (ddPCR) is an emerging method for more and more applications in DNA (and RNA) analysis. Special requirements when establishing ddPCR for analysis of genetically modified organisms (GMO) in a laboratory include the choice between validated official qPCR methods and the optimization of these assays for a ddPCR format. Differentiation between droplets with positive reaction and negative droplets, that is setting of an appropriate threshold, can be crucial for a correct measurement. This holds true in particular when independent transgene and plant-specific reference gene copy numbers have to be combined to determine the content of GM material in a sample. Droplets which show fluorescent units ranging between those of explicit positive and negative droplets are called 'rain'. Signals of such droplets can hinder analysis and the correct setting of a threshold. In this manuscript, a computer-based algorithm has been carefully designed to evaluate assay performance and facilitate objective criteria for assay optimization. Optimized assays in return minimize the impact of rain on ddPCR analysis. We developed an Excel based 'experience matrix' that reflects the assay parameters of GMO ddPCR tests performed in our laboratory. Parameters considered include singleplex/duplex ddPCR, assay volume, thermal cycler, probe manufacturer, oligonucleotide concentration, annealing/elongation temperature, and a droplet separation evaluation. We additionally propose an objective droplet separation value which is based on both absolute fluorescence signal distance of positive and negative droplet populations and the variation within these droplet populations. The proposed performance classification in the experience matrix can be used for a rating of different assays for the same GMO target, thus enabling employment of the best suited assay parameters. Main optimization parameters include annealing/extension temperature and oligonucleotide concentrations. The droplet separation value allows for easy and reproducible assay performance evaluation. The combination of separation value with the experience matrix simplifies the choice of adequate assay parameters for a given GMO event.

Identification of genes and gene pathways associated with major depressive disorder by integrative brain analysis of rat and human prefrontal cortex transcriptomes

PubMed Central

Malki, K; Pain, O; Tosto, M G; Du Rietz, E; Carboni, L; Schalkwyk, L C

2015-01-01

Despite moderate heritability estimates, progress in uncovering the molecular substrate underpinning major depressive disorder (MDD) has been slow. In this study, we used prefrontal cortex (PFC) gene expression from a genetic rat model of MDD to inform probe set prioritization in PFC in a human post-mortem study to uncover genes and gene pathways associated with MDD. Gene expression differences between Flinders sensitive (FSL) and Flinders resistant (FRL) rat lines were statistically evaluated using the RankProd, non-parametric algorithm. Top ranking probe sets in the rat study were subsequently used to prioritize orthologous selection in a human PFC in a case–control post-mortem study on MDD from the Stanley Brain Consortium. Candidate genes in the human post-mortem study were then tested against a matched control sample using the RankProd method. A total of 1767 probe sets were differentially expressed in the PFC between FSL and FRL rat lines at (q⩽0.001). A total of 898 orthologous probe sets was found on Affymetrix's HG-U95A chip used in the human study. Correcting for the number of multiple, non-independent tests, 20 probe sets were found to be significantly dysregulated between human cases and controls at q⩽0.05. These probe sets tagged the expression profile of 18 human genes (11 upregulated and seven downregulated). Using an integrative rat–human study, a number of convergent genes that may have a role in pathogenesis of MDD were uncovered. Eighty percent of these genes were functionally associated with a key stress response signalling cascade, involving NF-κB (nuclear factor kappa-light-chain-enhancer of activated B cells), AP-1 (activator protein 1) and ERK/MAPK, which has been systematically associated with MDD, neuroplasticity and neurogenesis. PMID:25734512

Application of a unique server-based oligonucleotide probe selection tool toward a novel biosensor for the detection of Streptococcus pyogenes.

PubMed

Nugen, Sam R; Leonard, Barbara; Baeumner, Antje J

2007-05-15

We developed a software program for the rapid selection of detection probes to be used in nucleic acid-based assays. In comparison to commercially available software packages, our program allows the addition of oligotags as required by nucleic acid sequence-based amplification (NASBA) as well as automatic BLAST searches for all probe/primer pairs. We then demonstrated the usefulness of the program by designing a novel lateral flow biosensor for Streptococcus pyogenes that does not rely on amplification methods such as the polymerase chain reaction (PCR) or NASBA to obtain low limits of detection, but instead uses multiple reporter and capture probes per target sequence and an instantaneous amplification via dye-encapsulating liposomes. These assays will decrease the detection time to just a 20 min hybridization reaction and avoid costly enzymatic gene amplification reactions. The lateral flow assay was developed quantifying the 16S rRNA from S. pyogenes by designing reporter and capture probes that specifically hybridize with the RNA and form a sandwich. DNA reporter probes were tagged with dye-encapsulating liposomes, biotinylated DNA oligonucleotides were used as capture probes. From the initial number of capture and reporter probes chosen, a combination of two capture and three reporter probes were found to provide optimal signal generation and significant enhancement over single capture/reporter probe combinations. The selectivity of the biosensor was proven by analyzing organisms closely related to S. pyogenes, such as other Streptococcus and Enterococcus species. All probes had been selected by the software program within minutes and no iterative optimization and re-design of the oligonucleotides was required which enabled a very rapid biosensor prototyping. While the sensitivity obtained with the biosensor was only 135 ng, future experiments will decrease this significantly by the addition of more reporter and capture probes for either the same rRNA or a different nucleic acid target molecule. This will lead to the possibility of detecting S. pyogenes with a rugged assay that does not require a cell culturing or gene amplification step and will therefore enable rapid, specific and sensitive onsite testing.

PCR Amplicon Prediction from Multiplex Degenerate Primer and Probe Sets

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

Gardner, S. N.

2013-08-08

Assessing primer specificity and predicting both desired and off-target amplification products is an essential step for robust PCR assay design. Code is described to predict potential polymerase chain reaction (PCR) amplicons in a large sequence database such as NCBI nt from either singleplex or a large multiplexed set of primers, allowing degenerate primer and probe bases, with target mismatch annotates amplicons with gene information automatically downloaded from NCBI, and optionally it can predict whether there are also TaqMan/Luminex probe matches within predicted amplicons.

An Eddy Current Testing Platform System for Pipe Defect Inspection Based on an Optimized Eddy Current Technique Probe Design

PubMed Central

Rifai, Damhuji; Abdalla, Ahmed N.; Razali, Ramdan; Ali, Kharudin; Faraj, Moneer A.

2017-01-01

The use of the eddy current technique (ECT) for the non-destructive testing of conducting materials has become increasingly important in the past few years. The use of the non-destructive ECT plays a key role in the ensuring the safety and integrity of the large industrial structures such as oil and gas pipelines. This paper introduce a novel ECT probe design integrated with the distributed ECT inspection system (DSECT) use for crack inspection on inner ferromagnetic pipes. The system consists of an array of giant magneto-resistive (GMR) sensors, a pneumatic system, a rotating magnetic field excitation source and a host PC acting as the data analysis center. Probe design parameters, namely probe diameter, an excitation coil and the number of GMR sensors in the array sensor is optimized using numerical optimization based on the desirability approach. The main benefits of DSECT can be seen in terms of its modularity and flexibility for the use of different types of magnetic transducers/sensors, and signals of a different nature with either digital or analog outputs, making it suited for the ECT probe design using an array of GMR magnetic sensors. A real-time application of the DSECT distributed system for ECT inspection can be exploited for the inspection of 70 mm carbon steel pipe. In order to predict the axial and circumference defect detection, a mathematical model is developed based on the technique known as response surface methodology (RSM). The inspection results of a carbon steel pipe sample with artificial defects indicate that the system design is highly efficient. PMID:28335399

Optimization of peptide nucleic acid fluorescence in situ hybridization (PNA-FISH) for the detection of bacteria: The effect of pH, dextran sulfate and probe concentration.

PubMed

Rocha, Rui; Santos, Rita S; Madureira, Pedro; Almeida, Carina; Azevedo, Nuno F

2016-05-20

Fluorescence in situ hybridization (FISH) is a molecular technique widely used for the detection and characterization of microbial populations. FISH is affected by a wide variety of abiotic and biotic variables and the way they interact with each other. This is translated into a wide variability of FISH procedures found in the literature. The aim of this work is to systematically study the effects of pH, dextran sulfate and probe concentration in the FISH protocol, using a general peptide nucleic acid (PNA) probe for the Eubacteria domain. For this, response surface methodology was used to optimize these 3 PNA-FISH parameters for Gram-negative (Escherichia coli and Pseudomonas fluorescens) and Gram-positive species (Listeria innocua, Staphylococcus epidermidis and Bacillus cereus). The obtained results show that a probe concentration higher than 300nM is favorable for both groups. Interestingly, a clear distinction between the two groups regarding the optimal pH and dextran sulfate concentration was found: a high pH (approx. 10), combined with lower dextran sulfate concentration (approx. 2% [w/v]) for Gram-negative species and near-neutral pH (approx. 8), together with higher dextran sulfate concentrations (approx. 10% [w/v]) for Gram-positive species. This behavior seems to result from an interplay between pH and dextran sulfate and their ability to influence probe concentration and diffusion towards the rRNA target. This study shows that, for an optimum hybridization protocol, dextran sulfate and pH should be adjusted according to the target bacteria. Copyright © 2016 Elsevier B.V. All rights reserved.

Electrophysiological correlates of proactive interference in the 'Recent Probes' verbal working memory task.

PubMed

Zhang, John X; Wu, Renhua; Kong, Lingyue; Weng, Xuchu; Du, Yingchun

2010-06-01

Using event-related potentials (ERPs), the present study examined the temporal dynamics of proactive interference in working memory using a recent probes task. Participants memorized and retained a target set of four letters over a short retention interval. They then responded to a recognition probe by judging whether it was from the memory set. ERP waveforms elicited by positive probes compared to those from negative probes showed positive shifts in a fronto-central early N2 component and a parietal late positive component (LPC). The LPC was identified as the electrophysiological signature of proactive interference, as it differentiated between two types of negative probes defined based on whether they were recently encountered. These results indicate that the proactive interference we observed arises from a mismatch between familiarity and contextual information during recognition memory. When considered together with related studies in the literature, the results also suggest that there are different forms of proactive interference associated with different neural correlates. Copyright 2010 Elsevier Ltd. All rights reserved.

Huygens Titan Probe Trajectory Reconstruction Using Traditional Methods and the Program to Optimize Simulated Trajectories II

NASA Technical Reports Server (NTRS)

Striepe, Scott A.; Blanchard, Robert C.; Kirsch, Michael F.; Fowler, Wallace T.

2007-01-01

On January 14, 2005, ESA's Huygens probe separated from NASA's Cassini spacecraft, entered the Titan atmosphere and landed on its surface. As part of NASA Engineering Safety Center Independent Technical Assessment of the Huygens entry, descent, and landing, and an agreement with ESA, NASA provided results of all EDL analyses and associated findings to the Huygens project team prior to probe entry. In return, NASA was provided the flight data from the probe so that trajectory reconstruction could be done and simulation models assessed. Trajectory reconstruction of the Huygens entry probe at Titan was accomplished using two independent approaches: a traditional method and a POST2-based method. Results from both approaches are discussed in this paper.

MPAI (mass probes aided ionization) method for total analysis of biomolecules by mass spectrometry.

PubMed

Honda, Aki; Hayashi, Shinichiro; Hifumi, Hiroki; Honma, Yuya; Tanji, Noriyuki; Iwasawa, Naoko; Suzuki, Yoshio; Suzuki, Koji

2007-01-01

We have designed and synthesized various mass probes, which enable us to effectively ionize various molecules to be detected with mass spectrometry. We call the ionization method using mass probes the "MPAI (mass probes aided ionization)" method. We aim at the sensitive detection of various biological molecules, and also the detection of bio-molecules by a single mass spectrometry serially without changing the mechanical settings. Here, we review mass probes for small molecules with various functional groups and mass probes for proteins. Further, we introduce newly developed mass probes for proteins for highly sensitive detection.

Optimization of (131)I doses for the treatment of hyperthyroidism.

PubMed

Araujo, F; Rebelo, A M O; Pereira, A C; Moura, M B; Lucena, E A; Dantas, A L A; Dantas, B M; Corbo, R

2009-11-15

Several methods can be used to determine the activity of (131)I in the treatment of hyperthyroidism. However, many of them do not consider all the parameters necessary for optimum dose calculation. The relationship between the dose absorbed by the thyroid and the activity administered depends basically on three parameters: organ mass, iodine uptake and effective half-life of iodine in the thyroid. Such parameters should be individually determined for each patient in order to optimize the administered activity. The objective of this work is to develop a methodology for individualized treatment with (131)I in patients with hyperthyroidism of the Grave's Disease. A neck-thyroid phantom developed at the IRD was used to calibrate a scintillation camera and a uptake probe SCT-13004 at the Nuclear Medicine Center of the University Hospital of Rio de Janeiro and a uptake probe SCT-13002, available at the Nuclear Medicine Institute in Goiânia. The biokinetic parameters were determined based on measurements performed in eight voluntary patients. It is concluded that the use of the equipment available at the hospital (scintillation camera and uptake probe) has shown to be a suitable and feasible procedure for dose optimization in terms of effectiveness, simplicity and cost.

Photoaffinity labeling in target- and binding-site identification

PubMed Central

Smith, Ewan; Collins, Ian

2015-01-01

Photoaffinity labeling (PAL) using a chemical probe to covalently bind its target in response to activation by light has become a frequently used tool in drug discovery for identifying new drug targets and molecular interactions, and for probing the location and structure of binding sites. Methods to identify the specific target proteins of hit molecules from phenotypic screens are highly valuable in early drug discovery. In this review, we summarize the principles of PAL including probe design and experimental techniques for in vitro and live cell investigations. We emphasize the need to optimize and validate probes and highlight examples of the successful application of PAL across multiple disease areas. PMID:25686004

Optimisation of specimen temperature and pulse fraction in atom probe microscopy experiments on a microalloyed steel.

PubMed

Yao, L; Cairney, J M; Zhu, C; Ringer, S P

2011-05-01

This paper details the effects of systematic changes to the experimental parameters for atom probe microscopy of microalloyed steels. We have used assessments of the signal-to-noise ratio (SNR), compositional measurements and field desorption images to establish the optimal instrumental parameters. These corresponded to probing at the lowest possible temperature (down to 20K) with the highest possible pulse fraction (up to 30%). A steel containing a fine dispersion of solute atom clusters was used as an archetype to demonstrate the importance of running the atom probe at optimum conditions. Crown Copyright © 2010. Published by Elsevier B.V. All rights reserved.

Number-unconstrained quantum sensing

NASA Astrophysics Data System (ADS)

Mitchell, Morgan W.

2017-12-01

Quantum sensing is commonly described as a constrained optimization problem: maximize the information gained about an unknown quantity using a limited number of particles. Important sensors including gravitational wave interferometers and some atomic sensors do not appear to fit this description, because there is no external constraint on particle number. Here, we develop the theory of particle-number-unconstrained quantum sensing, and describe how optimal particle numbers emerge from the competition of particle-environment and particle-particle interactions. We apply the theory to optical probing of an atomic medium modeled as a resonant, saturable absorber, and observe the emergence of well-defined finite optima without external constraints. The results contradict some expectations from number-constrained quantum sensing and show that probing with squeezed beams can give a large sensitivity advantage over classical strategies when each is optimized for particle number.

Characterization of classical static noise via qubit as probe

NASA Astrophysics Data System (ADS)

Javed, Muhammad; Khan, Salman; Ullah, Sayed Arif

2018-03-01

The dynamics of quantum Fisher information (QFI) of a single qubit coupled to classical static noise is investigated. The analytical relation for QFI fixes the optimal initial state of the qubit that maximizes it. An approximate limit for the time of coupling that leads to physically useful results is identified. Moreover, using the approach of quantum estimation theory and the analytical relation for QFI, the qubit is used as a probe to precisely estimate the disordered parameter of the environment. Relation for optimal interaction time with the environment is obtained, and condition for the optimal measurement of the noise parameter of the environment is given. It is shown that all values, in the mentioned range, of the noise parameter are estimable with equal precision. A comparison of our results with the previous studies in different classical environments is made.

Rational chemical design of the next generation of molecular imaging probes based on physics and biology: mixing modalities, colors and signals

PubMed Central

Longmire, Michelle R.; Ogawa, Mikako; Choyke, Peter L.

2012-01-01

In recent years, numerous in vivo molecular imaging probes have been developed. As a consequence, much has been published on the design and synthesis of molecular imaging probes focusing on each modality, each type of material, or each target disease. More recently, second generation molecular imaging probes with unique, multi-functional, or multiplexed characteristics have been designed. This critical review focuses on (i) molecular imaging using combinations of modalities and signals that employ the full range of the electromagnetic spectra, (ii) optimized chemical design of molecular imaging probes for in vivo kinetics based on biology and physiology across a range of physical sizes, (iii) practical examples of second generation molecular imaging probes designed to extract complementary data from targets using multiple modalities, color, and comprehensive signals (277 references). PMID:21607237

Comparison of interball-2 spacecraft potential from IESP and KM-7 experiments in high-latitude regions of the magnetosphere at altitudes of 2-3 RE

NASA Astrophysics Data System (ADS)

Smirnova, N.; Afonin, V.; Smilauer, Ja.; Stanev, G.

Measurements of Interball-2 spacecraft potential by two instruments, IESP and KM-7, are reviewed and simultaneous measurements are compared. Unacceptable discrepancy between results of spacecraft potential measurements, including opposite signs, was found. Actually, both experiments are methodically identical: they used the same type of sensor - spherical Langmuir probes operating in the ``floating'' mode, and they have measured the same parameter - the voltage difference between the probe and the satellite structure. The IESP instrument measured one value of this parameter at fixed bias current to the probe. The KM-7 measured the whole current-voltage characteristic (the probe current as a function of the probe potential), which consists of 11 IESP-type measurements at different values of bias current. The difference lies only in the way of technical implementation, as the probes were operating in different ambient conditions. The IESP probes were mounted at the ends of long booms and thus were affected by the solar UV emission, while the KM-7 probe was rather well protected against UV emission by proper mounting and screening the head of the sensor from both direct UV emission and those reflected from spacecraft elements. The comparison of two data sets and variations along the orbit has shown, that KM-7 correctly measures the spacecraft potential. In high-latitude inner magnetosphere (in auroral region and polar cap) at altitudes 2-3 RE the spacecraft potential was predominantly negative down to -10 V, increasing up to about +5 V in some locations at rather extended parts of the satellite orbit. Reasonably good agreement between two experiments was obtained only at spacecraft potential <= -2 V and after inversion the sign of available calibration curve of IESP experiment; in this case both experiments very accurately reflect variation of potential data even in the small details. The operation mode of IESP experiment was not optimal and requires further analysis. The wave results obtained with IESP may be considered as reliable only when both experiments show, after inversion of available IESP calibration curve, coincident data, but the phase relations, if any, will be inversed in any case. The method of spacecraft potential measurements adopted in IESP should be used only for positive potential; if realspacecraft potential is negative, the method gives wrong and misleading results.

Frequency Domain Fluorescent Molecular Tomography and Molecular Probes for Small Animal Imaging

NASA Astrophysics Data System (ADS)

Kujala, Naresh Gandhi

Fluorescent molecular tomography (FMT) is a noninvasive biomedical optical imaging that enables 3-dimensional quantitative determination of fluorochromes distributed in biological tissues. There are three methods for imaging large volume tissues based on different light sources: (a) using a light source of constant intensity, through a continuous or constant wave, (b) using a light source that is intensity modulated with a radio frequency (RF), and (c) using ultrafast pulses in the femtosecond range. In this study, we have developed a frequency domain fluorescent molecular tomographic system based on the heterodyne technique, using a single source and detector pair that can be used for small animal imaging. In our system, the intensity of the laser source is modulated with a RF frequency to produce a diffuse photon density wave in the tissue. The phase of the diffuse photon density wave is measured by comparing the reference signal with the signal from the tissue using a phasemeter. The data acquisition was performed by using a Labview program. The results suggest that we can measure the phase change from the heterogeneous inside tissue. Combined with fiber optics and filter sets, the system can be used to sensitively image the targeted fluorescent molecular probes, allowing the detection of cancer at an early stage. We used the system to detect the tumor-targeting molecular probe Alexa Fluor 680 and Alexa Fluor 750 bombesin peptide conjugates in phantoms as well as mouse tissues. We also developed and evaluated fluorescent Bombesin (BBN) probes to target gastrin-releasing peptide (GRP) receptors for optical molecular imaging. GRP receptors are over-expressed in several types of human cancer cells, including breast, prostate, small cell lung, and pancreatic cancers. BBN is a 14 amino acid peptide that is an analogue to human gastrin-releasing peptide that binds specifically to GRPr receptors. BBN conjugates are significant in cancer detection and therapy. The optical molecular probe AF750 BBN peptide exhibits optimal pharmacokinetic properties for targeting GRPr in mice. Fluorescent microscopic imaging of the molecular probe in PC-3 prostate and T-47D breast cancer cell lines indicated specific uptake, internalization, and receptor blocking of these probes. In vivo investigations in severely compromised immunodeficient (SCID) mice bearing xenografted PC-3 prostate and T47-D breast cancer lesions demonstrated the ability of this new molecular probe to specifically target tumor tissue with high selectively and affinity.

Probing the localization of magnetic dichroism by atomic-size astigmatic and vortex electron beams.

PubMed

Negi, Devendra Singh; Idrobo, Juan Carlos; Rusz, Ján

2018-03-05

We report localization of a magnetic dichroic signal on atomic columns in electron magnetic circular dichroism (EMCD), probed by beam distorted by four-fold astigmatism and electron vortex beam. With astigmatic probe, magnetic signal to noise ratio can be enhanced by blocking the intensity from the central part of probe. However, the simulations show that for atomic resolution magnetic measurements, vortex beam is a more effective probe, with much higher magnetic signal to noise ratio. For all considered beam shapes, the optimal SNR constrains the signal detection at low collection angles of approximately 6-8 mrad. Irrespective of the material thickness, the magnetic signal remains strongly localized within the probed atomic column with vortex beam, whereas for astigmatic probes, the magnetic signal originates mostly from the nearest neighbor atomic columns. Due to excellent signal localization at probing individual atomic columns, vortex beams are predicted to be a strong candidate for studying the crystal site specific magnetic properties, magnetic properties at interfaces, or magnetism arising from individual atomic impurities.

Surface-enhanced Raman scattering based nonfluorescent probe for multiplex DNA detection.

PubMed

Sun, Lan; Yu, Chenxu; Irudayaraj, Joseph

2007-06-01

To provide rapid and accurate detection of DNA markers in a straightforward, inexpensive, and multiplex format, an alternative surface-enhanced Raman scattering based probe was designed and fabricated to covalently attach both DNA probing sequence and nonfluorescent Raman tags to the surface of gold nanoparticles (DNA-AuP-RTag). The intensity of Raman signal of the probes could be controlled through the surface coverage of the nonfluorescent Raman tags (RTags). Detection sensitivity of these probes could be optimized by fine-tuning the amount of DNA molecules and RTags on the probes. Long-term stability of the DNA-AuP-RTag probes was found to be good (over 3 months). Excellent multiplexing capability of the DNA-AuP-RTag scheme was demonstrated by simultaneous identification of up to eight probes in a mixture. Detection of hybridization of single-stranded DNA to its complementary targets was successfully accomplished with a long-term goal to use nonfluorescent RTags in a Raman-based DNA microarray platform.

Surface-Enhanced Raman Scattering Based Nonfluorescent Probe for Multiplex DNA Detection

PubMed Central

Sun, Lan; Yu, Chenxu; Irudayaraj, Joseph

2008-01-01

To provide rapid and accurate detection of DNA markers in a straightforward, inexpensive and multiplex format, an alternative surface enhanced Raman scattering (SERS) based probe was designed and fabricated to covalently attach both DNA probing sequence and non-fluorescent Raman tags to the surface of gold nanoparticles (DNA-AuP-RTag). The intensity of Raman signal of the probes could be controlled through the surface coverage of the non-fluorescent Raman tags (RTags). Detection sensitivity of these probes could be optimized by fine-tuning the amount of DNA molecules and RTags on the probes. Long-term stability of the DNA-AuP-RTag probes was found to be good (over 3 months). Excellent multiplexing capability of the DNA-AuP-RTag scheme was demonstrated by simultaneous identification of up to eight probes in a mixture. Detection of hybridization of single-stranded DNA (ssDNA) to its complementary targets was successfully accomplished with a long-term goal to use non-fluorescent RTags in a Raman-based DNA microarray platform. PMID:17465531

Lens-free all-fiber probe with an optimized output beam for optical coherence tomography.

PubMed

Ding, Zhihua; Qiu, Jianrong; Shen, Yi; Chen, Zhiyan; Bao, Wen

2017-07-15

A high-efficiency lensless all-fiber probe for optical coherence tomography (OCT) is presented. The probe is composed of a segment of large-core multimode fiber (MMF), a segment of tapered MMF, and a length of single-mode fiber (SMF). A controllable output beam can be designed by a simple adjustment of its probe structure parameters (PSPs), instead of the selection of fibers with different optical parameters. A side-view probe with a diameter of 340 μm and a rigid length of 6.37 mm was fabricated, which provides an effective imaging range of ∼0.6  mm with a full width at half-maximum beam diameter of less than 30 μm. The insertion loss of the probe was measured to be 0.81 dB, ensuring a high sensitivity of 102.25 dB. Satisfactory images were obtained by the probe-based OCT system, demonstrating the feasibility of the probe for endoscopic OCT applications.

Chitosan stabilized gold nanoparticle mediated self-assembled gliP nanobiosensor for diagnosis of Invasive Aspergillosis.

PubMed

Bhatnagar, Ira; Mahato, Kuldeep; Ealla, Kranthi Kiran Reddy; Asthana, Amit; Chandra, Pranjal

2018-04-15

Diagnosis of Invasive Aspergillosis (IA) casused by Aspergillus fumigatus in miniaturized setting is challenging with great importance in human health. In this direction, we have designed a sensitive electrochemical nanobiosensor for diagnosis of IA through detecting the virulent glip target gene (glip-T) in a miniaturized experimetal setting. The sensor probe was fabricated using 1,6-Hexanedithiol and chitosan stabilized gold nanoparticle mediated self-assembly of glip probes (glip-P) on gold electrode. It was characterized by UV-visible spectroscopy, cyclic voltametry and electrochemical impedance spectroscopy. The ability of sensor to detect glip-T was analysed based on the hybridyzation reaction and the signal obtained using toluidine blue as indicator molecule. Analytical parameters were optimized in terms of glip-P concentration, temperature, reaction time, and concentration of toluidine blue. The biosensor showed the dynamic range between 1 × 10 -14 - 1 × 10 -2  M with the detection limit of 0.32 ± 0.01 × 10 -14 (RSD < 5.2%). The regeneration of biosensor was evaluated and the interference due to non-target oligonucleotide sequences was evaluated individualy as well as in mixed sample to validate the high selectivity of the designed sensor. The stability of the designed sensor was examined and practical applicability of biosensor was tested by detecting glip-T in real sample environment. Copyright © 2017 Elsevier B.V. All rights reserved.

Ensemble stump classifiers and gene expression signatures in lung cancer.

PubMed

Frey, Lewis; Edgerton, Mary; Fisher, Douglas; Levy, Shawn

2007-01-01

Microarray data sets for cancer tumor tissue generally have very few samples, each sample having thousands of probes (i.e., continuous variables). The sparsity of samples makes it difficult for machine learning techniques to discover probes relevant to the classification of tumor tissue. By combining data from different platforms (i.e., data sources), data sparsity is reduced, but this typically requires normalizing data from the different platforms, which can be non-trivial. This paper proposes a variant on the idea of ensemble learners to circumvent the need for normalization. To facilitate comprehension we build ensembles of very simple classifiers known as decision stumps--decision trees of one test each. The Ensemble Stump Classifier (ESC) identifies an mRNA signature having three probes and high accuracy for distinguishing between adenocarcinoma and squamous cell carcinoma of the lung across four data sets. In terms of accuracy, ESC outperforms a decision tree classifier on all four data sets, outperforms ensemble decision trees on three data sets, and simple stump classifiers on two data sets.

Confocal Raman spectroscopic analysis of cross-linked ultra-high molecular weight polyethylene for application in artificial hip joints.

PubMed

Pezzotti, Giuseppe; Kumakura, Tsuyoshi; Yamada, Kiyotaka; Tateiwa, Toshiyuki; Puppulin, Leonardo; Zhu, Wenliang; Yamamoto, Kengo

2007-01-01

Confocal spectroscopic techniques are applied to selected Raman bands to study the microscopic features of acetabular cups made of ultra-high molecular weight polyethylene (UHMWPE) before and after implantation in vivo. The micrometric lateral resolution of a laser beam focused on the polymeric surface (or subsurface) enables a highly resolved visualization of 2-D conformational population patterns, including crystalline, amorphous, orthorhombic phase fractions, and oxidation index. An optimized confocal probe configuration, aided by a computational deconvolution of the optical probe, allows minimization of the probe size along the in-depth direction and a nondestructive evaluation of microstructural properties along the material subsurface. Computational deconvolution is also attempted, based on an experimental assessment of the probe response function of the polyethylene Raman spectrum, according to a defocusing technique. A statistical set of high-resolution microstructural data are collected on a fully 3-D level on gamma-ray irradiated UHMWPE acetabular cups both as-received from the maker and after retrieval from a human body. Microstructural properties reveal significant gradients along the immediate material subsurface and distinct differences are found due to the loading history in vivo, which cannot be revealed by conventional optical spectroscopy. The applicability of the confocal spectroscopic technique is valid beyond the particular retrieval cases examined in this study, and can be easily extended to evaluate in-vitro tested components or to quality control of new polyethylene brands. Confocal Raman spectroscopy may also contribute to rationalize the complex effects of gamma-ray irradiation on the surface of medical grade UHMWPE for total joint replacement and, ultimately, to predict their actual lifetime in vivo.

Design of a phased array for the generation of adaptive radiation force along a path surrounding a breast lesion for dynamic ultrasound elastography imaging.

PubMed

Ekeom, Didace; Hadj Henni, Anis; Cloutier, Guy

2013-03-01

This work demonstrates, with numerical simulations, the potential of an octagonal probe for the generation of radiation forces in a set of points following a path surrounding a breast lesion in the context of dynamic ultrasound elastography imaging. Because of the in-going wave adaptive focusing strategy, the proposed method is adapted to induce shear wave fronts to interact optimally with complex lesions. Transducer elements were based on 1-3 piezocomposite material. Three-dimensional simulations combining the finite element method and boundary element method with periodic boundary conditions in the elevation direction were used to predict acoustic wave radiation in a targeted region of interest. The coupling factor of the piezocomposite material and the radiated power of the transducer were optimized. The transducer's electrical impedance was targeted to 50 Ω. The probe was simulated by assembling the designed transducer elements to build an octagonal phased-array with 256 elements on each edge (for a total of 2048 elements). The central frequency is 4.54 MHz; simulated transducer elements are able to deliver enough power and can generate the radiation force with a relatively low level of voltage excitation. Using dynamic transmitter beamforming techniques, the radiation force along a path and resulting acoustic pattern in the breast were simulated assuming a linear isotropic medium. Magnitude and orientation of the acoustic intensity (radiation force) at any point of a generation path could be controlled for the case of an example representing a heterogeneous medium with an embedded soft mechanical inclusion.

Probe-And-Socket Fasteners For Robotic Assembly

NASA Technical Reports Server (NTRS)

Nyberg, Karen

1995-01-01

Self-alignment and simplicity of actuation make mechanism amenable to robotic assembly. Includes socket, mounted on structure at worksite, and probe, mounted on piece of equipment to be attached to structure at socket. Probe-and-socket mechanism used in conjunction with fixed target aiding in placement of end effector of robot during grasping, and with handle or handles on structure. Intended to enable robot to set up workstation in hostile environment. Workstation then used by astronaut, aquanaut, or other human, spending minimum time in environment. Human concentrates on performing quality work rather than on setting up equipment, with consequent reduction of risk.

Microwave resonances in dielectric samples probed in Corbino geometry: simulation and experiment.

PubMed

Felger, M Maximilian; Dressel, Martin; Scheffler, Marc

2013-11-01

The Corbino approach, where the sample of interest terminates a coaxial cable, is a well-established method for microwave spectroscopy. If the sample is dielectric and if the probe geometry basically forms a conductive cavity, this combination can sustain well-defined microwave resonances that are detrimental for broadband measurements. Here, we present detailed simulations and measurements to investigate the resonance frequencies as a function of sample and probe size and of sample permittivity. This allows a quantitative optimization to increase the frequency of the lowest-lying resonance.

Experimental aspects in acquisition of wide bandwidth solid-state MAS NMR spectra of low-γ nuclei with different opportunities on two commercial NMR spectrometers

NASA Astrophysics Data System (ADS)

Jakobsen, Hans J.; Bildsøe, Henrik; Gan, Zhehong; Brey, William W.

2011-08-01

The acquisition and different appearances observed for wide bandwidth solid-state MAS NMR spectra of low-γ nuclei, using 14N as an illustrative nucleus and employing two different commercial spectrometers (Varian, 14.1 T and Bruker, 19.6 T), have been compared/evaluated and optimized from an experimental NMR and an electronic engineering point of view, to account for the huge differences in these spectra. The large differences in their spectral appearances, employing the recommended/standard experimental set-up for the two different spectrometers, are shown to be associated with quite large differences in the electronic design of the two types of preamplifiers, which are connected to their respective probes through a 50 Ω cable, and are here completely accounted for. This has led to different opportunities for optimum performances in the acquisition of nearly ideal wide bandwidth spectra for low-γ nuclei on the two spectrometers by careful evaluation of the length for the 50 Ω probe-to-preamp cable for the Varian system and appropriate changes to the bandwidth ( Q) of the NMR probe used on the Bruker spectrometer. Earlier, we reported quite distorted spectra obtained with Varian Unity INOVA spectrometers (at 11.4 and 14.1 T) in several exploratory wide bandwidth 14N MAS NMR studies of inorganic nitrates and amino acids. These spectra have now been compared/evaluated with fully analyzed 14N MAS spectra correspondingly acquired at 19.6 T on a Bruker spectrometer. It is shown that our upgraded version of the STARS simulation/iterative-fitting software is capable of providing identical sets for the molecular spectral parameters and corresponding fits to the experimental spectra, which fully agree with the electronic measurements, despite the highly different appearances for the MAS NMR spectra acquired on the Varian and Bruker spectrometers.

The influence of voxel size on atom probe tomography data.

PubMed

Torres, K L; Daniil, M; Willard, M A; Thompson, G B

2011-05-01

A methodology for determining the optimal voxel size for phase thresholding in nanostructured materials was developed using an atom simulator and a model system of a fixed two-phase composition and volume fraction. The voxel size range was banded by the atom count within each voxel. Some voxel edge lengths were found to be too large, resulting in an averaging of compositional fluctuations; others were too small with concomitant decreases in the signal-to-noise ratio for phase identification. The simulated methodology was then applied to the more complex experimentally determined data set collected from a (Co(0.95)Fe(0.05))(88)Zr(6)Hf(1)B(4)Cu(1) two-phase nanocomposite alloy to validate the approach. In this alloy, Zr and Hf segregated to an intergranular amorphous phase while Fe preferentially segregated to a crystalline phase during the isothermal annealing step that promoted primary crystallization. The atom probe data analysis of the volume fraction was compared to transmission electron microscopy (TEM) dark-field imaging analysis and a lever rule analysis of the volume fraction within the amorphous and crystalline phases of the ribbon. Copyright © 2011 Elsevier B.V. All rights reserved.

A Microfluidic Love-Wave Biosensing Device for PSA Detection Based on an Aptamer Beacon Probe.

PubMed

Zhang, Feng; Li, Shuangming; Cao, Kang; Wang, Pengjuan; Su, Yan; Zhu, Xinhua; Wan, Ying

2015-06-11

A label-free and selective aptamer beacon-based Love-wave biosensing device was developed for prostate specific antigen (PSA) detection. The device consists of the following parts: LiTaO3 substrate with SiO2 film as wave guide layer, two set of inter-digital transducers (IDT), gold film for immobilization of the biorecongniton layer and a polydimethylsiloxane (PDMS) microfluidic channels. DNA aptamer, or "artificial antibody", was used as the specific biorecognition probe for PSA capture. Some nucleotides were added to the 3'-end of the aptamer to form a duplex with the 3'-end, turning the aptamer into an aptamer-beacon. Taking advantage of the selective target-induced assembly changes arising from the "aptamer beacon", highly selective and specific detection of PSA was achieved. Furthermore, PDMS microfluidic channels were designed and fabricated to realize automated quantitative sample injection. After optimization of the experimental conditions, the established device showed good performance for PSA detection between 10 ng/mL to 1 μg/mL, with a detection limit of 10 ng/mL. The proposed sensor might be a promising alternative for point of care diagnostics.

Overcoming the errors of in-house PCR used in the clinical laboratory for the diagnosis of extrapulmonary tuberculosis.

PubMed

Kunakorn, M; Raksakai, K; Pracharktam, R; Sattaudom, C

1999-03-01

Our experiences from 1993 to 1997 in the development and use of IS6110 base PCR for the diagnosis of extrapulmonary tuberculosis in a routine clinical setting revealed that error-correcting processes can improve existing diagnostic methodology. The reamplification method initially used had a sensitivity of 90.91% and a specificity of 93.75%. The concern was focused on the false positive results of this method caused by product-carryover contamination. This method was changed to single round PCR with carryover prevention by uracil DNA glycosylase (UDG), resulting in a 100% specificity but only 63% sensitivity. Dot blot hybridization was added after the single round PCR, increasing the sensitivity to 87.50%. However, false positivity resulted from the nonspecific dot blot hybridization signal, reducing the specificity to 89.47%. The hybridization of PCR was changed to a Southern blot with a new oligonucleotide probe giving the sensitivity of 85.71% and raising the specificity to 99.52%. We conclude that the PCR protocol for routine clinical use should include UDG for carryover prevention and hybridization with specific probes to optimize diagnostic sensitivity and specificity in extrapulmonary tuberculosis testing.

Insights into electrode/electrolyte interfacial processes and the effect of nanostructured cobalt oxides loading on graphene-based hybrids by scanning electrochemical microscopy

NASA Astrophysics Data System (ADS)

Gupta, Sanju; Carrizosa, Sara B.

2016-12-01

Nanostructured cobalt oxide polymorphs (CoO and Co3O4) deposited via electrodeposition allowed optimal loading on supercapacitive graphene nanosheets producing a set of graphene-based hybrids namely, CoO/GO, CoO/ErGO, Co3O4/GO, Co3O4/rGO, and Co3O4/ErGO, as pseudocapacitive electrochemical electrodes. We gained fundamental insights into the complex physicochemical interfacial processes at electrode surfaces and electrode/electrolyte (or solid/liquid) interfaces by scanning electrochemical microscopy operating in the feedback probe approach and imaging modes while monitoring and mapping the redox probe (re)activity behavior. We determined the various experimental descriptors including diffusion coefficient, electron transfer rate, and electroactive site distribution on electrodes. We emphasize the interplay of (1) heterogeneous basal and edge plane active sites, (2) graphene surface functional moieties (conducting/semiconducting), and (3) crystalline spinel cobalt oxides (semiconducting/insulating) coated graphene, reinforcing the available electron density of states in the vicinity of the Fermi level contributing to higher electroactivity, faster interfacial diffusion, and shorter distances for electron transfer, facilitated through molecular and chemical bridges obtained by electrodeposition as compared with the physical deposition.

Detection limit of intragenic deletions with targeted array comparative genomic hybridization

PubMed Central

2013-01-01

Background Pathogenic mutations range from single nucleotide changes to deletions or duplications that encompass a single exon to several genes. The use of gene-centric high-density array comparative genomic hybridization (aCGH) has revolutionized the detection of intragenic copy number variations. We implemented an exon-centric design of high-resolution aCGH to detect single- and multi-exon deletions and duplications in a large set of genes using the OGT 60 K and 180 K arrays. Here we describe the molecular characterization and breakpoint mapping of deletions at the smaller end of the detectable range in several genes using aCGH. Results The method initially implemented to detect single to multiple exon deletions, was able to detect deletions much smaller than anticipated. The selected deletions we describe vary in size, ranging from over 2 kb to as small as 12 base pairs. The smallest of these deletions are only detectable after careful manual review during data analysis. Suspected deletions smaller than the detection size for which the method was optimized, were rigorously followed up and confirmed with PCR-based investigations to uncover the true detection size limit of intragenic deletions with this technology. False-positive deletion calls often demonstrated single nucleotide changes or an insertion causing lower hybridization of probes demonstrating the sensitivity of aCGH. Conclusions With optimizing aCGH design and careful review process, aCGH can uncover intragenic deletions as small as dozen bases. These data provide insight that will help optimize probe coverage in array design and illustrate the true assay sensitivity. Mapping of the breakpoints confirms smaller deletions and contributes to the understanding of the mechanism behind these events. Our knowledge of the mutation spectra of several genes can be expected to change as previously unrecognized intragenic deletions are uncovered. PMID:24304607

Super-quenched Molecular Probe Based on Aggregation-Induced Emission and Photoinduced Electron Transfer Mechanisms for Formaldehyde Detection in Human Serum.

PubMed

Yang, Haitao; Wang, Fujia; Zheng, Jilin; Lin, Hao; Liu, Bin; Tang, Yi-Da; Zhang, Chong-Jing

2018-06-04

Energy transfer between fluorescent dyes and quenchers is widely used in the design of light-up probes. Although dual quenchers are more effective in offering lower background signals and higher turn-on ratios than one quencher, such probes are less explored in practice as they require both quenchers to be within the proximity of the fluorescent core. In this contribution, we utilized intramolecular motion and photoinduced electron transfer (PET) as quenching mechanisms to build super-quenched light-up probes based on fluorogens with aggregation-induced emission. The optimized light-up probe possesses negligible background and is able to detect not only free formaldehyde (FA) but also polymeric FA, with an unprecedented turn-on ratio of >4900. We envision that this novel dual quenching strategy will help to develop various light-up probes for analyte sensing. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Hybrid photonic-plasmonic near-field probe for efficient light conversion into the nanoscale hot spot.

PubMed

Koshelev, Alexander; Munechika, Keiko; Cabrini, Stefano

2017-11-01

In this Letter, we present a design and simulations of the novel hybrid photonic-plasmonic near-field probe. Near-field optics is a unique imaging tool that provides optical images with resolution down to tens of nanometers. One of the main limitations of this technology is its low light sensitivity. The presented hybrid probe solves this problem by combining a campanile plasmonic probe with the photonic layer, consisting of the diffractive optic element (DOE). The DOE is designed to match the plasmonic field at the broad side of the campanile probe with the fiber mode. This makes it possible to optimize the size of the campanile tip to convert light efficiently into the hot spot. The simulations show that the hybrid probe is ∼540 times more efficient compared with the conventional campanile on average in the 600-900 nm spectral range.

Optical design of a robotic TV camera probe for minimally invasive abdominal surgery

NASA Astrophysics Data System (ADS)

Todaro, Susanna; He, Weiyi; Killinger, Dennis

2011-03-01

Minimally invasive techniques are a promising new field of surgery; however, they limit the surgeon's access points and maneuverability. In order to increase the number of access points in minimally invasive abdominal surgery, a proposed implantable medical probe braces to the abdominal wall and provides illumination and video signal. The probe is cylindrical, about 25 mm long and 10 mm in diameter. A ring of LEDs on the end of the probe illuminates the tissue, and the resulting image is focused onto an HD video detector. It was necessary to apply beam-shaping reflectors to collimate the light onto a small target area, to avoid illuminating areas not picked up by the video. These reflectors were designed and simulated using the optical ray tracing software TracePro. Two LED chip geometries and three types of reflector geometries were analyzed, and the parameters for each geometry were optimized. For the straight-edged reflectors, the intensity patterns and optimization were compared to experimental results. Although parabolic reflectors produced the best collimation, cone reflectors with a 20-degree half-angle produced significant collimation at a much cheaper price. This work was supported by NSF REU program (award No DMR-1004873).

GeneChip{sup {trademark}} screening assay for cystic fibrosis mutations

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

Cronn, M.T.; Miyada, C.G.; Fucini, R.V.

1994-09-01

GeneChip{sup {trademark}} assays are based on high density, carefully designed arrays of short oligonucleotide probes (13-16 bases) built directly on derivatized silica substrates. DNA target sequence analysis is achieved by hybridizing fluorescently labeled amplification products to these arrays. Fluorescent hybridization signals located within the probe array are translated into target sequence information using the known probe sequence at each array feature. The mutation screening assay for cystic fibrosis includes sets of oligonucleotide probes designed to detect numerous different mutations that have been described in 14 exons and one intron of the CFTR gene. Each mutation site is addressed by amore » sub-array of at least 40 probe sequences, half designed to detect the wild type gene sequence and half designed to detect the reported mutant sequence. Hybridization with homozygous mutant, homozygous wild type or heterozygous targets results in distinctive hybridization patterns within a sub-array, permitting specific discrimination of each mutation. The GeneChip probe arrays are very small (approximately 1 cm{sup 2}). There miniature size coupled with their high information content make GeneChip probe arrays a useful and practical means for providing CF mutation analysis in a clinical setting.« less

Measurement of Flow Pattern Within a Rotating Stall Cell in an Axial Compressor

NASA Technical Reports Server (NTRS)

Lepicovsky, Jan; Braunscheidel, Edward P.

2006-01-01

Effective active control of rotating stall in axial compressors requires detailed understanding of flow instabilities associated with this compressor regime. Newly designed miniature high frequency response total and static pressure probes as well as commercial thermoanemometric probes are suitable tools for this task. However, during the rotating stall cycle the probes are subjected to flow direction changes that are far larger than the range of probe incidence acceptance, and therefore probe data without a proper correction would misrepresent unsteady variations of flow parameters. A methodology, based on ensemble averaging, is proposed to circumvent this problem. In this approach the ensemble averaged signals acquired for various probe setting angles are segmented, and only the sections for probe setting angles close to the actual flow angle are used for signal recombination. The methodology was verified by excellent agreement between velocity distributions obtained from pressure probe data, and data measured with thermoanemometric probes. Vector plots of unsteady flow behavior during the rotating stall regime indicate reversed flow within the rotating stall cell that spreads over to adjacent rotor blade channels. Results of this study confirmed that the NASA Low Speed Axial Compressor (LSAC) while in a rotating stall regime at rotor design speed exhibits one stall cell that rotates at a speed equal to 50.6 percent of the rotor shaft speed.

Uprobe: a genome-wide universal probe resource for comparative physical mapping in vertebrates.

PubMed

Kellner, Wendy A; Sullivan, Robert T; Carlson, Brian H; Thomas, James W

2005-01-01

Interspecies comparisons are important for deciphering the functional content and evolution of genomes. The expansive array of >70 public vertebrate genomic bacterial artificial chromosome (BAC) libraries can provide a means of comparative mapping, sequencing, and functional analysis of targeted chromosomal segments that is independent and complementary to whole-genome sequencing. However, at the present time, no complementary resource exists for the efficient targeted physical mapping of the majority of these BAC libraries. Universal overgo-hybridization probes, designed from regions of sequenced genomes that are highly conserved between species, have been demonstrated to be an effective resource for the isolation of orthologous regions from multiple BAC libraries in parallel. Here we report the application of the universal probe design principal across entire genomes, and the subsequent creation of a complementary probe resource, Uprobe, for screening vertebrate BAC libraries. Uprobe currently consists of whole-genome sets of universal overgo-hybridization probes designed for screening mammalian or avian/reptilian libraries. Retrospective analysis, experimental validation of the probe design process on a panel of representative BAC libraries, and estimates of probe coverage across the genome indicate that the majority of all eutherian and avian/reptilian genes or regions of interest can be isolated using Uprobe. Future implementation of the universal probe design strategy will be used to create an expanded number of whole-genome probe sets that will encompass all vertebrate genomes.

Optimization of the Divergent method for genotyping single nucleotide variations using SYBR Green-based single-tube real-time PCR.

PubMed

Gentilini, Fabio; Turba, Maria E

2014-01-01

A novel technique, called Divergent, for single-tube real-time PCR genotyping of point mutations without the use of fluorescently labeled probes has recently been reported. This novel PCR technique utilizes a set of four primers and a particular denaturation temperature for simultaneously amplifying two different amplicons which extend in opposite directions from the point mutation. The two amplicons can readily be detected using the melt curve analysis downstream to a closed-tube real-time PCR. In the present study, some critical aspects of the original method were specifically addressed to further implement the technique for genotyping the DNM1 c.G767T mutation responsible for exercise-induced collapse in Labrador retriever dogs. The improved Divergent assay was easily set up using a standard two-step real-time PCR protocol. The melting temperature difference between the mutated and the wild-type amplicons was approximately 5°C which could be promptly detected by all the thermal cyclers. The upgraded assay yielded accurate results with 157pg of genomic DNA per reaction. This optimized technique represents a flexible and inexpensive alternative to the minor grove binder fluorescently labeled method and to high resolution melt analysis for high-throughput, robust and cheap genotyping of single nucleotide variations. Copyright © 2014 Elsevier B.V. All rights reserved.

Calling Chromosome Alterations, DNA Methylation Statuses, and Mutations in Tumors by Simple Targeted Next-Generation Sequencing: A Solution for Transferring Integrated Pangenomic Studies into Routine Practice?

PubMed

Garinet, Simon; Néou, Mario; de La Villéon, Bruno; Faillot, Simon; Sakat, Julien; Da Fonseca, Juliana P; Jouinot, Anne; Le Tourneau, Christophe; Kamal, Maud; Luscap-Rondof, Windy; Boeva, Valentina; Gaujoux, Sebastien; Vidaud, Michel; Pasmant, Eric; Letourneur, Franck; Bertherat, Jérôme; Assié, Guillaume

2017-09-01

Pangenomic studies identified distinct molecular classes for many cancers, with major clinical applications. However, routine use requires cost-effective assays. We assessed whether targeted next-generation sequencing (NGS) could call chromosomal alterations and DNA methylation status. A training set of 77 tumors and a validation set of 449 (43 tumor types) were analyzed by targeted NGS and single-nucleotide polymorphism (SNP) arrays. Thirty-two tumors were analyzed by NGS after bisulfite conversion, and compared to methylation array or methylation-specific multiplex ligation-dependent probe amplification. Considering allelic ratios, correlation was strong between targeted NGS and SNP arrays (r = 0.88). In contrast, considering DNA copy number, for variations of one DNA copy, correlation was weaker between read counts and SNP array (r = 0.49). Thus, we generated TARGOMICs, optimized for detecting chromosome alterations by combining allelic ratios and read counts generated by targeted NGS. Sensitivity for calling normal, lost, and gained chromosomes was 89%, 72%, and 31%, respectively. Specificity was 81%, 93%, and 98%, respectively. These results were confirmed in the validation set. Finally, TARGOMICs could efficiently align and compute proportions of methylated cytosines from bisulfite-converted DNA from targeted NGS. In conclusion, beyond calling mutations, targeted NGS efficiently calls chromosome alterations and methylation status in tumors. A single run and minor design/protocol adaptations are sufficient. Optimizing targeted NGS should expand translation of genomics to clinical routine. Copyright © 2017 American Society for Investigative Pathology and the Association for Molecular Pathology. Published by Elsevier Inc. All rights reserved.

A new device for performing reference point indentation without a reference probe

NASA Astrophysics Data System (ADS)

Bridges, Daniel; Randall, Connor; Hansma, Paul K.

2012-04-01

Here we describe a novel, hand-held reference point indentation (RPI), instrument that is designed for clinical measurements of bone material properties in living patients. This instrument differs from previous RPI instruments in that it requires neither a reference probe nor removal of the periosteum that covers the bone, thus significantly simplifying its use in patient testing. After describing the instrument, we discuss five guidelines for optimal and reproducible results. These are: (1) the angle between the normal to the surface and the axis of the instrument should be less than 10°, (2) the compression of the main spring to trigger the device must be performed slowly (>1 s), (3) the probe tip should be sharper than 10 μm; however, a normalized parameter with a calibration phantom can correct for dull tips up to a 100 μm radius, (4) the ambient room temperature should be between 4 °C and 37 °C, and (5) the effective mass of the bone or material under test must exceed 1 kg, or if under 1 kg, the specimen should be securely anchored in a fixation device with sufficient mass (which is not a requirement of previous RPI instruments). Our experience is that a person can be trained with these guidelines in about 5 min and thereafter obtain accurate and reproducible results. The portability, ease of use, and minimal training make this instrument suitable to measure bone material properties in a clinical setting.

Characterization of a Raman spectroscopy probe system for intraoperative brain tissue classification

PubMed Central

Desroches, Joannie; Jermyn, Michael; Mok, Kelvin; Lemieux-Leduc, Cédric; Mercier, Jeanne; St-Arnaud, Karl; Urmey, Kirk; Guiot, Marie-Christine; Marple, Eric; Petrecca, Kevin; Leblond, Frédéric

2015-01-01

A detailed characterization study is presented of a Raman spectroscopy system designed to maximize the volume of resected cancer tissue in glioma surgery based on in vivo molecular tissue characterization. It consists of a hand-held probe system measuring spectrally resolved inelastically scattered light interacting with tissue, designed and optimized for in vivo measurements. Factors such as linearity of the signal with integration time and laser power, and their impact on signal to noise ratio, are studied leading to optimal data acquisition parameters. The impact of ambient light sources in the operating room is assessed and recommendations made for optimal operating conditions. In vivo Raman spectra of normal brain, cancer and necrotic tissue were measured in 10 patients, demonstrating that real-time inelastic scattering measurements can distinguish necrosis from vital tissue (including tumor and normal brain tissue) with an accuracy of 87%, a sensitivity of 84% and a specificity of 89%. PMID:26203368

Creating and optimizing interfaces for electric-field and photon-induced charge transfer.

PubMed

Park, Byoungnam; Whitham, Kevin; Cho, Jiung; Reichmanis, Elsa

2012-11-27

We create and optimize a structurally well-defined electron donor-acceptor planar heterojunction interface in which electric-field and/or photon-induced charge transfer occurs. Electric-field-induced charge transfer in the dark and exciton dissociation at a pentacene/PCBM interface were probed by in situ thickness-dependent threshold voltage shift measurements in field-effect transistor devices during the formation of the interface. Electric-field-induced charge transfer at the interface in the dark is correlated with development of the pentacene accumulation layer close to PCBM, that is, including interface area, and dielectric relaxation time in PCBM. Further, we demonstrate an in situ test structure that allows probing of both exciton diffusion length and charge transport properties, crucial for optimizing optoelectronic devices. Competition between the optical absorption length and the exciton diffusion length in pentacene governs exciton dissociation at the interface. Charge transfer mechanisms in the dark and under illumination are detailed.

Development and application of a microarray meter tool to optimize microarray experiments

PubMed Central

Rouse, Richard JD; Field, Katrine; Lapira, Jennifer; Lee, Allen; Wick, Ivan; Eckhardt, Colleen; Bhasker, C Ramana; Soverchia, Laura; Hardiman, Gary

2008-01-01

Background Successful microarray experimentation requires a complex interplay between the slide chemistry, the printing pins, the nucleic acid probes and targets, and the hybridization milieu. Optimization of these parameters and a careful evaluation of emerging slide chemistries are a prerequisite to any large scale array fabrication effort. We have developed a 'microarray meter' tool which assesses the inherent variations associated with microarray measurement prior to embarking on large scale projects. Findings The microarray meter consists of nucleic acid targets (reference and dynamic range control) and probe components. Different plate designs containing identical probe material were formulated to accommodate different robotic and pin designs. We examined the variability in probe quality and quantity (as judged by the amount of DNA printed and remaining post-hybridization) using three robots equipped with capillary printing pins. Discussion The generation of microarray data with minimal variation requires consistent quality control of the (DNA microarray) manufacturing and experimental processes. Spot reproducibility is a measure primarily of the variations associated with printing. The microarray meter assesses array quality by measuring the DNA content for every feature. It provides a post-hybridization analysis of array quality by scoring probe performance using three metrics, a) a measure of variability in the signal intensities, b) a measure of the signal dynamic range and c) a measure of variability of the spot morphologies. PMID:18710498

Analysis and Design of a Fiber-optic Probe for DNA Sensors Final Report CRADA No. TSB-1147-95

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

Molau, Nicole; Vail, Curtis

In 1995, a challenge in the field of genetics dealt with the acquisition of efficient DNA sequencing techniques for reading the 3 billion base-pairs that comprised the human genome. AccuPhotonics, Inc. proposed to develop and manufacture a state-of-the-art near-field scanning optical microscopy (NSOM) fiber-optic probe that was expected to increase probe efficiency by two orders of magnitude over the existing state-of-the-art and to improve resolution to 10Å. The detailed design calculation and optimization of electrical properties of the fiber-optic probe tip geometry would be performed at LLNL, using existing finite-difference time-domain (FDTD) electromagnetic (EM) codes.

Development of background-free tame fluorescent probes for intracellular live cell imaging

PubMed Central

Alamudi, Samira Husen; Satapathy, Rudrakanta; Kim, Jihyo; Su, Dongdong; Ren, Haiyan; Das, Rajkumar; Hu, Lingna; Alvarado-Martínez, Enrique; Lee, Jung Yeol; Hoppmann, Christian; Peña-Cabrera, Eduardo; Ha, Hyung-Ho; Park, Hee-Sung; Wang, Lei; Chang, Young-Tae

2016-01-01

Fluorescence labelling of an intracellular biomolecule in native living cells is a powerful strategy to achieve in-depth understanding of the biomolecule's roles and functions. Besides being nontoxic and specific, desirable labelling probes should be highly cell permeable without nonspecific interactions with other cellular components to warrant high signal-to-noise ratio. While it is critical, rational design for such probes is tricky. Here we report the first predictive model for cell permeable background-free probe development through optimized lipophilicity, water solubility and charged van der Waals surface area. The model was developed by utilizing high-throughput screening in combination with cheminformatics. We demonstrate its reliability by developing CO-1 and AzG-1, a cyclooctyne- and azide-containing BODIPY probe, respectively, which specifically label intracellular target organelles and engineered proteins with minimum background. The results provide an efficient strategy for development of background-free probes, referred to as ‘tame' probes, and novel tools for live cell intracellular imaging. PMID:27321135

PhylArray: phylogenetic probe design algorithm for microarray.

PubMed

Militon, Cécile; Rimour, Sébastien; Missaoui, Mohieddine; Biderre, Corinne; Barra, Vincent; Hill, David; Moné, Anne; Gagne, Geneviève; Meier, Harald; Peyretaillade, Eric; Peyret, Pierre

2007-10-01

Microbial diversity is still largely unknown in most environments, such as soils. In order to get access to this microbial 'black-box', the development of powerful tools such as microarrays are necessary. However, the reliability of this approach relies on probe efficiency, in particular sensitivity, specificity and explorative power, in order to obtain an image of the microbial communities that is close to reality. We propose a new probe design algorithm that is able to select microarray probes targeting SSU rRNA at any phylogenetic level. This original approach, implemented in a program called 'PhylArray', designs a combination of degenerate and non-degenerate probes for each target taxon. Comparative experimental evaluations indicate that probes designed with PhylArray yield a higher sensitivity and specificity than those designed by conventional approaches. Applying the combined PhyArray/GoArrays strategy helps to optimize the hybridization performance of short probes. Finally, hybridizations with environmental targets have shown that the use of the PhylArray strategy can draw attention to even previously unknown bacteria.

Design and Application of Hybrid Magnetic Field-Eddy Current Probe

NASA Technical Reports Server (NTRS)

Wincheski, Buzz; Wallace, Terryl; Newman, Andy; Leser, Paul; Simpson, John

2013-01-01

The incorporation of magnetic field sensors into eddy current probes can result in novel probe designs with unique performance characteristics. One such example is a recently developed electromagnetic probe consisting of a two-channel magnetoresistive sensor with an embedded single-strand eddy current inducer. Magnetic flux leakage maps of ferrous materials are generated from the DC sensor response while high-resolution eddy current imaging is simultaneously performed at frequencies up to 5 megahertz. In this work the design and optimization of this probe will be presented, along with an application toward analysis of sensory materials with embedded ferromagnetic shape-memory alloy (FSMA) particles. The sensory material is designed to produce a paramagnetic to ferromagnetic transition in the FSMA particles under strain. Mapping of the stray magnetic field and eddy current response of the sample with the hybrid probe can thereby image locations in the structure which have experienced an overstrain condition. Numerical modeling of the probe response is performed with good agreement with experimental results.

Three-dimensional macroporous nanoelectronic networks as minimally invasive brain probes

NASA Astrophysics Data System (ADS)

Xie, Chong; Liu, Jia; Fu, Tian-Ming; Dai, Xiaochuan; Zhou, Wei; Lieber, Charles M.

2015-12-01

Direct electrical recording and stimulation of neural activity using micro-fabricated silicon and metal micro-wire probes have contributed extensively to basic neuroscience and therapeutic applications; however, the dimensional and mechanical mismatch of these probes with the brain tissue limits their stability in chronic implants and decreases the neuron-device contact. Here, we demonstrate the realization of a three-dimensional macroporous nanoelectronic brain probe that combines ultra-flexibility and subcellular feature sizes to overcome these limitations. Built-in strains controlling the local geometry of the macroporous devices are designed to optimize the neuron/probe interface and to promote integration with the brain tissue while introducing minimal mechanical perturbation. The ultra-flexible probes were implanted frozen into rodent brains and used to record multiplexed local field potentials and single-unit action potentials from the somatosensory cortex. Significantly, histology analysis revealed filling-in of neural tissue through the macroporous network and attractive neuron-probe interactions, consistent with long-term biocompatibility of the device.

Sterile working in ultrasonography: the use of dedicated ultrasound covers and sterile ultrasound gel.

PubMed

Marhofer, Peter; Fritsch, Gerhard

2015-01-01

Ultrasound is currently an important tool for diagnostic and interventional procedures. Ultrasound imaging provides significant advantages as compared to other imaging methods. The widespread use of ultrasound also carries the risk of drawbacks such as cross-infections. A large body of literature reports this possibly life-threatening side effect and specific patient populations are particularly at risk (e.g., neonates). Various methods of ultrasound probe disinfection are described; however, none of the mechanical or chemical probe disinfection procedures is optimal and, in particular, disinfection with high concentration of alcohol might be associated with ultrasound probe damage. The preparation of ultrasound probes with dedicated probe covers is a useful alternative for sterile working conditions. One ultrasound probe cover discussed in this paper is directly glued on to the ultrasound probe without the use of ultrasound coupling gel. By the use of sterile ultrasound coupling gel at the outer surface, additional effects on aseptic working conditions can be obtained.

Rapid real-time diagnostic PCR for Trichophyton rubrum and Trichophyton mentagrophytes in patients with tinea unguium and tinea pedis using specific fluorescent probes.

PubMed

Miyajima, Yoshiharu; Satoh, Kazuo; Uchida, Takao; Yamada, Tsuyoshi; Abe, Michiko; Watanabe, Shin-ichi; Makimura, Miho; Makimura, Koichi

2013-03-01

Trichophyton rubrum and Trichophyton mentagrophytes human-type (synonym, Trichophyton interdigitale (anthropophilic)) are major causative pathogens of tinea unguium. For suitable diagnosis and treatment, rapid and accurate identification of etiologic agents in clinical samples using reliable molecular based method is required. For identification of organisms causing tinea unguium, we developed a new real-time polymerase chain reaction (PCR) with a pan-fungal primer set and probe, as well as specific primer sets and probes for T. rubrum and T. mentagrophytes human-type. We designed two sets of primers from the internal transcribed spacer 1 (ITS1) region of fungal ribosomal DNA (rDNA) and three quadruple fluorescent probes, one for detection wide range pathogenic fungi and two for classification of T. rubrum and T. mentagrophytes by specific binding to different sites in the ITS1 region. We investigated the specificity of these primer sets and probes using fungal genomic DNA, and also examined 42 clinical specimens with our real-time PCR. The primers and probes specifically detected T. rubrum, T. mentagrophytes, and a wide range of pathogenic fungi. The causative pathogens were identified in 42 nail and skin samples from 32 patients. The total time required for identification of fungal species in each clinical specimen was about 3h. The copy number of each fungal DNA in the clinical specimens was estimated from the intensity of fluorescence simultaneously. This PCR system is one of the most rapid and sensitive methods available for diagnosing dermatophytosis, including tinea unguium and tinea pedis. Copyright © 2012 Japanese Society for Investigative Dermatology. Published by Elsevier Ireland Ltd. All rights reserved.

Design and development of high frequency matrix phased-array ultrasonic probes

NASA Astrophysics Data System (ADS)

Na, Jeong K.; Spencer, Roger L.

2012-05-01

High frequency matrix phased-array (MPA) probes have been designed and developed for more accurate and repeatable assessment of weld conditions of thin sheet metals commonly used in the auto industry. Unlike the line focused ultrasonic beam generated by a linear phased-array (LPA) probe, a MPA probe can form a circular shaped focused beam in addition to the typical beam steering capabilities of phased-array probes. A CIVA based modeling and simulation method has been used to design the probes in terms of various probe parameters such as number of elements, element size, overall dimensions, frequency etc. Challenges associated with the thicknesses of thin sheet metals have been resolved by optimizing these probe design parameters. A further improvement made on the design of the MPA probe proved that a three-dimensionally shaped matrix element can provide a better performing probe at a much lower probe manufacturing cost by reducing the total number of elements and lowering the operational frequency. This three dimensional probe naturally matches to the indentation shape of the weld on the thin sheet metals and hence a wider inspection area with the same level of spatial resolution obtained by a twodimensional flat MPA probe operating at a higher frequency. The two aspects, a wider inspection area and a lower probe manufacturing cost, make this three-dimensional MPA sensor more attractive to auto manufacturers demanding a quantitative nondestructive inspection method.

A Novel Approach for Lie Detection Based on F-Score and Extreme Learning Machine

PubMed Central

Gao, Junfeng; Wang, Zhao; Yang, Yong; Zhang, Wenjia; Tao, Chunyi; Guan, Jinan; Rao, Nini

2013-01-01

A new machine learning method referred to as F-score_ELM was proposed to classify the lying and truth-telling using the electroencephalogram (EEG) signals from 28 guilty and innocent subjects. Thirty-one features were extracted from the probe responses from these subjects. Then, a recently-developed classifier called extreme learning machine (ELM) was combined with F-score, a simple but effective feature selection method, to jointly optimize the number of the hidden nodes of ELM and the feature subset by a grid-searching training procedure. The method was compared to two classification models combining principal component analysis with back-propagation network and support vector machine classifiers. We thoroughly assessed the performance of these classification models including the training and testing time, sensitivity and specificity from the training and testing sets, as well as network size. The experimental results showed that the number of the hidden nodes can be effectively optimized by the proposed method. Also, F-score_ELM obtained the best classification accuracy and required the shortest training and testing time. PMID:23755136

Framework for reanalysis of publicly available Affymetrix® GeneChip® data sets based on functional regions of interest.

PubMed

Saka, Ernur; Harrison, Benjamin J; West, Kirk; Petruska, Jeffrey C; Rouchka, Eric C

2017-12-06

Since the introduction of microarrays in 1995, researchers world-wide have used both commercial and custom-designed microarrays for understanding differential expression of transcribed genes. Public databases such as ArrayExpress and the Gene Expression Omnibus (GEO) have made millions of samples readily available. One main drawback to microarray data analysis involves the selection of probes to represent a specific transcript of interest, particularly in light of the fact that transcript-specific knowledge (notably alternative splicing) is dynamic in nature. We therefore developed a framework for reannotating and reassigning probe groups for Affymetrix® GeneChip® technology based on functional regions of interest. This framework addresses three issues of Affymetrix® GeneChip® data analyses: removing nonspecific probes, updating probe target mapping based on the latest genome knowledge and grouping probes into gene, transcript and region-based (UTR, individual exon, CDS) probe sets. Updated gene and transcript probe sets provide more specific analysis results based on current genomic and transcriptomic knowledge. The framework selects unique probes, aligns them to gene annotations and generates a custom Chip Description File (CDF). The analysis reveals only 87% of the Affymetrix® GeneChip® HG-U133 Plus 2 probes uniquely align to the current hg38 human assembly without mismatches. We also tested new mappings on the publicly available data series using rat and human data from GSE48611 and GSE72551 obtained from GEO, and illustrate that functional grouping allows for the subtle detection of regions of interest likely to have phenotypical consequences. Through reanalysis of the publicly available data series GSE48611 and GSE72551, we profiled the contribution of UTR and CDS regions to the gene expression levels globally. The comparison between region and gene based results indicated that the detected expressed genes by gene-based and region-based CDFs show high consistency and regions based results allows us to detection of changes in transcript formation.

Two-photon high-resolution measurement of partial pressure of oxygen in cerebral vasculature and tissue.

PubMed

Sakadzić, Sava; Roussakis, Emmanuel; Yaseen, Mohammad A; Mandeville, Emiri T; Srinivasan, Vivek J; Arai, Ken; Ruvinskaya, Svetlana; Devor, Anna; Lo, Eng H; Vinogradov, Sergei A; Boas, David A

2010-09-01

Measurements of oxygen partial pressure (pO(2)) with high temporal and spatial resolution in three dimensions is crucial for understanding oxygen delivery and consumption in normal and diseased brain. Among existing pO(2) measurement methods, phosphorescence quenching is optimally suited for the task. However, previous attempts to couple phosphorescence with two-photon laser scanning microscopy have faced substantial difficulties because of extremely low two-photon absorption cross-sections of conventional phosphorescent probes. Here we report to our knowledge the first practical in vivo two-photon high-resolution pO(2) measurements in small rodents' cortical microvasculature and tissue, made possible by combining an optimized imaging system with a two-photon-enhanced phosphorescent nanoprobe. The method features a measurement depth of up to 250 microm, sub-second temporal resolution and requires low probe concentration. The properties of the probe allowed for direct high-resolution measurement of cortical extravascular (tissue) pO(2), opening many possibilities for functional metabolic brain studies.

Design of Selective Substrates and Activity-Based Probes for Hydrolase Important for Pathogenesis 1 (HIP1) from Mycobacterium tuberculosis.

PubMed

Lentz, Christian S; Ordonez, Alvaro A; Kasperkiewicz, Paulina; La Greca, Florencia; O'Donoghue, Anthony J; Schulze, Christopher J; Powers, James C; Craik, Charles S; Drag, Marcin; Jain, Sanjay K; Bogyo, Matthew

2016-11-11

Although serine proteases are important mediators of Mycobacterium tuberculosis (Mtb) virulence, there are currently no tools to selectively block or visualize members of this family of enzymes. Selective reporter substrates or activity-based probes (ABPs) could provide a means to monitor infection and response to therapy using imaging methods. Here, we use a combination of substrate selectivity profiling and focused screening to identify optimized reporter substrates and ABPs for the Mtb "Hydrolase important for pathogenesis 1" (Hip1) serine protease. Hip1 is a cell-envelope-associated enzyme with minimal homology to host proteases, making it an ideal target for probe development. We identified substituted 7-amino-4-chloro-3-(2-bromoethoxy)isocoumarins as irreversible inhibitor scaffolds. Furthermore, we used specificity data to generate selective reporter substrates and to further optimize a selective chloroisocoumarin inhibitor. These new reagents are potentially useful in delineating the roles of Hip1 during pathogenesis or as diagnostic imaging tools for specifically monitoring Mtb infections.

Design of Selective Substrates and Activity-Based Probes for Hydrolase Important for Pathogenesis 1 (HIP1) from Mycobacterium tuberculosis

PubMed Central

2016-01-01

Although serine proteases are important mediators of Mycobacterium tuberculosis (Mtb) virulence, there are currently no tools to selectively block or visualize members of this family of enzymes. Selective reporter substrates or activity-based probes (ABPs) could provide a means to monitor infection and response to therapy using imaging methods. Here, we use a combination of substrate selectivity profiling and focused screening to identify optimized reporter substrates and ABPs for the Mtb “Hydrolase important for pathogenesis 1” (Hip1) serine protease. Hip1 is a cell-envelope-associated enzyme with minimal homology to host proteases, making it an ideal target for probe development. We identified substituted 7-amino-4-chloro-3-(2-bromoethoxy)isocoumarins as irreversible inhibitor scaffolds. Furthermore, we used specificity data to generate selective reporter substrates and to further optimize a selective chloroisocoumarin inhibitor. These new reagents are potentially useful in delineating the roles of Hip1 during pathogenesis or as diagnostic imaging tools for specifically monitoring Mtb infections. PMID:27739665

Design of ultrasensitive probes for human neutrophil elastase through hybrid combinatorial substrate library profiling

PubMed Central

Kasperkiewicz, Paulina; Poreba, Marcin; Snipas, Scott J.; Parker, Heather; Winterbourn, Christine C.; Salvesen, Guy S.; Drag, Marcin

2014-01-01

The exploration of protease substrate specificity is generally restricted to naturally occurring amino acids, limiting the degree of conformational space that can be surveyed. We substantially enhanced this by incorporating 102 unnatural amino acids to explore the S1–S4 pockets of human neutrophil elastase. This approach provides hybrid natural and unnatural amino acid sequences, and thus we termed it the Hybrid Combinatorial Substrate Library. Library results were validated by the synthesis of individual tetrapeptide substrates, with the optimal substrate demonstrating more than three orders of magnitude higher catalytic efficiency than commonly used substrates of elastase. This optimal substrate was converted to an activity-based probe that demonstrated high selectivity and revealed the specific presence of active elastase during the process of neutrophil extracellular trap formation. We propose that this approach can be successfully used for any type of endopeptidase to deliver high activity and selectivity in substrates and probes. PMID:24550277

Hairpin DNA Switch for Ultrasensitive Spectrophotometric Detection of DNA Hybridization Based on Gold Nanoparticles and Enzyme Signal Amplification

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

Zhang, Youyu; Tang, Zhiwen; Wang, Jun

2010-08-01

A novel DNA detection platform based on a hairpin-DNA switch, nanoparticles, and enzyme signal amplification for ultrasensitive detection of DNA hybridization has been developed in this work. In this DNA assay, a “stem-loop” DNA probe dually labeled with a thiol at its 5’ end and a biotin at its 3’ end, respectively, was used. This probe was immobilized on the gold nanoparticles (AuNPs) anchored by a protein, globulin, on a 96-well microplate. In the absence of target DNA, the immobilized probe with the stem-loop structure shields the biotin from being approached by a bulky horseradish peroxidase linked-avidin (avidin-HRP) conjugate duemore » to the steric hindrance. However, in the presence of target DNA, the hybridization between the hairpin DNA probe and the target DNA causes significant conformational change of the probe, which forces biotin away from the surface of AuNPs. As a result, the biotin becomes accessible by the avidin-HRP, and the target hybridization event can be sensitively detected via the HRP catalyzed substrate 3, 3', 5, 5'-tetramethylbenzidine using spectrophometric method. Some experimental parameters governing the performance of the assay have been optimized. At optimal conditions, this DNA assay can detect DNA at the concentration of femtomolar level by means of a signal amplification strategy based on the combination of enzymes and nanoparticles. This approach also has shown excellent specificity to distinguish single-base mismatches of DNA targets because of the intrinsic high selectivity of the hairpin DNA probe.« less

Specific probe selection from landscape phage display library and its application in enzyme-linked immunosorbent assay of free prostate-specific antigen.

PubMed

Lang, Qiaolin; Wang, Fei; Yin, Long; Liu, Mingjun; Petrenko, Valery A; Liu, Aihua

2014-03-04

Probes against targets can be selected from the landscape phage library f8/8, displaying random octapeptides on the pVIII coat protein of the phage fd-tet and demonstrating many excellent features including multivalency, stability, and high structural homogeneity. Prostate-specific antigen (PSA) is usually determined by immunoassay, by which antibodies are frequently used as the specific probes. Herein we found that more advanced probes against free prostate-specific antigen (f-PSA) can be screened from the landscape phage library. Four phage monoclones were selected and identified by the specificity array. One phage clone displaying the fusion peptide ERNSVSPS showed good specificity and affinity to f-PSA and was used as a PSA capture probe in a sandwich enzyme-linked immunosorbent assay (ELISA) array. An anti-human PSA monoclonal antibody (anti-PSA mAb) was used to recognize the captured antigen, followed by horseradish peroxidase-conjugated antibody (HRP-IgG) and o-phenylenediamine, which were successively added to develop plate color. The ELISA conditions such as effect of blocking agent, coating buffer pH, phage concentration, antigen incubation time, and anti-PSA mAb dilution for phage ELISA were optimized. On the basis of the optimal phage ELISA conditions, the absorbance taken at 492 nm on a microplate reader was linear with f-PSA concentration within 0.825-165 ng/mL with a low limit of detection of 0.16 ng/mL. Thus, the landscape phage is an attractive biomolecular probe in bioanalysis.

Probing the localization of magnetic dichroism by atomic-size astigmatic and vortex electron beams

DOE PAGES

Negi, Devendra Singh; Idrobo, Juan Carlos; Rusz, Ján

2018-03-05

We report localization of a magnetic dichroic signal on atomic columns in electron magnetic circular dichroism (EMCD), probed by beam distorted by four-fold astigmatism and electron vortex beam. With astigmatic probe, magnetic signal to noise ratio can be enhanced by blocking the intensity from the central part of probe. However, the simulations show that for atomic resolution magnetic measurements, vortex beam is a more effective probe, with much higher magnetic signal to noise ratio. For all considered beam shapes, the optimal SNR constrains the signal detection at low collection angles of approximately 6–8 mrad. Irrespective of the material thickness, themore » magnetic signal remains strongly localized within the probed atomic column with vortex beam, whereas for astigmatic probes, the magnetic signal originates mostly from the nearest neighbor atomic columns. Due to excellent signal localization at probing individual atomic columns, vortex beams are predicted to be a strong candidate for studying the crystal site specific magnetic properties, magnetic properties at interfaces, or magnetism arising from individual atomic impurities.« less

Probing the localization of magnetic dichroism by atomic-size astigmatic and vortex electron beams

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

Negi, Devendra Singh; Idrobo, Juan Carlos; Rusz, Ján

We report localization of a magnetic dichroic signal on atomic columns in electron magnetic circular dichroism (EMCD), probed by beam distorted by four-fold astigmatism and electron vortex beam. With astigmatic probe, magnetic signal to noise ratio can be enhanced by blocking the intensity from the central part of probe. However, the simulations show that for atomic resolution magnetic measurements, vortex beam is a more effective probe, with much higher magnetic signal to noise ratio. For all considered beam shapes, the optimal SNR constrains the signal detection at low collection angles of approximately 6–8 mrad. Irrespective of the material thickness, themore » magnetic signal remains strongly localized within the probed atomic column with vortex beam, whereas for astigmatic probes, the magnetic signal originates mostly from the nearest neighbor atomic columns. Due to excellent signal localization at probing individual atomic columns, vortex beams are predicted to be a strong candidate for studying the crystal site specific magnetic properties, magnetic properties at interfaces, or magnetism arising from individual atomic impurities.« less

Dynamic Pressure Probes Developed for Supersonic Flow-Field Measurements

NASA Technical Reports Server (NTRS)

Porro, A. Robert

2001-01-01

A series of dynamic flow-field pressure probes were developed for use in large-scale supersonic wind tunnels at the NASA Glenn Research Center. These flow-field probes include pitot and static pressure probes that can capture fast-acting flow-field pressure transients occurring on a millisecond timescale. The pitot and static probes can be used to determine local Mach number time histories during a transient event. The flow-field pressure probe contains four major components: 1) Static pressure aerodynamic tip; 2) Pressure-sensing cartridge assembly; 3) Pitot pressure aerodynamic tip; 4) Mounting stem. This modular design allows for a variety of probe tips to be used for a specific application. Here, the focus is on flow-field pressure measurements in supersonic flows, so we developed a cone-cylinder static pressure tip and a pitot pressure tip. Alternatively, probe tips optimized for subsonic and transonic flows could be used with this design. The pressure-sensing cartridge assembly allows the simultaneous measurement of steady-state and transient pressure which allows continuous calibration of the dynamic pressure transducer.

Hollow Au-Ag Nanoparticles Labeled Immunochromatography Strip for Highly Sensitive Detection of Clenbuterol

NASA Astrophysics Data System (ADS)

Wang, Jingyun; Zhang, Lei; Huang, Youju; Dandapat, Anirban; Dai, Liwei; Zhang, Ganggang; Lu, Xuefei; Zhang, Jiawei; Lai, Weihua; Chen, Tao

2017-01-01

The probe materials play a significant role in improving the detection efficiency and sensitivity of lateral-flow immunochromatographic test strip (ICTS). Unlike conventional ICTS assay usually uses single-component, solid gold nanoparticles as labeled probes, in our present study, a bimetallic, hollow Au-Ag nanoparticles (NPs) labeled ICTS was successfully developed for the detection of clenbuterol (CLE). The hollow Au-Ag NPs with different Au/Ag mole ratio and tunable size were synthesized by varying the volume ratio of [HAuCl4]:[Ag NPs] via the galvanic replacement reaction. The surface of hollow Ag-Au NPs was functionalized with 11-mercaptoundecanoic acid (MUA) for further covalently bonded with anti-CLE monoclonal antibody. Overall size of the Au-Ag NPs, size of the holes within individual NPs and also Au/Ag mole ratio have been systematically optimized to amplify both the visual inspection signals and the quantitative data. The sensitivity of optimized hollow Au-Ag NPs probes has been achieved even as low as 2 ppb in a short time (within 15 min), which is superior over the detection performance of conventional test strip using Au NPs. The optimized hollow Au-Ag NPs labeled test strip can be used as an ideal candidate for the rapid screening of CLE in food samples.

Mechanisms of small molecule–DNA interactions probed by single-molecule force spectroscopy

PubMed Central

Almaqwashi, Ali A.; Paramanathan, Thayaparan; Rouzina, Ioulia; Williams, Mark C.

2016-01-01

There is a wide range of applications for non-covalent DNA binding ligands, and optimization of such interactions requires detailed understanding of the binding mechanisms. One important class of these ligands is that of intercalators, which bind DNA by inserting aromatic moieties between adjacent DNA base pairs. Characterizing the dynamic and equilibrium aspects of DNA-intercalator complex assembly may allow optimization of DNA binding for specific functions. Single-molecule force spectroscopy studies have recently revealed new details about the molecular mechanisms governing DNA intercalation. These studies can provide the binding kinetics and affinity as well as determining the magnitude of the double helix structural deformations during the dynamic assembly of DNA–ligand complexes. These results may in turn guide the rational design of intercalators synthesized for DNA-targeted drugs, optical probes, or integrated biological self-assembly processes. Herein, we survey the progress in experimental methods as well as the corresponding analysis framework for understanding single molecule DNA binding mechanisms. We discuss briefly minor and major groove binding ligands, and then focus on intercalators, which have been probed extensively with these methods. Conventional mono-intercalators and bis-intercalators are discussed, followed by unconventional DNA intercalation. We then consider the prospects for using these methods in optimizing conventional and unconventional DNA-intercalating small molecules. PMID:27085806

Benchmarking Ligand-Based Virtual High-Throughput Screening with the PubChem Database

PubMed Central

Butkiewicz, Mariusz; Lowe, Edward W.; Mueller, Ralf; Mendenhall, Jeffrey L.; Teixeira, Pedro L.; Weaver, C. David; Meiler, Jens

2013-01-01

With the rapidly increasing availability of High-Throughput Screening (HTS) data in the public domain, such as the PubChem database, methods for ligand-based computer-aided drug discovery (LB-CADD) have the potential to accelerate and reduce the cost of probe development and drug discovery efforts in academia. We assemble nine data sets from realistic HTS campaigns representing major families of drug target proteins for benchmarking LB-CADD methods. Each data set is public domain through PubChem and carefully collated through confirmation screens validating active compounds. These data sets provide the foundation for benchmarking a new cheminformatics framework BCL::ChemInfo, which is freely available for non-commercial use. Quantitative structure activity relationship (QSAR) models are built using Artificial Neural Networks (ANNs), Support Vector Machines (SVMs), Decision Trees (DTs), and Kohonen networks (KNs). Problem-specific descriptor optimization protocols are assessed including Sequential Feature Forward Selection (SFFS) and various information content measures. Measures of predictive power and confidence are evaluated through cross-validation, and a consensus prediction scheme is tested that combines orthogonal machine learning algorithms into a single predictor. Enrichments ranging from 15 to 101 for a TPR cutoff of 25% are observed. PMID:23299552

Optimal probes for withdrawal of uncontaminated fluid samples

NASA Astrophysics Data System (ADS)

Sherwood, J. D.

2005-08-01

Withdrawal of fluid by a composite probe pushed against the face z =0 of a porous half-space z >0 is modeled assuming incompressible Darcy flow. The probe is circular, of radius a, with an inner sampling section of radius αa and a concentric outer guard probe αa βa is saturated with fluid 2; the two fluids have the same viscosity. It is assumed that the interface between the two fluids is sharp and remains so as it moves through the rock. The pressure in the probe is lower than that of the pore fluid in the rock, so that the fluid interface is convected with the fluids towards the probe. This idealized axisymmetric problem is solved numerically, and it is shown that an analysis based on far-field spherical flow towards a point sink is a good approximation when the nondimensional depth of fluid 1 is large, i.e., β ≫1. The inner sampling probe eventually produces pure fluid 2, and this technique has been proposed for sampling pore fluids in rock surrounding an oil well [A. Hrametz, C. Gardner, M. Wais, and M. Proett, U.S. Patent No. 6,301,959 B1 (16 October 2001)]. Fluid 1 is drilling fluid filtrate, which has displaced the original pore fluid (fluid 2), a pure sample of which is required. The time required to collect an uncontaminated sample of original pore fluid can be minimized by a suitable choice of the probe geometry α [J. Sherwood, J. Fitzgerald and B. Hill, U.S. Patent No. 6,719,049 B2 (13 April 2004)]. It is shown that the optimal choice of α depends on the depth of filtrate invasion β and the volume of sample required.

Pivot methods for global optimization

NASA Astrophysics Data System (ADS)

Stanton, Aaron Fletcher

A new algorithm is presented for the location of the global minimum of a multiple minima problem. It begins with a series of randomly placed probes in phase space, and then uses an iterative redistribution of the worst probes into better regions of phase space until a chosen convergence criterion is fulfilled. The method quickly converges, does not require derivatives, and is resistant to becoming trapped in local minima. Comparison of this algorithm with others using a standard test suite demonstrates that the number of function calls has been decreased conservatively by a factor of about three with the same degrees of accuracy. Two major variations of the method are presented, differing primarily in the method of choosing the probes that act as the basis for the new probes. The first variation, termed the lowest energy pivot method, ranks all probes by their energy and keeps the best probes. The probes being discarded select from those being kept as the basis for the new cycle. In the second variation, the nearest neighbor pivot method, all probes are paired with their nearest neighbor. The member of each pair with the higher energy is relocated in the vicinity of its neighbor. Both methods are tested against a standard test suite of functions to determine their relative efficiency, and the nearest neighbor pivot method is found to be the more efficient. A series of Lennard-Jones clusters is optimized with the nearest neighbor method, and a scaling law is found for cpu time versus the number of particles in the system. The two methods are then compared more explicitly, and finally a study in the use of the pivot method for solving the Schroedinger equation is presented. The nearest neighbor method is found to be able to solve the ground state of the quantum harmonic oscillator from a pure random initialization of the wavefunction.

Influenza Risk Management: Lessons Learned from an A(H1N1) pdm09 Outbreak Investigation in an Operational Military Setting

DTIC Science & Technology

2013-07-10

of the virus in Spain was detected during an outbreak investigation of influenza -like illness (ILI) in soldiers from an engineering military academy...SwInfA primer and probe set) and specific A(H1N1) pdm09 influenza A viruses using SwH1 primer and probe set developed by CDC, Atlanta (WHO...CY062374, CY062375 and CY062376. Viral culture Influenza viruses were isolated from clinical samples by infecting Madin Darby Canine Kidney (MDCK

Superparamagnetic nanoparticles for enhanced magnetic resonance and multimodal imaging

NASA Astrophysics Data System (ADS)

Sikma, Elise Ann Schultz

Magnetic resonance imaging (MRI) is a powerful tool for noninvasive tomographic imaging of biological systems with high spatial and temporal resolution. Superparamagnetic (SPM) nanoparticles have emerged as highly effective MR contrast agents due to their biocompatibility, ease of surface modification and magnetic properties. Conventional nanoparticle contrast agents suffer from difficult synthetic reproducibility, polydisperse sizes and weak magnetism. Numerous synthetic techniques and nanoparticle formulations have been developed to overcome these barriers. However, there are still major limitations in the development of new nanoparticle-based probes for MR and multimodal imaging including low signal amplification and absence of biochemical reporters. To address these issues, a set of multimodal (T2/optical) and dual contrast (T1/T2) nanoparticle probes has been developed. Their unique magnetic properties and imaging capabilities were thoroughly explored. An enzyme-activatable contrast agent is currently being developed as an innovative means for early in vivo detection of cancer at the cellular level. Multimodal probes function by combining the strengths of multiple imaging techniques into a single agent. Co-registration of data obtained by multiple imaging modalities validates the data, enhancing its quality and reliability. A series of T2/optical probes were successfully synthesized by attachment of a fluorescent dye to the surface of different types of nanoparticles. The multimodal nanoparticles generated sufficient MR and fluorescence signal to image transplanted islets in vivo. Dual contrast T1/T2 imaging probes were designed to overcome disadvantages inherent in the individual T1 and T2 components. A class of T1/T2 agents was developed consisting of a gadolinium (III) complex (DTPA chelate or DO3A macrocycle) conjugated to a biocompatible silica-coated metal oxide nanoparticle through a disulfide linker. The disulfide linker has the ability to be reduced in vivo by glutathione, releasing large payloads of signal-enhancing T1 probes into the surrounding environment. Optimization of the agent occurred over three sequential generations, with each generation addressing a new challenge. The result was a T2 nanoparticle containing high levels of conjugated T1 complex demonstrating enhanced MR relaxation properties. The probes created here have the potential to play a key role in the advancement of nanoparticle-based agents in biomedical MRI applications.

Toward of a highly integrated probe for improving wireless network quality

NASA Astrophysics Data System (ADS)

Ding, Fei; Song, Aiguo; Wu, Zhenyang; Pan, Zhiwen; You, Xiaohu

2016-10-01

Quality of service and customer perception is the focus of the telecommunications industry. This paper proposes a low-cost approach to the acquisition of terminal data, collected from LTE networks with the application of a soft probe, based on the Java language. The soft probe includes support for fast call in the form of a referenced library, and can be integrated into various Android-based applications to automatically monitor any exception event in the network. Soft probe-based acquisition of terminal data has the advantages of low cost and can be applied on large scale. Experiment shows that a soft probe can efficiently obtain terminal network data. With this method, the quality of service of LTE networks can be determined from acquired wireless data. This work contributes to efficient network optimization, and the analysis of abnormal network events.

Designing future dark energy space missions. II. Photometric redshift of space weak lensing optimized surveys

NASA Astrophysics Data System (ADS)

Jouvel, S.; Kneib, J.-P.; Bernstein, G.; Ilbert, O.; Jelinsky, P.; Milliard, B.; Ealet, A.; Schimd, C.; Dahlen, T.; Arnouts, S.

2011-08-01

Context. With the discovery of the accelerated expansion of the universe, different observational probes have been proposed to investigate the presence of dark energy, including possible modifications to the gravitation laws by accurately measuring the expansion of the Universe and the growth of structures. We need to optimize the return from future dark energy surveys to obtain the best results from these probes. Aims: A high precision weak-lensing analysis requires not an only accurate measurement of galaxy shapes but also a precise and unbiased measurement of galaxy redshifts. The survey strategy has to be defined following both the photometric redshift and shape measurement accuracy. Methods: We define the key properties of the weak-lensing instrument and compute the effective PSF and the overall throughput and sensitivities. We then investigate the impact of the pixel scale on the sampling of the effective PSF, and place upper limits on the pixel scale. We then define the survey strategy computing the survey area including in particular both the Galactic absorption and Zodiacal light variation accross the sky. Using the Le Phare photometric redshift code and realistic galaxy mock catalog, we investigate the properties of different filter-sets and the importance of the u-band photometry quality to optimize the photometric redshift and the dark energy figure of merit (FoM). Results: Using the predicted photometric redshift quality, simple shape measurement requirements, and a proper sky model, we explore what could be an optimal weak-lensing dark energy mission based on FoM calculation. We find that we can derive the most accurate the photometric redshifts for the bulk of the faint galaxy population when filters have a resolution ℛ ~ 3.2. We show that an optimal mission would survey the sky through eight filters using two cameras (visible and near infrared). Assuming a five-year mission duration, a mirror size of 1.5 m and a 0.5 deg2 FOV with a visible pixel scale of 0.15'', we found that a homogeneous survey reaching a survey population of IAB = 25.6 (10σ) with a sky coverage of ~11 000 deg2 maximizes the weak lensing FoM. The effective number density of galaxies used for WL is then ~45 gal/arcmin2, which is at least a factor of two higher than ground-based surveys. Conclusions: This study demonstrates that a full account of the observational strategy is required to properly optimize the instrument parameters and maximize the FoM of the future weak-lensing space dark energy mission.

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

Hirode, Mitsuhiro; Ono, Atsushi; Miyagishima, Toshikazu

We have constructed a large-scale transcriptome database of rat liver treated with various drugs. In an effort to identify a biomarker for diagnosis of hepatic phospholipidosis, we extracted 78 probe sets of rat hepatic genes from data of 5 drugs, amiodarone, amitriptyline, clomipramine, imipramine, and ketoconazole, which actually induced this phenotype. Principal component analysis (PCA) using these probes clearly separated dose- and time-dependent clusters of treated groups from their controls. Moreover, 6 drugs (chloramphenicol, chlorpromazine, gentamicin, perhexiline, promethazine, and tamoxifen), which were reported to cause phospholipidosis but judged as negative by histopathological examination, were designated as positive by PCA usingmore » these probe sets. Eight drugs (carbon tetrachloride, coumarin, tetracycline, metformin, hydroxyzine, diltiazem, 2-bromoethylamine, and ethionamide), which showed phospholipidosis-like vacuolar formation in the histopathology, could be distinguished from the typical drugs causing phospholipidosis. Moreover, the possible induction of phospholipidosis was predictable by the expression of these genes 24 h after single administration in some of the drugs. We conclude that these identified 78 probe sets could be useful for diagnosis of phospholipidosis, and that toxicogenomics would be a promising approach for prediction of this type of toxicity.« less

Bayesian `hyper-parameters' approach to joint estimation: the Hubble constant from CMB measurements

NASA Astrophysics Data System (ADS)

Lahav, O.; Bridle, S. L.; Hobson, M. P.; Lasenby, A. N.; Sodré, L.

2000-07-01

Recently several studies have jointly analysed data from different cosmological probes with the motivation of estimating cosmological parameters. Here we generalize this procedure to allow freedom in the relative weights of various probes. This is done by including in the joint χ2 function a set of `hyper-parameters', which are dealt with using Bayesian considerations. The resulting algorithm, which assumes uniform priors on the log of the hyper-parameters, is very simple: instead of minimizing \\sum \\chi_j2 (where \\chi_j2 is per data set j) we propose to minimize \\sum Nj (\\chi_j2) (where Nj is the number of data points per data set j). We illustrate the method by estimating the Hubble constant H0 from different sets of recent cosmic microwave background (CMB) experiments (including Saskatoon, Python V, MSAM1, TOCO and Boomerang). The approach can be generalized for combinations of cosmic probes, and for other priors on the hyper-parameters.

A fundamental study of laser-induced breakdown spectroscopy using fiber optics for remote measurements of trace metals. Interim progress report

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

Goode, S.R.; Angel, S.M.

1997-01-01

'The long-term goal of this project is to develop a system to measure the elemental composition of unprepared samples using laser-induced breakdown spectroscopy, LIBS, with a fiber-optic probe. From images shown in this report it is evident that the temporal and spatial behavior of laser-induced plasmas IS a complex process. However, through the use of spectral imaging, optimal conditions can be determined for collecting the atomic emission signal in these plasmas. By tailoring signal collection to the regions of the plasma that contain the highest emission signal with the least amount of background interference both the detection limits and themore » precision of LIBS measurements could be improved. The optimal regions for both gated and possibly non-gated LIBS measurements have been shown to correspond to the inner regions and outer regions, respectively, in an axial plasma. By using this data fiber-optic LIBS probe designs can be optimized for collecting plasma emission at the optimal regions for improved detection limits and precision in a LIBS measurement.'« less

Electromagnetic microscope compared with a conventional pulsed eddy-current probe

NASA Astrophysics Data System (ADS)

Podney, Walter N.

1998-03-01

A superconductive probe presently can detect a crack at a rivet hole that is two to three times smaller than the smallest crack detectable by a conventional probe. As the technology matures and noise resolution approaches a limit set by SQUIDS, approximately 1 fH, it will enable detecting submillimeter cracks down to approximately 15 mm.

Using phylogenetic probes for quantification of stable isotope labeling and microbial community analysis

DOEpatents

Brodie, Eoin L; DeSantis, Todd Z; Karaoz, Ulas; Andersen, Gary L

2014-12-09

Herein is described methods for a high-sensitivity means to measure the incorporation of stable isotope labeled substrates into RNA following stable isotope probing experiments (SIP). RNA is hybridized to a set of probes such as phylogenetic microarrays and isotope incorporation is quantified such as by secondary ion mass spectrometer imaging (NanoSIMS).

Retrieval of ice crystals' mass from ice water content and particle distribution measurements: a numerical optimization approach

NASA Astrophysics Data System (ADS)

Coutris, Pierre; Leroy, Delphine; Fontaine, Emmanuel; Schwarzenboeck, Alfons; Strapp, J. Walter

2016-04-01

A new method to retrieve cloud water content from in-situ measured 2D particle images from optical array probes (OAP) is presented. With the overall objective to build a statistical model of crystals' mass as a function of their size, environmental temperature and crystal microphysical history, this study presents the methodology to retrieve the mass of crystals sorted by size from 2D images using a numerical optimization approach. The methodology is validated using two datasets of in-situ measurements gathered during two airborne field campaigns held in Darwin, Australia (2014), and Cayenne, France (2015), in the frame of the High Altitude Ice Crystals (HAIC) / High Ice Water Content (HIWC) projects. During these campaigns, a Falcon F-20 research aircraft equipped with state-of-the art microphysical instrumentation sampled numerous mesoscale convective systems (MCS) in order to study dynamical and microphysical properties and processes of high ice water content areas. Experimentally, an isokinetic evaporator probe, referred to as IKP-2, provides a reference measurement of the total water content (TWC) which equals ice water content, (IWC) when (supercooled) liquid water is absent. Two optical array probes, namely 2D-S and PIP, produce 2D images of individual crystals ranging from 50 μm to 12840 μm from which particle size distributions (PSD) are derived. Mathematically, the problem is formulated as an inverse problem in which the crystals' mass is assumed constant over a size class and is computed for each size class from IWC and PSD data: PSD.m = IW C This problem is solved using numerical optimization technique in which an objective function is minimized. The objective function is defined as follows: 2 J(m)=∥P SD.m - IW C ∥ + λ.R (m) where the regularization parameter λ and the regularization function R(m) are tuned based on data characteristics. The method is implemented in two steps. First, the method is developed on synthetic crystal populations in order to evaluate the behavior of the iterative algorithm, the influence of data noise on the quality of the results, and to set up a regularization strategy. Therefore, 3D synthetic crystals have been generated and numerically processed to recreate the noise caused by 2D projections of randomly oriented 3D crystals and by the discretization of the PSD into size classes of predefined width. Subsequently, the method is applied to the experimental datasets and the comparison between the retrieved TWC (this methodology) and the measured ones (IKP-2 data) will enable the evaluation of the consistency and accuracy of the mass solution retrieved by the numerical optimization approach as well as preliminary assessment of the influence of temperature and dynamical parameters on crystals' masses.

Microlensed dual-fiber probe for depth-resolved fluorescence measurements

NASA Astrophysics Data System (ADS)

Choi, Hae Young; Ryu, Seon Young; Kim, Jae Young; Kim, Geon Hee; Park, Seong Jun; Lee, Byeong Ha; Chang, Ki Soo

2011-07-01

We propose and demonstrate a compact microlensed dual-fiber probe that has a good collection efficiency and a high depth-resolution ability for fluorescence measurements. The probe is formed with a conventional fusion splicer creating a common focusing lens on two fibers placed side by side. The collection efficiency of the fabricated probe was evaluated by measuring the fluorescence signal of a fresh ginkgo leaf. It was shown experimentally that the proposed probe could effectively collect the fluorescence signal with a six-fold increase compared to that of a general flat-tipped probe. The beam propagation method was used to design a probe with an optimized working distance and an improved resolving depth. It was found that the working distance depends mainly on the radius of curvature of the lens, whereas the resolving depth is determined by the core diameters of the illumination and collection fibers. The depth-resolved ability of probes with working distances of ~100 μm and 300 μm was validated by using a two-layer tissue phantom. The experimental results demonstrate that the microlensed dual-fiber probe has the potential to facilitate depth-resolved fluorescence detection of epithelial tissue.

Sparse sampling and reconstruction for electron and scanning probe microscope imaging

DOEpatents

Anderson, Hyrum; Helms, Jovana; Wheeler, Jason W.; Larson, Kurt W.; Rohrer, Brandon R.

2015-07-28

Systems and methods for conducting electron or scanning probe microscopy are provided herein. In a general embodiment, the systems and methods for conducting electron or scanning probe microscopy with an undersampled data set include: driving an electron beam or probe to scan across a sample and visit a subset of pixel locations of the sample that are randomly or pseudo-randomly designated; determining actual pixel locations on the sample that are visited by the electron beam or probe; and processing data collected by detectors from the visits of the electron beam or probe at the actual pixel locations and recovering a reconstructed image of the sample.

The Automatic Neuroscientist: A framework for optimizing experimental design with closed-loop real-time fMRI

PubMed Central

Lorenz, Romy; Monti, Ricardo Pio; Violante, Inês R.; Anagnostopoulos, Christoforos; Faisal, Aldo A.; Montana, Giovanni; Leech, Robert

2016-01-01

Functional neuroimaging typically explores how a particular task activates a set of brain regions. Importantly though, the same neural system can be activated by inherently different tasks. To date, there is no approach available that systematically explores whether and how distinct tasks probe the same neural system. Here, we propose and validate an alternative framework, the Automatic Neuroscientist, which turns the standard fMRI approach on its head. We use real-time fMRI in combination with modern machine-learning techniques to automatically design the optimal experiment to evoke a desired target brain state. In this work, we present two proof-of-principle studies involving perceptual stimuli. In both studies optimization algorithms of varying complexity were employed; the first involved a stochastic approximation method while the second incorporated a more sophisticated Bayesian optimization technique. In the first study, we achieved convergence for the hypothesized optimum in 11 out of 14 runs in less than 10 min. Results of the second study showed how our closed-loop framework accurately and with high efficiency estimated the underlying relationship between stimuli and neural responses for each subject in one to two runs: with each run lasting 6.3 min. Moreover, we demonstrate that using only the first run produced a reliable solution at a group-level. Supporting simulation analyses provided evidence on the robustness of the Bayesian optimization approach for scenarios with low contrast-to-noise ratio. This framework is generalizable to numerous applications, ranging from optimizing stimuli in neuroimaging pilot studies to tailoring clinical rehabilitation therapy to patients and can be used with multiple imaging modalities in humans and animals. PMID:26804778

The Automatic Neuroscientist: A framework for optimizing experimental design with closed-loop real-time fMRI.

PubMed

Lorenz, Romy; Monti, Ricardo Pio; Violante, Inês R; Anagnostopoulos, Christoforos; Faisal, Aldo A; Montana, Giovanni; Leech, Robert

2016-04-01

Functional neuroimaging typically explores how a particular task activates a set of brain regions. Importantly though, the same neural system can be activated by inherently different tasks. To date, there is no approach available that systematically explores whether and how distinct tasks probe the same neural system. Here, we propose and validate an alternative framework, the Automatic Neuroscientist, which turns the standard fMRI approach on its head. We use real-time fMRI in combination with modern machine-learning techniques to automatically design the optimal experiment to evoke a desired target brain state. In this work, we present two proof-of-principle studies involving perceptual stimuli. In both studies optimization algorithms of varying complexity were employed; the first involved a stochastic approximation method while the second incorporated a more sophisticated Bayesian optimization technique. In the first study, we achieved convergence for the hypothesized optimum in 11 out of 14 runs in less than 10 min. Results of the second study showed how our closed-loop framework accurately and with high efficiency estimated the underlying relationship between stimuli and neural responses for each subject in one to two runs: with each run lasting 6.3 min. Moreover, we demonstrate that using only the first run produced a reliable solution at a group-level. Supporting simulation analyses provided evidence on the robustness of the Bayesian optimization approach for scenarios with low contrast-to-noise ratio. This framework is generalizable to numerous applications, ranging from optimizing stimuli in neuroimaging pilot studies to tailoring clinical rehabilitation therapy to patients and can be used with multiple imaging modalities in humans and animals. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

Developments in Scanning Hall Probe Microscopy

NASA Astrophysics Data System (ADS)

Chouinard, Taras; Chu, Ricky; David, Nigel; Broun, David

2009-05-01

Low temperature scanning Hall probe microscopy is a sensitive means of imaging magnetic structures with high spatial resolution and magnetic flux sensitivity approaching that of a Superconducting Quantum Interference Device. We have developed a scanning Hall probe microscope with novel features, including highly reliable coarse positioning, in situ optimization of sensor-sample alignment and capacitive transducers for linear, long range positioning measurement. This has been motivated by the need to reposition accurately above fabricated nanostructures such as small superconducting rings. Details of the design and performance will be presented as well as recent progress towards time-resolved measurements with sub nanosecond resolution.

Community Analysis of Biofilters Using Fluorescence In Situ Hybridization Including a New Probe for the Xanthomonas Branch of the Class Proteobacteria

PubMed Central

Friedrich, Udo; Naismith, Michèle M.; Altendorf, Karlheinz; Lipski, André

1999-01-01

Domain-, class-, and subclass-specific rRNA-targeted probes were applied to investigate the microbial communities of three industrial and three laboratory-scale biofilters. The set of probes also included a new probe (named XAN818) specific for the Xanthomonas branch of the class Proteobacteria; this probe is described in this study. The members of the Xanthomonas branch do not hybridize with previously developed rRNA-targeted oligonucleotide probes for the α-, β-, and γ-Proteobacteria. Bacteria of the Xanthomonas branch accounted for up to 4.5% of total direct counts obtained with 4′,6-diamidino-2-phenylindole. In biofilter samples, the relative abundance of these bacteria was similar to that of the γ-Proteobacteria. Actinobacteria (gram-positive bacteria with a high G+C DNA content) and α-Proteobacteria were the most dominant groups. Detection rates obtained with probe EUB338 varied between about 40 and 70%. For samples with high contents of gram-positive bacteria, these percentages were substantially improved when the calculations were corrected for the reduced permeability of gram-positive bacteria when formaldehyde was used as a fixative. The set of applied bacterial class- and subclass-specific probes yielded, on average, 58.5% (± a standard deviation of 23.0%) of the corrected eubacterial detection rates, thus indicating the necessity of additional probes for studies of biofilter communities. The Xanthomonas-specific probe presented here may serve as an efficient tool for identifying potential phytopathogens. In situ hybridization proved to be a practical tool for microbiological studies of biofiltration systems. PMID:10427047

A Comparative Theoretical and Computational Study on Robust Counterpart Optimization: I. Robust Linear Optimization and Robust Mixed Integer Linear Optimization

PubMed Central

Li, Zukui; Ding, Ran; Floudas, Christodoulos A.

2011-01-01

Robust counterpart optimization techniques for linear optimization and mixed integer linear optimization problems are studied in this paper. Different uncertainty sets, including those studied in literature (i.e., interval set; combined interval and ellipsoidal set; combined interval and polyhedral set) and new ones (i.e., adjustable box; pure ellipsoidal; pure polyhedral; combined interval, ellipsoidal, and polyhedral set) are studied in this work and their geometric relationship is discussed. For uncertainty in the left hand side, right hand side, and objective function of the optimization problems, robust counterpart optimization formulations induced by those different uncertainty sets are derived. Numerical studies are performed to compare the solutions of the robust counterpart optimization models and applications in refinery production planning and batch process scheduling problem are presented. PMID:21935263

Peptide Probe for Crystalline Hydroxyapatite: In Situ Detection of Biomineralization

NASA Astrophysics Data System (ADS)

Cicerone, Marcus; Becker, Matthew; Simon, Carl; Chatterjee, Kaushik

2009-03-01

While cells template mineralization in vitro and in vivo, specific detection strategies that impart chemical and structural information on this process have proven elusive. Recently we have developed an in situ based peptide probe via phage display methods that is specific to crystalline hydroxyapatite (HA). We are using this in fluorescence based assays to characterize mineralization. One application being explored is the screening of tissue engineering scaffolds for their ability to support osteogenesis. Specifically, osteoblasts are being cultured in hydrogel scaffolds possessing property gradients to provide a test bed for the HA peptide probe. Hydrogel properties that support osteogenesis and HA deposition will be identified using the probe to demonstrate its utility in optimizing design of tissue scaffolds.

Four-probe measurements with a three-probe scanning tunneling microscope.

PubMed

Salomons, Mark; Martins, Bruno V C; Zikovsky, Janik; Wolkow, Robert A

2014-04-01

We present an ultrahigh vacuum (UHV) three-probe scanning tunneling microscope in which each probe is capable of atomic resolution. A UHV JEOL scanning electron microscope aids in the placement of the probes on the sample. The machine also has a field ion microscope to clean, atomically image, and shape the probe tips. The machine uses bare conductive samples and tips with a homebuilt set of pliers for heating and loading. Automated feedback controlled tip-surface contacts allow for electrical stability and reproducibility while also greatly reducing tip and surface damage due to contact formation. The ability to register inter-tip position by imaging of a single surface feature by multiple tips is demonstrated. Four-probe material characterization is achieved by deploying two tips as fixed current probes and the third tip as a movable voltage probe.

Genetic Determinants of Drug Resistance in Mycobacterium tuberculosis and Their Diagnostic Value.

PubMed

Farhat, Maha R; Sultana, Razvan; Iartchouk, Oleg; Bozeman, Sam; Galagan, James; Sisk, Peter; Stolte, Christian; Nebenzahl-Guimaraes, Hanna; Jacobson, Karen; Sloutsky, Alexander; Kaur, Devinder; Posey, James; Kreiswirth, Barry N; Kurepina, Natalia; Rigouts, Leen; Streicher, Elizabeth M; Victor, Tommie C; Warren, Robin M; van Soolingen, Dick; Murray, Megan

2016-09-01

The development of molecular diagnostics that detect both the presence of Mycobacterium tuberculosis in clinical samples and drug resistance-conferring mutations promises to revolutionize patient care and interrupt transmission by ensuring early diagnosis. However, these tools require the identification of genetic determinants of resistance to the full range of antituberculosis drugs. To determine the optimal molecular approach needed, we sought to create a comprehensive catalog of resistance mutations and assess their sensitivity and specificity in diagnosing drug resistance. We developed and validated molecular inversion probes for DNA capture and deep sequencing of 28 drug-resistance loci in M. tuberculosis. We used the probes for targeted sequencing of a geographically diverse set of 1,397 clinical M. tuberculosis isolates with known drug resistance phenotypes. We identified a minimal set of mutations to predict resistance to first- and second-line antituberculosis drugs and validated our predictions in an independent dataset. We constructed and piloted a web-based database that provides public access to the sequence data and prediction tool. The predicted resistance to rifampicin and isoniazid exceeded 90% sensitivity and specificity but was lower for other drugs. The number of mutations needed to diagnose resistance is large, and for the 13 drugs studied it was 238 across 18 genetic loci. These data suggest that a comprehensive M. tuberculosis drug resistance diagnostic will need to allow for a high dimension of mutation detection. They also support the hypothesis that currently unknown genetic determinants, potentially discoverable by whole-genome sequencing, encode resistance to second-line tuberculosis drugs.

Genetic Determinants of Drug Resistance in Mycobacterium tuberculosis and Their Diagnostic Value

PubMed Central

Sultana, Razvan; Iartchouk, Oleg; Bozeman, Sam; Galagan, James; Sisk, Peter; Stolte, Christian; Nebenzahl-Guimaraes, Hanna; Jacobson, Karen; Sloutsky, Alexander; Kaur, Devinder; Posey, James; Kreiswirth, Barry N.; Kurepina, Natalia; Rigouts, Leen; Streicher, Elizabeth M.; Victor, Tommie C.; Warren, Robin M.; van Soolingen, Dick; Murray, Megan

2016-01-01

Rationale: The development of molecular diagnostics that detect both the presence of Mycobacterium tuberculosis in clinical samples and drug resistance–conferring mutations promises to revolutionize patient care and interrupt transmission by ensuring early diagnosis. However, these tools require the identification of genetic determinants of resistance to the full range of antituberculosis drugs. Objectives: To determine the optimal molecular approach needed, we sought to create a comprehensive catalog of resistance mutations and assess their sensitivity and specificity in diagnosing drug resistance. Methods: We developed and validated molecular inversion probes for DNA capture and deep sequencing of 28 drug-resistance loci in M. tuberculosis. We used the probes for targeted sequencing of a geographically diverse set of 1,397 clinical M. tuberculosis isolates with known drug resistance phenotypes. We identified a minimal set of mutations to predict resistance to first- and second-line antituberculosis drugs and validated our predictions in an independent dataset. We constructed and piloted a web-based database that provides public access to the sequence data and prediction tool. Measurements and Main Results: The predicted resistance to rifampicin and isoniazid exceeded 90% sensitivity and specificity but was lower for other drugs. The number of mutations needed to diagnose resistance is large, and for the 13 drugs studied it was 238 across 18 genetic loci. Conclusions: These data suggest that a comprehensive M. tuberculosis drug resistance diagnostic will need to allow for a high dimension of mutation detection. They also support the hypothesis that currently unknown genetic determinants, potentially discoverable by whole-genome sequencing, encode resistance to second-line tuberculosis drugs. PMID:26910495

Colorimetric DNA detection of transgenic plants using gold nanoparticles functionalized with L-shaped DNA probes

NASA Astrophysics Data System (ADS)

Nourisaeid, Elham; Mousavi, Amir; Arpanaei, Ayyoob

2016-01-01

In this study, a DNA colorimetric detection system based on gold nanoparticles functionalized with L-shaped DNA probes was prepared and evaluated. We investigated the hybridization efficiency of the L-shaped probes and studied the effect of nanoparticle size and the L-shaped DNA probe length on the performance of the as-prepared system. Probes were attached to the surface of gold nanoparticles using an adenine sequence. An optimal sequence of 35S rRNA gene promoter from the cauliflower mosaic virus, which is frequently used in the development of transgenic plants, and the two complementary ends of this gene were employed as model target strands and probe molecules, respectively. The spectrophotometric properties of the as-prepared systems indicated that the large NPs show better changes in the absorption spectrum and consequently present a better performance. The results of this study revealed that the probe/Au-NPs prepared using a vertical spacer containing 5 thymine oligonucleotides exhibited a stronger spectrophotometric response in comparison to that of larger probes. These results in general indicate the suitable performance of the L-shaped DNA probe-functionalized Au-NPs, and in particular emphasize the important role of the gold nanoparticle size and length of the DNA probes in enhancing the performance of such a system.

High-throughput, 384-well, LC-MS/MS CYP inhibition assay using automation, cassette-analysis technique, and streamlined data analysis.

PubMed

Halladay, Jason S; Delarosa, Erlie Marie; Tran, Daniel; Wang, Leslie; Wong, Susan; Khojasteh, S Cyrus

2011-08-01

Here we describe a high capacity and high-throughput, automated, 384-well CYP inhibition assay using well-known HLM-based MS probes. We provide consistently robust IC(50) values at the lead optimization stage of the drug discovery process. Our method uses the Agilent Technologies/Velocity11 BioCel 1200 system, timesaving techniques for sample analysis, and streamlined data processing steps. For each experiment, we generate IC(50) values for up to 344 compounds and positive controls for five major CYP isoforms (probe substrate): CYP1A2 (phenacetin), CYP2C9 ((S)-warfarin), CYP2C19 ((S)-mephenytoin), CYP2D6 (dextromethorphan), and CYP3A4/5 (testosterone and midazolam). Each compound is incubated separately at four concentrations with each CYP probe substrate under the optimized incubation condition. Each incubation is quenched with acetonitrile containing the deuterated internal standard of the respective metabolite for each probe substrate. To minimize the number of samples to be analyzed by LC-MS/MS and reduce the amount of valuable MS runtime, we utilize timesaving techniques of cassette analysis (pooling the incubation samples at the end of each CYP probe incubation into one) and column switching (reducing the amount of MS runtime). Here we also report on the comparison of IC(50) results for five major CYP isoforms using our method compared to values reported in the literature.

Theoretical characterization of annular array as a volumetric optoacoustic ultrasound handheld probe

NASA Astrophysics Data System (ADS)

Kalkhoran, Mohammad Azizian; Vray, Didier

2018-02-01

Optoacoustic ultrasound (OPUS) is a promising hybridized technique for simultaneous acquisition of functional and morphological data. The optical specificity of optoacoustic leverages the diagnostic aptitude of ultrasonography beyond anatomy. However, this integration has been rarely practiced for volumetric imaging. The challenge lies in the effective imaging probes that preserve the functionality of both modalities. The potentials of a sparse annular array for volumetric OPUS imaging are theoretically investigated. In order to evaluate and optimize the performance characteristics of the probe, series of analysis in the framework of system model matrix was carried out. The two criteria of voxel crosstalk and eigenanalysis have been employed to unveil information about the spatial sensitivity, aliasing, and number of definable spatial frequency components. Based on these benchmarks, the optimal parameters for volumetric handheld probe are determined. In particular, the number, size, and the arrangement of the elements and overall aperture dimension were investigated. The result of the numerical simulation suggests that the segmented-annular array of 128 negatively focused elements with 1λ × 20λ size, operating at 5-MHz central frequency showcases a good agreement with the physical requirement of both imaging systems. We hypothesize that these features enable a high-throughput volumetric passive/active ultrasonic imaging system with great potential for clinical applications.

A novel dicyanoisophorone based red-emitting fluorescent probe with a large Stokes shift for detection of hydrazine in solution and living cells

NASA Astrophysics Data System (ADS)

Lv, Hongshui; Sun, Haiyan; Wang, Shoujuan; Kong, Fangong

2018-05-01

A novel dicyanoisophorone based fluorescent probe HP was developed to detect hydrazine. Upon the addition of hydrazine, probe HP displayed turn-on fluorescence in the red region with a large Stokes shift (180 nm). This probe exhibited high selectivity and high sensitivity to hydrazine in solution. The detection limit of HP was found to be 3.26 ppb, which was lower than the threshold limit value set by USEPA (10 ppb). Moreover, the probe was successfully applied to detect hydrazine in different water samples and living cells.

A relay identification fluorescence probe for Fe3 + and phosphate anion and its applications

NASA Astrophysics Data System (ADS)

Tang, Xu; Wang, Yun; Han, Juan; Ni, Liang; Wang, Lei; Li, Longhua; Zhang, Huiqin; Li, Cheng; Li, Jing; Li, Haoran

2018-02-01

A simple relay identification fluorescence probe for Fe3 + and phosphate anion with ;on-off-on; switching was designed and synthesized based on the phenylthiazole and biphenylcarbonitrile. Probe 1 displayed highly selective and sensitive recognition to Fe3 + in HEPES aqueous buffer (EtOH/H2O = 2:8, v/v, pH = 7.4) solutions. The optimized structures and HOMO and LUMO of probe 1 and [1-Fe3 +] complex were obtained by the density functional theory (DFT) calculations with B3LYP as the exchange and correlation functional using a suite of Gaussian 09 programs. The [1-Fe3 +] complex solution also showed a high selectivity toward PO43 -. The lower limits of detection of probe 1 to Fe3 + and [1-Fe3 +] complex to PO43 - were estimated to 1.09 × 10- 7 M and 1.86 × 10- 7 M. Besides, the probe 1 also was used to detected the target ions in real water sample and living cells successfully.

Using membrane composition to fine-tune the pKa of an optical liposome pH sensor.

PubMed

Clear, Kasey J; Virga, Katelyn; Gray, Lawrence; Smith, Bradley D

2016-04-14

Liposomes containing membrane-anchored pH-sensitive optical probes are valuable sensors for monitoring pH in various biomedical samples. The dynamic range of the sensor is maximized when the probe p K a is close to the expected sample pH. While some biomedical samples are close to neutral pH there are several circumstances where the pH is 1 or 2 units lower. Thus, there is a need to fine-tune the probe p K a in a predictable way. This investigation examined two lipid-conjugated optical probes, each with appended deep-red cyanine dyes containing indoline nitrogen atoms that are protonated in acid. The presence of anionic phospholipids in the liposomes stabilized the protonated probes and increased the probe p K a values by < 1 unit. The results show that rational modification of the membrane composition is a general non-covalent way to fine-tune the p K a of an optical liposome sensor for optimal pH sensing performance.

Comparison of the structure function F 2 as measured by charged lepton and neutrino scattering from iron targets

DOE PAGES

Kalantarians, N.; Keppel, C.; Christy, M. E.

2017-09-12

A comparison study of world data for the structure function F 2 for Iron, as measured by both charged lepton and neutrino scattering experiments, is presented. Consistency of results for both charged lepton and neutrino scattering is observed for the full global data set in the valence regime. Consistency is also observed at low x for the various neutrino data sets, as well as for the charged lepton data sets, independently. However, data from the two probes exhibit differences on the order of 15% in the shadowing/anti-shadowing transition region where the Bjorken scaling variable x is < 0.15. This observationmore » is indicative that neutrino probes of nucleon structure might be sensitive to different nuclear effects than charged lepton probes. Details and results of the data comparison are here presented.« less

Comparison of the structure function F 2 as measured by charged lepton and neutrino scattering from iron targets

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

Kalantarians, N.; Keppel, C.; Christy, M. E.

A comparison study of world data for the structure function F 2 for Iron, as measured by both charged lepton and neutrino scattering experiments, is presented. Consistency of results for both charged lepton and neutrino scattering is observed for the full global data set in the valence regime. Consistency is also observed at low x for the various neutrino data sets, as well as for the charged lepton data sets, independently. However, data from the two probes exhibit differences on the order of 15% in the shadowing/anti-shadowing transition region where the Bjorken scaling variable x is < 0.15. This observationmore » is indicative that neutrino probes of nucleon structure might be sensitive to different nuclear effects than charged lepton probes. Details and results of the data comparison are here presented.« less

Reference-free spectroscopic determination of fat and protein in milk in the visible and near infrared region below 1000nm using spatially resolved diffuse reflectance fiber probe.

PubMed

Bogomolov, Andrey; Belikova, Valeria; Galyanin, Vladislav; Melenteva, Anastasiia; Meyer, Hans

2017-05-15

New technique of diffuse reflectance spectroscopic analysis of milk fat and total protein content in the visible (Vis) and adjacent near infrared (NIR) region (400-995nm) has been developed and tested. Sample analysis was performed through a probe having eight 200-µm fiber channels forming a linear array. One of the end fibers was used for the illumination and other seven - for the spectroscopic detection of diffusely reflected light. One of the detection channels was used as a reference to normalize the spectra and to convert them into absorbance-equivalent units. The method has been tested experimentally using a designed sample set prepared from industrial raw milk standards with widely varying fat and protein content. To increase the modelling robustness all milk samples were measured in three different homogenization degrees. Comprehensive data analysis has shown the advantage of combining both spectral and spatial resolution in the same measurement and revealed the most relevant channels and wavelength regions. The modelling accuracy was further improved using joint variable selection and preprocessing optimization method based on the genetic algorithm. The root mean-square errors of different validation methods were below 0.10% for fat and below 0.08% for total protein content. Based on the present experimental data, it was computationally shown that the full-spectrum analysis in this method can be replaced by a sensor measurement at several specific wavelengths, for instance, using light-emitting diodes (LEDs) for illumination. Two optimal sensor configurations have been suggested: with nine LEDs for the analysis of fat and seven - for protein content. Both simulated sensors exhibit nearly the same component determination accuracy as corresponding full-spectrum analysis. Copyright © 2017 Elsevier B.V. All rights reserved.

High-throughput microarray technology in diagnostics of enterobacteria based on genome-wide probe selection and regression analysis.

PubMed

Friedrich, Torben; Rahmann, Sven; Weigel, Wilfried; Rabsch, Wolfgang; Fruth, Angelika; Ron, Eliora; Gunzer, Florian; Dandekar, Thomas; Hacker, Jörg; Müller, Tobias; Dobrindt, Ulrich

2010-10-21

The Enterobacteriaceae comprise a large number of clinically relevant species with several individual subspecies. Overlapping virulence-associated gene pools and the high overall genome plasticity often interferes with correct enterobacterial strain typing and risk assessment. Array technology offers a fast, reproducible and standardisable means for bacterial typing and thus provides many advantages for bacterial diagnostics, risk assessment and surveillance. The development of highly discriminative broad-range microbial diagnostic microarrays remains a challenge, because of marked genome plasticity of many bacterial pathogens. We developed a DNA microarray for strain typing and detection of major antimicrobial resistance genes of clinically relevant enterobacteria. For this purpose, we applied a global genome-wide probe selection strategy on 32 available complete enterobacterial genomes combined with a regression model for pathogen classification. The discriminative power of the probe set was further tested in silico on 15 additional complete enterobacterial genome sequences. DNA microarrays based on the selected probes were used to type 92 clinical enterobacterial isolates. Phenotypic tests confirmed the array-based typing results and corroborate that the selected probes allowed correct typing and prediction of major antibiotic resistances of clinically relevant Enterobacteriaceae, including the subspecies level, e.g. the reliable distinction of different E. coli pathotypes. Our results demonstrate that the global probe selection approach based on longest common factor statistics as well as the design of a DNA microarray with a restricted set of discriminative probes enables robust discrimination of different enterobacterial variants and represents a proof of concept that can be adopted for diagnostics of a wide range of microbial pathogens. Our approach circumvents misclassifications arising from the application of virulence markers, which are highly affected by horizontal gene transfer. Moreover, a broad range of pathogens have been covered by an efficient probe set size enabling the design of high-throughput diagnostics.

Approximate Evaluation of Acoustical Focal Beams by Phased Array Probes for Austenitic Weld Inspections

NASA Astrophysics Data System (ADS)

Kono, Naoyuki; Miki, Masahiro; Nakamura, Motoyuki; Ehara, Kazuya

2007-03-01

Phased array techniques are capable of the sensitive detection and precise sizing of flaws or cracks in components of nuclear power plants by using arbitrary focal beams with various depths, positions and angles. Aquantitative investigation of these focal beams is essential for the optimization of array probes, especially for austenitic weld inspection, in order to improve the detectability, sizing accuracy, and signal-to-noise ratio using these beams. In the present work, focal beams generated by phased array probes are calculated based on the Fresnel-Kirchhoff diffraction integral (FKDI) method, and an approximation formula between the actual focal depth and optical focal depth is proposed as an extension of the theory for conventional spherically focusing probes. The validity of the approximation formula for the array probes is confirmed by a comparison with simulation data using the FKDI method, and the experimental data.

Continuously tunable nucleic acid hybridization probes.

PubMed

Wu, Lucia R; Wang, Juexiao Sherry; Fang, John Z; Evans, Emily R; Pinto, Alessandro; Pekker, Irena; Boykin, Richard; Ngouenet, Celine; Webster, Philippa J; Beechem, Joseph; Zhang, David Yu

2015-12-01

In silico-designed nucleic acid probes and primers often do not achieve favorable specificity and sensitivity tradeoffs on the first try, and iterative empirical sequence-based optimization is needed, particularly in multiplexed assays. We present a novel, on-the-fly method of tuning probe affinity and selectivity by adjusting the stoichiometry of auxiliary species, which allows for independent and decoupled adjustment of the hybridization yield for different probes in multiplexed assays. Using this method, we achieved near-continuous tuning of probe effective free energy. To demonstrate our approach, we enforced uniform capture efficiency of 31 DNA molecules (GC content, 0-100%), maximized the signal difference for 11 pairs of single-nucleotide variants and performed tunable hybrid capture of mRNA from total RNA. Using the Nanostring nCounter platform, we applied stoichiometric tuning to simultaneously adjust yields for a 24-plex assay, and we show multiplexed quantitation of RNA sequences and variants from formalin-fixed, paraffin-embedded samples.

Design and construction of high-frequency magnetic probe system on the HL-2A tokamak

NASA Astrophysics Data System (ADS)

Liang, S. Y.; Ji, X. Q.; Sun, T. F.; Xu, Yuan; Lu, J.; Yuan, B. S.; Ren, L. L.; Yang, Q. W.

2017-12-01

A high-frequency magnetic probe system is designed, calibrated and constructed on the HL-2A tokamak. To investigate the factors which affect the probe frequency response, the inductance and capacitance in the probe system are analyzed using an equivalent circuit. Suitable sizes and turn number of the coil, and the length of transmission cable are optimized based on the theory and detailed test in the calibration. To deal with the frequency response limitation and bake-out, the ceramic grooved technique is used and the probe is wound with a bare copper wire. A cascade filter is manufactured with a suitable bandwidth as well as a good phase consistency between channels. The system has been used in the experiment to measure high frequency (≤300 kHz) magnetohydrodynamic fluctuations, which can meet the requirement of physical analysis on HL-2A.

Measurement of locus copy number by hybridisation with amplifiable probes

PubMed Central

Armour, John A. L.; Sismani, Carolina; Patsalis, Philippos C.; Cross, Gareth

2000-01-01

Despite its fundamental importance in genome analysis, it is only recently that systematic approaches have been developed to assess copy number at specific genetic loci, or to examine genomic DNA for submicroscopic deletions of unknown location. In this report we show that short probes can be recovered and amplified quantitatively following hybridisation to genomic DNA. This simple observation forms the basis of a new approach to determining locus copy number in complex genomes. The power and specificity of multiplex amplifiable probe hybridisation is demonstrated by the simultaneous assessment of copy number at a set of 40 human loci, including detection of deletions causing Duchenne muscular dystrophy and Prader–Willi/Angelman syndromes. Assembly of other probe sets will allow novel, technically simple approaches to a wide variety of genetic analyses, including the potential for extension to high resolution genome-wide screens for deletions and amplifications. PMID:10606661

Measurement of locus copy number by hybridisation with amplifiable probes.

PubMed

Armour, J A; Sismani, C; Patsalis, P C; Cross, G

2000-01-15

Despite its fundamental importance in genome analysis, it is only recently that systematic approaches have been developed to assess copy number at specific genetic loci, or to examine genomic DNA for submicro-scopic deletions of unknown location. In this report we show that short probes can be recovered and amplified quantitatively following hybridisation to genomic DNA. This simple observation forms the basis of a new approach to determining locus copy number in complex genomes. The power and specificity of multiplex amplifiable probe hybridisation is demonstrated by the simultaneous assessment of copy number at a set of 40 human loci, including detection of deletions causing Duchenne muscular dystrophy and Prader-Willi/Angelman syndromes. Assembly of other probe sets will allow novel, technically simple approaches to a wide variety of genetic analyses, including the potential for extension to high resolution genome-wide screens for deletions and amplifications.

Bohm-criterion approximation versus optimal matched solution for a cylindrical probe in radial-motion theory

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

Din, Alif

2016-08-15

The theory of positive-ion collection by a probe immersed in a low-pressure plasma was reviewed and extended by Allen et al. [Proc. Phys. Soc. 70, 297 (1957)]. The numerical computations for cylindrical and spherical probes in a sheath region were presented by F. F. Chen [J. Nucl. Energy C 7, 41 (1965)]. Here, in this paper, the sheath and presheath solutions for a cylindrical probe are matched through a numerical matching procedure to yield “matched” potential profile or “M solution.” The solution based on the Bohm criterion approach “B solution” is discussed for this particular problem. The comparison of cylindricalmore » probe characteristics obtained from the correct potential profile (M solution) and the approximated Bohm-criterion approach are different. This raises questions about the correctness of cylindrical probe theories relying only on the Bohm-criterion approach. Also the comparison between theoretical and experimental ion current characteristics shows that in an argon plasma the ions motion towards the probe is almost radial.« less

Probabilistic determination of probe locations from distance data

PubMed Central

Xu, Xiao-Ping; Slaughter, Brian D.; Volkmann, Niels

2013-01-01

Distance constraints, in principle, can be employed to determine information about the location of probes within a three-dimensional volume. Traditional methods for locating probes from distance constraints involve optimization of scoring functions that measure how well the probe location fits the distance data, exploring only a small subset of the scoring function landscape in the process. These methods are not guaranteed to find the global optimum and provide no means to relate the identified optimum to all other optima in scoring space. Here, we introduce a method for the location of probes from distance information that is based on probability calculus. This method allows exploration of the entire scoring space by directly combining probability functions representing the distance data and information about attachment sites. The approach is guaranteed to identify the global optimum and enables the derivation of confidence intervals for the probe location as well as statistical quantification of ambiguities. We apply the method to determine the location of a fluorescence probe using distances derived by FRET and show that the resulting location matches that independently derived by electron microscopy. PMID:23770585

High sensitive and direct fluorescence detection of single viral DNA sequences by integration of double strand probes onto microgels particles.

PubMed

Aliberti, A; Cusano, A M; Battista, E; Causa, F; Netti, P A

2016-02-21

A novel class of probes for fluorescence detection was developed and combined to microgel particles for a high sensitive fluorescence detection of nucleic acids. A double strand probe with an optimized fluorescent-quencher couple was designed for the detection of different lengths of nucleic acids (39 nt and 100 nt). Such probe proved efficient in target detection in different contests and specific even in presence of serum proteins. The conjugation of double strand probes onto polymeric microgels allows for a sensitive detection of DNA sequences from HIV, HCV and SARS corona viruses with a LOD of 1.4 fM, 3.7 fM and 1.4 fM, respectively, and with a dynamic range of 10(-9)-10(-15) M. Such combination enhances the sensitivity of the detection of almost five orders of magnitude when compared to the only probe. The proposed platform based on the integration of innovative double strand probe into microgels particles represents an attractive alternative to conventional sensitive DNA detection technologies that rely on amplifications methods.

Ultrasonic simulation—Imagine3D and SimScan: Tools to solve the inverse problem for complex turbine components

NASA Astrophysics Data System (ADS)

Mair, H. D.; Ciorau, P.; Owen, D.; Hazelton, T.; Dunning, G.

2000-05-01

Two ultrasonic simulation packages: Imagine 3D and SIMSCAN have specifically been developed to solve the inverse problem for blade root and rotor steeple of low-pressure turbine. The software was integrated with the 3D drawing of the inspected parts, and with the dimensions of linear phased-array probes. SIMSCAN simulates the inspection scenario in both optional conditions: defect location and probe movement/refracted angle range. The results are displayed into Imagine 3-D, with a variety of options: rendering, display 1:1, grid, generated UT beam. The results are very useful for procedure developer, training and to optimize the phased-array probe inspection sequence. A spreadsheet is generated to correlate the defect coordinates with UT data (probe position, skew and refracted angle, UT path, and probe movement). The simulation models were validated during experimental work with phased-array systems. The accuracy in probe position is ±1 mm, and the refracted/skew angle is within ±0.5°. Representative examples of phased array focal laws/probe movement for a specific defect location, are also included.

Self-Nulling Eddy Current Probe for Surface and Subsurface Flaw Detection

NASA Technical Reports Server (NTRS)

Wincheski, B.; Fulton, J. P.; Nath, S.; Namkung, M.; Simpson, J. W.

1994-01-01

An eddy current probe which provides a null-signal in the presence of unflawed material without the need for any balancing circuitry has been developed at NASA Langley Research Center. Such a unique capability of the probe reduces set-up time, eliminates tester configuration errors, and decreases instrumentation requirements. The probe is highly sensitive to surface breaking fatigue cracks, and shows excellent resolution for the measurement of material thickness, including material loss due to corrosion damage. The presence of flaws in the material under test causes an increase in the extremely stable and reproducible output voltage of the probe. The design of the probe and some examples illustrating its flaw detection capabilities are presented.

A practical model for pressure probe system response estimation (with review of existing models)

NASA Astrophysics Data System (ADS)

Hall, B. F.; Povey, T.

2018-04-01

The accurate estimation of the unsteady response (bandwidth) of pneumatic pressure probe systems (probe, line and transducer volume) is a common practical problem encountered in the design of aerodynamic experiments. Understanding the bandwidth of the probe system is necessary to capture unsteady flow features accurately. Where traversing probes are used, the desired traverse speed and spatial gradients in the flow dictate the minimum probe system bandwidth required to resolve the flow. Existing approaches for bandwidth estimation are either complex or inaccurate in implementation, so probes are often designed based on experience. Where probe system bandwidth is characterized, it is often done experimentally, requiring careful experimental set-up and analysis. There is a need for a relatively simple but accurate model for estimation of probe system bandwidth. A new model is presented for the accurate estimation of pressure probe bandwidth for simple probes commonly used in wind tunnel environments; experimental validation is provided. An additional, simple graphical method for air is included for convenience.

Four-probe measurements with a three-probe scanning tunneling microscope

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

Salomons, Mark; Martins, Bruno V. C.; Zikovsky, Janik

2014-04-15

We present an ultrahigh vacuum (UHV) three-probe scanning tunneling microscope in which each probe is capable of atomic resolution. A UHV JEOL scanning electron microscope aids in the placement of the probes on the sample. The machine also has a field ion microscope to clean, atomically image, and shape the probe tips. The machine uses bare conductive samples and tips with a homebuilt set of pliers for heating and loading. Automated feedback controlled tip-surface contacts allow for electrical stability and reproducibility while also greatly reducing tip and surface damage due to contact formation. The ability to register inter-tip position bymore » imaging of a single surface feature by multiple tips is demonstrated. Four-probe material characterization is achieved by deploying two tips as fixed current probes and the third tip as a movable voltage probe.« less

Multiwaveguide implantable probe for light delivery to sets of distributed brain targets.

PubMed

Zorzos, Anthony N; Boyden, Edward S; Fonstad, Clifton G

2010-12-15

Optical fibers are commonly inserted into living tissues such as the brain in order to deliver light to deep targets for neuroscientific and neuroengineering applications such as optogenetics, in which light is used to activate or silence neurons expressing specific photosensitive proteins. However, an optical fiber is limited to delivering light to a single target within the three-dimensional structure of the brain. We here demonstrate a multiwaveguide probe capable of independently delivering light to multiple targets along the probe axis, thus enabling versatile optical control of sets of distributed brain targets. The 1.45-cm-long probe is microfabricated in the form of a 360-μm-wide array of 12 parallel silicon oxynitride (SiON) multimode waveguides clad with SiO(2) and coated with aluminum; probes of custom dimensions are easily created as well. The waveguide array accepts light from a set of sources at the input end and guides the light down each waveguide to an aluminum corner mirror that efficiently deflects light away from the probe axis. Light losses at each stage are small (input coupling loss, 0.4 ± 0.3 dB; bend loss, negligible; propagation loss, 3.1 ± 1 dB/cm using the outscattering method and 3.2 ± 0.4 dB/cm using the cutback method; corner mirror loss, 1.5 ± 0.4 dB); a waveguide coupled, for example, to a 5 mW source will deliver over 1.5 mW to a target at a depth of 1 cm.

Technique Developed for Optimizing Traveling-Wave Tubes

NASA Technical Reports Server (NTRS)

Wilson, Jeffrey D.

1999-01-01

A traveling-wave tube (TWT) is an electron beam device that is used to amplify electromagnetic communication waves at radio and microwave frequencies. TWT s are critical components in deep-space probes, geosynchronous communication satellites, and high-power radar systems. Power efficiency is of paramount importance for TWT s employed in deep-space probes and communications satellites. Consequently, increasing the power efficiency of TWT s has been the primary goal of the TWT group at the NASA Lewis Research Center over the last 25 years. An in-house effort produced a technique (ref. 1) to design TWT's for optimized power efficiency. This technique is based on simulated annealing, which has an advantage over conventional optimization techniques in that it enables the best possible solution to be obtained (ref. 2). A simulated annealing algorithm was created and integrated into the NASA TWT computer model (ref. 3). The new technique almost doubled the computed conversion power efficiency of a TWT from 7.1 to 13.5 percent (ref. 1).

Dynamic variable selection in SNP genotype autocalling from APEX microarray data.

PubMed

Podder, Mohua; Welch, William J; Zamar, Ruben H; Tebbutt, Scott J

2006-11-30

Single nucleotide polymorphisms (SNPs) are DNA sequence variations, occurring when a single nucleotide--adenine (A), thymine (T), cytosine (C) or guanine (G)--is altered. Arguably, SNPs account for more than 90% of human genetic variation. Our laboratory has developed a highly redundant SNP genotyping assay consisting of multiple probes with signals from multiple channels for a single SNP, based on arrayed primer extension (APEX). This mini-sequencing method is a powerful combination of a highly parallel microarray with distinctive Sanger-based dideoxy terminator sequencing chemistry. Using this microarray platform, our current genotype calling system (known as SNP Chart) is capable of calling single SNP genotypes by manual inspection of the APEX data, which is time-consuming and exposed to user subjectivity bias. Using a set of 32 Coriell DNA samples plus three negative PCR controls as a training data set, we have developed a fully-automated genotyping algorithm based on simple linear discriminant analysis (LDA) using dynamic variable selection. The algorithm combines separate analyses based on the multiple probe sets to give a final posterior probability for each candidate genotype. We have tested our algorithm on a completely independent data set of 270 DNA samples, with validated genotypes, from patients admitted to the intensive care unit (ICU) of St. Paul's Hospital (plus one negative PCR control sample). Our method achieves a concordance rate of 98.9% with a 99.6% call rate for a set of 96 SNPs. By adjusting the threshold value for the final posterior probability of the called genotype, the call rate reduces to 94.9% with a higher concordance rate of 99.6%. We also reversed the two independent data sets in their training and testing roles, achieving a concordance rate up to 99.8%. The strength of this APEX chemistry-based platform is its unique redundancy having multiple probes for a single SNP. Our model-based genotype calling algorithm captures the redundancy in the system considering all the underlying probe features of a particular SNP, automatically down-weighting any 'bad data' corresponding to image artifacts on the microarray slide or failure of a specific chemistry. In this regard, our method is able to automatically select the probes which work well and reduce the effect of other so-called bad performing probes in a sample-specific manner, for any number of SNPs.

Emulation of reionization simulations for Bayesian inference of astrophysics parameters using neural networks

NASA Astrophysics Data System (ADS)

Schmit, C. J.; Pritchard, J. R.

2018-03-01

Next generation radio experiments such as LOFAR, HERA, and SKA are expected to probe the Epoch of Reionization (EoR) and claim a first direct detection of the cosmic 21cm signal within the next decade. Data volumes will be enormous and can thus potentially revolutionize our understanding of the early Universe and galaxy formation. However, numerical modelling of the EoR can be prohibitively expensive for Bayesian parameter inference and how to optimally extract information from incoming data is currently unclear. Emulation techniques for fast model evaluations have recently been proposed as a way to bypass costly simulations. We consider the use of artificial neural networks as a blind emulation technique. We study the impact of training duration and training set size on the quality of the network prediction and the resulting best-fitting values of a parameter search. A direct comparison is drawn between our emulation technique and an equivalent analysis using 21CMMC. We find good predictive capabilities of our network using training sets of as low as 100 model evaluations, which is within the capabilities of fully numerical radiative transfer codes.

High-speed adaptive contact-mode atomic force microscopy imaging with near-minimum-force

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

Ren, Juan; Zou, Qingze, E-mail: qzzou@rci.rutgers.edu

In this paper, an adaptive contact-mode imaging approach is proposed to replace the traditional contact-mode imaging by addressing the major concerns in both the speed and the force exerted to the sample. The speed of the traditional contact-mode imaging is largely limited by the need to maintain precision tracking of the sample topography over the entire imaged sample surface, while large image distortion and excessive probe-sample interaction force occur during high-speed imaging. In this work, first, the image distortion caused by the topography tracking error is accounted for in the topography quantification. Second, the quantified sample topography is utilized inmore » a gradient-based optimization method to adjust the cantilever deflection set-point for each scanline closely around the minimal level needed for maintaining stable probe-sample contact, and a data-driven iterative feedforward control that utilizes a prediction of the next-line topography is integrated to the topography feeedback loop to enhance the sample topography tracking. The proposed approach is demonstrated and evaluated through imaging a calibration sample of square pitches at both high speeds (e.g., scan rate of 75 Hz and 130 Hz) and large sizes (e.g., scan size of 30 μm and 80 μm). The experimental results show that compared to the traditional constant-force contact-mode imaging, the imaging speed can be increased by over 30 folds (with the scanning speed at 13 mm/s), and the probe-sample interaction force can be reduced by more than 15% while maintaining the same image quality.« less

High-speed adaptive contact-mode atomic force microscopy imaging with near-minimum-force.

PubMed

Ren, Juan; Zou, Qingze

2014-07-01

In this paper, an adaptive contact-mode imaging approach is proposed to replace the traditional contact-mode imaging by addressing the major concerns in both the speed and the force exerted to the sample. The speed of the traditional contact-mode imaging is largely limited by the need to maintain precision tracking of the sample topography over the entire imaged sample surface, while large image distortion and excessive probe-sample interaction force occur during high-speed imaging. In this work, first, the image distortion caused by the topography tracking error is accounted for in the topography quantification. Second, the quantified sample topography is utilized in a gradient-based optimization method to adjust the cantilever deflection set-point for each scanline closely around the minimal level needed for maintaining stable probe-sample contact, and a data-driven iterative feedforward control that utilizes a prediction of the next-line topography is integrated to the topography feeedback loop to enhance the sample topography tracking. The proposed approach is demonstrated and evaluated through imaging a calibration sample of square pitches at both high speeds (e.g., scan rate of 75 Hz and 130 Hz) and large sizes (e.g., scan size of 30 μm and 80 μm). The experimental results show that compared to the traditional constant-force contact-mode imaging, the imaging speed can be increased by over 30 folds (with the scanning speed at 13 mm/s), and the probe-sample interaction force can be reduced by more than 15% while maintaining the same image quality.

Interaction-free measurement as quantum channel discrimination

NASA Astrophysics Data System (ADS)

Zhou, You; Yung, Man-Hong

2017-12-01

Interaction-free measurement is a quantum process where, in the ideal situation, an object can be detected as if no interaction took place with the probing photon. Here we show that the problem of interaction-free measurement can be regarded as a problem of quantum-channel discrimination. In particular, we look for the optimal photonic states that can minimize the detection error and the photon loss in detecting the presence or absence of the object, which is taken to be semitransparent, and the number of the interrogation cycle is assumed to be finite. Furthermore, we also investigated the possibility of minimizing the detection error through the use of entangled photons, which is essentially a setting of quantum illumination. However, our results indicate that entanglement does not exhibit a clear advantage; the same performance can be achieved with unentangled photonic states.

An evaluation of multi-probe locality sensitive hashing for computing similarities over web-scale query logs.

PubMed

Cormode, Graham; Dasgupta, Anirban; Goyal, Amit; Lee, Chi Hoon

2018-01-01

Many modern applications of AI such as web search, mobile browsing, image processing, and natural language processing rely on finding similar items from a large database of complex objects. Due to the very large scale of data involved (e.g., users' queries from commercial search engines), computing such near or nearest neighbors is a non-trivial task, as the computational cost grows significantly with the number of items. To address this challenge, we adopt Locality Sensitive Hashing (a.k.a, LSH) methods and evaluate four variants in a distributed computing environment (specifically, Hadoop). We identify several optimizations which improve performance, suitable for deployment in very large scale settings. The experimental results demonstrate our variants of LSH achieve the robust performance with better recall compared with "vanilla" LSH, even when using the same amount of space.

Method for determining thermal conductivity and thermal capacity per unit volume of earth in situ

DOEpatents

Poppendiek, Heinz F.

1982-01-01

A method for determining the thermal conductivity of the earth in situ is based upon a cylindrical probe (10) having a thermopile (16) for measuring the temperature gradient between sets of thermocouple junctions (18 and 20) of the probe after it has been positioned in a borehole and has reached thermal equilibrium with its surroundings, and having means (14) for heating one set of thermocouple junctions (20) of the probe at a constant rate while the temperature gradient of the probe is recorded as a rise in temperature over several hours (more than about 3 hours). A fluid annulus thermally couples the probe to the surrounding earth. The recorded temperature curves are related to the earth's thermal conductivity, k.sub..infin., and to the thermal capacity per unit volume, (.gamma.c.sub.p).sub..infin., by comparison with calculated curves using estimates of k.sub..infin. and (.gamma.c.sub.p).sub..infin. in an equation which relates these parameters to a rise in the earth's temperature for a known and constant heating rate.

Energy-optimal path planning by stochastic dynamically orthogonal level-set optimization

NASA Astrophysics Data System (ADS)

Subramani, Deepak N.; Lermusiaux, Pierre F. J.

2016-04-01

A stochastic optimization methodology is formulated for computing energy-optimal paths from among time-optimal paths of autonomous vehicles navigating in a dynamic flow field. Based on partial differential equations, the methodology rigorously leverages the level-set equation that governs time-optimal reachability fronts for a given relative vehicle-speed function. To set up the energy optimization, the relative vehicle-speed and headings are considered to be stochastic and new stochastic Dynamically Orthogonal (DO) level-set equations are derived. Their solution provides the distribution of time-optimal reachability fronts and corresponding distribution of time-optimal paths. An optimization is then performed on the vehicle's energy-time joint distribution to select the energy-optimal paths for each arrival time, among all stochastic time-optimal paths for that arrival time. Numerical schemes to solve the reduced stochastic DO level-set equations are obtained, and accuracy and efficiency considerations are discussed. These reduced equations are first shown to be efficient at solving the governing stochastic level-sets, in part by comparisons with direct Monte Carlo simulations. To validate the methodology and illustrate its accuracy, comparisons with semi-analytical energy-optimal path solutions are then completed. In particular, we consider the energy-optimal crossing of a canonical steady front and set up its semi-analytical solution using a energy-time nested nonlinear double-optimization scheme. We then showcase the inner workings and nuances of the energy-optimal path planning, considering different mission scenarios. Finally, we study and discuss results of energy-optimal missions in a wind-driven barotropic quasi-geostrophic double-gyre ocean circulation.

Experimental evaluation of neural probe’s insertion induced injury based on digital image correlation method

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

Zhang, Wenguang, E-mail: zhwg@sjtu.edu.cn; Ma, Yakun; Li, Zhengwei

Purpose: The application of neural probes in clinic has been challenged by probes’ short lifetime when implanted into brain tissue. The primary goal is to develop an evaluation system for testing brain tissue injury induced by neural probe’s insertion using microscope based digital image correlation method. Methods: A brain tissue phantom made of silicone rubber with speckle pattern on its surface was fabricated. To obtain the optimal speckle pattern, mean intensity gradient parameter was used for quality assessment. The designed testing system consists of three modules: (a) load module for simulating neural electrode implantation process; (b) data acquisition module tomore » capture micrographs of speckle pattern and to obtain reactive forces during the insertion of the probe; (c) postprocessing module for extracting tissue deformation information from the captured speckle patterns. On the basis of the evaluation system, the effects of probe wedge angle, insertion speed, and probe streamline on insertion induced tissue injury were investigated. Results: The optimal quality speckle pattern can be attained by the following fabrication parameters: spin coating rate—1000 r/min, silicone rubber component A: silicone rubber component B: softener: graphite = 5 ml: 5 ml: 2 ml: 0.6 g. The probe wedge angle has a significant effect on tissue injury. Compared to wedge angle 40° and 20°, maximum principal strain of 60° wedge angle was increased by 40.3% and 87.5%, respectively; compared with a relatively higher speed (500 μm/s), the maximum principle strain within the tissue induced by slow insertion speed (100 μm/s) was increased by 14.3%; insertion force required by probe with convex streamline was smaller than the force of traditional probe. Based on the experimental results, a novel neural probe that has a rounded tip covered by a biodegradable silk protein coating with convex streamline was proposed, which has both lower insertion and micromotion induced tissue injury. Conclusions: The established evaluation system has provided a simulation environment for testing brain tissue injury produced by various insertion conditions. At the same time, it eliminates the adverse effect of biological factors on tissue deformation during the experiment, improving the repeatability of measurement results. As a result, the evaluation system will provide support on novel neural probe design that can reduce the acute tissue injury during the implantation of the probe.« less

Personalized Medicine in Veterans with Traumatic Brain Injuries

DTIC Science & Technology

2012-05-01

UPGMA ) based on cosine correlation of row mean centered log2 signal values; this was the top 50%-tile, 3) In the DA top 50%-tile, selected probe sets...GeneMaths XT following row mean centering of log2 trans- formed MAS5.0 signal values; probe set cluster- ing was performed by the UPGMA method using...hierarchical clustering analysis using the UPGMA algorithm with cosine correlation as the similarity metric. Results are presented as a heat map (left

The genomic response of skeletal muscle to methylprednisolone using microarrays: tailoring data mining to the structure of the pharmacogenomic time series

PubMed Central

DuBois, Debra C; Piel, William H; Jusko, William J

2008-01-01

High-throughput data collection using gene microarrays has great potential as a method for addressing the pharmacogenomics of complex biological systems. Similarly, mechanism-based pharmacokinetic/pharmacodynamic modeling provides a tool for formulating quantitative testable hypotheses concerning the responses of complex biological systems. As the response of such systems to drugs generally entails cascades of molecular events in time, a time series design provides the best approach to capturing the full scope of drug effects. A major problem in using microarrays for high-throughput data collection is sorting through the massive amount of data in order to identify probe sets and genes of interest. Due to its inherent redundancy, a rich time series containing many time points and multiple samples per time point allows for the use of less stringent criteria of expression, expression change and data quality for initial filtering of unwanted probe sets. The remaining probe sets can then become the focus of more intense scrutiny by other methods, including temporal clustering, functional clustering and pharmacokinetic/pharmacodynamic modeling, which provide additional ways of identifying the probes and genes of pharmacological interest. PMID:15212590

Passively Driven Probe Based on Miniaturized Propeller for Intravascular Optical Coherence Tomography.

PubMed

Lu, Yu; Li, Zhongliang; Nan, Nan; Bu, Yang; Liu, Xuebo; Xu, Xiangdong; Wang, Xuan; Sasaki, Osami; Wang, Xiangzhao

2018-03-26

Optical coherent tomography (OCT) has enabled clinical applications ranging from ophthalmology to cardiology that revolutionized in vivo medical diagnostics in the last few decades, and a variety of endoscopic probes have been developed in order to meet the needs of various endoscopic OCT imaging. We propose a passive driven intravascular optical coherent tomography (IV-OCT) probe in this paper. Instead of using any electrically driven scanning device, the probe makes use of the kinetic energy of the fluid that flushes away the blood during the intravascular optical coherence tomography imaging. The probe converts it into the rotational kinetic energy of the propeller, and the rotation of the rectangular prism mounted on the propeller shaft enables the scanning of the beam. The probe is low cost, and enables unobstructed stable circumferential scanning over 360 deg. The experimental results show that the probe scanning speed can exceed 100 rotations per second (rps). Spectral-domain OCT imaging of a phantom and porcine cardiac artery are demonstrated with axial resolution of 13.6 μm, lateral resolution of 22 μm, and sensitivity of 101.7 dB. We present technically the passively driven IV-OCT probe in full detail and discuss how to optimize the probe in further.

Effect of Front-Side Silver Metallization on Underlying n+-p Junction in Multicrystalline Silicon Solar Cells: Preprint

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

Jiang, C. S.; Li, Z. G.; Moutinho, H. R.

2012-06-01

We report on the effect of front-side Ag metallization on the underlying n+-p junction of multicrystalline Si solar cells. The junction quality beneath the contacts was investigated by characterizing the uniformities of the electrostatic potential and doping concentration across the junction, using scanning Kelvin probe force microscopy and scanning capacitance microscopy. We investigated cells with a commercial Ag paste (DuPont PV159) and fired at furnace setting temperatures of 800 degrees, 840 degrees, and 930 degrees C, which results in actual cell temperatures ~100 degrees C lower than the setting temperature and the three cells being under-, optimal-, and over-fired. Wemore » found that the uniformity of the junction beneath the Ag contact was significantly degraded by the over-firing, whereas the junction retained good uniformity with the optimal- and under-fire temperatures. Further, Ag crystallites with widely distributed sizes from <100 nm to several μm were found at the Ag/Si interface of the over-fired cell. Large crystallites were imaged as protrusions into Si deeper than the junction depth. However, the junction was not broken down; instead, it was reformed on the entire front of the crystallite/Si interface. We propose a mechanism of the junction-quality degradation, based on emitter Si melting at the temperature around the Ag-Si eutectic point during firing, and subsequent recrystallization with incorporation of impurities in the Ag paste and with formation of crystallographic defects during quenching.« less

Silver-dendrimer nanocomposites as oligonucleotide labels for electrochemical stripping detection of DNA hybridization.

PubMed

Jin, Xin; Zhou, Ling; Zhu, Bo; Jiang, Xue; Zhu, Ningning

2018-06-01

Silver-dendrimer nanocomposites were synthesized and used as oligonucleotide labels for electrochemical stripping detection of DNA hybridization. The synthesized silver-dendrimer nanocomposites were characterized by UV-vis spectrophotometry, X-ray photoelectron spectroscopy (XPS) and transmission electron microscopy (TEM). Ratios of silver/dendrimer were optimized in order to obtain stable nanocomposites with maximal silver loading in the interior of a polymeric shell. The silver-dendrimer nanocomposites were attached to sequence-known DNA probes specific to colitoxin, and used to detect probe hybridization by dissolution of the silver nanoparticles in the interior of dendrimer in a diluted nitric acid, followed by measurement of Ag + ions by anodic stripping voltammetry (ASV). Use of differential pulse voltammetry for the stripping step, along with optimization of the ASV conditions, enabled a detection limit of 0.78 pM. The present strategy, in combination with dendrimer-encapsulated copper labeled oligonucleotides probe reported previously, could potentially be used to detect single or multiple DNA targets in one sample. Copyright © 2018 Elsevier B.V. All rights reserved.

Proton-beam writing channel based on an electrostatic accelerator

NASA Astrophysics Data System (ADS)

Lapin, A. S.; Rebrov, V. A.; Kolin'ko, S. V.; Salivon, V. F.; Ponomarev, A. G.

2016-09-01

We have described the structure of the proton-beam writing channel as a continuation of a nuclear scanning microprobe channel. The problem of the accuracy of positioning a probe by constructing a new high-frequency electrostatic scanning system has been solved. Special attention has been paid to designing the probe-forming system and its various configurations have been considered. The probe-forming system that best corresponds to the conditions of the lithographic process has been found based on solving the problem of optimizing proton beam formation. A system for controlling beam scanning using multifunctional module of integrated programmable logic systems has been developed.

Evaluation of a pneumatic Martian soil sampler concept

NASA Technical Reports Server (NTRS)

Schaefer, John L.; Neathery, James K.; Stencel, John M.

1994-01-01

The pneumatic soil sampler concept was successfully demonstrated by penetrating a Martian simulant soil to a depth of 2 meters. Working gas pressure, composition, and pulsing were evaluated with the objective of minimizing gas usage. Also, the probe penetration force was investigated with the objective of minimizing probe weight. Gas and probe penetration force, while not yet optimized, are within the range which make the soil sampler concept feasible. While the tests described in this report did not answer all the questions and address all the variables associated with pneumatic soil sampling, valuable data experience and knowledge were gained which can be used to further develop the concept.

Identification of random nucleic acid sequence aberrations using dual capture probes which hybridize to different chromosome regions

DOEpatents

Lucas, J.N.; Straume, T.; Bogen, K.T.

1998-03-24

A method is provided for detecting nucleic acid sequence aberrations using two immobilization steps. According to the method, a nucleic acid sequence aberration is detected by detecting nucleic acid sequences having both a first nucleic acid sequence type (e.g., from a first chromosome) and a second nucleic acid sequence type (e.g., from a second chromosome), the presence of the first and the second nucleic acid sequence type on the same nucleic acid sequence indicating the presence of a nucleic acid sequence aberration. In the method, immobilization of a first hybridization probe is used to isolate a first set of nucleic acids in the sample which contain the first nucleic acid sequence type. Immobilization of a second hybridization probe is then used to isolate a second set of nucleic acids from within the first set of nucleic acids which contain the second nucleic acid sequence type. The second set of nucleic acids are then detected, their presence indicating the presence of a nucleic acid sequence aberration. 14 figs.

Identification of random nucleic acid sequence aberrations using dual capture probes which hybridize to different chromosome regions

DOEpatents

Lucas, Joe N.; Straume, Tore; Bogen, Kenneth T.

1998-01-01

A method is provided for detecting nucleic acid sequence aberrations using two immobilization steps. According to the method, a nucleic acid sequence aberration is detected by detecting nucleic acid sequences having both a first nucleic acid sequence type (e.g., from a first chromosome) and a second nucleic acid sequence type (e.g., from a second chromosome), the presence of the first and the second nucleic acid sequence type on the same nucleic acid sequence indicating the presence of a nucleic acid sequence aberration. In the method, immobilization of a first hybridization probe is used to isolate a first set of nucleic acids in the sample which contain the first nucleic acid sequence type. Immobilization of a second hybridization probe is then used to isolate a second set of nucleic acids from within the first set of nucleic acids which contain the second nucleic acid sequence type. The second set of nucleic acids are then detected, their presence indicating the presence of a nucleic acid sequence aberration.

Double-labeled donor probe can enhance the signal of fluorescence resonance energy transfer (FRET) in detection of nucleic acid hybridization

PubMed Central

Okamura, Yukio; Kondo, Satoshi; Sase, Ichiro; Suga, Takayuki; Mise, Kazuyuki; Furusawa, Iwao; Kawakami, Shigeki; Watanabe, Yuichiro

2000-01-01

A set of fluorescently-labeled DNA probes that hybridize with the target RNA and produce fluorescence resonance energy transfer (FRET) signals can be utilized for the detection of specific RNA. We have developed probe sets to detect and discriminate single-strand RNA molecules of plant viral genome, and sought a method to improve the FRET signals to handle in vivo applications. Consequently, we found that a double-labeled donor probe labeled with Bodipy dye yielded a remarkable increase in fluorescence intensity compared to a single-labeled donor probe used in an ordinary FRET. This double-labeled donor system can be easily applied to improve various FRET probes since the dependence upon sequence and label position in enhancement is not as strict. Furthermore this method could be applied to other nucleic acid substances, such as oligo RNA and phosphorothioate oligonucleotides (S-oligos) to enhance FRET signal. Although the double-labeled donor probes labeled with a variety of fluorophores had unexpected properties (strange UV-visible absorption spectra, decrease of intensity and decay of donor fluorescence) compared with single-labeled ones, they had no relation to FRET enhancement. This signal amplification mechanism cannot be explained simply based on our current results and knowledge of FRET. Yet it is possible to utilize this double-labeled donor system in various applications of FRET as a simple signal-enhancement method. PMID:11121494

Screening for specific chromosome involvement in hematological malignancies using a set of seven chromosome painting probes. An alternative approach for chromosome analysis using standard FISH instrumentation.

PubMed

Nacheva, E P; Gribble, S; Andrews, K; Wienberg, J; Grace, C D

2000-10-15

We report the application of multi-color fluorescence in situ hydribidization (FISH) for bone marrow metaphase cell analysis of hematological malignancies using a sub-set of the human karyotype for chromosome painting. A combination of chromosome probes labeled with three haptens enabled the construction of a "painting probe" which detects seven different chromosomes. The probe was used to screen three chronic myeloid leukemia (CML) derived cell lines and ten CML patient bone marrow samples for aberrations, additional to the Ph rearrangement, that are associated with the onset of blast crisis of CML. This approach was shown to identify karyotype changes commonly seen by conventional karyotyping, and in addition revealed chromosome changes unresolved or undetected by conventional cytogenetic analysis. The seven-color painting probe provides a useful, fast, and reliable complementary tool for chromosome analysis, especially in cases with poor chromosome morphology. This is a simple approach, since the probes can be displayed in a standard red/green/blue format accessible to standard fluorescence microscopes and image-processing software. The proposed approach using panels of locus-specific probes as well as chromosome paints will be useful in all diagnostic routine environments where analysis is directed towards screening for genetic rearrangements and/or specific patterns of chromosome involvement with diagnostic/prognostic value.

Synthesis and characterization of the fluorescent probes for the labeling of Microthrix parvicella.

PubMed

Li, Songya; Fei, Xuening; Jiao, Xiumei; Lin, Dayong; Zhang, Baolian; Cao, Lingyun

2016-03-01

Although the fluorescent in situ hybridization (FISH) has been widely used to identify the Microthrix parvicella (M. parvicella), there are a few disadvantages and difficulties, such as complicated process, time consuming, etc. In this work, a series of fluorescent probes, which were modified by long-chain alkane with hydrophobic property and based on the property of M. parvicella utilizing long-chain fatty acids (LCFA), for the labeling of M. parvicella in bulking sludge were designed, synthesized, and characterized. The probes were characterized by ultraviolet-visible (UV-Vis) absorption spectra, fluorescence spectra, (1)H NMR spectra, and mass spectra, and the photostability and hydrophobic property of probes were investigated. All the results showed that the probes were quite stable and suitable for the fluorescent labeling. The probes had a large stoke shift of 98-137 nm, which was benefit for the fluorescent labeling. In the fluorescent labeling of M. parvicella by the synthesized probes, the probes had excellent labeling effects. By comparison of the images and the Image Pro Plus 6.0 analysis, the optimal concentration of the probes in the activated sludge sample for labeling was 0.010 mmol/L and the probe 3d had the best labeling. In addition, the effect of the duration time of probes was also investigated, and the results showed that the fluorescent intensity of probes hardly changed in a long period of time and it was suitable for labeling.

A functional gene array for detection of bacterial virulence elements

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

Jaing, C

2007-11-01

We report our development of the first of a series of microarrays designed to detect pathogens with known mechanisms of virulence and antibiotic resistance. By targeting virulence gene families as well as genes unique to specific biothreat agents, these arrays will provide important data about the pathogenic potential and drug resistance profiles of unknown organisms in environmental samples. To validate our approach, we developed a first generation array targeting genes from Escherichia coli strains K12 and CFT073, Enterococcus faecalis and Staphylococcus aureus. We determined optimal probe design parameters for microorganism detection and discrimination, measured the required target concentration, and assessedmore » tolerance for mismatches between probe and target sequences. Mismatch tolerance is a priority for this application, due to DNA sequence variability among members of gene families. Arrays were created using the NimbleGen Maskless Array Synthesizer at Lawrence Livermore National Laboratory. Purified genomic DNA from combinations of one or more of the four target organisms, pure cultures of four related organisms, and environmental aerosol samples with spiked-in genomic DNA were hybridized to the arrays. Based on the success of this prototype, we plan to design further arrays in this series, with the goal of detecting all known virulence and antibiotic resistance gene families in a greatly expanded set of organisms.« less

Distributed shared memory for roaming large volumes.

PubMed

Castanié, Laurent; Mion, Christophe; Cavin, Xavier; Lévy, Bruno

2006-01-01

We present a cluster-based volume rendering system for roaming very large volumes. This system allows to move a gigabyte-sized probe inside a total volume of several tens or hundreds of gigabytes in real-time. While the size of the probe is limited by the total amount of texture memory on the cluster, the size of the total data set has no theoretical limit. The cluster is used as a distributed graphics processing unit that both aggregates graphics power and graphics memory. A hardware-accelerated volume renderer runs in parallel on the cluster nodes and the final image compositing is implemented using a pipelined sort-last rendering algorithm. Meanwhile, volume bricking and volume paging allow efficient data caching. On each rendering node, a distributed hierarchical cache system implements a global software-based distributed shared memory on the cluster. In case of a cache miss, this system first checks page residency on the other cluster nodes instead of directly accessing local disks. Using two Gigabit Ethernet network interfaces per node, we accelerate data fetching by a factor of 4 compared to directly accessing local disks. The system also implements asynchronous disk access and texture loading, which makes it possible to overlap data loading, volume slicing and rendering for optimal volume roaming.

Three-dimensional wide-field pump-probe structured illumination microscopy

PubMed Central

Kim, Yang-Hyo; So, Peter T.C.

2017-01-01

We propose a new structured illumination scheme for achieving depth resolved wide-field pump-probe microscopy with sub-diffraction limit resolution. By acquiring coherent pump-probe images using a set of 3D structured light illumination patterns, a 3D super-resolution pump-probe image can be reconstructed. We derive the theoretical framework to describe the coherent image formation and reconstruction scheme for this structured illumination pump-probe imaging system and carry out numerical simulations to investigate its imaging performance. The results demonstrate a lateral resolution improvement by a factor of three and providing 0.5 µm level axial optical sectioning. PMID:28380860

Measurement of damping and temperature: Precision bounds in Gaussian dissipative channels

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

Monras, Alex; Illuminati, Fabrizio

2011-01-15

We present a comprehensive analysis of the performance of different classes of Gaussian states in the estimation of Gaussian phase-insensitive dissipative channels. In particular, we investigate the optimal estimation of the damping constant and reservoir temperature. We show that, for two-mode squeezed vacuum probe states, the quantum-limited accuracy of both parameters can be achieved simultaneously. Moreover, we show that for both parameters two-mode squeezed vacuum states are more efficient than coherent, thermal, or single-mode squeezed states. This suggests that at high-energy regimes, two-mode squeezed vacuum states are optimal within the Gaussian setup. This optimality result indicates a stronger form ofmore » compatibility for the estimation of the two parameters. Indeed, not only the minimum variance can be achieved at fixed probe states, but also the optimal state is common to both parameters. Additionally, we explore numerically the performance of non-Gaussian states for particular parameter values to find that maximally entangled states within d-dimensional cutoff subspaces (d{<=}6) perform better than any randomly sampled states with similar energy. However, we also find that states with very similar performance and energy exist with much less entanglement than the maximally entangled ones.« less

Transcriptomic Analysis of Grape (Vitis vinifera L.) Leaves after Exposure to Ultraviolet C Irradiation

PubMed Central

Xi, Huifen; Ma, Ling; Liu, Guotian; Wang, Nian; Wang, Junfang; Wang, Lina; Dai, Zhanwu; Li, Shaohua; Wang, Lijun

2014-01-01

Background Only a small amount of solar ultraviolet C (UV-C) radiation reaches the Earth's surface. This is because of the filtering effects of the stratospheric ozone layer. Artificial UV-C irradiation is used on leaves and fruits to stimulate different biological processes in plants. Grapes are a major fruit crop and are grown in many parts of the world. Research has shown that UV-C irradiation induces the biosynthesis of phenols in grape leaves. However, few studies have analyzed the overall changes in gene expression in grape leaves exposed to UV-C. Methodology/Principal Findings In the present study, transcriptional responses were investigated in grape (Vitis vinifera L.) leaves before and after exposure to UV-C irradiation (6 W·m−2 for 10 min) using an Affymetrix Vitis vinifera (Grape) Genome Array (15,700 transcripts). A total of 5274 differentially expressed probe sets were defined, including 3564 (67.58%) probe sets that appeared at both 6 and 12 h after exposure to UV-C irradiation but not before exposure. A total of 468 (8.87%) probe sets and 1242 (23.55%) probe sets were specifically expressed at these times. The probe sets were associated with a large number of important traits and biological pathways, including cell rescue (i.e., antioxidant enzymes), protein fate (i.e., HSPs), primary and secondary metabolism, and transcription factors. Interestingly, some of the genes involved in secondary metabolism, such as stilbene synthase, responded intensely to irradiation. Some of the MYB and WRKY family transcription factors, such as VvMYBPA1, VvMYB14, VvMYB4, WRKY57-like, and WRKY 65, were also strongly up-regulated (about 100 to 200 fold). Conclusions UV-C irridiation has an important role in some biology processes, especially cell rescue, protein fate, secondary metabolism, and regulation of transcription.These results opened up ways of exploring the molecular mechanisms underlying the effects of UV-C irradiation on grape leaves and have great implications for further studies. PMID:25464056

Transcriptomic analysis of grape (Vitis vinifera L.) leaves after exposure to ultraviolet C irradiation.

PubMed

Xi, Huifen; Ma, Ling; Liu, Guotian; Wang, Nian; Wang, Junfang; Wang, Lina; Dai, Zhanwu; Li, Shaohua; Wang, Lijun

2014-01-01

Only a small amount of solar ultraviolet C (UV-C) radiation reaches the Earth's surface. This is because of the filtering effects of the stratospheric ozone layer. Artificial UV-C irradiation is used on leaves and fruits to stimulate different biological processes in plants. Grapes are a major fruit crop and are grown in many parts of the world. Research has shown that UV-C irradiation induces the biosynthesis of phenols in grape leaves. However, few studies have analyzed the overall changes in gene expression in grape leaves exposed to UV-C. In the present study, transcriptional responses were investigated in grape (Vitis vinifera L.) leaves before and after exposure to UV-C irradiation (6 W·m-2 for 10 min) using an Affymetrix Vitis vinifera (Grape) Genome Array (15,700 transcripts). A total of 5274 differentially expressed probe sets were defined, including 3564 (67.58%) probe sets that appeared at both 6 and 12 h after exposure to UV-C irradiation but not before exposure. A total of 468 (8.87%) probe sets and 1242 (23.55%) probe sets were specifically expressed at these times. The probe sets were associated with a large number of important traits and biological pathways, including cell rescue (i.e., antioxidant enzymes), protein fate (i.e., HSPs), primary and secondary metabolism, and transcription factors. Interestingly, some of the genes involved in secondary metabolism, such as stilbene synthase, responded intensely to irradiation. Some of the MYB and WRKY family transcription factors, such as VvMYBPA1, VvMYB14, VvMYB4, WRKY57-like, and WRKY 65, were also strongly up-regulated (about 100 to 200 fold). UV-C irridiation has an important role in some biology processes, especially cell rescue, protein fate, secondary metabolism, and regulation of transcription.These results opened up ways of exploring the molecular mechanisms underlying the effects of UV-C irradiation on grape leaves and have great implications for further studies.

Time-Resolved Data Acquisition for In Situ Subsurface Planetary Geochemistry

NASA Technical Reports Server (NTRS)

Bodnarik, Julia Gates; Burger, Dan M.; Burger, Arnold; Evans, Larry G.; Parsons, Ann M.; Starr, Richard D.; Stassun, Keivan G.

2012-01-01

The current gamma-ray/neutron instrumentation development effort at NASA Goddard Space Flight Center aims to extend the use of active pulsed neutron interrogation techniques to probe the subsurface geochemistry of planetary bodies in situ. All previous NASA planetary science missions, that used neutron and/or gamma-ray spectroscopy instruments, have relied on a constant neutron source produced from galactic cosmic rays. One of the distinguishing features of this effort is the inclusion of a high intensity 14.1 MeV pulsed neutron generator synchronized with a custom data acquisition system to time each event relative to the pulse. With usually only one opportunity to collect data, it is difficult to set a priori time-gating windows to obtain the best possible results. Acquiring time-tagged, event-by-event data from nuclear induced reactions provides raw data sets containing channel/energy, and event time for each gamma ray or neutron detected. The resulting data set can be plotted as a function of time or energy using optimized analysis windows after the data are acquired. Time windows can now be chosen to produce energy spectra that yield the most statistically significant and accurate elemental composition results that can be derived from the complete data set. The advantages of post-processing gamma-ray time-tagged event-by-event data in experimental tests using our prototype instrument will be demonstrated.

Time-resolved Neutron-gamma-ray Data Acquisition for in Situ Subsurface Planetary Geochemistry

NASA Technical Reports Server (NTRS)

Bodnarik, Julie G.; Burger, Dan Michael; Burger, A.; Evans, L. G.; Parsons, A. M.; Schweitzer, J. S.; Starr R. D.; Stassun, K. G.

2013-01-01

The current gamma-ray/neutron instrumentation development effort at NASA Goddard Space Flight Center aims to extend the use of active pulsed neutron interrogation techniques to probe the subsurface elemental composition of planetary bodies in situ. Previous NASA planetary science missions, that used neutron and/or gamma-ray spectroscopy instruments, have relied on neutrons produced from galactic cosmic rays. One of the distinguishing features of this effort is the inclusion of a high intensity 14.1 MeV pulsed neutron generator synchronized with a custom data acquisition system to time each event relative to the pulse. With usually only one opportunity to collect data, it is difficult to set a priori time-gating windows to obtain the best possible results. Acquiring time-tagged, event-by-event data from nuclear induced reactions provides raw data sets containing channel/energy, and event time for each gamma ray or neutron detected. The resulting data set can be plotted as a function of time or energy using optimized analysis windows after the data are acquired. Time windows can now be chosen to produce energy spectra that yield the most statistically significant and accurate elemental composition results that can be derived from the complete data set. The advantages of post-processing gamma-ray time-tagged event-by-event data in experimental tests using our prototype instrument will be demonstrated.

Dendritic polymer imaging systems for the evaluation of conjugate uptake and cleavage

NASA Astrophysics Data System (ADS)

Krüger, Harald R.; Nagel, Gregor; Wedepohl, Stefanie; Calderón, Marcelo

2015-02-01

Fluorescent turn-on probes combined with polymers have a broad range of applications, e.g. for intracellular sensing of ions, small molecules, or DNA. In the field of polymer therapeutics, these probes can be applied to extend the in vitro characterization of novel conjugates beyond cytotoxicity and cellular uptake studies. This is particularly true in cases in which polymer conjugates contain drugs attached by cleavable linkers. Better information on the intracellular linker cleavage and drug release would allow a faster evaluation and optimization of novel polymer therapeutic concepts. We therefore developed a fluorescent turn-on probe that enables direct monitoring of pH-mediated cleavage processes over time. This is achieved by exploiting the fluorescence resonance energy transfer (FRET) between two dyes that have been coupled to a dendritic polymer. We demonstrate the use of this probe to evaluate polymer uptake and intracellular release of cargo in a cell based microplate assay that is suitable for high throughput screening.Fluorescent turn-on probes combined with polymers have a broad range of applications, e.g. for intracellular sensing of ions, small molecules, or DNA. In the field of polymer therapeutics, these probes can be applied to extend the in vitro characterization of novel conjugates beyond cytotoxicity and cellular uptake studies. This is particularly true in cases in which polymer conjugates contain drugs attached by cleavable linkers. Better information on the intracellular linker cleavage and drug release would allow a faster evaluation and optimization of novel polymer therapeutic concepts. We therefore developed a fluorescent turn-on probe that enables direct monitoring of pH-mediated cleavage processes over time. This is achieved by exploiting the fluorescence resonance energy transfer (FRET) between two dyes that have been coupled to a dendritic polymer. We demonstrate the use of this probe to evaluate polymer uptake and intracellular release of cargo in a cell based microplate assay that is suitable for high throughput screening. Electronic supplementary information (ESI) available: Including detailed synthetic procedures of the dye and conjugate synthesis, as well as cellular uptake and inhibitor studies. See DOI: 10.1039/c4nr04467c

Enabling low-noise null-point scanning thermal microscopy by the optimization of scanning thermal microscope probe through a rigorous theory of quantitative measurement.

PubMed

Hwang, Gwangseok; Chung, Jaehun; Kwon, Ohmyoung

2014-11-01

The application of conventional scanning thermal microscopy (SThM) is severely limited by three major problems: (i) distortion of the measured signal due to heat transfer through the air, (ii) the unknown and variable value of the tip-sample thermal contact resistance, and (iii) perturbation of the sample temperature due to the heat flux through the tip-sample thermal contact. Recently, we proposed null-point scanning thermal microscopy (NP SThM) as a way of overcoming these problems in principle by tracking the thermal equilibrium between the end of the SThM tip and the sample surface. However, in order to obtain high spatial resolution, which is the primary motivation for SThM, NP SThM requires an extremely sensitive SThM probe that can trace the vanishingly small heat flux through the tip-sample nano-thermal contact. Herein, we derive a relation between the spatial resolution and the design parameters of a SThM probe, optimize the thermal and electrical design, and develop a batch-fabrication process. We also quantitatively demonstrate significantly improved sensitivity, lower measurement noise, and higher spatial resolution of the fabricated SThM probes. By utilizing the exceptional performance of these fabricated probes, we show that NP SThM can be used to obtain a quantitative temperature profile with nanoscale resolution independent of the changing tip-sample thermal contact resistance and without perturbation of the sample temperature or distortion due to the heat transfer through the air.

Tuning the field distribution and fabrication of an Al@ZnO core-shell nanostructure for a SPR-based fiber optic phenyl hydrazine sensor.

PubMed

Tabassum, Rana; Kaur, Parvinder; Gupta, Banshi D

2016-05-27

We report the fabrication and characterization of a surface plasmon resonance (SPR)-based fiber optic sensor that uses coatings of silver and aluminum (Al)-zinc oxide (ZnO) core-shell nanostructure (Al@ZnO) for the detection of phenyl hydrazine (Ph-Hyd). To optimize the volume fraction (f) of Al in ZnO and the thickness of the core-shell nanostructure layer (d), the electric field intensity along the normal to the multilayer system is simulated using the two-dimensional multilayer matrix method. The Al@ZnO core-shell nanostructure is prepared using the laser ablation technique. Various probes are fabricated with different values of f and an optimized thickness of core-shell nanostructure for the characterization of the Ph-Hyd sensor. The performance of the Ph-Hyd sensor is evaluated in terms of sensitivity. It is found that the Ag/Al@ZnO nanostructure core-shell-coated SPR probe with f = 0.25 and d = 0.040 μm possesses the maximum sensitivity towards Ph-Hyd. These results are in agreement with the simulated ones obtained using electric field intensity. In addition, the performance of the proposed probe is compared with that of probes coated with (i) Al@ZnO nanocomposite, (ii) Al nanoparticles and (iii) ZnO nanoparticles. It is found that the probe coated with an Al@ZnO core-shell nanostructure shows the largest resonance wavelength shift. The detailed mechanism of the sensing (involving chemical reactions) is presented. The sensor also manifests optimum performance at pH 7.

Remote in-situ laser-induced breakdown spectroscopy using optical fibers

NASA Astrophysics Data System (ADS)

Marquardt, Brian James

The following dissertation describes the development of methods for performing remote Laser-Induced Breakdown Spectroscopy (LIBS) using optical fibers. Studies were performed to determine the optimal excitation and collection parameters for remote LIBS measurements of glasses, soils and paint. A number of fiber-optic LIBS probes were developed and used to characterize various samples by plasma emission spectroscopy. A novel method for launching high-power laser pulses into optical fibers without causing catastrophic failure is introduced. A systematic study of a number of commercially available optical fibers was performed to determine which optical fibers were best suited for delivering high-power laser pulses. The general design of an all fiber-optic LIBS probe is described and applied to the determination of Pb in soil. A fiber-optic probe was developed for the microanalysis of solid samples remotely by LIBS, Raman spectroscopy and Raman imaging. The design of the probe allows for real-time sample imaging in-situ using coherent imaging fibers. This allows for precise atomic emission and Raman measurements to be performed remotely on samples in hostile or inaccessible environments. A novel technique was developed for collecting spectral plasma images using an acousto-optic tunable filter (AOTF). The spatial and temporal characteristics of the plasma were studied as a function of delay time. From the plasma images the distribution of Pb emission could be determined and fiber-optic designs could be optimized for signal collection. The performance of a two fiber LIBS probe is demonstrated for the determination of the amount of lead in samples of dry paint. It is shown that dry paint samples can be analyzed for their Pb content in-situ using a fiber-optic LIBS probe with detection limits well below the levels currently regulated by the Consumer Products Safety Commission. It is also shown that these measurements can be performed on both latex and enamel paints, and that Pb containing paint can be detected even under layers of non-lead containing paint. Experiments were performed to determine the optimal measurement parameters for performing LIBS studies of Department of Energy "waste" glasses. Calibration data for a Al and Ti metals contained in the waste glass is presented. The effects of laser power on plasma temperature, emission intensity and mass of sample ablated are introduced.

An integrated chemical biology approach reveals the mechanism of action of HIV replication inhibitors.

PubMed

Pagano, Nicholas; Teriete, Peter; Mattmann, Margrith E; Yang, Li; Snyder, Beth A; Cai, Zhaohui; Heil, Marintha L; Cosford, Nicholas D P

2017-12-01

Continuous flow (microfluidic) chemistry was employed to prepare a small focused library of dihydropyrimidinone (DHPM) derivatives. Compounds in this class have been reported to exhibit activity against the human immunodeficiency virus (HIV), but their molecular target had not been identified. We tested the initial set of DHPMs in phenotypic assays providing a hit (1i) that inhibited the replication of the human immunodeficiency virus HIV in cells. Flow chemistry-driven optimization of 1i led to the identification of HIV replication inhibitors such as 1l with cellular potency comparable with the clinical drug nevirapine (NVP). Mechanism of action (MOA) studies using cellular and biochemical assays coupled with 3D fingerprinting and in silico modeling demonstrated that these drug-like probe compounds exert their effects by inhibiting the viral reverse transcriptase polymerase (RT). This led to the design and synthesis of the novel DHPM 1at that inhibits the replication of drug resistant strains of HIV. Our work demonstrates that combining flow chemistry-driven analogue refinement with phenotypic assays, in silico modeling and MOA studies is a highly effective strategy for hit-to-lead optimization applicable to the discovery of future therapeutic agents. Copyright © 2017. Published by Elsevier Ltd.

Standard Practices for Usage of Inductive Magnetic Field Probes with Application to Electric Propulsion Testing

NASA Technical Reports Server (NTRS)

Polzin, Kurt A.; Hill, Carrie S.; Turchi, Peter J.; Burton, Rodney L.; Messer, Sarah; Lovberg, Ralph H.; Hallock, Ashley K.

2013-01-01

Inductive magnetic field probes (also known as B-dot probes and sometimes as B-probes or magnetic probes) are often employed to perform field measurements in electric propulsion applications where there are time-varying fields. Magnetic field probes provide the means to measure these magnetic fields and can even be used to measure the plasma current density indirectly through the application of Ampere's law. Measurements of this type can yield either global information related to a thruster and its performance or detailed, local data related to the specific physical processes occurring in the plasma. Results of the development of a standard for B-dot probe measurements are presented, condensing the available literature on the subject into an accessible set of rules, guidelines, and techniques to standardize the performance and presentation of future measurements.

Observation of NMR noise from solid samples.

PubMed

Schlagnitweit, Judith; Dumez, Jean-Nicolas; Nausner, Martin; Jerschow, Alexej; Elena-Herrmann, Bénédicte; Müller, Norbert

2010-11-01

We demonstrate that proton NMR noise signals, i.e. NMR spectra without excitation by radio frequency, can be obtained from solid samples. Experimental results are shown for static and magic-angle spinning conditions. In addition, a tuning procedure based on the probes' NMR noise characteristics and similar to the one described previously for liquids probes can also be used to optimize signal-to-noise ratios in ¹H-MAS experiments. Copyright © 2010 Elsevier Inc. All rights reserved.

Molecular Profiling of EPI-001: An Inhibitor of Androgen Receptor Signaling With a Disputed Mechanism of Action

DTIC Science & Technology

2016-09-01

analogues and to determine their protein - binding partners in prostate cancer cell lines. The anticipated outcome is the annotation of the activity...associated protein targets of EPI-001 that will be valuable in future drug development efforts. The progress achieved during this 1-year award include...cells to afford probe- protein adducts, (3) optimizing protocols for the isolation of probe- protein adducts over monomeric avidin resin and demonstrating

Developing Fast Fluorescent Protein Voltage Sensors by Optimizing FRET Interactions

PubMed Central

Sung, Uhna; Sepehri-Rad, Masoud; Piao, Hong Hua; Jin, Lei; Hughes, Thomas; Cohen, Lawrence B.; Baker, Bradley J.

2015-01-01

FRET (Förster Resonance Energy Transfer)-based protein voltage sensors can be useful for monitoring neuronal activity in vivo because the ratio of signals between the donor and acceptor pair reduces common sources of noise such as heart beat artifacts. We improved the performance of FRET based genetically encoded Fluorescent Protein (FP) voltage sensors by optimizing the location of donor and acceptor FPs flanking the voltage sensitive domain of the Ciona intestinalis voltage sensitive phosphatase. First, we created 39 different “Nabi1” constructs by positioning the donor FP, UKG, at 8 different locations downstream of the voltage-sensing domain and the acceptor FP, mKO, at 6 positions upstream. Several of these combinations resulted in large voltage dependent signals and relatively fast kinetics. Nabi1 probes responded with signal size up to 11% ΔF/F for a 100 mV depolarization and fast response time constants both for signal activation (~2 ms) and signal decay (~3 ms). We improved expression in neuronal cells by replacing the mKO and UKG FRET pair with Clover (donor FP) and mRuby2 (acceptor FP) to create Nabi2 probes. Nabi2 probes also had large signals and relatively fast time constants in HEK293 cells. In primary neuronal culture, a Nabi2 probe was able to differentiate individual action potentials at 45 Hz. PMID:26587834

Predicting the photoinduced electron transfer thermodynamics in polyfluorinated 1,3,5-triarylpyrazolines based on multiple linear free energy relationships†

PubMed Central

Verma, Manjusha; Chaudhry, Aneese F.; Fahrni, Christoph J.

2010-01-01

The photophysical properties of 1,3,5-triarylpyrazolines are strongly influenced by the nature and position of substituents attached to the aryl-rings, rendering this fluorophore platform well suited for the design of fluorescent probes utilizing a photoinduced electron transfer (PET) switching mechanism. To explore the tunability of two key parameters that govern the PET thermodynamics, the excited state energy ΔE00 and acceptor potential E(A/A−), a library of polyfluoro-substituted 1,3-diaryl-5-phenyl-pyrazolines was synthesized and characterized. The observed trends for the PET parameters were effectively captured through multiple Hammett linear free energy relationships (LFER) using a set of independent substituent constants for each of the two aryl rings. Given the lack of experimental Hammett constants for polyfluoro substituted aromatics, theoretically derived constants based on the electrostatic potential at the nucleus (EPN) of carbon atoms were employed as quantum chemical descriptors. The performance of the LFER was evaluated with a set of compounds that were not included in the training set, yielding a mean unsigned error of 0.05 eV for the prediction of the combined PET parameters. The outlined LFER approach should be well suited to design and optimize the performance of cation-responsive 1,3,5-triarylpyrazolines. PMID:19343239

Visual attention is required for multiple object tracking.

PubMed

Tran, Annie; Hoffman, James E

2016-12-01

In the multiple object tracking task, participants attempt to keep track of a moving set of target objects embedded in an identical set of moving distractors. Depending on several display parameters, observers are usually only able to accurately track 3 to 4 objects. Various proposals attribute this limit to a fixed number of discrete indexes (Pylyshyn, 1989), limits in visual attention (Cavanagh & Alvarez, 2005), or "architectural limits" in visual cortical areas (Franconeri, 2013). The present set of experiments examined the specific role of visual attention in tracking using a dual-task methodology in which participants tracked objects while identifying letter probes appearing on the tracked objects and distractors. As predicted by the visual attention model, probe identification was faster and/or more accurate when probes appeared on tracked objects. This was the case even when probes were more than twice as likely to appear on distractors suggesting that some minimum amount of attention is required to maintain accurate tracking performance. When the need to protect tracking accuracy was relaxed, participants were able to allocate more attention to distractors when probes were likely to appear there but only at the expense of large reductions in tracking accuracy. A final experiment showed that people attend to tracked objects even when letters appearing on them are task-irrelevant, suggesting that allocation of attention to tracked objects is an obligatory process. These results support the claim that visual attention is required for tracking objects. (PsycINFO Database Record (c) 2016 APA, all rights reserved).

Measurement Sensitivity Of Liquid Droplet Parameters Using Optical Fibers

NASA Astrophysics Data System (ADS)

Das, Alok K.; Mandal, Anup K.

1990-02-01

A new clad probing technique is used to measure the size, number, refractive index and viscosity of liquid droplets sprayed from a pressure nozzle on an uncoated core-clad fiber. The probe monitors the clad mode power loss within the leaky ray zone represented as a three region fiber. Liquid droplets measured are Glycerine, commercial grade Turpentine, Linseed oil and some oil mixtures. The measurement sensitivity depends on probing conditions and clad diameter which is observed experimentally and verified analytically. A maximum sensitivity is obtained for the tapered probe-fiber diameter made equal to the clad thickness. A slowly tapered probe-fiber and a small end angle as well as separation of the sensor-fiber and the probe-fiber further improve the sensitivity. Under the best probing condition for 90-percent Glycerine droplets of - 50 micron diameter and a 50/125 micron sensor fiber with clad refractive index of 1.465 and 0.2 NA, the measured sensitivity per drop is 0.015 and 0.006 dB, respectively, for (10-20) and (100-200) droplets. Sensitivities for different systems are shown. The sensitivity is optimized by choosing proper fiber for known liquids.

Focusing in Arthurs-Kelly-type joint measurements with correlated probes.

PubMed

Bullock, Thomas J; Busch, Paul

2014-09-19

Joint approximate measurement schemes of position and momentum provide us with a means of inferring pieces of complementary information if we allow for the irreducible noise required by quantum theory. One such scheme is given by the Arthurs-Kelly model, where information about a system is extracted via indirect probe measurements, assuming separable uncorrelated probes. Here, following Di Lorenzo [Phys. Rev. Lett. 110, 120403 (2013)], we extend this model to both entangled and classically correlated probes, achieving full generality. We show that correlated probes can produce more precise joint measurement outcomes than the same probes can achieve if applied alone to realize a position or momentum measurement. This phenomenon of focusing may be useful where one tries to optimize measurements with limited physical resources. Contrary to Di Lorenzo's claim, we find that there are no violations of Heisenberg's error-disturbance relation in these generalized Arthurs-Kelly models. This is simply due to the fact that, as we show, the measured observable of the system under consideration is covariant under phase space translations and as such is known to obey a tight joint measurement error relation.

A monolithic microsphere-fiber probe for spatially resolved Raman spectroscopy: Application to head and neck squamous cell carcinomas

NASA Astrophysics Data System (ADS)

Holler, S.; Haig, B.; Donovan, M. J.; Sobrero, M.; Miles, B. A.

2018-03-01

The ability to identify precise cancer margins in vivo during a surgical excision is critical to the well-being of the patient. Decreased operative time has been linked to shorter patient recovery time, and there are risks associated with removing either too much or too little tissue from the surgical site. The more rapidly and accurately a surgeon can identify and excise diseased tissue, the better the prognosis for the patient. To this end, we investigate both malignant and healthy oral cavity tissue using the Raman spectroscopy, with a monolithic microsphere-fiber probe. Our results indicate that this probe has decreased the size of the analyzed area by more than an order of magnitude, as compared to a conventional fiber reflection probe. Scanning the probe across the tissues reveals variations in the Raman spectra that enable us to differentiate between malignant and healthy tissues. Consequently, we anticipate that the high spatial resolution afforded by the probe will permit us to identify tumor margins in detail, thereby optimizing tissue removal and improving patient outcomes.

Mapping Rotational Wavepacket Dynamics with Chirped Probe Pulses

NASA Astrophysics Data System (ADS)

Romanov, Dmitri; Odhner, Johanan; Levis, Robert

2014-05-01

We develop an analytical model description of the strong-field pump-probe polarization spectroscopy of rotational transients in molecular gases in a situation when the probe pulse is considerably chirped: the frequency modulation over the pulse duration is comparable with the carrier frequency. In this scenario, a femtosecond pump laser pulse prepares a rotational wavepacket in a gas-phase sample at room temperature. The rotational revivals of the wavepacket are then mapped onto a chirped broadband probe pulse derived from a laser filament. The slow-varying envelope approximation being inapplicable, an alternative approach is proposed which is capable of incorporating the substantial chirp and the related temporal dispersion of refractive indices. Analytical expressions are obtained for the probe signal modulation over the interaction region and for the resulting heterodyned transient birefringence spectra. Dependencies of the outputs on the probe pulse parameters reveal the trade-offs and the ways to optimize the temporal-spectral imaging. The results are in good agreement with the experiments on snapshot imaging of rotational revival patterns in nitrogen gas. We gratefully acknowledge financial support through AFOSR MURI Grant No. FA9550-10-1-0561.

A Hand-Held, Intra-Operative Positron Imaging Probe for Surgical Applications

NASA Astrophysics Data System (ADS)

Sabet, Hamid; Stack, Brendan C.; Nagarkar, Vivek V.

2015-10-01

We have developed a prototype intra-operative β+ imaging probe to help tumor removal and malignant tissue resection. The probe can be used during surgery to provide clear delineation of malignant tissues. Our probe consists of a hybrid scintillator coupled to a silicon photomultiplier (SiPM) array with associated front-end electronics encapsulated in an ergonomic aluminum housing. Pulse shape discrimination electronics has been implemented and integrated into the downstream data acquisition system. The field of view of the probe is 10 ×10 mm2 realized by a 0.4 mm thick CsI:Tl scintillator coupled to a 1 mm thick LYSO. While CsI:Tl layer acts as β+ sensitive detector, LYSO detects gamma radiation where the gamma response can be subtracted from the total signal to improve SNR and contrast. The thickness of the LYSO scintillator is optimized such that it acts as light diffuser to spread the scintillation light generated in CsI:Tl over multiple SiPM pixels for accurate estimation of the β+ interaction location. The probe shows FWHM spatial resolution in the presence of large background radiation. The probe was used to study rabbits with tongue tumors. The experimental results show that the probe can successfully locate the tongue tumors in its active imaging area.

A Fiber Optic Probe for the Detection of Cataracts

NASA Technical Reports Server (NTRS)

Ansari, Rafat R.; Dhadwal, Harbans S.

1993-01-01

A compact fiber optic probe developed for on-orbit science experiments was used to detect the onset of cataracts, a capability that could eliminate physicians' guesswork and result in new drugs to 'dissolve' or slow down the cataract formation before surgery is necessary. The probe is based upon dynamic light scattering (DLS) principles. It has no moving parts, no apertures, and requires no optical alignment. It is flexible and easy to use. Results are presented for excised but intact human eye lenses. In a clinical setting, the device can be easily incorporated into a slit-lamp apparatus (ophthalmoscope) for complete eye diagnostics. In this set-up, the integrated fiber optic probe, the size of a pencil, delivers a low power cone of laser light into the eye of a patient and guides the light which is backscattered by the protein molecules of the lens through a receiving optical fiber to a photo detector. The non-invasive DLS measurements provide rapid determination of protein crystalline size and its size distribution in the eye lens.

Density Waves in Saturn's Rings from Cassini Radio Occultations

NASA Astrophysics Data System (ADS)

French, R. G.; Rappaport, N. J.; Marouf, E. A.; McGhee, C. A.

2005-12-01

The Cassini Radio Science Team conducted a set of optimized diametric occultations by Saturn and its rings from May to September 2005, providing 11 separate probes of Saturn's ionosphere and atmosphere, and 12 optical depth profiles of the complete ring system. Each event was observed by the stations of the Deep Space Net (DSN) at three radio frequencies (S, X, Ka bands, with corresponding wavelengths of ? = 13, 3.6, and 0.9 cm). Very accurate pointing by the spacecraft and ground antennas resulted in stable baseline signal levels, and the relatively large ring opening angle (B=19-25°) permitted us to probe even quite dense ring regions with excellent SNR. The RSS occultation technique enables us to recover very fine detailed radial structure by correcting for diffraction effects. Multiple occultation chords, covering a variety of ring longitudes and ring opening angles, reveal the structure of the rings in remarkable detail, including density and bending waves, satellite wakes, and subtle variations at the 100-m radius scale. Janus and Epimetheus are responsible for a particularly rich set of density waves, and their coorbital interactions result in a complex interplay of time-variable ring structure over the 8-year libration period of the two satellites. We compare the first-order 2:1, 4:3, 5:4, and 6:5 coorbital density waves from multiple occultation chords to linear density wave models based on a dynamical model of the orbital exchange between the moons. From the observed dispersion relation of the wave crests, we infer the surface mass density and eccentricity gradient of particle streamlines, and match the detailed shapes of the wave crests using a non-linear analysis. Second-order coorbital features are also evident, and there are even hints of third-order density waves in the high SNR radio occultation data.

Maximizing the probability of satisfying the clinical goals in radiation therapy treatment planning under setup uncertainty

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

Fredriksson, Albin, E-mail: albin.fredriksson@raysearchlabs.com; Hårdemark, Björn; Forsgren, Anders

2015-07-15

Purpose: This paper introduces a method that maximizes the probability of satisfying the clinical goals in intensity-modulated radiation therapy treatments subject to setup uncertainty. Methods: The authors perform robust optimization in which the clinical goals are constrained to be satisfied whenever the setup error falls within an uncertainty set. The shape of the uncertainty set is included as a variable in the optimization. The goal of the optimization is to modify the shape of the uncertainty set in order to maximize the probability that the setup error will fall within the modified set. Because the constraints enforce the clinical goalsmore » to be satisfied under all setup errors within the uncertainty set, this is equivalent to maximizing the probability of satisfying the clinical goals. This type of robust optimization is studied with respect to photon and proton therapy applied to a prostate case and compared to robust optimization using an a priori defined uncertainty set. Results: Slight reductions of the uncertainty sets resulted in plans that satisfied a larger number of clinical goals than optimization with respect to a priori defined uncertainty sets, both within the reduced uncertainty sets and within the a priori, nonreduced, uncertainty sets. For the prostate case, the plans taking reduced uncertainty sets into account satisfied 1.4 (photons) and 1.5 (protons) times as many clinical goals over the scenarios as the method taking a priori uncertainty sets into account. Conclusions: Reducing the uncertainty sets enabled the optimization to find better solutions with respect to the errors within the reduced as well as the nonreduced uncertainty sets and thereby achieve higher probability of satisfying the clinical goals. This shows that asking for a little less in the optimization sometimes leads to better overall plan quality.« less

Comprehensive viral enrichment enables sensitive respiratory virus genomic identification and analysis by next generation sequencing.

PubMed

O'Flaherty, Brigid M; Li, Yan; Tao, Ying; Paden, Clinton R; Queen, Krista; Zhang, Jing; Dinwiddie, Darrell L; Gross, Stephen M; Schroth, Gary P; Tong, Suxiang

2018-06-01

Next generation sequencing (NGS) technologies have revolutionized the genomics field and are becoming more commonplace for identification of human infectious diseases. However, due to the low abundance of viral nucleic acids (NAs) in relation to host, viral identification using direct NGS technologies often lacks sufficient sensitivity. Here, we describe an approach based on two complementary enrichment strategies that significantly improves the sensitivity of NGS-based virus identification. To start, we developed two sets of DNA probes to enrich virus NAs associated with respiratory diseases. The first set of probes spans the genomes, allowing for identification of known viruses and full genome sequencing, while the second set targets regions conserved among viral families or genera, providing the ability to detect both known and potentially novel members of those virus groups. Efficiency of enrichment was assessed by NGS testing reference virus and clinical samples with known infection. We show significant improvement in viral identification using enriched NGS compared to unenriched NGS. Without enrichment, we observed an average of 0.3% targeted viral reads per sample. However, after enrichment, 50%-99% of the reads per sample were the targeted viral reads for both the reference isolates and clinical specimens using both probe sets. Importantly, dramatic improvements on genome coverage were also observed following virus-specific probe enrichment. The methods described here provide improved sensitivity for virus identification by NGS, allowing for a more comprehensive analysis of disease etiology. © 2018 O'Flaherty et al.; Published by Cold Spring Harbor Laboratory Press.

A highly sensitive turn-on fluorescent chemosensor for recognition of Zn2 + and Hg2 + and applications

NASA Astrophysics Data System (ADS)

Tang, Xu; Han, Juan; Wang, Yun; Bao, Xu; Ni, Liang; Wang, Lei; Li, Longhua

2017-09-01

A fluorescence probe has been designed and synthesized, and applied with a combined theoretical and experimental study. Research suggests that the probe can be used to sense Zn2 + and Hg2 + through selective turn-on fluorescence responses in the aqueous HEPES buffer (0.05M, pH = 7.4). The limit of detection (LOD) were determined as 1.46 × 10- 7 M (Zn2 +) and 2.50 × 10- 7 M (Hg2 +). Moreover, based on DFT, the geometry optimizations of probe 1, [1-Hg2 +] complex and [1-Zn2 +] complex were carried out using the Gaussian 09 program, in which the B3LYP function was used. The electronic properties of free probe 1 and the metal complexes were studied based on the Natural Bond Orbital (NBO) analyses. The probe 1 has also been successfully applied to detection of Zn2 + and Hg2 + in living cells.

Continuously Tunable Nucleic Acid Hybridization Probes

PubMed Central

Wu, Lucia R.; Wang, J. Sherry; Fang, John Z.; Reiser, Emily; Pinto, Alessandro; Pekker, Irena; Boykin, Richard; Ngouenet, Celine; Webster, Philippa J.; Beechem, Joseph; Zhang, David Yu

2015-01-01

In silico designed nucleic acid probes and primers often fail to achieve favorable specificity and sensitivity tradeoffs on the first try, and iterative empirical sequence-based optimization is needed, particularly in multiplexed assays. Here, we present a novel, on-the-fly method of tuning probe affinity and selectivity via the stoichiometry of auxiliary species, allowing independent and decoupled adjustment of hybridization yield for different probes in multiplexed assays. Using this method, we achieve near-continuous tuning of probe effective free energy (0.03 kcal·mol−1 granularity). As applications, we enforced uniform capture efficiency of 31 DNA molecules (GC content 0% – 100%), maximized signal difference for 11 pairs of single nucleotide variants, and performed tunable hybrid-capture of mRNA from total RNA. Using the Nanostring nCounter platform, we applied stoichiometric tuning to simultaneously adjust yields for a 24-plex assay, and we show multiplexed quantitation of RNA sequences and variants from formalin-fixed, paraffin-embedded samples (FFPE). PMID:26480474

In situ identification of the synthrophic protein fermentative Coprothermobacter spp. involved in the thermophilic anaerobic digestion process.

PubMed

Gagliano, Maria Cristina; Braguglia, Camilla Maria; Rossetti, Simona

2014-09-01

Thermophilic bacteria have recently attracted great attention because of their potential application in improving different biochemical processes such as anaerobic digestion of various substrates, wastewater treatment or hydrogen production. In this study we report on the design of a specific 16S rRNA-targeted oligonucleotide probe for detecting members of Coprothermobacter genus characterized by a strong protease activity to degrade proteins and peptides. The newly designed CTH485 probe and helper probes hCTH429 and hCTH439 were optimized for use in fluorescence in situ hybridization (FISH) on thermophilic anaerobic sludge samples. In situ probing revealed that thermo-adaptive mechanisms shaping the 16S rRNA gene may affect the identification of thermophilic microorganisms. The novel developed FISH probe extends the possibility to study the widespread thermophilic syntrophic interaction of Coprothermobacter spp. with hydrogenotrophic methanogenic archaea, whose establishment is a great benefit for the whole anaerobic system. © 2014 Federation of European Microbiological Societies. Published by John Wiley & Sons Ltd. All rights reserved.

A dual sensor for real-time monitoring of glucose and oxygen

PubMed Central

Zhang, Liqiang; Su, Fengyu; Buizer, Sean; Lu, Hongguang; Gao, Weimin; Tian, Yanqing; Meldrum, Deirdre

2013-01-01

A dual glucose and oxygen sensor in a polymer format was developed. The dual sensor composed of a blue emitter as the glucose probe, a red emitter as an oxygen probe, and a yellow emitter as a built-in reference probe which does not respond to either glucose or oxygen. All the three probes were chemically immobilized in a polyacrylamide-based matrix. Therefore, the dual sensor possesses three well separated emission colors and ratiometric approach is applicable for analysis of the glucose and oxygen concentration at biological conditions. The sensor was applied for real-time monitoring of glucose and oxygen consumption of bacterial cells, Escherichia coli (E. coli) and Bacillus subtilis (B. subtilis), and mammalian cells of mouse macrophage J774 and human cervical cancer HeLa cell lines. On the other hand, in order to achieve satisfactory sensing performance for glucose, compositions of the matrices among poly(2-hydroxyethyl methacrylate), polyacrylamide, and poly(6-aminohexyl methacrylamide) which is a linker polymer for grafting the glucose probe, were optimized. PMID:24090834

Nanobits, Nembranes and Micro Four-Point Probes: Customizable Tools for insitu Manipulation and Characterisation of Nanostructures

NASA Astrophysics Data System (ADS)

Boggild, Peter; Hjorth Petersen, Dirch; Sardan Sukas, Ozlem; Dam, Henrik Friis; Lei, Anders; Booth, Timothy; Molhave, Kristian; Eicchorn, Volkmar

2010-03-01

We present a range of highly adaptable microtools for direct interaction with nanoscale structures; (i) semiautomatic pick-and-place assembly of multiwalled carbon nanotubes onto cantilevers for high-aspect ratio scanning probe microscopy, using electrothermal microgrippers inside a SEM. Topology optimisation was used to calculate the optimal gripper shape defined by the boundary conditions, resulting in 10-100 times better performance. By instead pre-defining detachable tips using electron beam lithography, free-form scanning probe tips (Nanobits) can be mounted in virtually any position on a cantilever; (ii) scanning micro four point probes allow fast, non- destructive mapping of local electrical properties (sheet resistance and Hall mobility) and hysteresis effects of graphene sheets; (iii) sub 100 nm freestanding devices with wires, heaters, actuators, sensors, resonators and probes were defined in a 100 nm thin membrane with focused ion beam milling. By patterning generic membrane templates (Nembranes) the fabrication time of a TEM compatible NEMS device is effectively reduced to less around 20 minutes.

Experimental validation of an 8 element EMAT phased array probe for longitudinal wave generation

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

Le Bourdais, Florian, E-mail: florian.lebourdais@cea.fr; Marchand, Benoit, E-mail: florian.lebourdais@cea.fr

2015-03-31

Sodium cooled Fast Reactors (SFR) use liquid sodium as a coolant. Liquid sodium being opaque, optical techniques cannot be applied to reactor vessel inspection. This makes it necessary to develop alternative ways of assessing the state of the structures immersed in the medium. Ultrasonic pressure waves are well suited for inspection tasks in this environment, especially using pulsed electromagnetic acoustic transducers (EMAT) that generate the ultrasound directly in the liquid sodium. The work carried out at CEA LIST is aimed at developing phased array EMAT probes conditioned for reactor use. The present work focuses on the experimental validation of amore » newly manufactured 8 element probe which was designed for beam forming imaging in a liquid sodium environment. A parametric study is carried out to determine the optimal setup of the magnetic assembly used in this probe. First laboratory tests on an aluminium block show that the probe has the required beam steering capabilities.« less

Neurosurgical hand-held optical coherence tomography (OCT) forward-viewing probe

NASA Astrophysics Data System (ADS)

Sun, Cuiru; Lee, Kenneth K. C.; Vuong, Barry; Cusimano, Michael; Brukson, Alexander; Mariampillai, Adrian; Standish, Beau A.; Yang, Victor X. D.

2012-02-01

A prototype neurosurgical hand-held optical coherence tomography (OCT) imaging probe has been developed to provide micron resolution cross-sectional images of subsurface tissue during open surgery. This new ergonomic hand-held probe has been designed based on our group's previous work on electrostatically driven optical fibers. It has been packaged into a catheter probe in the familiar form factor of the clinically accepted Bayonet shaped neurosurgical non-imaging Doppler ultrasound probes. The optical design was optimized using ZEMAX simulation. Optical properties of the probe were tested to yield an ~20 um spot size, 5 mm working distance and a 3.5 mm field of view. The scan frequency can be increased or decreased by changing the applied voltage. Typically a scan frequency of less than 60Hz is chosen to keep the applied voltage to less than 2000V. The axial resolution of the probe was ~15 um (in air) as determined by the OCT system. A custom-triggering methodology has been developed to provide continuous stable imaging, which is crucial for clinical utility. Feasibility of this probe, in combination with a 1310 nm swept source OCT system was tested and images are presented to highlight the usefulness of such a forward viewing handheld OCT imaging probe. Knowledge gained from this research will lay the foundation for developing new OCT technologies for endovascular management of cerebral aneurysms and transsphenoidal neuroendoscopic treatment of pituitary tumors.

Arrays of probes for positional sequencing by hybridization

DOEpatents

Cantor, Charles R [Boston, MA; Prezetakiewiczr, Marek [East Boston, MA; Smith, Cassandra L [Boston, MA; Sano, Takeshi [Waltham, MA

2008-01-15

This invention is directed to methods and reagents useful for sequencing nucleic acid targets utilizing sequencing by hybridization technology comprising probes, arrays of probes and methods whereby sequence information is obtained rapidly and efficiently in discrete packages. That information can be used for the detection, identification, purification and complete or partial sequencing of a particular target nucleic acid. When coupled with a ligation step, these methods can be performed under a single set of hybridization conditions. The invention also relates to the replication of probe arrays and methods for making and replicating arrays of probes which are useful for the large scale manufacture of diagnostic aids used to screen biological samples for specific target sequences. Arrays created using PCR technology may comprise probes with 5'- and/or 3'-overhangs.

Capacitively coupled RF voltage probe having optimized flux linkage

DOEpatents

Moore, James A.; Sparks, Dennis O.

1999-02-02

An RF sensor having a novel current sensing probe and a voltage sensing probe to measure voltage and current. The current sensor is disposed in a transmission line to link all of the flux generated by the flowing current in order to obtain an accurate measurement. The voltage sensor is a flat plate which operates as a capacitive plate to sense voltage on a center conductor of the transmission line, in which the measured voltage is obtained across a resistance leg of a R-C differentiator circuit formed by the characteristic impedance of a connecting transmission line and a capacitance of the plate, which is positioned proximal to the center conductor.

Evaluation of a duplex reverse-transcription real-time PCR assay for the detection of encephalomyocarditis virus.

PubMed

Qin, Shaomin; Underwood, Darren; Driver, Luke; Kistler, Carol; Diallo, Ibrahim; Kirkland, Peter D

2018-06-01

We evaluated a fluorogenic probe-based assay for the detection of encephalomyocarditis virus (EMCV) by comparing a set of published primers and probe to a new set of primers and probe. The published reagents failed to amplify a range of Australian isolates and an Italian reference strain of EMCV. In contrast, an assay based on 2 new sets of primers and probes that were run in a duplex reverse-transcription real-time PCR (RT-rtPCR) worked well, with high amplification efficiency. The analytical sensitivity was ~100-fold higher than virus isolation in cell culture. The intra-assay variation was 0.21-4.90%. No cross-reactivity was observed with a range of other porcine viruses. One hundred and twenty-two clinical specimens were tested simultaneously by RT-rtPCR and virus isolation in cell culture; 72 specimens gave positive results by RT-rtPCR, and 63 of these were also positive by virus isolation. Of 245 archived cell culture isolates of EMCV that were tested in the RT-rtPCR, 242 samples were positive. The new duplex RT-rtPCR assay is a reliable tool for the detection of EMCV in clinical specimens and for use in epidemiologic investigations.

Cryptic Translocation Identification in Human and Mouse using Several Telomeric Multiplex FISH (TM-FISH) Strategies

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

Henegariu, O; Artan, S; Greally, J M

2003-08-19

Experimental data published in recent years showed that up to 10% of all cases with mild to severe idiopathic mental retardation may result from small rearrangements of the subtelomeric regions of human chromosomes. To detect such cryptic translocations, we developed a ''telomeric'' multiplex FISH assay, using a set of previously published and commercially available subtelomeric probes. This set of probes includes 41 cosmid/PAC/P1 clones located from less than 100kb to about 1 Mb from the end of the chromosomes. Similarly, a published mouse probe set, comprised of BACs hybridizing to the closest known marker toward the centromere and telomere ofmore » each mouse chromosome, was used to develop a mouse-specific ''telomeric'' M-FISH. Three different combinatorial labeling strategies were used to simultaneously detect all human sub-telomeric regions on one slide. The simplest approach uses only three fluors, and can be performed in laboratories lacking sophisticated imaging equipment or personnel highly trained in cytogenetics. A standard fluorescence microscope equipped with only three filters is sufficient. Fluor-dUTPs and labeled probes can be custom-made, thus dramatically reducing costs. Images can be prepared using generic imaging software (Adobe Photoshop), and analysis performed by simple visual inspection.« less

Task probability and report of feature information: what you know about what you 'see' depends on what you expect to need.

PubMed

Pilling, Michael; Gellatly, Angus

2013-07-01

We investigated the influence of dimensional set on report of object feature information using an immediate memory probe task. Participants viewed displays containing up to 36 coloured geometric shapes which were presented for several hundred milliseconds before one item was abruptly occluded by a probe. A cue presented simultaneously with the probe instructed participants to report either about the colour or shape of the probe item. A dimensional set towards the colour or shape of the presented items was induced by manipulating task probability - the relative probability with which the two feature dimensions required report. This was done across two participant groups: One group was given trials where there was a higher report probability of colour, the other a higher report probability of shape. Two experiments showed that features were reported most accurately when they were of high task probability, though in both cases the effect was largely driven by the colour dimension. Importantly the task probability effect did not interact with display set size. This is interpreted as tentative evidence that this manipulation influences feature processing in a global manner and at a stage prior to visual short term memory. Copyright © 2013 Elsevier B.V. All rights reserved.

Estimating three-demensional energy transfer in isotropic turbulence

NASA Technical Reports Server (NTRS)

Li, K. S.; Helland, K. N.; Rosenblatt, M.

1980-01-01

To obtain an estimate of the spectral transfer function that indicates the rate of decay of energy, an x-wire probe was set at a fixed position, and two single wire probes were set at a number of locations in the same plane perpendicular to the mean flow in the wind tunnel. The locations of the single wire probes are determined by pseudo-random numbers (Monte Carlo). Second order spectra and cross spectra are estimated. The assumption of isotropy relative to second order spectra is examined. Third order spectra are also estimated corresponding to the positions specified. A Monte Carlo Fourier transformation of the downstream bispectra corresponding to integration across the plane perpendicular to the flow is carried out assuming isotropy. Further integration is carried out over spherical energy shells.

Information geometry of Gaussian channels

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

Monras, Alex; CNR-INFM Coherentia, Napoli; CNISM Unita di Salerno

2010-06-15

We define a local Riemannian metric tensor in the manifold of Gaussian channels and the distance that it induces. We adopt an information-geometric approach and define a metric derived from the Bures-Fisher metric for quantum states. The resulting metric inherits several desirable properties from the Bures-Fisher metric and is operationally motivated by distinguishability considerations: It serves as an upper bound to the attainable quantum Fisher information for the channel parameters using Gaussian states, under generic constraints on the physically available resources. Our approach naturally includes the use of entangled Gaussian probe states. We prove that the metric enjoys some desirablemore » properties like stability and covariance. As a by-product, we also obtain some general results in Gaussian channel estimation that are the continuous-variable analogs of previously known results in finite dimensions. We prove that optimal probe states are always pure and bounded in the number of ancillary modes, even in the presence of constraints on the reduced state input in the channel. This has experimental and computational implications. It limits the complexity of optimal experimental setups for channel estimation and reduces the computational requirements for the evaluation of the metric: Indeed, we construct a converging algorithm for its computation. We provide explicit formulas for computing the multiparametric quantum Fisher information for dissipative channels probed with arbitrary Gaussian states and provide the optimal observables for the estimation of the channel parameters (e.g., bath couplings, squeezing, and temperature).« less

Versatile robotic probe calibration for position tracking in ultrasound imaging.

PubMed

Bø, Lars Eirik; Hofstad, Erlend Fagertun; Lindseth, Frank; Hernes, Toril A N

2015-05-07

Within the field of ultrasound-guided procedures, there are a number of methods for ultrasound probe calibration. While these methods are usually developed for a specific probe, they are in principle easily adapted to other probes. In practice, however, the adaptation often proves tedious and this is impractical in a research setting, where new probes are tested regularly. Therefore, we developed a method which can be applied to a large variety of probes without adaptation. The method used a robot arm to move a plastic sphere submerged in water through the ultrasound image plane, providing a slow and precise movement. The sphere was then segmented from the recorded ultrasound images using a MATLAB programme and the calibration matrix was computed based on this segmentation in combination with tracking information. The method was tested on three very different probes demonstrating both great versatility and high accuracy.

Versatile robotic probe calibration for position tracking in ultrasound imaging

NASA Astrophysics Data System (ADS)

Eirik Bø, Lars; Fagertun Hofstad, Erlend; Lindseth, Frank; Hernes, Toril A. N.

2015-05-01

Within the field of ultrasound-guided procedures, there are a number of methods for ultrasound probe calibration. While these methods are usually developed for a specific probe, they are in principle easily adapted to other probes. In practice, however, the adaptation often proves tedious and this is impractical in a research setting, where new probes are tested regularly. Therefore, we developed a method which can be applied to a large variety of probes without adaptation. The method used a robot arm to move a plastic sphere submerged in water through the ultrasound image plane, providing a slow and precise movement. The sphere was then segmented from the recorded ultrasound images using a MATLAB programme and the calibration matrix was computed based on this segmentation in combination with tracking information. The method was tested on three very different probes demonstrating both great versatility and high accuracy.

Development and characterization of a handheld hyperspectral Raman imaging probe system for molecular characterization of tissue on mesoscopic scales.

PubMed

St-Arnaud, Karl; Aubertin, Kelly; Strupler, Mathias; Madore, Wendy-Julie; Grosset, Andrée-Anne; Petrecca, Kevin; Trudel, Dominique; Leblond, Frédéric

2018-01-01

Raman spectroscopy is a promising cancer detection technique for surgical guidance applications. It can provide quantitative information relating to global tissue properties associated with structural, metabolic, immunological, and genetic biochemical phenomena in terms of molecular species including amino acids, lipids, proteins, and nucleic acid (DNA). To date in vivo Raman spectroscopy systems mostly included probes and biopsy needles typically limited to single-point tissue interrogation over a scale between 100 and 500 microns. The development of wider field handheld systems could improve tumor localization for a range of open surgery applications including brain, ovarian, and skin cancers. Here we present a novel Raman spectroscopy implementation using a coherent imaging bundle of fibers to create a probe capable of reconstructing molecular images over mesoscopic fields of view. Detection is performed using linear scanning with a rotation mirror and an imaging spectrometer. Different slits widths were tested at the entrance of the spectrometer to optimize spatial and spectral resolution while preserving sufficient signal-to-noise ratios to detect the principal Raman tissue features. The nonbiological samples, calcite and polytetrafluoroethylene (PTFE), were used to characterize the performance of the system. The new wide-field probe was tested on ex vivo samples of calf brain and swine tissue. Raman spectral content of both tissue types were validated with data from the literature and compared with data acquired with a single-point Raman spectroscopy probe. The single-point probe was used as the gold standard against which the new instrument was benchmarked as it has already been thoroughly validated for biological tissue characterization. We have developed and characterized a practical noncontact handheld Raman imager providing tissue information at a spatial resolution of 115 microns over a field of view >14 mm 2 and a spectral resolution of 6 cm -1 over the whole fingerprint region. Typical integration time to acquire an entire Raman image over swine tissue was set to approximately 100 s. Spectra acquired with both probes (single-point and wide-field) showed good agreement, with a Pearson correlation factor >0.85 over different tissue categories. Protein and lipid content of imaged tissue were manifested into the measured spectra which correlated well with previous findings in the literature. An example of quantitative molecular map is presented for swine tissue and calf brain based on the ratio of protein-to-lipid content showing clear delineations between white and gray matter as well as between adipose and muscle tissue. We presented the development of a Raman imaging probe with a field of view of a few millimeters and a spatial resolution consistent with standard surgical imaging methods using an imaging bundle. Spectra acquired with the newly developed system on swine tissue and calf brain correlated well with an establish single-point probe and observed spectral features agreed with previous finding in the literature. The imaging probe has demonstrated its ability to reconstruct molecular images of soft tissues. The approach presented here has a lot of potential for the development of surgical Raman imaging probe to guide the surgeon during cancer surgery. © 2017 American Association of Physicists in Medicine.

Colour-Difference Measurement Method for Evaluation of Quality of Electrolessly Deposited Copper on Polymer after Laser-Induced Selective Activation

PubMed Central

Gedvilas, Mindaugas; Ratautas, Karolis; Kacar, Elif; Stankevičienė, Ina; Jagminienė, Aldona; Norkus, Eugenijus; Li Pira, Nello; Račiukaitis, Gediminas

2016-01-01

In this work a novel colour-difference measurement method for the quality evaluation of copper deposited on a polymer is proposed. Laser-induced selective activation (LISA) was performed onto the surface of the polycarbonate/acrylonitrile butadiene styrene (PC/ABS) polymer by using nanosecond laser irradiation. The laser activated PC/ABS polymer was copper plated by using the electroless copper plating (ECP) procedure. The sheet resistance measured by using a four-point probe technique was found to decrease by the power law with the colour-difference of the sample images after LISA and ECP procedures. The percolation theory of the electrical conductivity of the insulator conductor mixture has been adopted in order to explain the experimental results. The new proposed method was used to determine an optimal set of the laser processing parameters for best plating conditions. PMID:26960432

A 2D range Hausdorff approach to 3D facial recognition.

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

Koch, Mark William; Russ, Trina Denise; Little, Charles Quentin

2004-11-01

This paper presents a 3D facial recognition algorithm based on the Hausdorff distance metric. The standard 3D formulation of the Hausdorff matching algorithm has been modified to operate on a 2D range image, enabling a reduction in computation from O(N2) to O(N) without large storage requirements. The Hausdorff distance is known for its robustness to data outliers and inconsistent data between two data sets, making it a suitable choice for dealing with the inherent problems in many 3D datasets due to sensor noise and object self-occlusion. For optimal performance, the algorithm assumes a good initial alignment between probe and templatemore » datasets. However, to minimize the error between two faces, the alignment can be iteratively refined. Results from the algorithm are presented using 3D face images from the Face Recognition Grand Challenge database version 1.0.« less

A guide to SPECT equipment for brain imaging

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

Hoffer, P.B.; Zubal, G.

1991-12-31

Single photon emission computed tomography (SPECT) was started by Kuhl and Edwards about 30 years ago. Their original instrument consisted of four focused Nal probes mounted on a moving gantry. During the 1980s, clinical SPECT imaging was most frequently performed using single-headed Anger-type cameras which were modified for rotational as well as static imaging. Such instruments are still available and may be useful in settings where there are few patients and SPECT is used only occasionally. More frequently, however, dedicated SPECT devices are purchased which optimize equipment potential while being user-friendly. Modern SPECT instrumentation incorporates improvements in the detector, computers,more » mathematical formulations, electronics and display systems. A comprehensive discussion of all aspects of SPECT is beyond the scope of this article. The authors, however, discuss general concepts of SPECT, the current state-of-the-art in clinical SPECT instrumentation, and areas of common misunderstanding. 9 refs.« less

An evaluation of multi-probe locality sensitive hashing for computing similarities over web-scale query logs

PubMed Central

2018-01-01

Many modern applications of AI such as web search, mobile browsing, image processing, and natural language processing rely on finding similar items from a large database of complex objects. Due to the very large scale of data involved (e.g., users’ queries from commercial search engines), computing such near or nearest neighbors is a non-trivial task, as the computational cost grows significantly with the number of items. To address this challenge, we adopt Locality Sensitive Hashing (a.k.a, LSH) methods and evaluate four variants in a distributed computing environment (specifically, Hadoop). We identify several optimizations which improve performance, suitable for deployment in very large scale settings. The experimental results demonstrate our variants of LSH achieve the robust performance with better recall compared with “vanilla” LSH, even when using the same amount of space. PMID:29346410

Orthogonal Luciferase-Luciferin Pairs for Bioluminescence Imaging.

PubMed

Jones, Krysten A; Porterfield, William B; Rathbun, Colin M; McCutcheon, David C; Paley, Miranda A; Prescher, Jennifer A

2017-02-15

Bioluminescence imaging with luciferase-luciferin pairs is widely used in biomedical research. Several luciferases have been identified in nature, and many have been adapted for tracking cells in whole animals. Unfortunately, the optimal luciferases for imaging in vivo utilize the same substrate and therefore cannot easily differentiate multiple cell types in a single subject. To develop a broader set of distinguishable probes, we crafted custom luciferins that can be selectively processed by engineered luciferases. Libraries of mutant enzymes were iteratively screened with sterically modified luciferins, and orthogonal enzyme-substrate "hits" were identified. These tools produced light when complementary enzyme-substrate partners interacted both in vitro and in cultured cell models. Based on their selectivity, these designer pairs will bolster multicomponent imaging and enable the direct interrogation of cell networks not currently possible with existing tools. Our screening platform is also general and will expedite the identification of more unique luciferases and luciferins, further expanding the bioluminescence toolkit.

Physical limitations in sensors for a drag-free deep space probe

NASA Technical Reports Server (NTRS)

Juillerat, R.

1971-01-01

The inner perturbing forces acting on sensors were analyzed, taking into account the technological limitations imposed on the proof mass position pickup and proof mass acquisition system. The resulting perturbing accelerations are evaluated as a function of the drag-free sensor parameters. Perturbations included gravitational attraction, electrical action, magnetic action, pressure effects, radiation effects, and action of the position pickup. These data can be used to study the laws of guidance, providing an optimization of the space probe as a whole.

The Solar Probe mission - Mission design concepts and requirements

NASA Technical Reports Server (NTRS)

Ayon, Juan A.

1992-01-01

The Solar Probe concept as studied by the Jet Propulsion Laboratory represents the first mission to combine out-of-the-ecliptic scientific coverage with multiple, close solar encounters (at 4 solar radii). The scientific objectives of the mission have driven the investigation and analysis of several mission design concepts, all optimized to meet the science/mission requirements. This paper reviews those mission design concepts developed, the science objectives that drive the mission design, and the principle mission requirements associated with these various concepts.

Structure design and characteristic analysis of micro-nano probe based on six dimensional micro-force measuring principle

NASA Astrophysics Data System (ADS)

Yang, Hong-tao; Cai, Chun-mei; Fang, Chuan-zhi; Wu, Tian-feng

2013-10-01

In order to develop micro-nano probe having error self-correcting function and good rigidity structure, a new micro-nano probe system was developed based on six-dimensional micro-force measuring principle. The structure and working principle of the probe was introduced in detail. The static nonlinear decoupling method was established with BP neural network to do the static decoupling for the dimension coupling existing in each direction force measurements. The optimal parameters of BP neural network were selected and the decoupling simulation experiments were done. The maximum probe coupling rate after decoupling is 0.039% in X direction, 0.025% in Y direction and 0.027% in Z direction. The static measurement sensitivity of the probe can reach 10.76μɛ / mN in Z direction and 14.55μɛ / mN in X and Y direction. The modal analysis and harmonic response analysis under three dimensional harmonic load of the probe were done by using finite element method. The natural frequencies under different vibration modes were obtained and the working frequency of the probe was determined, which is higher than 10000 Hz . The transient response analysis of the probe was done, which indicates that the response time of the probe can reach 0.4 ms. From the above results, it is shown that the developed micro-nano probe meets triggering requirements of micro-nano probe. Three dimension measuring force can be measured precisely by the developed probe, which can be used to predict and correct the force deformation error and the touch error of the measuring ball and the measuring rod.

On the optimization of Gaussian basis sets

NASA Astrophysics Data System (ADS)

Petersson, George A.; Zhong, Shijun; Montgomery, John A.; Frisch, Michael J.

2003-01-01

A new procedure for the optimization of the exponents, αj, of Gaussian basis functions, Ylm(ϑ,φ)rle-αjr2, is proposed and evaluated. The direct optimization of the exponents is hindered by the very strong coupling between these nonlinear variational parameters. However, expansion of the logarithms of the exponents in the orthonormal Legendre polynomials, Pk, of the index, j: ln αj=∑k=0kmaxAkPk((2j-2)/(Nprim-1)-1), yields a new set of well-conditioned parameters, Ak, and a complete sequence of well-conditioned exponent optimizations proceeding from the even-tempered basis set (kmax=1) to a fully optimized basis set (kmax=Nprim-1). The error relative to the exact numerical self-consistent field limit for a six-term expansion is consistently no more than 25% larger than the error for the completely optimized basis set. Thus, there is no need to optimize more than six well-conditioned variational parameters, even for the largest sets of Gaussian primitives.

Optimization of oligonucleotide arrays and RNA amplification protocols for analysis of transcript structure and alternative splicing.

PubMed

Castle, John; Garrett-Engele, Phil; Armour, Christopher D; Duenwald, Sven J; Loerch, Patrick M; Meyer, Michael R; Schadt, Eric E; Stoughton, Roland; Parrish, Mark L; Shoemaker, Daniel D; Johnson, Jason M

2003-01-01

Microarrays offer a high-resolution means for monitoring pre-mRNA splicing on a genomic scale. We have developed a novel, unbiased amplification protocol that permits labeling of entire transcripts. Also, hybridization conditions, probe characteristics, and analysis algorithms were optimized for detection of exons, exon-intron edges, and exon junctions. These optimized protocols can be used to detect small variations and isoform mixtures, map the tissue specificity of known human alternative isoforms, and provide a robust, scalable platform for high-throughput discovery of alternative splicing.

Optimization of oligonucleotide arrays and RNA amplification protocols for analysis of transcript structure and alternative splicing

PubMed Central

Castle, John; Garrett-Engele, Phil; Armour, Christopher D; Duenwald, Sven J; Loerch, Patrick M; Meyer, Michael R; Schadt, Eric E; Stoughton, Roland; Parrish, Mark L; Shoemaker, Daniel D; Johnson, Jason M

2003-01-01

Microarrays offer a high-resolution means for monitoring pre-mRNA splicing on a genomic scale. We have developed a novel, unbiased amplification protocol that permits labeling of entire transcripts. Also, hybridization conditions, probe characteristics, and analysis algorithms were optimized for detection of exons, exon-intron edges, and exon junctions. These optimized protocols can be used to detect small variations and isoform mixtures, map the tissue specificity of known human alternative isoforms, and provide a robust, scalable platform for high-throughput discovery of alternative splicing. PMID:14519201

SPRUCE S1 Bog Peat Depth Determined by Push Probe and GPR: 2009-2010

DOE Data Explorer

Slater, L. [Oak Ridge National Laboratory, U.S. Department of Energy, Oak Ridge, Tennessee, U.S.A.; Hanson, P. J. [Oak Ridge National Laboratory, U.S. Department of Energy, Oak Ridge, Tennessee, U.S.A.; Hook, L. A. [Oak Ridge National Laboratory, U.S. Department of Energy, Oak Ridge, Tennessee, U.S.A.

2012-01-01

This data set reports the thickness of peat for the S1 Bog measured directly with manual push probes on September 21 and 22, 2009, and measured by ground penetrating radar (GPR) across transects from January 26 to February 2, 2010 and June 2 to June 9, 2010. Also included are interpolated values of peat depth from both probe and GPR data for the S1 Bog at 1 meter square horizontal resolution.

SU-F-R-10: Selecting the Optimal Solution for Multi-Objective Radiomics Model

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

Zhou, Z; Folkert, M; Wang, J

2016-06-15

Purpose: To develop an evidential reasoning approach for selecting the optimal solution from a Pareto solution set obtained by a multi-objective radiomics model for predicting distant failure in lung SBRT. Methods: In the multi-objective radiomics model, both sensitivity and specificity are considered as the objective functions simultaneously. A Pareto solution set with many feasible solutions will be resulted from the multi-objective optimization. In this work, an optimal solution Selection methodology for Multi-Objective radiomics Learning model using the Evidential Reasoning approach (SMOLER) was proposed to select the optimal solution from the Pareto solution set. The proposed SMOLER method used the evidentialmore » reasoning approach to calculate the utility of each solution based on pre-set optimal solution selection rules. The solution with the highest utility was chosen as the optimal solution. In SMOLER, an optimal learning model coupled with clonal selection algorithm was used to optimize model parameters. In this study, PET, CT image features and clinical parameters were utilized for predicting distant failure in lung SBRT. Results: Total 126 solution sets were generated by adjusting predictive model parameters. Each Pareto set contains 100 feasible solutions. The solution selected by SMOLER within each Pareto set was compared to the manually selected optimal solution. Five-cross-validation was used to evaluate the optimal solution selection accuracy of SMOLER. The selection accuracies for five folds were 80.00%, 69.23%, 84.00%, 84.00%, 80.00%, respectively. Conclusion: An optimal solution selection methodology for multi-objective radiomics learning model using the evidential reasoning approach (SMOLER) was proposed. Experimental results show that the optimal solution can be found in approximately 80% cases.« less

Novel analytical approach to a multi-sugar whole gut permeability assay.

PubMed

van Wijck, Kim; van Eijk, Hans M H; Buurman, Wim A; Dejong, Cornelis H C; Lenaerts, Kaatje

2011-09-15

Many pathophysiological conditions are associated with increased gastrointestinal permeability, reflecting an elevated risk of endotoxaemia, inflammation, and sepsis. Permeability tests are increasingly used in clinical practice to obtain information on gastrointestinal functioning, but tests are often restricted to the small intestine, and require large oral sugar doses. Therefore, a novel multi-sugar assay was developed, allowing assessment of whole gut permeability changes in urinary and plasma samples collected at regular intervals from 10 healthy volunteers at baseline and after intake of monosaccharides (rhamnose and erythritol) and disaccharides (sucrose, lactulose, and sucralose). Samples were analyzed by isocratic cation-exchange LC-MS. Sample preparation and detection conditions were optimized. After centrifugation, chromatographic separation was achieved on an IOA-1000 column set at 30°C. Column effluent was mixed with ammonia for sugar-ammonium adduct formation. The lower limit of detection was 0.05 μmol/L for disaccharides and 0.1 μmol/L for monosaccharides. Linearity for each probe was between 1 and 1000 μmol/L (R(2): 0.9987-0.9999). Coefficients of variation were <5% in urine, and <9% in plasma. Recovery data were within the 90% to 110% range at all spiked concentrations. This highly sensitive novel LC-MS approach resulted in a significant decrease of the detection limit for all sugar probes, allowing a 5-fold reduction of the commonly used lactulose dose and the addition of sugar probes to also assess the gastroduodenal and colon permeability. In combination with its extended application in plasma, these features make the novel assay a promising tool in the assessment of site-specific changes in gastrointestinal permeability in clinical practice. Copyright © 2011 Elsevier B.V. All rights reserved.

Spatiotemporal characterization of soil moisture fields in agricultural areas using cosmic-ray neutron probes and data fusion

NASA Astrophysics Data System (ADS)

Franz, Trenton; Wang, Tiejun

2015-04-01

Approximately 40% of global food production comes from irrigated agriculture. With the increasing demand for food even greater pressures will be placed on water resources within these systems. In this work we aimed to characterize the spatial and temporal patterns of soil moisture at the field-scale (~500 m) using the newly developed cosmic-ray neutron rover near Waco, NE USA. Here we mapped soil moisture of 144 quarter section fields (a mix of maize, soybean, and natural areas) each week during the 2014 growing season (May to September). The 12 by 12 km study domain also contained three stationary cosmic-ray neutron probes for independent validation of the rover surveys. Basic statistical analysis of the domain indicated a strong relationship between the mean and variance of soil moisture at several averaging scales. The relationships between the mean and higher order moments were not significant. Scaling analysis indicated strong power law behavior between the variance of soil moisture and averaging area with minimal dependence of mean soil moisture on the slope of the power law function. In addition, we combined the data from the three stationary cosmic-ray neutron probes and mobile surveys using linear regression to derive a daily soil moisture product at 1, 3, and 12 km spatial resolutions for the entire growing season. The statistical relationships derived from the rover dataset offer a novel set of observations that will be useful in: 1) calibrating and validating land surface models, 2) calibrating and validating crop models, 3) soil moisture covariance estimates for statistical downscaling of remote sensing products such as SMOS and SMAP, and 4) provide daily center-pivot scale mean soil moisture data for optimal irrigation timing and volume amounts.

Restoring Behavior via Inverse Neurocontroller in a Lesioned Cortical Spiking Model Driving a Virtual Arm

PubMed Central

Dura-Bernal, Salvador; Li, Kan; Neymotin, Samuel A.; Francis, Joseph T.; Principe, Jose C.; Lytton, William W.

2016-01-01

Neural stimulation can be used as a tool to elicit natural sensations or behaviors by modulating neural activity. This can be potentially used to mitigate the damage of brain lesions or neural disorders. However, in order to obtain the optimal stimulation sequences, it is necessary to develop neural control methods, for example by constructing an inverse model of the target system. For real brains, this can be very challenging, and often unfeasible, as it requires repeatedly stimulating the neural system to obtain enough probing data, and depends on an unwarranted assumption of stationarity. By contrast, detailed brain simulations may provide an alternative testbed for understanding the interactions between ongoing neural activity and external stimulation. Unlike real brains, the artificial system can be probed extensively and precisely, and detailed output information is readily available. Here we employed a spiking network model of sensorimotor cortex trained to drive a realistic virtual musculoskeletal arm to reach a target. The network was then perturbed, in order to simulate a lesion, by either silencing neurons or removing synaptic connections. All lesions led to significant behvaioral impairments during the reaching task. The remaining cells were then systematically probed with a set of single and multiple-cell stimulations, and results were used to build an inverse model of the neural system. The inverse model was constructed using a kernel adaptive filtering method, and was used to predict the neural stimulation pattern required to recover the pre-lesion neural activity. Applying the derived neurostimulation to the lesioned network improved the reaching behavior performance. This work proposes a novel neurocontrol method, and provides theoretical groundwork on the use biomimetic brain models to develop and evaluate neurocontrollers that restore the function of damaged brain regions and the corresponding motor behaviors. PMID:26903796

A Combined Time Domain Impedance Probe And Plasma Wave Receiver System For Small Satellite Applications.

NASA Astrophysics Data System (ADS)

Spencer, E. A.; Clark, D. C.; Vadepu, S. K.; Patra, S.

2017-12-01

A Time Domain Impedance Probe (TDIP) measures electron density and electron neutral collision frequencies in the ionosphere. This instrument has been tested on a sounding rocket flight and is now being further developed to fly on a NASA Undergraduate Student Instrument Program (USIP) cubesat to be launched out of the ISS in 2019. Here we report on the development of a new combined TDIP and plasma wave instrument that can be used on cubesat platforms to measure local electron parameters, and also to receive or transmit electron scale waves. This combined instrument can be used to study short time and space scale phenomena in the upper ionosphere using only RF signals. The front end analog circuitry is dual-purposed to perform active or passive probing of the ambient plasma. Two dipole antennas are used, one is optimzed for impedance measurements, while the other is optimized for transmitter-receiver performance. We show our circuit realization, and initial results from laboratory measurements using the TDIP prototype modified for receiver function. We also show Finite Difference Time Domain (FDTD) simulations of an electrically long antenna immersed in a magnetized plasma used to optimize the transmitter receiver performance.

Plasma Diagnostics: Use and Justification in an Industrial Environment

NASA Astrophysics Data System (ADS)

Loewenhardt, Peter

1998-10-01

The usefulness and importance of plasma diagnostics have played a major role in the development of plasma processing tools in the semiconductor industry. As can be seen through marketing materials from semiconductor equipment manufacturers, results from plasma diagnostic equipment can be a powerful tool in selling the technological leadership of tool design. Some diagnostics have long been used for simple process control such as optical emission for endpoint determination, but in recent years more sophisticated and involved diagnostic tools have been utilized in chamber and plasma source development and optimization. It is now common to find an assortment of tools at semiconductor equipment companies such as Langmuir probes, mass spectrometers, spatial optical emission probes, impedance, ion energy and ion flux probes. An outline of how the importance of plasma diagnostics has grown at an equipment manufacturer over the last decade will be given, with examples of significant and useful results obtained. Examples will include the development and optimization of an inductive plasma source, trends and hardware effects on ion energy distributions, mass spectrometry influences on process development and investigations of plasma-wall interactions. Plasma diagnostic focus, in-house development and proliferation in an environment where financial justification requirements are both strong and necessary will be discussed.

Probe for high resolution NMR with sample reorientation

DOEpatents

Pines, Alexander; Samoson, Ago

1990-01-01

An improved NMR probe and method are described which substantially improve the resolution of NMR measurements made on powdered or amorphous or otherwise orientationally disordered samples. The apparatus mechanically varies the orientation of the sample such that the time average of two or more sets of spherical harmonic functions are zero.

Acoustics of the piezo-electric pressure probe

NASA Technical Reports Server (NTRS)

Dutt, G. S.

1974-01-01

Acoustical properties of a piezoelectric device are reported for measuring the pressure in the plasma flow from an MPD arc. A description and analysis of the acoustical behavior in a piezoelectric probe is presented for impedance matching and damping. The experimental results are presented in a set of oscillographic records.

Evolution and Persistence of 5-um Hot Spots at the Galileo Probe entry Latitude

NASA Technical Reports Server (NTRS)

Fisher, B. M.

1997-01-01

We present a study on the longtudinal locations, morphology and evolution of the 5-um hot spots at 6.5 deg. N latitude (planetocentric), from an extensive IRTF-NSFCAM data set spanning more that 3 years, which includes the date of the Galileo Probe entry.

Xanthine oxidase functionalized Ta2O5 nanostructures as a novel scaffold for highly sensitive SPR based fiber optic xanthine sensor.

PubMed

Kant, Ravi; Tabassum, Rana; Gupta, Banshi D

2018-01-15

Fabrication and characterization of a surface plasmon resonance based fiber optic xanthine sensor using entrapment of xanthine oxidase (XO) enzyme in several nanostructures of tantalum (v) oxide (Ta 2 O 5 ) have been reported. Chemical route was adopted for synthesizing Ta 2 O 5 nanoparticles, nanorods, nanotubes and nanowires while Ta 2 O 5 nanofibers were prepared by electrospinning technique. The synthesized Ta 2 O 5 nanostructures were characterized by photoluminescence, scanning electron microscopy, UV-Visible spectra and X-ray diffraction pattern. The probes were fabricated by coating an unclad core of the fiber with silver layer followed by the deposition of XO entrapped Ta 2 O 5 nanostructures. The crux of sensing mechanism relies on the modification of dielectric function of sensing layer upon exposure to xanthine solution of diverse concentrations, reflected in terms of shift in resonance wavelength. The sensing probe coated with XO entrapped Ta 2 O 5 nanofibers has been turned out to possess maximum sensitivity amongst the synthesized nanostructures. The probe was optimized in terms of pH of the sample and the concentration of XO entrapped in Ta 2 O 5 nanofibers. The optimized sensing probe possesses a remarkably good sensitivity of 26.2nm/µM in addition to linear range from 0 to 3µM with an invincible LOD value of 0.0127µM together with a response time of 1min. Furthermore, probe selectivity with real sample analysis ensure the usage of the sensor for practical scenario. The results reported open a novel perspective towards a sensitive, rapid, reliable and selective detection of xanthine. Copyright © 2017 Elsevier B.V. All rights reserved.

Expanding probe repertoire and improving reproducibility in human genomic hybridization

PubMed Central

Dorman, Stephanie N.; Shirley, Ben C.; Knoll, Joan H. M.; Rogan, Peter K.

2013-01-01

Diagnostic DNA hybridization relies on probes composed of single copy (sc) genomic sequences. Sc sequences in probe design ensure high specificity and avoid cross-hybridization to other regions of the genome, which could lead to ambiguous results that are difficult to interpret. We examine how the distribution and composition of repetitive sequences in the genome affects sc probe performance. A divide and conquer algorithm was implemented to design sc probes. With this approach, sc probes can include divergent repetitive elements, which hybridize to unique genomic targets under higher stringency experimental conditions. Genome-wide custom probe sets were created for fluorescent in situ hybridization (FISH) and microarray genomic hybridization. The scFISH probes were developed for detection of copy number changes within small tumour suppressor genes and oncogenes. The microarrays demonstrated increased reproducibility by eliminating cross-hybridization to repetitive sequences adjacent to probe targets. The genome-wide microarrays exhibited lower median coefficients of variation (17.8%) for two HapMap family trios. The coefficients of variations of commercial probes within 300 nt of a repetitive element were 48.3% higher than the nearest custom probe. Furthermore, the custom microarray called a chromosome 15q11.2q13 deletion more consistently. This method for sc probe design increases probe coverage for FISH and lowers variability in genomic microarrays. PMID:23376933

Synthesis of Bipartite Tetracysteine PNA Probes for DNA In Situ Fluorescent Labeling.

PubMed

Fang, Ge-Min; Seitz, Oliver

2017-12-24

"Label-free" fluorescent probes that avoid additional steps or building blocks for conjugation of fluorescent dyes with oligonucleotides can significantly reduce the time and cost of parallel bioanalysis of a large number of nucleic acid samples. A method for the synthesis of "label-free" bicysteine-modified PNA probes using solid-phase synthesis and procedures for sequence-specific DNA in situ fluorescent labeling is described here. The concept is based on the adjacent alignment of two bicysteine-modified peptide nucleic acids on a DNA target to form a structurally optimized bipartite tetracysteine motif, which induces a sequence-specific fluorogenic reaction with commercially available biarsenic dyes, even in complex media such as cell lysate. This unit will help researchers to quickly synthesize bipartite tetracysteine PNA probes and carry out low-cost DNA in situ fluorescent labeling experiments. © 2017 by John Wiley & Sons, Inc. Copyright © 2017 John Wiley & Sons, Inc.

Computer-Assisted Traffic Engineering Using Assignment, Optimal Signal Setting, and Modal Split

DOT National Transportation Integrated Search

1978-05-01

Methods of traffic assignment, traffic signal setting, and modal split analysis are combined in a set of computer-assisted traffic engineering programs. The system optimization and user optimization traffic assignments are described. Travel time func...

Probe penetration in relation to the connective tissue attachment level: influence of tine shape and probing force.

PubMed

Bulthuis, H M; Barendregt, D S; Timmerman, M F; Loos, B G; van der Velden, U

1998-05-01

Previous research has shown that probing force and probe tine shape influence the clinically assessed probing depth. The purpose of the present study was to investigate the effect of tine shape and probing force on probe penetration, in relation to the microscopically assessed attachment level in untreated periodontal disease. In 22 patients, scheduled for partial or full mouth tooth extraction and no history of periodontal treatment, 135 teeth were selected. At mesial and distal sites of the teeth reference marks were cut. Three probe tines, mounted in a modified Florida Probe handpiece, were tested: a tapered, a parallel and a ball-ended; tip-diameter 0.5 mm. The three tines were distributed at random over the sites. At each site increasing probing forces of 0.10 N, 0.15 N, 0.20 N, 0.25 N were used. After extraction, the teeth were cleaned and stained for connective tissue fiber attachment. The distance between the reference mark and the attachment level was determined using a stereomicroscope. The results showed that the parallel and ball-ended tine measured significantly beyond the microscopically assessed attachment level at all force levels; with increasing forces, the parallel tine measured 0.96 to 1.38 mm and the ball-ended tine 0.73 to 1.06 mm deeper. The tapered tine did not deviate significantly from the microscopic values at the forces of 0.15, 0.20 and 0.25 N. It can be concluded that for the optimal assessment of the attachment level in inflamed periodontal conditions, a tapered probe with a tip diameter of 0.5 mm and exerting a probing force of 0.25 N may be most suitable.

Virtual solar field - An opportunity to optimize transient processes in line-focus CSP power plants

NASA Astrophysics Data System (ADS)

Noureldin, Kareem; Hirsch, Tobias; Pitz-Paal, Robert

2017-06-01

Optimizing solar field operation and control is a key factor to improve the competitiveness of line-focus solar thermal power plants. However, the risks of assessing new and innovative control strategies on operational power plants hinder such optimizations and result in applying more conservative control schemes. In this paper, we describe some applications for a whole solar field transient in-house simulation tool developed at the German Aerospace Centre (DLR), the Virtual Solar Field (VSF). The tool offers a virtual platform to simulate real solar fields while coupling the thermal and hydraulic conditions of the field with high computational efficiency. Using the tool, developers and operator can probe their control strategies and assess the potential benefits while avoiding the high risks and costs. In this paper, we study the benefits gained from controlling the loop valves and of using direct normal irradiance maps and forecasts for the field control. Loop valve control is interesting for many solar field operators since it provides a high degree of flexibility to the control of the solar field through regulating the flow rate in each loop. This improves the reaction to transient condition, such as passing clouds and field start-up in the morning. Nevertheless, due to the large number of loops and the sensitivity of the field control to the valve settings, this process needs to be automated and the effect of changing the setting of each valve on the whole field control needs to be taken into account. We used VSF to implement simple control algorithms to control the loop valves and to study the benefits that could be gained from using active loop valve control during transient conditions. Secondly, we study how using short-term highly spatially-resolved DNI forecasts provided by cloud cameras could improve the plant energy yield. Both cases show an improvement in the plant efficiency and outlet temperature stability. This paves the road for further investigations of new control strategies or for optimizations of the currently implemented ones.

Technical Note: Millimeter precision in ultrasound based patient positioning: Experimental quantification of inherent technical limitations

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

Ballhausen, Hendrik, E-mail: hendrik.ballhausen@med.uni-muenchen.de; Hieber, Sheila; Li, Minglun

2014-08-15

Purpose: To identify the relevant technical sources of error of a system based on three-dimensional ultrasound (3D US) for patient positioning in external beam radiotherapy. To quantify these sources of error in a controlled laboratory setting. To estimate the resulting end-to-end geometric precision of the intramodality protocol. Methods: Two identical free-hand 3D US systems at both the planning-CT and the treatment room were calibrated to the laboratory frame of reference. Every step of the calibration chain was repeated multiple times to estimate its contribution to overall systematic and random error. Optimal margins were computed given the identified and quantified systematicmore » and random errors. Results: In descending order of magnitude, the identified and quantified sources of error were: alignment of calibration phantom to laser marks 0.78 mm, alignment of lasers in treatment vs planning room 0.51 mm, calibration and tracking of 3D US probe 0.49 mm, alignment of stereoscopic infrared camera to calibration phantom 0.03 mm. Under ideal laboratory conditions, these errors are expected to limit ultrasound-based positioning to an accuracy of 1.05 mm radially. Conclusions: The investigated 3D ultrasound system achieves an intramodal accuracy of about 1 mm radially in a controlled laboratory setting. The identified systematic and random errors require an optimal clinical tumor volume to planning target volume margin of about 3 mm. These inherent technical limitations do not prevent clinical use, including hypofractionation or stereotactic body radiation therapy.« less

Experimental and TD-DFT study of optical absorption of six explosive molecules: RDX, HMX, PETN, TNT, TATP, and HMTD.

PubMed

Cooper, Jason K; Grant, Christian D; Zhang, Jin Z

2013-07-25

Time dependent density function theory (TD-DFT) has been utilized to calculate the excitation energies and oscillator strengths of six common explosives: RDX (1,3,5-trinitroperhydro-1,3,5-triazine), β-HMX (octahydro-1,3,5,7-tetranitro-1,3,5,7-tetrazocine), TATP (triacetone triperoxide), HMTD (hexamethylene triperoxide diamine), TNT (2,4,6-trinitrotoluene), and PETN (pentaerythritol tetranitrate). The results were compared to experimental UV-vis absorption spectra collected in acetonitrile. Four computational methods were tested including: B3LYP, CAM-B3LYP, ωB97XD, and PBE0. PBE0 outperforms the other methods tested. Basis set effects on the electronic energies and oscillator strengths were evaluated with 6-31G(d), 6-31+G(d), 6-31+G(d,p), and 6-311+G(d,p). The minimal basis set required was 6-31+G(d); however, additional calculations were performed with 6-311+G(d,p). For each molecule studied, the natural transition orbitals (NTOs) were reported for the most prominent singlet excitations. The TD-DFT results have been combined with the IPv calculated by CBS-QB3 to construct energy level diagrams for the six compounds. The results suggest optimization approaches for fluorescence based detection methods for these explosives by guiding materials selections for optimal band alignment between fluorescent probe and explosive analyte. Also, the role of the TNT Meisenheimer complex formation and the resulting electronic structure thereof on of the quenching mechanism of II-VI semiconductors is discussed.

Cosmological Parameters and Hyper-Parameters: The Hubble Constant from Boomerang and Maxima

NASA Astrophysics Data System (ADS)

Lahav, Ofer

Recently several studies have jointly analysed data from different cosmological probes with the motivation of estimating cosmological parameters. Here we generalise this procedure to allow freedom in the relative weights of various probes. This is done by including in the joint likelihood function a set of `Hyper-Parameters', which are dealt with using Bayesian considerations. The resulting algorithm, which assumes uniform priors on the log of the Hyper-Parameters, is very simple to implement. We illustrate the method by estimating the Hubble constant H0 from different sets of recent CMB experiments (including Saskatoon, Python V, MSAM1, TOCO, Boomerang and Maxima). The approach can be generalised for a combination of cosmic probes, and for other priors on the Hyper-Parameters. Reference: Lahav, Bridle, Hobson, Lasenby & Sodre, 2000, MNRAS, in press (astro-ph/9912105)

Development of the polymerase chain reaction for diagnosis of chancroid.

PubMed Central

Chui, L; Albritton, W; Paster, B; Maclean, I; Marusyk, R

1993-01-01

The published nucleotide sequences of the 16S rRNA gene of Haemophilus ducreyi were used to develop primer sets and probes for the diagnosis of chancroid by polymerase chain reaction (PCR) DNA amplification. One set of broad specificity primers yielded a 303-bp PCR product from all bacteria tested. Two 16-base probes internal to this sequence were species specific for H. ducreyi when tested with 12 species of the families Pasteurellaceae and Enterobacteriaceae. The two probes in combination with the broad specificity primers were 100% sensitive with 51 strains of H. ducreyi isolated from six continents over a 15-year period. The direct detection of H. ducreyi from 100 clinical specimens by PCR showed a sensitivity of 83 to 98% and a specificity of 51 to 67%, depending on the number of amplification cycles. Images PMID:8458959

Comparing student performance on paper- and computer-based math curriculum-based measures.

PubMed

Hensley, Kiersten; Rankin, Angelica; Hosp, John

2017-01-01

As the number of computerized curriculum-based measurement (CBM) tools increases, it is necessary to examine whether or not student performance can generalize across a variety of test administration modes (i.e., paper or computer). The purpose of this study is to compare math fact fluency on paper versus computer for 197 upper elementary students. Students completed identical sets of probes on paper and on the computer, which were then scored for digits correct, problems correct, and accuracy. Results showed a significant difference in performance between the two sets of probes, with higher fluency rates on the paper probes. Because decisions about levels of student support and interventions often rely on measures such as these, more research in this area is needed to examine the potential differences in student performance between paper-based and computer-based CBMs.

Ligation with Nucleic Acid Sequence–Based Amplification

PubMed Central

Ong, Carmichael; Tai, Warren; Sarma, Aartik; Opal, Steven M.; Artenstein, Andrew W.; Tripathi, Anubhav

2012-01-01

This work presents a novel method for detecting nucleic acid targets using a ligation step along with an isothermal, exponential amplification step. We use an engineered ssDNA with two variable regions on the ends, allowing us to design the probe for optimal reaction kinetics and primer binding. This two-part probe is ligated by T4 DNA Ligase only when both parts bind adjacently to the target. The assay demonstrates that the expected 72-nt RNA product appears only when the synthetic target, T4 ligase, and both probe fragments are present during the ligation step. An extraneous 38-nt RNA product also appears due to linear amplification of unligated probe (P3), but its presence does not cause a false-positive result. In addition, 40 mmol/L KCl in the final amplification mix was found to be optimal. It was also found that increasing P5 in excess of P3 helped with ligation and reduced the extraneous 38-nt RNA product. The assay was also tested with a single nucleotide polymorphism target, changing one base at the ligation site. The assay was able to yield a negative signal despite only a single-base change. Finally, using P3 and P5 with longer binding sites results in increased overall sensitivity of the reaction, showing that increasing ligation efficiency can improve the assay overall. We believe that this method can be used effectively for a number of diagnostic assays. PMID:22449695

Noise performance of frequency modulation Kelvin force microscopy

PubMed Central

Deresmes, Dominique; Mélin, Thierry

2014-01-01

Summary Noise performance of a phase-locked loop (PLL) based frequency modulation Kelvin force microscope (FM-KFM) is assessed. Noise propagation is modeled step by step throughout the setup using both exact closed loop noise gains and an approximation known as “noise gain” from operational amplifier (OpAmp) design that offers the advantage of decoupling the noise performance study from considerations of stability and ideal loop response. The bandwidth can be chosen depending on how much noise is acceptable and it is shown that stability is not an issue up to a limit that will be discussed. With thermal and detector noise as the only sources, both approaches yield PLL frequency noise expressions equal to the theoretical value for self-oscillating circuits and in agreement with measurement, demonstrating that the PLL components neither modify nor contribute noise. Kelvin output noise is then investigated by modeling the surrounding bias feedback loop. A design rule is proposed that allows choosing the AC modulation frequency for optimized sharing of the PLL bandwidth between Kelvin and topography loops. A crossover criterion determines as a function of bandwidth, temperature and probe parameters whether thermal or detector noise is the dominating noise source. Probe merit factors for both cases are then established, suggesting how to tackle noise performance by probe design. Typical merit factors of common probe types are compared. This comprehensive study is an encouraging step toward a more integral performance assessment and a remedy against focusing on single aspects and optimizing around randomly chosen key values. PMID:24455457

Gamma-Ray Imaging Probes.

NASA Astrophysics Data System (ADS)

Wild, Walter James

1988-12-01

External nuclear medicine diagnostic imaging of early primary and metastatic lung cancer tumors is difficult due to the poor sensitivity and resolution of existing gamma cameras. Nonimaging counting detectors used for internal tumor detection give ambiguous results because distant background variations are difficult to discriminate from neighboring tumor sites. This suggests that an internal imaging nuclear medicine probe, particularly an esophageal probe, may be advantageously used to detect small tumors because of the ability to discriminate against background variations and the capability to get close to sites neighboring the esophagus. The design, theory of operation, preliminary bench tests, characterization of noise behavior and optimization of such an imaging probe is the central theme of this work. The central concept lies in the representation of the aperture shell by a sequence of binary digits. This, coupled with the mode of operation which is data encoding within an axial slice of space, leads to the fundamental imaging equation in which the coding operation is conveniently described by a circulant matrix operator. The coding/decoding process is a classic coded-aperture problem, and various estimators to achieve decoding are discussed. Some estimators require a priori information about the object (or object class) being imaged; the only unbiased estimator that does not impose this requirement is the simple inverse-matrix operator. The effects of noise on the estimate (or reconstruction) is discussed for general noise models and various codes/decoding operators. The choice of an optimal aperture for detector count times of clinical relevance is examined using a statistical class-separability formalism.

Tapered Optical Fiber Probe Assembled with Plasmonic Nanostructures for Surface-Enhanced Raman Scattering Application.

PubMed

Huang, Zhulin; Lei, Xing; Liu, Ye; Wang, Zhiwei; Wang, Xiujuan; Wang, Zhaoming; Mao, Qinghe; Meng, Guowen

2015-08-12

Optical fiber-Raman devices integrated with plasmonic nanostructures have promising potentials for in situ probing remote liquid samples and biological samples. In this system, the fiber probe is required to simultaneously demonstrate stable surface enhanced Raman scattering (SERS) signals and high sensitivity toward the target species. Here we demonstrate a generic approach to integrate presynthesized plasmonic nanostructures with tapered fiber probes that are prepared by a dipping-etching method, through reversed electrostatic attraction between the silane couple agent modified silica fiber probe and the nanostructures. Using this approach, both negatively and positively charged plasmonic nanostructures with various morphologies (such as Au nanosphere, Ag nanocube, Au nanorod, Au@Ag core-shell nanorod) can be stably assembled on the tapered silica fiber probes. Attributed to the electrostatic force between the plasmonic units and the fiber surface, the nanostructures do not disperse in liquid samples easily, making the relative standard deviation of SERS signals as low as 2% in analyte solution. Importantly, the detection sensitivity of the system can be optimized by adjusting the cone angle (from 3.6° to 22°) and the morphology of nanostructures assembled on the fiber. Thus, the nanostructures-sensitized optical fiber-Raman probes show great potentials in the applications of SERS-based environmental detection of liquid samples.

Heuristic and optimal policy computations in the human brain during sequential decision-making.

PubMed

Korn, Christoph W; Bach, Dominik R

2018-01-23

Optimal decisions across extended time horizons require value calculations over multiple probabilistic future states. Humans may circumvent such complex computations by resorting to easy-to-compute heuristics that approximate optimal solutions. To probe the potential interplay between heuristic and optimal computations, we develop a novel sequential decision-making task, framed as virtual foraging in which participants have to avoid virtual starvation. Rewards depend only on final outcomes over five-trial blocks, necessitating planning over five sequential decisions and probabilistic outcomes. Here, we report model comparisons demonstrating that participants primarily rely on the best available heuristic but also use the normatively optimal policy. FMRI signals in medial prefrontal cortex (MPFC) relate to heuristic and optimal policies and associated choice uncertainties. Crucially, reaction times and dorsal MPFC activity scale with discrepancies between heuristic and optimal policies. Thus, sequential decision-making in humans may emerge from integration between heuristic and optimal policies, implemented by controllers in MPFC.

Glowing locked nucleic acids: brightly fluorescent probes for detection of nucleic acids in cells.

PubMed

Østergaard, Michael E; Cheguru, Pallavi; Papasani, Madhusudhan R; Hill, Rodney A; Hrdlicka, Patrick J

2010-10-13

Fluorophore-modified oligonucleotides have found widespread use in genomics and enable detection of single-nucleotide polymorphisms, real-time monitoring of PCR, and imaging of mRNA in living cells. Hybridization probes modified with polarity-sensitive fluorophores and molecular beacons (MBs) are among the most popular approaches to produce hybridization-induced increases in fluorescence intensity for nucleic acid detection. In the present study, we demonstrate that the 2'-N-(pyren-1-yl)carbonyl-2'-amino locked nucleic acid (LNA) monomer X is a highly versatile building block for generation of efficient hybridization probes and quencher-free MBs. The hybridization and fluorescence properties of these Glowing LNA probes are efficiently modulated and optimized by changes in probe backbone chemistry and architecture. Correctly designed probes are shown to exhibit (a) high affinity toward RNA targets, (b) excellent mismatch discrimination, (c) high biostability, and (d) pronounced hybridization-induced increases in fluorescence intensity leading to formation of brightly fluorescent duplexes with unprecedented emission quantum yields (Φ(F) = 0.45-0.89) among pyrene-labeled oligonucleotides. Finally, specific binding between messenger RNA and multilabeled quencher-free MBs based on Glowing LNA monomers is demonstrated (a) using in vitro transcription assays and (b) by quantitative fluorometric assays and direct microscopic observation of probes bound to mRNA in its native form. These features render Glowing LNA as promising diagnostic probes for biomedical applications.

Handheld scanning probes for optical coherence tomography: developments, applications, and perspectives

NASA Astrophysics Data System (ADS)

Duma, V.-F.; Demian, D.; Sinescu, C.; Cernat, R.; Dobre, G.; Negrutiu, M. L.; Topala, F. I.; Hutiu, Gh.; Bradu, A.; Podoleanu, A. G.

2016-03-01

We present the handheld scanning probes that we have recently developed in our current project for biomedical imaging in general and for Optical Coherence Tomography (OCT) in particular. OCT is an established, but dynamic imagistic technique based on laser interferometry, which offers micrometer resolutions and millimeters penetration depths. With regard to existing devices, the newly developed handheld probes are simple, light and relatively low cost. Their design is described in detail to allow for the reproduction in any lab, including for educational purposes. Two probes are constructed almost entirely from off-the-shelf components, while a third, final variant is constructed with dedicated components, in an ergonomic design. The handheld probes have uni-dimensional (1D) galvanometer scanners therefore they achieve transversal sections through the biological sample investigated - in contrast to handheld probes equipped with bi-dimensional (2D) scanners that can also achieve volumetric (3D) reconstructions of the samples. These latter handheld probes are therefore also discussed, as well as the possibility to equip them with galvanometer 2D scanners or with Risley prisms. For galvanometer scanners the optimal scanning functions studied in a series of previous works are pointed out; these functions offer a higher temporal efficiency/duty cycle of the scanning process, as well as artifact-free OCT images. The testing of the handheld scanning probes in dental applications is presented, for metal ceramic prosthesis and for teeth.

A revised design for microarray experiments to account for experimental noise and uncertainty of probe response.

PubMed

Pozhitkov, Alex E; Noble, Peter A; Bryk, Jarosław; Tautz, Diethard

2014-01-01

Although microarrays are analysis tools in biomedical research, they are known to yield noisy output that usually requires experimental confirmation. To tackle this problem, many studies have developed rules for optimizing probe design and devised complex statistical tools to analyze the output. However, less emphasis has been placed on systematically identifying the noise component as part of the experimental procedure. One source of noise is the variance in probe binding, which can be assessed by replicating array probes. The second source is poor probe performance, which can be assessed by calibrating the array based on a dilution series of target molecules. Using model experiments for copy number variation and gene expression measurements, we investigate here a revised design for microarray experiments that addresses both of these sources of variance. Two custom arrays were used to evaluate the revised design: one based on 25 mer probes from an Affymetrix design and the other based on 60 mer probes from an Agilent design. To assess experimental variance in probe binding, all probes were replicated ten times. To assess probe performance, the probes were calibrated using a dilution series of target molecules and the signal response was fitted to an adsorption model. We found that significant variance of the signal could be controlled by averaging across probes and removing probes that are nonresponsive or poorly responsive in the calibration experiment. Taking this into account, one can obtain a more reliable signal with the added option of obtaining absolute rather than relative measurements. The assessment of technical variance within the experiments, combined with the calibration of probes allows to remove poorly responding probes and yields more reliable signals for the remaining ones. Once an array is properly calibrated, absolute quantification of signals becomes straight forward, alleviating the need for normalization and reference hybridizations.

The role of curvature in the slowing down acceleration scenario

NASA Astrophysics Data System (ADS)

Cárdenas, Víctor H.; Rivera, Marco

2012-04-01

We introduce the curvature Ωk as a new free parameter in the Bayesian analysis using SNIa, BAO and CMB data, in a model with variable equation of state parameter w(z). We compare the results using both the Constitution and Union 2 data sets, and also study possible low redshift transitions in the deceleration parameter q(z). We found that, incorporating Ωk in the analysis, it is possible to make all the three observational probes consistent using both SNIa data sets. Our results support dark energy evolution at small redshift, and show that the tension between small and large redshift probes is ameliorated. However, although the tension decreases, it is still not possible to find a consensus set of parameters that fit all the three data set using the Chevalier-Polarski-Linder CPL parametrization.

Probing gravity theory and cosmic acceleration using (in)consistency tests between cosmological data sets

NASA Astrophysics Data System (ADS)

Ishak-Boushaki, Mustapha B.

2018-06-01

Testing general relativity at cosmological scales and probing the cause of cosmic acceleration are among important objectives targeted by incoming and future astronomical surveys and experiments. I present our recent results on (in)consistency tests that can provide insights about the underlying gravity theory and cosmic acceleration using cosmological data sets. We use new statistical measures that can detect discordances between data sets when present. We use an algorithmic procedure based on these new measures that is able to identify in some cases whether an inconsistency is due to problems related to systematic effects in the data or to the underlying model. Some recent published tensions between data sets are also examined using our formalism, including the Hubble constant measurements, Planck and Large-Scale-Structure. (Work supported in part by NSF under Grant No. AST-1517768).

A Critical Evaluation of Studies Employing Alkenyl Halide ’Mechanistic Probe’ as Indicators of Single Electron Transfer Processes.

DTIC Science & Technology

1987-07-07

College Station, TX 77843 Pittsburgh, PA 15260 Introduction: Chemical reactions come about through the reorganization of valence electrons. The notion...Contmnue on reverie of necessary and odentify 0)’ Wooc ,7umor r) Recently it has been suggested that many reaction traditionally classed in polar terms may...evaluates the utility of these alkenyl halide probes as mechanistic probes for SET. Reactions which interfere with the standard analysis ~ include the

Observations of mesospheric turbulence by rocket probe and VHF radar, part 2.4A

NASA Astrophysics Data System (ADS)

Royrvik, O.; Smith, L. G.

1984-12-01

Data from the Jicamarca VHF radar and from a Languir probe fine-structure on a Nike Orion rocket launched from Punto Lobos, Peru, have been compared. A single mesospheric scattering layer was observed by the radar. The Langmuir probe detected irregularities in the electron-density profile in a narrow region between 85.2 and 86.6 km. It appears from a comparison between these two data sets that turbulence in the neutral atmosphere is the mechanism generating the refractive index irregularities.

Phase I Experimental Testing of a Generic Submarine Model in the DSTO Low Speed Wind Tunnel

DTIC Science & Technology

2012-07-01

used during the tests , along with the test methodology . A sub-set of the data gathered is also presented and briefly discussed. Overall, the force...total pressure probe when positioned close to the model. 4. Results Selected results from the testing of the generic submarine model in the...Appendix B summaries the test conditions. 4.3.1 Smoke Generator and Probe An Aerotech smoke generator and probe were used for visualisation of

Observations of Mesospheric Turbulence by Rocket Probe and VHF Radar, Part 2.4A

NASA Technical Reports Server (NTRS)

Royrvik, O.; Smith, L. G.

1984-01-01

Data from the Jicamarca VHF radar and from a Languir probe fine-structure on a Nike Orion rocket launched from Punto Lobos, Peru, have been compared. A single mesospheric scattering layer was observed by the radar. The Langmuir probe detected irregularities in the electron-density profile in a narrow region between 85.2 and 86.6 km. It appears from a comparison between these two data sets that turbulence in the neutral atmosphere is the mechanism generating the refractive index irregularities.

Langmuir probe diagnostic suite in the C-2 field-reversed configuration

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

Roche, T., E-mail: troche@trialphaenergy.com; Armstrong, S.; Knapp, K.

2014-11-15

Several in situ probes have been designed and implemented into the diagnostic array of the C-2 field-reversed configuration (FRC) at Tri Alpha Energy [M. Tuszewski et al. (the TAE Team), Phys. Rev. Lett. 108, 255008 (2012)]. The probes are all variations on the traditional Langmuir probe. They include linear arrays of triple probes, linear arrays of single-tipped swept probes, a multi-faced Gundestrup probe, and an ion-sensitive probe. The probes vary from 5 to 7 mm diameter in size to minimize plasma perturbations. They also have boron nitride outer casings that prevent unwanted electrical breakdown and reduce the introduction of impurities.more » The probes are mounted on motorized linear-actuators allowing for programmatic scans of the various plasma parameters over the course of several shots. Each probe has a custom set of electronics that allows for measurement of the desired signals. High frequency ( > 5MHz) analog optical-isolators ensure that plasma parameters can be measured at sub-microsecond time scales while providing electrical isolation between machine and data acquisition systems. With these probes time-resolved plasma parameters (temperature, density, spatial potential, flow, and electric field) can be directly/locally measured in the FRC jet and edge/scrape-off layer.« less

Phylogenetics of moth-like butterflies (Papilionoidea: Hedylidae) based on a new 13-locus target capture probe set.

PubMed

Kawahara, Akito Y; Breinholt, Jesse W; Espeland, Marianne; Storer, Caroline; Plotkin, David; Dexter, Kelly M; Toussaint, Emmanuel F A; St Laurent, Ryan A; Brehm, Gunnar; Vargas, Sergio; Forero, Dimitri; Pierce, Naomi E; Lohman, David J

2018-06-11

The Neotropical moth-like butterflies (Hedylidae) are perhaps the most unusual butterfly family. In addition to being species-poor, this family is predominantly nocturnal and has anti-bat ultrasound hearing organs. Evolutionary relationships among the 36 described species are largely unexplored. A new, target capture, anchored hybrid enrichment probe set ('BUTTERFLY2.0') was developed to infer relationships of hedylids and some of their butterfly relatives. The probe set includes 13 genes that have historically been used in butterfly phylogenetics. Our dataset comprised of up to 10,898 aligned base pairs from 22 hedylid species and 19 outgroups. Eleven of the thirteen loci were successfully captured from all samples, and the remaining loci were captured from ≥94% of samples. The inferred phylogeny was consistent with recent molecular studies by placing Hedylidae sister to Hesperiidae, and the tree had robust support for 80% of nodes. Our results are also consistent with morphological studies, with Macrosoma tipulata as the sister species to all remaining hedylids, followed by M. semiermis sister to the remaining species in the genus. We tested the hypothesis that nocturnality evolved once from diurnality in Hedylidae, and demonstrate that the ancestral condition was likely diurnal, with a shift to nocturnality early in the diversification of this family. The BUTTERFLY2.0 probe set includes standard butterfly phylogenetics markers, captures sequences from decades-old museum specimens, and is a cost-effective technique to infer phylogenetic relationships of the butterfly tree of life. Copyright © 2018 Elsevier Inc. All rights reserved.

Multiplex ligation-dependent probe amplification analysis on capillary electrophoresis instruments for a rapid gene copy number study.

PubMed

Jankowski, Stéphane; Currie-Fraser, Erica; Xu, Licen; Coffa, Jordy

2008-09-01

Annotated DNA samples that had been previously analyzed were tested using multiplex ligation-dependent probe amplification (MLPA) assays containing probes targeting BRCA1, BRCA2, and MMR (MLH1/MSH2 genes) and the 9p21 chromosomal region. MLPA polymerase chain reaction products were separated on a capillary electrophoresis platform, and the data were analyzed using GeneMapper v4.0 software (Applied Biosystems, Foster City, CA). After signal normalization, loci regions that had undergone deletions or duplications were identified using the GeneMapper Report Manager and verified using the DyeScale functionality. The results highlight an easy-to-use, optimal sample preparation and analysis workflow that can be used for both small- and large-scale studies.

Detection of iron-depositing Pedomicrobium species in native biofilms from the Odertal National Park by a new, specific FISH probe.

PubMed

Braun, Burga; Richert, Inga; Szewzyk, Ulrich

2009-10-01

Iron-depositing bacteria play an important role in technical water systems (water wells, distribution systems) due to their intense deposition of iron oxides and resulting clogging effects. Pedomicrobium is known as iron- and manganese-oxidizing and accumulating bacterium. The ability to detect and quantify members of this species in biofilm communities is therefore desirable. In this study the fluorescence in situ hybridization (FISH) method was used to detect Pedomicrobium in iron and manganese incrusted biofilms. Based on comparative sequence analysis, we designed and evaluated a specific oligonucleotide probe (Pedo 1250) complementary to the hypervariable region 8 of the 16S rRNA gene for Pedomicrobium. Probe specificities were tested against 3 different strains of Pedomicrobium and Sphingobium yanoikuyae as non-target organism. Using optimized conditions the probe hybridized with all tested strains of Pedomicrobium with an efficiency of 80%. The non-target organism showed no hybridization signals. The new FISH probe was applied successfully for the in situ detection of Pedomicrobium in different native, iron-depositing biofilms. The hybridization results of native bioflims using probe Pedo_1250 agreed with the results of the morphological structure of Pedomicrobium bioflims based on scanning electron microscopy.

Phosphorescent probes for two-photon microscopy of oxygen (Conference Presentation)

NASA Astrophysics Data System (ADS)

Vinogradov, Sergei A.; Esipova, Tatiana V.

2016-03-01

The ability to quantify oxygen in vivo in 3D with high spatial and temporal resolution is much needed in many areas of biological research. Our laboratory has been developing the phosphorescence quenching technique for biological oximetry - an optical method that possesses intrinsic microscopic capability. In the past we have developed dendritically protected oxygen probes for quantitative imaging of oxygen in tissue. More recently we expanded our design on special two-photon enhanced phosphorescent probes. These molecules brought about first demonstrations of the two-photon phosphorescence lifetime microscopy (2PLM) of oxygen in vivo, providing new information for neouroscience and stem cell biology. However, current two-photon oxygen probes suffer from a number of limitations, such as sub-optimal brightness and high cost of synthesis, which dramatically reduce imaging performance and limit usability of the method. In this paper we discuss principles of 2PLM and address the interplay between the probe chemistry, photophysics and spatial and temporal imaging resolution. We then present a new approach to brightly phosphorescent chromophores with internally enhanced two-photon absorption cross-sections, which pave a way to a new generation of 2PLM probes.

Versatile Gaussian probes for squeezing estimation

NASA Astrophysics Data System (ADS)

Rigovacca, Luca; Farace, Alessandro; Souza, Leonardo A. M.; De Pasquale, Antonella; Giovannetti, Vittorio; Adesso, Gerardo

2017-05-01

We consider an instance of "black-box" quantum metrology in the Gaussian framework, where we aim to estimate the amount of squeezing applied on an input probe, without previous knowledge on the phase of the applied squeezing. By taking the quantum Fisher information (QFI) as the figure of merit, we evaluate its average and variance with respect to this phase in order to identify probe states that yield good precision for many different squeezing directions. We first consider the case of single-mode Gaussian probes with the same energy, and find that pure squeezed states maximize the average quantum Fisher information (AvQFI) at the cost of a performance that oscillates strongly as the squeezing direction is changed. Although the variance can be brought to zero by correlating the probing system with a reference mode, the maximum AvQFI cannot be increased in the same way. A different scenario opens if one takes into account the effects of photon losses: coherent states represent the optimal single-mode choice when losses exceed a certain threshold and, moreover, correlated probes can now yield larger AvQFI values than all single-mode states, on top of having zero variance.

Investigations of the fabrication and the surface-enhanced Raman scattering detection applications for tapered fiber probes prepared with the laser-induced chemical deposition method.

PubMed

Fan, Qunfang; Cao, Jie; Liu, Ye; Yao, Bo; Mao, Qinghe

2013-09-01

The process of depositing nanoparticles onto tapered fiber probes with the laser-induced chemical deposition method (LICDM) and the surface-enhanced Raman scattering (SERS) detection performance of the prepared probes are experimentally investigated in this paper. Our results show that the nanoparticle-deposited tapered fiber probes prepared with the LICDM method depend strongly on the value of the cone angle. For small-angle tapered probes the nanoparticle-deposited areas are only focused at the taper tips, because the taper surfaces are mainly covered by a relatively low-intensity evanescent field. By lengthening the reaction time or increasing the induced power or solution concentration, it is still possible to deposit nanoparticles on small-angle tapers with the light-scattering effect. With 4-aminothiophenol as the testing molecule, it was found that for given preparation conditions, the cone angles for the tapered probes with the highest SERS spectral intensities for different excitation laser powers are almost the same. However, such an optimal cone angle is determined by the combined effects of both the localized surface plasmon resonance strength and the transmission loss generated by the nanoparticles deposited.

Ultra-compact switchable SLO/OCT handheld probe design

NASA Astrophysics Data System (ADS)

LaRocca, Francesco; Nankivil, Derek; DuBose, Theodore; Farsiu, Sina; Izatt, Joseph A.

2015-03-01

Handheld scanning laser ophthalmoscopy (SLO) and optical coherence tomography (OCT) systems facilitate imaging of young children and subjects that have difficulty fixating. More compact and lightweight probes allow for better portability and increased comfort for the operator of the handheld probe. We describe a very compact, novel SLO and OCT handheld probe design. A single 2D microelectromechanical systems (MEMS) scanner and a custom optical design using a converging beam prior to the scanner permitted significant reduction in the system size. Our design utilized a combination of commercial and custom optics that were optimized in Zemax to achieve near diffraction-limited resolution of 8 μm over a 7° field of view. The handheld probe has a form factor of 7 x 6 x 2.5 cm and a weight of only 94 g, which is over an order of magnitude lighter than prior SLO-OCT handheld probes. Images were acquired from a normal subject with an incident power on the eye under the ANSI limit. With this device, which is the world's lightest and smallest SLO-OCT system, we were able to visualize parafoveal cone photoreceptors and nerve fiber bundles without the use of adaptive optics.

Development of eddy current probe for fiber orientation assessment in carbon fiber composites

NASA Astrophysics Data System (ADS)

Wincheski, Russell A.; Zhao, Selina

2018-04-01

Measurement of the fiber orientation in a carbon fiber composite material is crucial in understanding the load carrying capability of the structure. As manufacturing conditions including resin flow and molding pressures can alter fiber orientation, verification of the as-designed fiber layup is necessary to ensure optimal performance of the structure. In this work, the development of an eddy current probe and data processing technique for analysis of fiber orientation in carbon fiber composites is presented. A proposed directional eddy current probe is modeled and its response to an anisotropic multi-layer conductor simulated. The modeling results are then used to finalize specifications of the eddy current probe. Experimental testing of the fabricated probe is presented for several samples including a truncated pyramid part with complex fiber orientation draped to the geometry for resin transfer molding. The inductively coupled single sided measurement enables fiber orientation characterization through the thickness of the part. The fast and cost-effective technique can be applied as a spot check or as a surface map of the fiber orientations across the structure. This paper will detail the results of the probe design, computer simulations, and experimental results.

A model of binding on DNA microarrays: understanding the combined effect of probe synthesis failure, cross-hybridization, DNA fragmentation and other experimental details of affymetrix arrays

PubMed Central

2012-01-01

Background DNA microarrays are used both for research and for diagnostics. In research, Affymetrix arrays are commonly used for genome wide association studies, resequencing, and for gene expression analysis. These arrays provide large amounts of data. This data is analyzed using statistical methods that quite often discard a large portion of the information. Most of the information that is lost comes from probes that systematically fail across chips and from batch effects. The aim of this study was to develop a comprehensive model for hybridization that predicts probe intensities for Affymetrix arrays and that could provide a basis for improved microarray analysis and probe development. The first part of the model calculates probe binding affinities to all the possible targets in the hybridization solution using the Langmuir isotherm. In the second part of the model we integrate details that are specific to each experiment and contribute to the differences between hybridization in solution and on the microarray. These details include fragmentation, wash stringency, temperature, salt concentration, and scanner settings. Furthermore, the model fits probe synthesis efficiency and target concentration parameters directly to the data. All the parameters used in the model have a well-established physical origin. Results For the 302 chips that were analyzed the mean correlation between expected and observed probe intensities was 0.701 with a range of 0.88 to 0.55. All available chips were included in the analysis regardless of the data quality. Our results show that batch effects arise from differences in probe synthesis, scanner settings, wash strength, and target fragmentation. We also show that probe synthesis efficiencies for different nucleotides are not uniform. Conclusions To date this is the most complete model for binding on microarrays. This is the first model that includes both probe synthesis efficiency and hybridization kinetics/cross-hybridization. These two factors are sequence dependent and have a large impact on probe intensity. The results presented here provide novel insight into the effect of probe synthesis errors on Affymetrix microarrays; furthermore, the algorithms developed in this work provide useful tools for the analysis of cross-hybridization, probe synthesis efficiency, fragmentation, wash stringency, temperature, and salt concentration on microarray intensities. PMID:23270536

Neuroeconomic approaches to mental disorders

PubMed Central

Kishida, Kenneth T.; King-Casas, Brooks; Montague, P. Read

2010-01-01

The pervasiveness of decision-making in every area of human endeavor highlights the importance of understanding choice mechanisms and their detailed relationship to underlying neurobiological function. This review surveys the recent and productive application of game theoretic probes (economic games) to mental disorders. Such games typically possess concrete concepts of optimal play, thus providing quantitative ways to track when subjects’ choices match or deviate from optimal. This feature equips economic games with natural classes of control signals that should guide learning and choice in the agents that play them. These signals and their underlying physical correlates in the brain are now being used to generate objective biomarkers that may prove useful for exposing and understanding the neurogenetic basis of normal and pathological human cognition. Thus, game theoretic probes represent some of the first steps toward producing computationally principled, objective measures of cognitive function and dysfunction useful for the diagnosis, treatment and understanding of mental disorders. PMID:20797532

Probing Photocurrent Nonuniformities in the Subcells of Monolithic Perovskite/Silicon Tandem Solar Cells.

PubMed

Song, Zhaoning; Werner, Jérémie; Shrestha, Niraj; Sahli, Florent; De Wolf, Stefaan; Niesen, Björn; Watthage, Suneth C; Phillips, Adam B; Ballif, Christophe; Ellingson, Randy J; Heben, Michael J

2016-12-15

Perovskite/silicon tandem solar cells with high power conversion efficiencies have the potential to become a commercially viable photovoltaic option in the near future. However, device design and optimization is challenging because conventional characterization methods do not give clear feedback on the localized chemical and physical factors that limit performance within individual subcells, especially when stability and degradation is a concern. In this study, we use light beam induced current (LBIC) to probe photocurrent collection nonuniformities in the individual subcells of perovskite/silicon tandems. The choices of lasers and light biasing conditions allow efficiency-limiting effects relating to processing defects, optical interference within the individual cells, and the evolution of water-induced device degradation to be spatially resolved. The results reveal several types of microscopic defects and demonstrate that eliminating these and managing the optical properties within the multilayer structures will be important for future optimization of perovskite/silicon tandem solar cells.

Stochastic hyperfine interactions modeling library-Version 2

NASA Astrophysics Data System (ADS)

Zacate, Matthew O.; Evenson, William E.

2016-02-01

The stochastic hyperfine interactions modeling library (SHIML) provides a set of routines to assist in the development and application of stochastic models of hyperfine interactions. The library provides routines written in the C programming language that (1) read a text description of a model for fluctuating hyperfine fields, (2) set up the Blume matrix, upon which the evolution operator of the system depends, and (3) find the eigenvalues and eigenvectors of the Blume matrix so that theoretical spectra of experimental techniques that measure hyperfine interactions can be calculated. The optimized vector and matrix operations of the BLAS and LAPACK libraries are utilized. The original version of SHIML constructed and solved Blume matrices for methods that measure hyperfine interactions of nuclear probes in a single spin state. Version 2 provides additional support for methods that measure interactions on two different spin states such as Mössbauer spectroscopy and nuclear resonant scattering of synchrotron radiation. Example codes are provided to illustrate the use of SHIML to (1) generate perturbed angular correlation spectra for the special case of polycrystalline samples when anisotropy terms of higher order than A22 can be neglected and (2) generate Mössbauer spectra for polycrystalline samples for pure dipole or pure quadrupole transitions.

Minimum Number of Observation Points for LEO Satellite Orbit Estimation by OWL Network

NASA Astrophysics Data System (ADS)

Park, Maru; Jo, Jung Hyun; Cho, Sungki; Choi, Jin; Kim, Chun-Hwey; Park, Jang-Hyun; Yim, Hong-Suh; Choi, Young-Jun; Moon, Hong-Kyu; Bae, Young-Ho; Park, Sun-Youp; Kim, Ji-Hye; Roh, Dong-Goo; Jang, Hyun-Jung; Park, Young-Sik; Jeong, Min-Ji

2015-12-01

By using the Optical Wide-field Patrol (OWL) network developed by the Korea Astronomy and Space Science Institute (KASI) we generated the right ascension and declination angle data from optical observation of Low Earth Orbit (LEO) satellites. We performed an analysis to verify the optimum number of observations needed per arc for successful estimation of orbit. The currently functioning OWL observatories are located in Daejeon (South Korea), Songino (Mongolia), and Oukaïmeden (Morocco). The Daejeon Observatory is functioning as a test bed. In this study, the observed targets were Gravity Probe B, COSMOS 1455, COSMOS 1726, COSMOS 2428, SEASAT 1, ATV-5, and CryoSat-2 (all in LEO). These satellites were observed from the test bed and the Songino Observatory of the OWL network during 21 nights in 2014 and 2015. After we estimated the orbit from systematically selected sets of observation points (20, 50, 100, and 150) for each pass, we compared the difference between the orbit estimates for each case, and the Two Line Element set (TLE) from the Joint Space Operation Center (JSpOC). Then, we determined the average of the difference and selected the optimal observation points by comparing the average values.

Database resources of the National Center for Biotechnology Information

PubMed Central

2015-01-01

The National Center for Biotechnology Information (NCBI) provides a large suite of online resources for biological information and data, including the GenBank® nucleic acid sequence database and the PubMed database of citations and abstracts for published life science journals. Additional NCBI resources focus on literature (Bookshelf, PubMed Central (PMC) and PubReader); medical genetics (ClinVar, dbMHC, the Genetic Testing Registry, HIV-1/Human Protein Interaction Database and MedGen); genes and genomics (BioProject, BioSample, dbSNP, dbVar, Epigenomics, Gene, Gene Expression Omnibus (GEO), Genome, HomoloGene, the Map Viewer, Nucleotide, PopSet, Probe, RefSeq, Sequence Read Archive, the Taxonomy Browser, Trace Archive and UniGene); and proteins and chemicals (Biosystems, COBALT, the Conserved Domain Database (CDD), the Conserved Domain Architecture Retrieval Tool (CDART), the Molecular Modeling Database (MMDB), Protein Clusters, Protein and the PubChem suite of small molecule databases). The Entrez system provides search and retrieval operations for many of these databases. Augmenting many of the Web applications are custom implementations of the BLAST program optimized to search specialized data sets. All of these resources can be accessed through the NCBI home page at http://www.ncbi.nlm.nih.gov. PMID:25398906

Left Posterior Parietal Cortex Participates in Both Task Preparation and Episodic Retrieval

PubMed Central

Phillips, Jeffrey S.; Velanova, Katerina; Wolk, David A.; Wheeler, Mark E.

2012-01-01

Optimal memory retrieval depends not only on the fidelity of stored information, but also on the attentional state of the subject. Factors such as mental preparedness to engage in stimulus processing can facilitate or hinder memory retrieval. The current study used functional magnetic resonance imaging (fMRI) to distinguish preparatory brain activity before episodic and semantic retrieval tasks from activity associated with retrieval itself. A catch-trial imaging paradigm permitted separation of neural responses to preparatory task cues and memory probes. Episodic and semantic task preparation engaged a common set of brain regions, including the bilateral intraparietal sulcus (IPS), left fusiform gyrus (FG), and the pre-supplementary motor area (pre-SMA). In the subsequent retrieval phase, the left IPS was among a set of frontoparietal regions that responded differently to old and new stimuli. In contrast, the right IPS responded to preparatory cues with little modulation during memory retrieval. The findings support a strong left-lateralization of retrieval success effects in left parietal cortex, and further indicate that left IPS performs operations that are common to both task preparation and memory retrieval. Such operations may be related to attentional control, monitoring of stimulus relevance, or retrieval. PMID:19285142

Optimal inverse functions created via population-based optimization.

PubMed

Jennings, Alan L; Ordóñez, Raúl

2014-06-01

Finding optimal inputs for a multiple-input, single-output system is taxing for a system operator. Population-based optimization is used to create sets of functions that produce a locally optimal input based on a desired output. An operator or higher level planner could use one of the functions in real time. For the optimization, each agent in the population uses the cost and output gradients to take steps lowering the cost while maintaining their current output. When an agent reaches an optimal input for its current output, additional agents are generated in the output gradient directions. The new agents then settle to the local optima for the new output values. The set of associated optimal points forms an inverse function, via spline interpolation, from a desired output to an optimal input. In this manner, multiple locally optimal functions can be created. These functions are naturally clustered in input and output spaces allowing for a continuous inverse function. The operator selects the best cluster over the anticipated range of desired outputs and adjusts the set point (desired output) while maintaining optimality. This reduces the demand from controlling multiple inputs, to controlling a single set point with no loss in performance. Results are demonstrated on a sample set of functions and on a robot control problem.

Molecular dynamics force-field refinement against quasi-elastic neutron scattering data

DOE PAGES

Borreguero Calvo, Jose M.; Lynch, Vickie E.

2015-11-23

Quasi-elastic neutron scattering (QENS) is one of the experimental techniques of choice for probing the dynamics at length and time scales that are also in the realm of full-atom molecular dynamics (MD) simulations. This overlap enables extension of current fitting methods that use time-independent equilibrium measurements to new methods fitting against dynamics data. We present an algorithm that fits simulation-derived incoherent dynamical structure factors against QENS data probing the diffusive dynamics of the system. We showcase the difficulties inherent to this type of fitting problem, namely, the disparity between simulation and experiment environment, as well as limitations in the simulationmore » due to incomplete sampling of phase space. We discuss a methodology to overcome these difficulties and apply it to a set of full-atom MD simulations for the purpose of refining the force-field parameter governing the activation energy of methyl rotation in the octa-methyl polyhedral oligomeric silsesquioxane molecule. Our optimal simulated activation energy agrees with the experimentally derived value up to a 5% difference, well within experimental error. We believe the method will find applicability to other types of diffusive motions and other representation of the systems such as coarse-grain models where empirical fitting is essential. In addition, the refinement method can be extended to the coherent dynamic structure factor with no additional effort.« less

Beyond vanilla dark matter: New channels in the multifaceted search for dark matter

NASA Astrophysics Data System (ADS)

Yaylali, David E.

Though we are extremely confident that non-baryonic dark matter exists in our universe, very little is known about its fundamental nature or its relationship with the Standard Model. Guided by theoretical motivations, a desire for generality in our experimental strategies, and a certain amount of hopeful optimism, we have established a basic framework and set of assumptions about the dark sector which we are now actively testing. After years of probing the parameter spaces of these vanilla dark-matter scenarios, through a variety of different search channels, a conclusive direct (non-gravitational) discovery of dark matter eludes us. This very well may suggest that our first-order expectations of the dark sector are too simplistic. This work describes two ways in which we can expand the experimental reach of vanilla dark-matter scenarios while maintaining the model-independent generality which is at this point still warranted. One way in which this is done is to consider coupling structures between the SM and the dark sector other than the two canonical types --- scalar and axial-vector --- leading to spin dependent and independent interactions at direct-detection experiments. The second way we generalize the vanilla scenarios is to consider multi-component dark sectors. We find that both of these generalizations lead to new and interesting phenomenology, and provide a richer complementarity structure between the different experimental probes we are using to search for dark matter.

Structure-based design and profiling of novel 17β-HSD14 inhibitors.

PubMed

Braun, Florian; Bertoletti, Nicole; Möller, Gabriele; Adamski, Jerzy; Frotscher, Martin; Guragossian, Nathalie; Madeira Gírio, Patrícia Alexandra; Le Borgne, Marc; Ettouati, Laurent; Falson, Pierre; Müller, Sebastian; Vollmer, Günther; Heine, Andreas; Klebe, Gerhard; Marchais-Oberwinkler, Sandrine

2018-05-22

The human enzyme 17β-hydroxysteroid dehydrogenase 14 (17β-HSD14) oxidizes the hydroxyl group at position 17 of estradiol and 5-androstenediol using NAD + as cofactor. However, the physiological role of the enzyme remains unclear. We recently described the first class of nonsteroidal inhibitors for this enzyme with compound 1 showing a high 17β-HSD14 inhibitory activity. Its crystal structure was used as starting point for a structure-based optimization in this study. The goal was to develop a promising chemical probe to further investigate the enzyme. The newly designed compounds revealed mostly very high inhibition of the enzyme and for seven of them the crystal structures of the corresponding inhibitor-enzyme complexes were resolved. The crystal structures disclosed that a small change in the substitution pattern of the compounds resulted in an alternative binding mode for one inhibitor. The profiling of a set of the most potent inhibitors identified 13 (K i  = 9 nM) with a good selectivity profile toward three 17β-HSDs and the estrogen receptor alpha. This inhibitor displayed no cytotoxicity, good solubility, and auspicious predicted bioavailability. Overall, 13 is a highly interesting 17β-HSD14 inhibitor, which might be used as chemical probe for further investigation of the target enzyme. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

A magneto-DNA nanoparticle system for the rapid and sensitive diagnosis of enteric fever

PubMed Central

Park, Ki Soo; Chung, Hyun Jung; Khanam, Farhana; Lee, Hakho; Rashu, Rasheduzzaman; Bhuiyan, Md. Taufiqur; Berger, Amanda; Harris, Jason B.; Calderwood, Stephen B.; Ryan, Edward T.; Qadri, Firdausi; Weissleder, Ralph; Charles, Richelle C.

2016-01-01

There is currently no widely available optimal assay for diagnosing patients with enteric fever. Here we present a novel assay designed to detect amplified Salmonella nucleic acid (mRNA) using magneto-DNA probes and a miniaturized nuclear magnetic resonance device. We designed primers for genes specific to S. Typhi, S. Paratyphi A, and genes conserved among Salmonella enterica spp. and utilized strongly magnetized nanoparticles to enhance the detection signal. Blood samples spiked with in vitro grown S. Typhi, S. Paratyphi A, S. Typhimurium, and E. coli were used to confirm the specificity of each probe-set, and serial 10-fold dilutions were used to determine the limit of the detection of the assay, 0.01–1.0 CFU/ml. For proof of principle, we applied our assay to 0.5 mL blood samples from 5 patients with culture-confirmed enteric fever from Bangladesh in comparison to 3 healthy controls. We were able to detect amplified target cDNA in all 5 cases of enteric fever; no detectable signal was seen in the healthy controls. Our results suggest that a magneto-DNA nanoparticle system, with an assay time from blood collection of 3.5 hours, may be a promising platform for the rapid and culture-free diagnosis of enteric fever and non-typhoidal Salmonella bacteremia. PMID:27605393

Designing an optimum pulsed magnetic field by a resistance/self-inductance/capacitance discharge system and alignment of carbon nanotubes embedded in polypyrrole matrix

NASA Astrophysics Data System (ADS)

Kazemikia, Kaveh; Bonabi, Fahimeh; Asadpoorchallo, Ali; Shokrzadeh, Majid

2015-02-01

In this work, an optimized pulsed magnetic field production apparatus is designed based on a RLC (Resistance/Self-inductance/Capacitance) discharge circuit. An algorithm for designing an optimum magnetic coil is presented. The coil is designed to work at room temperature. With a minor physical reinforcement, the magnetic flux density can be set up to 12 Tesla with 2 ms duration time. In our design process, the magnitude and the length of the magnetic pulse are the desired parameters. The magnetic field magnitude in the RLC circuit is maximized on the basis of the optimal design of the coil. The variables which are used in the optimization process are wire diameter and the number of coil layers. The coil design ensures the critically damped response of the RLC circuit. The electrical, mechanical, and thermal constraints are applied to the design process. A locus of probable magnetic flux density values versus wire diameter and coil layer is provided to locate the optimum coil parameters. Another locus of magnetic flux density values versus capacitance and initial voltage of the RLC circuit is extracted to locate the optimum circuit parameters. Finally, the application of high magnetic fields on carbon nanotube-PolyPyrrole (CNT-PPy) nano-composite is presented. Scanning probe microscopy technique is used to observe the orientation of CNTs after exposure to a magnetic field. The result shows alignment of CNTs in a 10.3 Tesla, 1.5 ms magnetic pulse.

Shortcomings of adherence counselling provided to caregivers of children receiving antiretroviral therapy in rural South Africa.

PubMed

Coetzee, Bronwyne; Kagee, Ashraf; Bland, Ruth

2016-03-01

In order to achieve optimal benefits of antiretroviral therapy (ART), caregivers of children receiving ART are required to attend routine clinic visits monthly and administer medication to the child as prescribed. Yet, the level of adherence to these behaviours varies considerably in many settings. As a way to achieve optimal adherence in rural KwaZulu-Natal, caregivers are required to attend routine counselling sessions at HIV treatment clinics that are centred on imparting information, motivation, and behavioural skills related to medication administration. According to the information-motivation-behavioural skills model, information related to adherence, motivation, and behavioural skills are necessary and fundamental determinants of adherence to ART. The purpose of the study was to observe and document the content of adherence counselling sessions that caregivers attending rural clinics in KwaZulu Natal receive. We observed 25 adherence counselling sessions, which lasted on average 8.1 minutes. Counselling typically consisted of counsellors recording patient attendance, reporting CD4 count and viral load results to caregivers, emphasising dose times, and asking caregivers to name their medications and dosage amounts. Patients were seldom asked to demonstrate how they measure the medication. They were also not probed for problems regarding treatment, even when an unsuppressed VL was reported to a caregiver. This paper calls attention to the sub-optimal level of counselling provided to patients on ART and the urgent need to standardise and improve the training, support, and debriefing provided to counsellors.

Open source machine-learning algorithms for the prediction of optimal cancer drug therapies.

PubMed

Huang, Cai; Mezencev, Roman; McDonald, John F; Vannberg, Fredrik

2017-01-01

Precision medicine is a rapidly growing area of modern medical science and open source machine-learning codes promise to be a critical component for the successful development of standardized and automated analysis of patient data. One important goal of precision cancer medicine is the accurate prediction of optimal drug therapies from the genomic profiles of individual patient tumors. We introduce here an open source software platform that employs a highly versatile support vector machine (SVM) algorithm combined with a standard recursive feature elimination (RFE) approach to predict personalized drug responses from gene expression profiles. Drug specific models were built using gene expression and drug response data from the National Cancer Institute panel of 60 human cancer cell lines (NCI-60). The models are highly accurate in predicting the drug responsiveness of a variety of cancer cell lines including those comprising the recent NCI-DREAM Challenge. We demonstrate that predictive accuracy is optimized when the learning dataset utilizes all probe-set expression values from a diversity of cancer cell types without pre-filtering for genes generally considered to be "drivers" of cancer onset/progression. Application of our models to publically available ovarian cancer (OC) patient gene expression datasets generated predictions consistent with observed responses previously reported in the literature. By making our algorithm "open source", we hope to facilitate its testing in a variety of cancer types and contexts leading to community-driven improvements and refinements in subsequent applications.

Probe for high resolution NMR with sample reorientation

DOEpatents

Pines, A.; Samoson, A.

1990-02-06

An improved NMR probe and method are described which substantially improve the resolution of NMR measurements made on powdered or amorphous or otherwise orientationally disordered samples. The apparatus mechanically varies the orientation of the sample such that the time average of two or more sets of spherical harmonic functions are zero. 8 figs.

Teaching Special Education Teachers How to Conduct Functional Analysis in Natural Settings

ERIC Educational Resources Information Center

Erbas, Dilek; Tekin-Iftar, Elif; Yucesoy, Serife

2006-01-01

Effects of a training program utilized to teach how to conduct functional analysis process to teachers of children with developmental disabilities was examined. Furthermore, teachers' opinions regarding this process were investigated. A multiple probe design across subjects with probe conditions was used. Teacher training was in two phases. In the…

Astigmatism corrected common path probe for optical coherence tomography.

PubMed

Singh, Kanwarpal; Yamada, Daisuke; Tearney, Guillermo

2017-03-01

Optical coherence tomography (OCT) catheters for intraluminal imaging are subject to various artifacts due to reference-sample arm dispersion imbalances and sample arm beam astigmatism. The goal of this work was to develop a probe that minimizes such artifacts. Our probe was fabricated using a single mode fiber at the tip of which a glass spacer and graded index objective lens were spliced to achieve the desired focal distance. The signal was reflected using a curved reflector to correct for astigmatism caused by the thin, protective, transparent sheath that surrounds the optics. The probe design was optimized using Zemax, a commercially available optical design software. Common path interferometric operation was achieved using Fresnel reflection from the tip of the focusing graded index objective lens. The performance of the probe was tested using a custom designed spectrometer-based OCT system. The probe achieved an axial resolution of 15.6 μm in air, a lateral resolution 33 μm, and a sensitivity of 103 dB. A scattering tissue phantom was imaged to test the performance of the probe for astigmatism correction. Images of the phantom confirmed that this common-path, astigmatism-corrected OCT imaging probe had minimal artifacts in the axial, and lateral dimensions. In this work, we developed an astigmatism-corrected, common path probe that minimizes artifacts associated with standard OCT probes. This design may be useful for OCT applications that require high axial and lateral resolutions. Lasers Surg. Med. 49:312-318, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Fluorescent signatures for variable DNA sequences

PubMed Central

Rice, John E.; Reis, Arthur H.; Rice, Lisa M.; Carver-Brown, Rachel K.; Wangh, Lawrence J.

2012-01-01

Life abounds with genetic variations writ in sequences that are often only a few hundred nucleotides long. Rapid detection of these variations for identification of genetic diseases, pathogens and organisms has become the mainstay of molecular science and medicine. This report describes a new, highly informative closed-tube polymerase chain reaction (PCR) strategy for analysis of both known and unknown sequence variations. It combines efficient quantitative amplification of single-stranded DNA targets through LATE-PCR with sets of Lights-On/Lights-Off probes that hybridize to their target sequences over a broad temperature range. Contiguous pairs of Lights-On/Lights-Off probes of the same fluorescent color are used to scan hundreds of nucleotides for the presence of mutations. Sets of probes in different colors can be combined in the same tube to analyze even longer single-stranded targets. Each set of hybridized Lights-On/Lights-Off probes generates a composite fluorescent contour, which is mathematically converted to a sequence-specific fluorescent signature. The versatility and broad utility of this new technology is illustrated in this report by characterization of variant sequences in three different DNA targets: the rpoB gene of Mycobacterium tuberculosis, a sequence in the mitochondrial cytochrome C oxidase subunit 1 gene of nematodes and the V3 hypervariable region of the bacterial 16 s ribosomal RNA gene. We anticipate widespread use of these technologies for diagnostics, species identification and basic research. PMID:22879378

Cyclic coding for Brillouin optical time-domain analyzers using probe dithering.

PubMed

Iribas, Haritz; Loayssa, Alayn; Sauser, Florian; Llera, Miguel; Le Floch, Sébastien

2017-04-17

We study the performance limits of mono-color cyclic coding applied to Brillouin optical time-domain analysis (BOTDA) sensors that use probe wave dithering. BOTDA analyzers with dithering of the probe use a dual-probe-sideband setup in which an optical frequency modulation of the probe waves along the fiber is introduced. This avoids non-local effects while keeping the Brillouin threshold at its highest level, thus preventing the spontaneous Brillouin scattering from generating noise in the deployed sensing fiber. In these conditions, it is possible to introduce an unprecedented high probe power into the sensing fiber, which leads to an enhancement of the signal-to-noise ratio (SNR) and consequently to a performance improvement of the analyzer. The addition of cyclic coding in these set-ups can further increase the SNR and accordingly enhance the performance. However, this unprecedented probe power levels that can be employed result in the appearance of detrimental effects in the measurement that had not previously been observed in other BOTDA set-ups. In this work, we analyze the distortion in the decoding process and the errors in the measurement that this distortion causes, due to three factors: the power difference of the successive pulses of a code sequence, the appearance of first-order non-local effects and the non-linear amplification of the probe wave that results when using mono-color cyclic coding of the pump pulses. We apply the results of this study to demonstrate the performance enhancement that can be achieved in a long-range dithered dual-probe BOTDA. A 164-km fiber-loop is measured with 1-m spatial resolution, obtaining 3-MHz Brillouin frequency shift measurement precision at the worst contrast location. To the best of our knowledge, this is the longest sensing distance achieved with a BOTDA sensor using mono-color cyclic coding.

Usability evaluation of a medication reconciliation tool: Embedding safety probes to assess users' detection of medication discrepancies.

PubMed

Russ, Alissa L; Jahn, Michelle A; Patel, Himalaya; Porter, Brian W; Nguyen, Khoa A; Zillich, Alan J; Linsky, Amy; Simon, Steven R

2018-06-01

An electronic medication reconciliation tool was previously developed by another research team to aid provider-patient communication for medication reconciliation. To evaluate the usability of this tool, we integrated artificial safety probes into standard usability methods. The objective of this article is to describe this method of using safety probes, which enabled us to evaluate how well the tool supports users' detection of medication discrepancies. We completed a mixed-method usability evaluation in a simulated setting with 30 participants: 20 healthcare professionals (HCPs) and 10 patients. We used factual scenarios but embedded three artificial safety probes: (1) a missing medication (i.e., omission); (2) an extraneous medication (i.e., commission); and (3) an inaccurate dose (i.e., dose discrepancy). We measured users' detection of each probe to estimate the probability that a HCP or patient would detect these discrepancies. Additionally, we recorded participants' detection of naturally occurring discrepancies. Each safety probe was detected by ≤50% of HCPs. Patients' detection rates were generally higher. Estimates indicate that a HCP and patient, together, would detect 44.8% of these medication discrepancies. Additionally, HCPs and patients detected 25 and 45 naturally-occurring discrepancies, respectively. Overall, detection of medication discrepancies was low. Findings indicate that more advanced interface designs are warranted. Future research is needed on how technologies can be designed to better aid HCPs' and patients' detection of medication discrepancies. This is one of the first studies to evaluate the usability of a collaborative medication reconciliation tool and assess HCPs' and patients' detection of medication discrepancies. Results demonstrate that embedded safety probes can enhance standard usability methods by measuring additional, clinically-focused usability outcomes. The novel safety probes we used may serve as an initial, standard set for future medication reconciliation research. More prevalent use of safety probes could strengthen usability research for a variety of health information technologies. Published by Elsevier Inc.

Optimization of ultrasound-assisted extraction of phenolic compounds from grapefruit (Citrus paradisi Macf.) leaves via D-optimal design and artificial neural network design with categorical and quantitative variables.

PubMed

Ciğeroğlu, Zeynep; Aras, Ömür; Pinto, Carlos A; Bayramoglu, Mahmut; Kırbaşlar, Ş İsmail; Lorenzo, José M; Barba, Francisco J; Saraiva, Jorge A; Şahin, Selin

2018-03-06

The extraction of phenolic compounds from grapefruit leaves assisted by ultrasound-assisted extraction (UAE) was optimized using response surface methodology (RSM) by means of D-optimal experimental design and artificial neural network (ANN). For this purpose, five numerical factors were selected: ethanol concentration (0-50%), extraction time (15-60 min), extraction temperature (25-50 °C), solid:liquid ratio (50-100 g L -1 ) and calorimetric energy density of ultrasound (0.25-0.50 kW L -1 ), whereas ultrasound probe horn diameter (13 or 19 mm) was chosen as categorical factor. The optimized experimental conditions yielded by RSM were: 10.80% for ethanol concentration; 58.52 min for extraction time; 30.37 °C for extraction temperature; 52.33 g L -1 for solid:liquid ratio; 0.457 kW L -1 for ultrasonic power density, with thick probe type. Under these conditions total phenolics content was found to be 19.04 mg gallic acid equivalents g -1 dried leaf. The same dataset was used to train multilayer feed-forward networks using different approaches via MATLAB, with ANN exhibiting superior performance to RSM (differences included categorical factor in one model and higher regression coefficients), while close values were obtained for the extraction variables under study, except for ethanol concentration and extraction time. © 2018 Society of Chemical Industry. © 2018 Society of Chemical Industry.

An optimized proportional-derivative controller for the human upper extremity with gravity.

PubMed

Jagodnik, Kathleen M; Blana, Dimitra; van den Bogert, Antonie J; Kirsch, Robert F

2015-10-15

When Functional Electrical Stimulation (FES) is used to restore movement in subjects with spinal cord injury (SCI), muscle stimulation patterns should be selected to generate accurate and efficient movements. Ideally, the controller for such a neuroprosthesis will have the simplest architecture possible, to facilitate translation into a clinical setting. In this study, we used the simulated annealing algorithm to optimize two proportional-derivative (PD) feedback controller gain sets for a 3-dimensional arm model that includes musculoskeletal dynamics and has 5 degrees of freedom and 22 muscles, performing goal-oriented reaching movements. Controller gains were optimized by minimizing a weighted sum of position errors, orientation errors, and muscle activations. After optimization, gain performance was evaluated on the basis of accuracy and efficiency of reaching movements, along with three other benchmark gain sets not optimized for our system, on a large set of dynamic reaching movements for which the controllers had not been optimized, to test ability to generalize. Robustness in the presence of weakened muscles was also tested. The two optimized gain sets were found to have very similar performance to each other on all metrics, and to exhibit significantly better accuracy, compared with the three standard gain sets. All gain sets investigated used physiologically acceptable amounts of muscular activation. It was concluded that optimization can yield significant improvements in controller performance while still maintaining muscular efficiency, and that optimization should be considered as a strategy for future neuroprosthesis controller design. Published by Elsevier Ltd.

Nanospot soldering polystyrene nanoparticles with an optical fiber probe laser irradiating a metallic AFM probe based on the near-field enhancement effect.

PubMed

Cui, Jianlei; Yang, Lijun; Wang, Yang; Mei, Xuesong; Wang, Wenjun; Hou, Chaojian

2015-02-04

With the development of nanoscience and nanotechnology for the bottom-up nanofabrication of nanostructures formed from polystyrene nanoparticles, joining technology is an essential step in the manufacturing and assembly of nanodevices and nanostructures in order to provide mechanical integration and connection. To study the nanospot welding of polystyrene nanoparticles, we propose a new nanospot-soldering method using the near-field enhancement effect of a metallic atomic force microscope (AFM) probe tip that is irradiated by an optical fiber probe laser. On the basis of our theoretical analysis of the near-field enhancement effect, we set up an experimental system for nanospot soldering; this approach is carried out by using an optical fiber probe laser to irradiate the AFM probe tip to sinter the nanoparticles, providing a promising technical approach for the application of nanosoldering in nanoscience and nanotechnology.

Solid phase sequencing of biopolymers

DOEpatents

Cantor, Charles; Koster, Hubert

2010-09-28

This invention relates to methods for detecting and sequencing target nucleic acid sequences, to mass modified nucleic acid probes and arrays of probes useful in these methods, and to kits and systems which contain these probes. Useful methods involve hybridizing the nucleic acids or nucleic acids which represent complementary or homologous sequences of the target to an array of nucleic acid probes. These probes comprise a single-stranded portion, an optional double-stranded portion and a variable sequence within the single-stranded portion. The molecular weights of the hybridized nucleic acids of the set can be determined by mass spectroscopy, and the sequence of the target determined from the molecular weights of the fragments. Nucleic acids whose sequences can be determined include DNA or RNA in biological samples such as patient biopsies and environmental samples. Probes may be fixed to a solid support such as a hybridization chip to facilitate automated molecular weight analysis and identification of the target sequence.

Choosing non-redundant representative subsets of protein sequence data sets using submodular optimization.

PubMed

Libbrecht, Maxwell W; Bilmes, Jeffrey A; Noble, William Stafford

2018-04-01

Selecting a non-redundant representative subset of sequences is a common step in many bioinformatics workflows, such as the creation of non-redundant training sets for sequence and structural models or selection of "operational taxonomic units" from metagenomics data. Previous methods for this task, such as CD-HIT, PISCES, and UCLUST, apply a heuristic threshold-based algorithm that has no theoretical guarantees. We propose a new approach based on submodular optimization. Submodular optimization, a discrete analogue to continuous convex optimization, has been used with great success for other representative set selection problems. We demonstrate that the submodular optimization approach results in representative protein sequence subsets with greater structural diversity than sets chosen by existing methods, using as a gold standard the SCOPe library of protein domain structures. In this setting, submodular optimization consistently yields protein sequence subsets that include more SCOPe domain families than sets of the same size selected by competing approaches. We also show how the optimization framework allows us to design a mixture objective function that performs well for both large and small representative sets. The framework we describe is the best possible in polynomial time (under some assumptions), and it is flexible and intuitive because it applies a suite of generic methods to optimize one of a variety of objective functions. © 2018 Wiley Periodicals, Inc.

Fast Open-World Person Re-Identification.

PubMed

Zhu, Xiatian; Wu, Botong; Huang, Dongcheng; Zheng, Wei-Shi

2018-05-01

Existing person re-identification (re-id) methods typically assume that: 1) any probe person is guaranteed to appear in the gallery target population during deployment (i.e., closed-world) and 2) the probe set contains only a limited number of people (i.e., small search scale). Both assumptions are artificial and breached in real-world applications, since the probe population in target people search can be extremely vast in practice due to the ambiguity of probe search space boundary. Therefore, it is unrealistic that any probe person is assumed as one target people, and a large-scale search in person images is inherently demanded. In this paper, we introduce a new person re-id search setting, called large scale open-world (LSOW) re-id, characterized by huge size probe images and open person population in search thus more close to practical deployments. Under LSOW, the under-studied problem of person re-id efficiency is essential in addition to that of commonly studied re-id accuracy. We, therefore, develop a novel fast person re-id method, called Cross-view Identity Correlation and vErification (X-ICE) hashing, for joint learning of cross-view identity representation binarisation and discrimination in a unified manner. Extensive comparative experiments on three large-scale benchmarks have been conducted to validate the superiority and advantages of the proposed X-ICE method over a wide range of the state-of-the-art hashing models, person re-id methods, and their combinations.

Large Scale Bacterial Colony Screening of Diversified FRET Biosensors

PubMed Central

Litzlbauer, Julia; Schifferer, Martina; Ng, David; Fabritius, Arne; Thestrup, Thomas; Griesbeck, Oliver

2015-01-01

Biosensors based on Förster Resonance Energy Transfer (FRET) between fluorescent protein mutants have started to revolutionize physiology and biochemistry. However, many types of FRET biosensors show relatively small FRET changes, making measurements with these probes challenging when used under sub-optimal experimental conditions. Thus, a major effort in the field currently lies in designing new optimization strategies for these types of sensors. Here we describe procedures for optimizing FRET changes by large scale screening of mutant biosensor libraries in bacterial colonies. We describe optimization of biosensor expression, permeabilization of bacteria, software tools for analysis, and screening conditions. The procedures reported here may help in improving FRET changes in multiple suitable classes of biosensors. PMID:26061878

Probing the electrolyte infiltration behaviour of activated carbon supercapacitor electrodes by in situ neutron scattering using aqueous NaCl as electrolyte

DOE PAGES

Liu, Yiqun; Li, Chen; Liu, Cong; ...

2018-04-24

In situ contrast-matched neutron scattering was used to probe the electrolyte infiltration behavior of activated supercapacitor carbon electrodes using an aquoeus 1 M NaCl solution. It was found that only about 20% of the pore volume was infiltrated at chemical equilibrium. The partial infiltration can be attributed to the co-existence of hydrophilic and hydrophilic pores. As a result, the study suggests that for the achievement of optimal capacitance, supercapacitor electrodes should be evacuated before electrolyte infiltration.

Probing the electrolyte infiltration behaviour of activated carbon supercapacitor electrodes by in situ neutron scattering using aqueous NaCl as electrolyte

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

Liu, Yiqun; Li, Chen; Liu, Cong

In situ contrast-matched neutron scattering was used to probe the electrolyte infiltration behavior of activated supercapacitor carbon electrodes using an aquoeus 1 M NaCl solution. It was found that only about 20% of the pore volume was infiltrated at chemical equilibrium. The partial infiltration can be attributed to the co-existence of hydrophilic and hydrophilic pores. As a result, the study suggests that for the achievement of optimal capacitance, supercapacitor electrodes should be evacuated before electrolyte infiltration.

77 FR 55847 - Center for Scientific Review; Notice of Closed Meetings

Federal Register 2010, 2011, 2012, 2013, 2014

2012-09-11

... Scientific Review Special Emphasis Panel; PAR09-259: Optimization of Small Molecule Probes For the Nervous System. Date: October 12, 2012. Time: 3 p.m. to 4 p.m. Agenda: To review and evaluate grant applications...

Signal amplification of padlock probes by rolling circle replication.

PubMed Central

Banér, J; Nilsson, M; Mendel-Hartvig, M; Landegren, U

1998-01-01

Circularizing oligonucleotide probes (padlock probes) have the potential to detect sets of gene sequences with high specificity and excellent selectivity for sequence variants, but sensitivity of detection has been limiting. By using a rolling circle replication (RCR) mechanism, circularized but not unreacted probes can yield a powerful signal amplification. We demonstrate here that in order for the reaction to proceed efficiently, the probes must be released from the topological link that forms with target molecules upon hybridization and ligation. If the target strand has a nearby free 3' end, then the probe-target hybrids can be displaced by the polymerase used for replication. The displaced probe can then slip off the targetstrand and a rolling circle amplification is initiated. Alternatively, the target sequence itself can prime an RCR after its non-base paired 3' end has been removed by exonucleolytic activity. We found the Phi29 DNA polymerase to be superior to the Klenow fragment in displacing the target DNA strand, and it maintained the polymerization reaction for at least 12 h, yielding an extension product that represents several thousand-fold the length of the padlock probe. PMID:9801302

Solid-phase microextraction/gas chromatography-mass spectrometry method optimization for characterization of surface adsorption forces of nanoparticles.

PubMed

Omanovic-Miklicanin, Enisa; Valzacchi, Sandro; Simoneau, Catherine; Gilliland, Douglas; Rossi, Francois

2014-10-01

A complete characterization of the different physico-chemical properties of nanoparticles (NPs) is necessary for the evaluation of their impact on health and environment. Among these properties, the surface characterization of the nanomaterial is the least developed and in many cases limited to the measurement of surface composition and zetapotential. The biological surface adsorption index approach (BSAI) for characterization of surface adsorption properties of NPs has recently been introduced (Xia et al. Nat Nanotechnol 5:671-675, 2010; Xia et al. ACS Nano 5(11):9074-9081, 2011). The BSAI approach offers in principle the possibility to characterize the different interaction forces exerted between a NP's surface and an organic--and by extension biological--entity. The present work further develops the BSAI approach and optimizes a solid-phase microextraction gas chromatography-mass spectrometry (SPME/GC-MS) method which, as an outcome, gives a better-defined quantification of the adsorption properties on NPs. We investigated the various aspects of the SPME/GC-MS method, including kinetics of adsorption of probe compounds on SPME fiber, kinetic of adsorption of probe compounds on NP's surface, and optimization of NP's concentration. The optimized conditions were then tested on 33 probe compounds and on Au NPs (15 nm) and SiO2 NPs (50 nm). The procedure allowed the identification of three compounds adsorbed by silica NPs and nine compounds by Au NPs, with equilibrium times which varied between 30 min and 12 h. Adsorption coefficients of 4.66 ± 0.23 and 4.44 ± 0.26 were calculated for 1-methylnaphtalene and biphenyl, compared to literature values of 4.89 and 5.18, respectively. The results demonstrated that the detailed optimization of the SPME/GC-MS method under various conditions is a critical factor and a prerequisite to the application of the BSAI approach as a tool to characterize surface adsorption properties of NPs and therefore to draw any further conclusions on their potential impact on health.

Gaussian interferometric power and Black box estimation of Unruh temperature

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

Wang, Jieci, E-mail: jcwang@hunnu.edu.cn; Beijing National Laboratory for Condensed Matter Physics, Institute of Physics, Chinese Academy of Sciences, Beijing 100190; Cao, Haixin

2016-10-15

We present a black box estimation paradigm of Unruh temperature in a relativistic bosonic continuous-variable setting. It is shown that the guaranteed precision for the estimation of Unruh temperature can be evaluated by the Gaussian interferometric power for a given probe state. We demonstrate that the amount of interferometric power is always beyond the entanglement type quantum correlations in a relativistic setting. It is found that due to the fact that Unruh radiation acts as a thermal bath on the probe system, it destroys available resources of the probe system and reduces the guaranteed precision of the estimation of Unruhmore » temperature. We also find that the thermal noise induced by Unruh effect will generate interferometric power between accelerated Bob and his auxiliary partner anti-Bob, while it does not generate any correlation between inertial Alice and anti-Bob.« less

The precedence of topological change over top-down attention in masked priming.

PubMed

Huang, Yan; Zhou, Tiangang; Chen, Lin

2011-10-14

Recent data indicate that unconscious masked priming can be mediated by top-down attentional set, so that priming effects of congruence between a masked prime and a subsequent probe vanish when the congruence ceases to be task relevant. Here, we show that, while the attentional set determines masked priming for color and orientation features, it does not fully determine priming based on the topological properties of stimuli. Specifically, across a series of different choice-RT tasks, we find that topological congruence between prime and probe stimuli affects RTs for the probes even when other stimulus information (e.g., color or orientation) is required for the response, whereas congruence priming effects of color or orientation occur only when these features are response relevant. Our results suggest that changes in topological properties take precedence over task-directed top-down attentional modulation in masked priming.

Quantitative ptychographic reconstruction by applying a probe constraint

NASA Astrophysics Data System (ADS)

Reinhardt, J.; Schroer, C. G.

2018-04-01

The coherent scanning technique X-ray ptychography has become a routine tool for high-resolution imaging and nanoanalysis in various fields of research such as chemistry, biology or materials science. Often the ptychographic reconstruction results are analysed in order to yield absolute quantitative values for the object transmission and illuminating probe function. In this work, we address a common ambiguity encountered in scaling the object transmission and probe intensity via the application of an additional constraint to the reconstruction algorithm. A ptychographic measurement of a model sample containing nanoparticles is used as a test data set against which to benchmark in the reconstruction results depending on the type of constraint used. Achieving quantitative absolute values for the reconstructed object transmission is essential for advanced investigation of samples that are changing over time, e.g., during in-situ experiments or in general when different data sets are compared.

Towards a Data-Optimized Coronal Magnetic Field Model (DOC-FM): Synthetic Test Beds and Multiwavelength Forward Modeling

NASA Astrophysics Data System (ADS)

Gibson, S. E.; Dalmasse, K.; Fan, Y.; Fineschi, S.; MacKay, D.; Rempel, M.; White, S. M.

2015-12-01

Understanding the physical state of the solar corona is key to deciphering the origins of space weather as well as to realistically representing the environment to be navigated by missions such as Solar Orbiter and Solar Probe Plus. However, inverting solar coronal observations to reconstruct this physical state -- and in particular the three-dimensional coronal magnetic field - is complicated by limited lines of sight and by projection effects. On the other hand, the sensitivity of multiwavelength observations to different physical mechanisms implies a potential for simultaneous probing of different parts of the coronal plasma. In order to study this complementarity, and to ultimately establish an optimal set of observations for constraining the three-dimensional coronal magnetic field, we are developing a suite of representative simulations to act as diagnostic test beds. We will present three such test beds: a coronal active region, a quiescent prominence, and a global corona. Each fully define the physical state of density, temperature, and vector magnetic field in three dimensions throughout the simulation domain. From these test beds, and using the FORWARD SolarSoft IDL codes, we will create a broad range of synthetic data. Radio observables will include intensity and circular polarization (including gyroresonance effects) and Faraday rotation for a range of frequencies. Infrared and visible forbidden line diagnostics of Zeeman and saturated Hanle effects will yield full Stokes vector (I, Q, U, V) synthetic data, and UV permitted line Hanle diagnostics will yield intensity and linear polarization. In addition, we will synthesize UV and SXR imager data, UV/EUV spectrometric data, and white light brightness and polarized brightness. All of these synthetic data, along with the "ground truth" physical state of the simulations from which they are derived, will be made available to the community for the purpose of testing coronal inversion techniques.

Optimizing the molecular diagnosis of CDKL5 gene-related epileptic encephalopathy in boys.

PubMed

Mei, Davide; Darra, Francesca; Barba, Carmen; Marini, Carla; Fontana, Elena; Chiti, Laura; Parrini, Elena; Dalla Bernardina, Bernardo; Guerrini, Renzo

2014-11-01

Mutations involving the cyclin-dependent kinase-like 5 (CDKL5) gene cause an early onset epileptic encephalopathy (EE) with severe neurologic impairment and a skewed 12:1 female-to-male ratio. To date, 18 mutations have been described in boys. We analyzed our cohort of boys with early onset EE to assess the diagnostic yield of our molecular approach. We studied 74 boys who presented early onset severe seizures, including infantile spasms and developmental delay, in the setting of EE, using Sanger sequencing, next-generation sequencing (NGS) and multiplex ligation-dependent probe amplification (MLPA). We identified alterations involving CDKL5 in four boys (5.4%) using NGS in one and MLPA in three. Three of four mutations were indicative of somatic mosaicism. CDKL5 gene mutations accounted for 5.4% of boys with early onset EE. Somatic mosaic mutations might be even more represented than germline mutations, probably because their less deleterious effect enhances viability of the male embryo. The molecular approach used for CDKL5 screening remarkably influences the diagnostic yield in boys. Diagnosis is optimized by Sanger sequencing combined with array-based methods or MLPA; alternatively, NGS targeted resequencing designed to also detect copy number alterations, may be performed. Wiley Periodicals, Inc. © 2014 International League Against Epilepsy.

Spectroscopic and molecular docking studies on N,N-di-tert-butoxycarbonyl (Boc)-2-amino pyridine: A potential bioactive agent for lung cancer treatment

NASA Astrophysics Data System (ADS)

Mohamed Asath, R.; Premkumar, R.; Mathavan, T.; Milton Franklin Benial, A.

2017-09-01

Potential energy surface scan was performed and the most stable molecular structure of the N,N-di-tert-butoxycarbonyl (Boc)-2-amino pyridine (DBAP) molecule was predicted. The most stable molecular structure of the molecule was optimized using B3LYP method with cc-pVTZ basis set. Anticancer activity of the DBAP molecule was evaluated by molecular docking analysis. The structural parameters and vibrational wavenumbers were calculated for the optimized molecular structure. The experimental and theoretical wavenumbers were assigned and compared. Ultraviolet-Visible spectrum was simulated and validated experimentally. The molecular electrostatic potential surface was simulated and Fukui function calculations were also carried out to investigate the reactive nature of the DBAP molecule. The natural bond orbital analysis was also performed to probe the intramolecular interactions and confirm the bioactivity of the DBAP molecule. The molecular docking analysis reveals the better inhibitory nature of the DBAP molecule against the epidermal growth factor receptor (EGFR) protein which causes lung cancer. Hence, the present study unveils the structural and bioactive nature of the title molecule. The DBAP molecule was identified as a potential inhibitor against the lung cancer which may be useful in further development of drug designing in the treatment of lung cancer.

Reliable prediction of heat transfer coefficient in three-phase bubble column reactor via adaptive neuro-fuzzy inference system and regularization network

NASA Astrophysics Data System (ADS)

Garmroodi Asil, A.; Nakhaei Pour, A.; Mirzaei, Sh.

2018-04-01

In the present article, generalization performances of regularization network (RN) and optimize adaptive neuro-fuzzy inference system (ANFIS) are compared with a conventional software for prediction of heat transfer coefficient (HTC) as a function of superficial gas velocity (5-25 cm/s) and solid fraction (0-40 wt%) at different axial and radial locations. The networks were trained by resorting several sets of experimental data collected from a specific system of air/hydrocarbon liquid phase/silica particle in a slurry bubble column reactor (SBCR). A special convection HTC measurement probe was manufactured and positioned in an axial distance of 40 and 130 cm above the sparger at center and near the wall of SBCR. The simulation results show that both in-house RN and optimized ANFIS due to powerful noise filtering capabilities provide superior performances compared to the conventional software of MATLAB ANFIS and ANN toolbox. For the case of 40 and 130 cm axial distance from center of sparger, at constant superficial gas velocity of 25 cm/s, adding 40 wt% silica particles to liquid phase leads to about 66% and 69% increasing in HTC respectively. The HTC in the column center for all the cases studied are about 9-14% larger than those near the wall region.

Effect of biased feedback on motor imagery learning in BCI-teleoperation system.

PubMed

Alimardani, Maryam; Nishio, Shuichi; Ishiguro, Hiroshi

2014-01-01

Feedback design is an important issue in motor imagery BCI systems. Regardless, to date it has not been reported how feedback presentation can optimize co-adaptation between a human brain and such systems. This paper assesses the effect of realistic visual feedback on users' BCI performance and motor imagery skills. We previously developed a tele-operation system for a pair of humanlike robotic hands and showed that BCI control of such hands along with first-person perspective visual feedback of movements can arouse a sense of embodiment in the operators. In the first stage of this study, we found that the intensity of this ownership illusion was associated with feedback presentation and subjects' performance during BCI motion control. In the second stage, we probed the effect of positive and negative feedback bias on subjects' BCI performance and motor imagery skills. Although the subject specific classifier, which was set up at the beginning of experiment, detected no significant change in the subjects' online performance, evaluation of brain activity patterns revealed that subjects' self-regulation of motor imagery features improved due to a positive bias of feedback and a possible occurrence of ownership illusion. Our findings suggest that in general training protocols for BCIs, manipulation of feedback can play an important role in the optimization of subjects' motor imagery skills.

Efficiency of fluorescence in situ hybridization for bacterial cell identification in temporary river sediments with contrasting water content.

PubMed

Fazi, Stefano; Amalfitano, Stefano; Pizzetti, Ilaria; Pernthaler, Jakob

2007-09-01

We studied the efficiency of two hybridization techniques for the analysis of benthic bacterial community composition under varying sediment water content. Microcosms were set up with sediments from four European temporary rivers. Wet sediments were dried, and dry sediments were artificially rewetted. The percentage of bacterial cells detected by fluorescence in situ hybridization with fluorescently monolabeled probes (FISH) significantly increased from dry to wet sediments, showing a positive correlation with the community activity measured via incorporation of (3)H leucine. FISH and signal amplification by catalyzed reporter deposition (CARD-FISH) could significantly better detect cells with low activity in dried sediments. Through the application of an optimized cell permeabilization protocol, the percentage of hybridized cells by CARD-FISH showed comparable values in dry and wet conditions. This approach was unrelated to (3)H leucine incorporation rates. Moreover, the optimized protocol allowed a significantly better visualization of Gram-positive Actinobacteria in the studied samples. CARD-FISH is, therefore, proposed as an effective technique to compare bacterial communities residing in sediments with contrasting water content, irrespective of differences in the activity state of target cells. Considering the increasing frequencies of flood and drought cycles in European temporary rivers, our approach may help to better understand the dynamics of microbial communities in such systems.

Seismic Characterizations of Fractures: Dynamic Diagnostics

NASA Astrophysics Data System (ADS)

Pyrak-Nolte, L. J.

2017-12-01

Fracture geometry controls fluid flow in a fracture, affects mechanical stability and influences energy partitioning that affects wave scattering. Our ability to detect and monitor fracture evolution is controlled by the frequency of the signal used to probe a fracture system, i.e. frequency selects the scales. No matter the frequency chosen, some set of discontinuities will be optimal for detection because different wavelengths sample different subsets of fractures. The select subset of fractures is based on the stiffness of the fractures which in turn is linked to fluid flow. A goal is obtaining information from scales outside the optimal detection regime. Fracture geometry trajectories are a potential approach to drive a fracture system across observation scales, i.e. moving systems between effective medium and scattering regimes. Dynamic trajectories (such as perturbing stress, fluid pressure, chemical alteration, etc.) can be used to perturb fracture geometry to enhance scattering or give rise to discrete modes that are intimately related to the micro-structural evolution of a fracture. However, identification of these signal features will require methods for identifying these micro-structural signatures in complicated scattered fields. Acknowledgment: This material is based upon work supported by the U.S. Department of Energy, Office of Science, Office of Basic Energy Sciences, Geosciences Research Program under Award Number (DE-FG02-09ER16022).

Effects of b-value and number of gradient directions on diffusion MRI measures obtained with Q-ball imaging

NASA Astrophysics Data System (ADS)

Schilling, Kurt G.; Nath, Vishwesh; Blaber, Justin; Harrigan, Robert L.; Ding, Zhaohua; Anderson, Adam W.; Landman, Bennett A.

2017-02-01

High-angular-resolution diffusion-weighted imaging (HARDI) MRI acquisitions have become common for use with higher order models of diffusion. Despite successes in resolving complex fiber configurations and probing microstructural properties of brain tissue, there is no common consensus on the optimal b-value and number of diffusion directions to use for these HARDI methods. While this question has been addressed by analysis of the diffusion-weighted signal directly, it is unclear how this translates to the information and metrics derived from the HARDI models themselves. Using a high angular resolution data set acquired at a range of b-values, and repeated 11 times on a single subject, we study how the b-value and number of diffusion directions impacts the reproducibility and precision of metrics derived from Q-ball imaging, a popular HARDI technique. We find that Q-ball metrics associated with tissue microstructure and white matter fiber orientation are sensitive to both the number of diffusion directions and the spherical harmonic representation of the Q-ball, and often are biased when under sampled. These results can advise researchers on appropriate acquisition and processing schemes, particularly when it comes to optimizing the number of diffusion directions needed for metrics derived from Q-ball imaging.

The Influence of Motivating Operations on Generalization Probes of Specific Mands by Children with Autism

ERIC Educational Resources Information Center

Fragale, Christina L.; O'Reilly, Mark F.; Aguilar, Jeannie; Pierce, Nigel; Lang, Russell; Sigafoos, Jeff; Lancioni, Giulio

2012-01-01

We investigated the influence of motivating operations on the generalization of newly taught mands across settings and communication partners for 3 children with autism. Two conditions were implemented prior to generalization probes. In the first condition, participants were given access to a preferred item until they rejected the item (i.e.,…

What is the Optimal Strategy for Adaptive Servo-Ventilation Therapy?

PubMed

Imamura, Teruhiko; Kinugawa, Koichiro

2018-05-23

Clinical advantages in the adaptive servo-ventilation (ASV) therapy have been reported in selected heart failure patients with/without sleep-disorder breathing, whereas multicenter randomized control trials could not demonstrate such advantages. Considering this discrepancy, optimal patient selection and device setting may be a key for the successful ASV therapy. Hemodynamic and echocardiographic parameters indicating pulmonary congestion such as elevated pulmonary capillary wedge pressure were reported as predictors of good response to ASV therapy. Recently, parameters indicating right ventricular dysfunction also have been reported as good predictors. Optimal device setting with appropriate pressure setting during appropriate time may also be a key. Large-scale prospective trial with optimal patient selection and optimal device setting is warranted.

Estimation of a melting probe's penetration velocity range to reach icy moons' subsurface ocean

NASA Astrophysics Data System (ADS)

Erokhina, Olga; Chumachenko, Eugene

2014-05-01

In modern space science one of the actual branches is icy satellites explorations. The main interest is concentrated around Jovian's moons Europa and Ganymede, Saturn's moons Titan and Enceladus that are covered by thick icy layer according to "Voyager1", "Voyager2", "Galileo" and "Cassini" missions. There is a big possibility that under icy shell could be a deep ocean. Also conditions on these satellites allow speculating about possible habitability, and considering these moons from an astrobiological point of view. One of the possible tasks of planned missions is a subsurface study. For this goal it is necessary to design special equipment that could be suitable for planetary application. One of the possible means is to use a melting probe which operates by melting and moves by gravitational force. Such a probe should be relatively small, should not weight too much and should require not too much energy. In terrestrial case such kind of probe has been successfully used for glaciers study. And it is possible to extrapolate the usage of such probe to extraterrestrial application. One of the tasks is to estimate melting probe's penetration velocity. Although there are other unsolved problems such as analyzing how the probe will move in low gravity and low atmospheric pressure; knowing whether hole will be closed or not when probe penetrate thick enough; and considering what order could be a penetration velocity. This study explores two techniques of melting probe's movement. One of them based on elasto-plastic theory and so-called "solid water" theory, and other one takes phase changing into account. These two techniques allow estimating melting probe's velocity range and study whole process. Based on these technique several cases of melting probe movement were considered, melting probe's velocity range estimated, influence of different factors studied and discussed and an easy way to optimize parameters of the melting probe proposed.

TARGETED PRINCIPLE COMPONENT ANALYSIS: A NEW MOTION ARTIFACT CORRECTION APPROACH FOR NEAR-INFRARED SPECTROSCOPY

PubMed Central

YÜCEL, MERYEM A.; SELB, JULIETTE; COOPER, ROBERT J.; BOAS, DAVID A.

2014-01-01

As near-infrared spectroscopy (NIRS) broadens its application area to different age and disease groups, motion artifacts in the NIRS signal due to subject movement is becoming an important challenge. Motion artifacts generally produce signal fluctuations that are larger than physiological NIRS signals, thus it is crucial to correct for them before obtaining an estimate of stimulus evoked hemodynamic responses. There are various methods for correction such as principle component analysis (PCA), wavelet-based filtering and spline interpolation. Here, we introduce a new approach to motion artifact correction, targeted principle component analysis (tPCA), which incorporates a PCA filter only on the segments of data identified as motion artifacts. It is expected that this will overcome the issues of filtering desired signals that plagues standard PCA filtering of entire data sets. We compared the new approach with the most effective motion artifact correction algorithms on a set of data acquired simultaneously with a collodion-fixed probe (low motion artifact content) and a standard Velcro probe (high motion artifact content). Our results show that tPCA gives statistically better results in recovering hemodynamic response function (HRF) as compared to wavelet-based filtering and spline interpolation for the Velcro probe. It results in a significant reduction in mean-squared error (MSE) and significant enhancement in Pearson’s correlation coefficient to the true HRF. The collodion-fixed fiber probe with no motion correction performed better than the Velcro probe corrected for motion artifacts in terms of MSE and Pearson’s correlation coefficient. Thus, if the experimental study permits, the use of a collodion-fixed fiber probe may be desirable. If the use of a collodion-fixed probe is not feasible, then we suggest the use of tPCA in the processing of motion artifact contaminated data. PMID:25360181

ProbFold: a probabilistic method for integration of probing data in RNA secondary structure prediction.

PubMed

Sahoo, Sudhakar; Świtnicki, Michał P; Pedersen, Jakob Skou

2016-09-01

Recently, new RNA secondary structure probing techniques have been developed, including Next Generation Sequencing based methods capable of probing transcriptome-wide. These techniques hold great promise for improving structure prediction accuracy. However, each new data type comes with its own signal properties and biases, which may even be experiment specific. There is therefore a growing need for RNA structure prediction methods that can be automatically trained on new data types and readily extended to integrate and fully exploit multiple types of data. Here, we develop and explore a modular probabilistic approach for integrating probing data in RNA structure prediction. It can be automatically trained given a set of known structures with probing data. The approach is demonstrated on SHAPE datasets, where we evaluate and selectively model specific correlations. The approach often makes superior use of the probing data signal compared to other methods. We illustrate the use of ProbFold on multiple data types using both simulations and a small set of structures with both SHAPE, DMS and CMCT data. Technically, the approach combines stochastic context-free grammars (SCFGs) with probabilistic graphical models. This approach allows rapid adaptation and integration of new probing data types. ProbFold is implemented in C ++. Models are specified using simple textual formats. Data reformatting is done using separate C ++ programs. Source code, statically compiled binaries for x86 Linux machines, C ++ programs, example datasets and a tutorial is available from http://moma.ki.au.dk/prj/probfold/ : jakob.skou@clin.au.dk Supplementary data are available at Bioinformatics online. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Parallel gene analysis with allele-specific padlock probes and tag microarrays

PubMed Central

Banér, Johan; Isaksson, Anders; Waldenström, Erik; Jarvius, Jonas; Landegren, Ulf; Nilsson, Mats

2003-01-01

Parallel, highly specific analysis methods are required to take advantage of the extensive information about DNA sequence variation and of expressed sequences. We present a scalable laboratory technique suitable to analyze numerous target sequences in multiplexed assays. Sets of padlock probes were applied to analyze single nucleotide variation directly in total genomic DNA or cDNA for parallel genotyping or gene expression analysis. All reacted probes were then co-amplified and identified by hybridization to a standard tag oligonucleotide array. The technique was illustrated by analyzing normal and pathogenic variation within the Wilson disease-related ATP7B gene, both at the level of DNA and RNA, using allele-specific padlock probes. PMID:12930977

Monte Carlo modeling of time-resolved fluorescence for depth-selective interrogation of layered tissue.

PubMed

Pfefer, T Joshua; Wang, Quanzeng; Drezek, Rebekah A

2011-11-01

Computational approaches for simulation of light-tissue interactions have provided extensive insight into biophotonic procedures for diagnosis and therapy. However, few studies have addressed simulation of time-resolved fluorescence (TRF) in tissue and none have combined Monte Carlo simulations with standard TRF processing algorithms to elucidate approaches for cancer detection in layered biological tissue. In this study, we investigate how illumination-collection parameters (e.g., collection angle and source-detector separation) influence the ability to measure fluorophore lifetime and tissue layer thickness. Decay curves are simulated with a Monte Carlo TRF light propagation model. Multi-exponential iterative deconvolution is used to determine lifetimes and fractional signal contributions. The ability to detect changes in mucosal thickness is optimized by probes that selectively interrogate regions superficial to the mucosal-submucosal boundary. Optimal accuracy in simultaneous determination of lifetimes in both layers is achieved when each layer contributes 40-60% of the signal. These results indicate that depth-selective approaches to TRF have the potential to enhance disease detection in layered biological tissue and that modeling can play an important role in probe design optimization. Published by Elsevier Ireland Ltd.

Speciation of antimony in airborne particulate matter using ultrasound probe fast extraction and analysis by HPLC-HG-AFS.

PubMed

Bellido-Martín, A; Gómez-Ariza, J L; Smichowsky, P; Sánchez-Rodas, D

2009-09-07

A fast extraction procedure has been developed for Sb(III) and Sb(V) oxoanions speciation in airborne particulate matter samples. Different extraction media (diammonium tartrate, hidroxilammonium clorhidrate, citric acid+ascorbic acid, phosphoric acid and citrate solutions) were tried, with assistance of an ultrasonic probe. The operation power and time of extraction were also optimized. The higher extraction recoveries were obtained with a 100 mmol L(-1) hidroxilammonium clorhidrate aqueous solution assisted by the ultrasound probe operated at 50 W during 3 min. The extracts were analyzed by HPLC-HG-AFS. The chromatographic separation of Sb(III) and Sb(V) was also optimized using diammonium tartrate and phthalic acid as mobile phases. The separation of both Sb species was performed in less than 3 min under isocratic conditions, using a 200 mmol L(-1) diammonium tartrate solution. The proposed extraction procedure and the HPLC-HG-AFS instrumental coupling have been successfully applied to airborne particulate matter samples, with high Sb content, collected in heavy traffic streets from Buenos Aires (Argentina). The results showed the presence of both Sb species at similar concentrations in the ng m(-3) level. The extraction yield was higher than 90% for all the analyzed samples.

Mechanistic and quantitative insight into cell surface targeted molecular imaging agent design.

PubMed

Zhang, Liang; Bhatnagar, Sumit; Deschenes, Emily; Thurber, Greg M

2016-05-05

Molecular imaging agent design involves simultaneously optimizing multiple probe properties. While several desired characteristics are straightforward, including high affinity and low non-specific background signal, in practice there are quantitative trade-offs between these properties. These include plasma clearance, where fast clearance lowers background signal but can reduce target uptake, and binding, where high affinity compounds sometimes suffer from lower stability or increased non-specific interactions. Further complicating probe development, many of the optimal parameters vary depending on both target tissue and imaging agent properties, making empirical approaches or previous experience difficult to translate. Here, we focus on low molecular weight compounds targeting extracellular receptors, which have some of the highest contrast values for imaging agents. We use a mechanistic approach to provide a quantitative framework for weighing trade-offs between molecules. Our results show that specific target uptake is well-described by quantitative simulations for a variety of targeting agents, whereas non-specific background signal is more difficult to predict. Two in vitro experimental methods for estimating background signal in vivo are compared - non-specific cellular uptake and plasma protein binding. Together, these data provide a quantitative method to guide probe design and focus animal work for more cost-effective and time-efficient development of molecular imaging agents.

Modeling Hybridization Kinetics of Gene Probes in a DNA Biochip Using FEMLAB

PubMed Central

Munir, Ahsan; Waseem, Hassan; Williams, Maggie R.; Stedtfeld, Robert D.; Gulari, Erdogan; Tiedje, James M.; Hashsham, Syed A.

2017-01-01

Microfluidic DNA biochips capable of detecting specific DNA sequences are useful in medical diagnostics, drug discovery, food safety monitoring and agriculture. They are used as miniaturized platforms for analysis of nucleic acids-based biomarkers. Binding kinetics between immobilized single stranded DNA on the surface and its complementary strand present in the sample are of interest. To achieve optimal sensitivity with minimum sample size and rapid hybridization, ability to predict the kinetics of hybridization based on the thermodynamic characteristics of the probe is crucial. In this study, a computer aided numerical model for the design and optimization of a flow-through biochip was developed using a finite element technique packaged software tool (FEMLAB; package included in COMSOL Multiphysics) to simulate the transport of DNA through a microfluidic chamber to the reaction surface. The model accounts for fluid flow, convection and diffusion in the channel and on the reaction surface. Concentration, association rate constant, dissociation rate constant, recirculation flow rate, and temperature were key parameters affecting the rate of hybridization. The model predicted the kinetic profile and signal intensities of eighteen 20-mer probes targeting vancomycin resistance genes (VRGs). Predicted signal intensities and hybridization kinetics strongly correlated with experimental data in the biochip (R2 = 0.8131). PMID:28555058

Design and technical evaluation of fibre-coupled Raman probes for the image-guided discrimination of cancerous skin

NASA Astrophysics Data System (ADS)

Schleusener, J.; Reble, C.; Helfmann, J.; Gersonde, I.; Cappius, H.-J.; Glanert, M.; Fluhr, J. W.; Meinke, M. C.

2014-03-01

Two different designs for fibre-coupled Raman probes are presented that are optimized for discriminating cancerous and normal skin by achieving high epithelial sensitivity to detect a major component of the Raman signal from the depth range of the epithelium. This is achieved by optimizing Raman spot diameters to the range of ≈200 µm, which distinguishes this approach from the common applications of either Raman microspectroscopy (1-5 µm) or measurements on larger sampling volume using spot sizes of a few mm. Video imaging with a depicted area in the order of a few cm, to allow comparing Raman measurements to the location of the histo-pathologic findings, is integrated in both designs. This is important due to the inhomogeneity of cancerous lesions. Video image acquisition is achieved using white light LED illumination, which avoids ambient light artefacts. The design requirements focus either on a compact light-weight configuration, for pen-like handling, or on a video-visible measurement spot to enable increased positioning accuracy. Both probes are evaluated with regard to spot size, Rayleigh suppression, background fluorescence, depth sensitivity, clinical handling and ambient light suppression. Ex vivo measurements on porcine ear skin correlates well with findings of other groups.

Modeling Hybridization Kinetics of Gene Probes in a DNA Biochip Using FEMLAB.

PubMed

Munir, Ahsan; Waseem, Hassan; Williams, Maggie R; Stedtfeld, Robert D; Gulari, Erdogan; Tiedje, James M; Hashsham, Syed A

2017-05-29

Microfluidic DNA biochips capable of detecting specific DNA sequences are useful in medical diagnostics, drug discovery, food safety monitoring and agriculture. They are used as miniaturized platforms for analysis of nucleic acids-based biomarkers. Binding kinetics between immobilized single stranded DNA on the surface and its complementary strand present in the sample are of interest. To achieve optimal sensitivity with minimum sample size and rapid hybridization, ability to predict the kinetics of hybridization based on the thermodynamic characteristics of the probe is crucial. In this study, a computer aided numerical model for the design and optimization of a flow-through biochip was developed using a finite element technique packaged software tool (FEMLAB; package included in COMSOL Multiphysics) to simulate the transport of DNA through a microfluidic chamber to the reaction surface. The model accounts for fluid flow, convection and diffusion in the channel and on the reaction surface. Concentration, association rate constant, dissociation rate constant, recirculation flow rate, and temperature were key parameters affecting the rate of hybridization. The model predicted the kinetic profile and signal intensities of eighteen 20-mer probes targeting vancomycin resistance genes (VRGs). Predicted signal intensities and hybridization kinetics strongly correlated with experimental data in the biochip (R² = 0.8131).

Synthesis of improved upconversion nanoparticles as ultrasensitive fluorescence probe for mycotoxins.

PubMed

Chen, Quansheng; Hu, Weiwei; Sun, Cuicui; Li, Huanhuan; Ouyang, Qin

2016-09-28

Rare earth-doped upconversion nanoparticles (UCNPs) have promising potentials in biodetection due to their unique frequency upconverting capability and high detection sensitivity. This paper reports an improved UCNPs-based fluorescence probe for dual-sensing of Aflatoxin B1 (AFB1) and Deoxynivalenol (DON) using a magnetism-induced separation and the specific formation of antibody-targets complex. Herein, the improved UCNPs, which were namely NaYF4:Yb/Ho/Gd and NaYF4:Yb/Tm/Gd, were systematically studied based on the optimization of reaction time, temperature and the concentration of dopant ions with simultaneous phase and size controlled NaYF4 nanoparticles; and the targets were detected using the pattern of competitive combination assay. Under an optimized condition, the advanced fluorescent probes revealed stronger fluorescent properties, broader biological applications and better storage stabilities compared to traditional UCNPs-based ones; and ultrasensitive determinations of AFB1 and DON were achieved under a wide sensing range of 0.001-0.1 ng ml(-1) with the limit of detection (LOD) of 0.001 ng ml(-1). Additionally, the applicability of the improved nanosensor for the detection of mycotoxins was also confirmed in adulterated oil samples. Copyright © 2016 Elsevier B.V. All rights reserved.

An ultra-sensitive Au nanoparticles functionalized DNA biosensor for electrochemical sensing of mercury ions.

PubMed

Zhang, Yanyan; Zhang, Cong; Ma, Rui; Du, Xin; Dong, Wenhao; Chen, Yuan; Chen, Qiang

2017-06-01

The present work describes an effective strategy to fabricate a highly sensitive and selective DNA-biosensor for the determination of mercury ions (Hg 2+ ). The DNA 1 was modified onto the surface of Au electrode by the interaction between sulfydryl group and Au electrode. DNA probe is complementary with DNA 1. In the presence of Hg 2+ , the electrochemical signal increases owing to that Hg 2+ -mediated thymine bases induce the conformation of DNA probe to change from line to hairpin and less DNA probes adsorb into DNA 1. Taking advantage of its reduction property, methylene blue is considered as the signal indicating molecule. For improving the sensitivity of the biosensor, Au nanoparticles (Au NPs) modified reporter DNA 3 is used to adsorb DNA 1. Electrochemical behaviors of the biosensor were evaluated by electrochemical impedance spectroscopy and cyclic voltammetry. Several important parameters which could affect the property of the biosensor were studied and optimized. Under the optimal conditions, the biosensor exhibits wide linear range, high sensitivity and low detection limit. Besides, it displays superior selectivity and excellent stability. The biosensor was also applied for water sample detection with satisfactory result. The novel strategy of fabricating biosensor provides a potential platform for fabricating a variety of metal ions biosensors. Copyright © 2017 Elsevier B.V. All rights reserved.

Using acoustic levitation in synchrotron based laser pump hard x-ray probe experiments

NASA Astrophysics Data System (ADS)

Hu, Bin; Lerch, Jason; Suthar, Kamlesh; Dichiara, Anthony

Acoustic levitation provides a platform to trap and hold a small amount of material by using standing pressure waves without a container. The technique has a potential to be used for laser pump x-ray probe experiments; x-ray scattering and laser distortion from the container can be avoided, sample consumption can be minimized, and unwanted chemistry that may occur at the container interface can be avoided. The method has been used at synchrotron sources for studying protein and pharmaceutical solutions using x-ray diffraction (XRD) and small angle x-ray scattering (SAXS). However, pump-probe experiments require homogeneously excited samples, smaller than the absorption depth of the material that must be held stably at the intersection of both the laser and x-ray beams. We discuss 1) the role of oscillations in acoustic levitation and the optimal acoustic trapping conditions for x-ray/laser experiments, 2) opportunities to automate acoustic levitation for fast sample loading and manipulation, and 3) our experimental results using SAXS to monitor laser induced thermal expansion in gold nanoparticles solution. We also performed Finite Element Analysis to optimize the trapping performance and stability of droplets ranging from 0.4 mm to 2 mm. Our early x-ray/laser demonstrated the potential of the technique for time-resolved X-ray science.

Electromagnetically induced transparency and Autler-Townes splitting in superconducting flux quantum circuits

NASA Astrophysics Data System (ADS)

Sun, Hui-Chen; Liu, Yu-xi; Ian, Hou; You, J. Q.; Il'ichev, E.; Nori, Franco

2014-06-01

We study the microwave absorption of a driven three-level quantum system, which is realized by a superconducting flux quantum circuit (SFQC), with a magnetic driving field applied to the two upper levels. The interaction between the three-level system and its environment is studied within the Born-Markov approximation, and we take into account the effects of the driving field on the damping rates of the three-level system. We study the linear response of the driven three-level SFQC to a weak probe field. The linear magnetic susceptibility of the SFQC can be changed by both the driving field and the bias magnetic flux. When the bias magnetic flux is at the optimal point, the transition from the ground state to the second-excited state is forbidden and the three-level SFQC has a ladder-type transition. Thus, the SFQC responds to the probe field like natural atoms with ladder-type transitions. However, when the bias magnetic flux deviates from the optimal point, the three-level SFQC has a cyclic transition, thus it responds to the probe field like a combination of natural atoms with ladder-type transitions and natural atoms with Λ-type transitions. In particular, we provide detailed discussions on the conditions for realizing electromagnetically induced transparency and Autler-Townes splitting in three-level SFQCs.

Enhanced solid-phase recombinase polymerase amplification and electrochemical detection.

PubMed

Del Río, Jonathan Sabaté; Lobato, Ivan Magriñà; Mayboroda, Olena; Katakis, Ioanis; O'Sullivan, Ciara K

2017-05-01

Recombinase polymerase amplification (RPA) is an elegant method for the rapid, isothermal amplification of nucleic acids. Here, we elucidate the optimal surface chemistry for rapid and efficient solid-phase RPA, which was fine-tuned in order to obtain a maximum signal-to-noise ratio, defining the optimal DNA probe density, probe-to-lateral spacer ratio (1:0, 1:1, 1:10 and 1:100) and length of a vertical spacer of the probe as well as investigating the effect of different types of lateral spacers. The use of different labelling strategies was also examined in order to reduce the number of steps required for the analysis, using biotin or horseradish peroxidase-labelled reverse primers. Optimisation of the amplification temperature used and the use of surface blocking agents were also pursued. The combination of these changes facilitated a significantly more rapid amplification and detection protocol, with a lowered limit of detection (LOD) of 1 · 10 -15 M. The optimised protocol was applied to the detection of Francisella tularensis in real samples from hares and a clear correlation with PCR and qPCR results observed and the solid-phase RPA demonstrated to be capable of detecting 500 fM target DNA in real samples. Graphical abstract Relative size of thiolated lateral spacers tested versus the primer and the uvsx recombinase protein.

Neutralizer Characterization of a NEXT Multi-Thruster Array With Electrostatic Probes

NASA Technical Reports Server (NTRS)

Foster, John E.; Patterson, Michael; Pencil, Eric; McEwen, Heather; Diaz, Esther

2006-01-01

Neutralizers in a multi-thruster array configuration were characterized using conventional diagnostics such as peak-to-peak keeper oscillation amplitude as well as unconventional methods which featured the application of electrostatic probes. The response of the array local plasma environment to neutralizer flow rate changes were documented using Langmuir probes and retarding potential analyzers. Such characterization is necessary for system efficiency and stability optimization. Because the local plasma environment was measured in conjunction with the neutralizer characterization, particle fluxes at the array and thus array lifetime impacts associated with neutralizer operating mode could also be investigated. Neutralizer operating condition was documented for a number of multithruster array configurations ranging from three-engines, three-neutralizers to a single engine, one-neutralizer all as a function of neutralizer flow rate.

Design of an optimised readout architecture for phase-change probe memory using Ge2Sb2Te5 media

NASA Astrophysics Data System (ADS)

Wang, Lei; Wright, C. David; Aziz, Mustafa M.; Yang, Ci-Hui; Yang, Guo-Wei

2014-02-01

Phase-change probe memory has recently received considerable attention on its writing performance, while its readout performance is rarely evaluated. Therefore, a three-dimensional readout model has been developed for the first time to calculate the reading contrast by varying the electrical conductivities and the thickness of the capping and under layers as well as the thickness of the Ge2Sb2Te5 layer. It is found that a phase-change probe architecture, consisting of a 10 nm Ge2Sb2Te5 layer sandwiched by a 2 nm, 50 Ω-1 m-1 capping layer and a 40 nm, 5 × 106 Ω-1 m-1 under layer, has the capability of providing the optimal readout performance.

Multiplex Ligation-Dependent Probe Amplification Analysis on Capillary Electrophoresis Instruments for a Rapid Gene Copy Number Study

PubMed Central

Jankowski, Stéphane; Currie-Fraser, Erica; Xu, Licen; Coffa, Jordy

2008-01-01

Annotated DNA samples that had been previously analyzed were tested using multiplex ligation-dependent probe amplification (MLPA) assays containing probes targeting BRCA1, BRCA2, and MMR (MLH1/MSH2 genes) and the 9p21 chromosomal region. MLPA polymerase chain reaction products were separated on a capillary electrophoresis platform, and the data were analyzed using GeneMapper v4.0 software (Applied Biosystems, Foster City, CA). After signal normalization, loci regions that had undergone deletions or duplications were identified using the GeneMapper Report Manager and verified using the DyeScale functionality. The results highlight an easy-to-use, optimal sample preparation and analysis workflow that can be used for both small- and large-scale studies. PMID:19137113

77 FR 33472 - Center for Scientific Review; Notice of Closed Meetings

Federal Register 2010, 2011, 2012, 2013, 2014

2012-06-06

... Scientific Review Special Emphasis Panel, PAR09-260: Optimization of Small Molecule Probes for the Nervous System. Date: June 29, 2012. Time: 3:00 p.m. to 5:00 p.m. Agenda: To review and evaluate grant...