Thermodynamics of DNA target site recognition by homing endonucleases

PubMed Central

Eastberg, Jennifer H.; Smith, Audrey McConnell; Zhao, Lei; Ashworth, Justin; Shen, Betty W.; Stoddard, Barry L.

2007-01-01

The thermodynamic profiles of target site recognition have been surveyed for homing endonucleases from various structural families. Similar to DNA-binding proteins that recognize shorter target sites, homing endonucleases display a narrow range of binding free energies and affinities, mediated by structural interactions that balance the magnitude of enthalpic and entropic forces. While the balance of ΔH and TΔS are not strongly correlated with the overall extent of DNA bending, unfavorable ΔHbinding is associated with unstacking of individual base steps in the target site. The effects of deleterious basepair substitutions in the optimal target sites of two LAGLIDADG homing endonucleases, and the subsequent effect of redesigning one of those endonucleases to accommodate that DNA sequence change, were also measured. The substitution of base-specific hydrogen bonds in a wild-type endonuclease/DNA complex with hydrophobic van der Waals contacts in a redesigned complex reduced the ability to discriminate between sites, due to nonspecific ΔSbinding. PMID:17947319

Prostate Cancer Clinical Consortium Clinical Research Site:Targeted Therapies

DTIC Science & Technology

2015-10-01

AWARD NUMBER: W81XWH-14-2-0159 TITLE: Prostate Cancer Clinical Consortium Clinical Research Site: Targeted Therapies PRINCIPAL INVESTIGATOR...Sep 2015 4. TITLE AND SUBTITLE 5a. CONTRACT NUMBER Prostate Cancer Clinical Consortium Clinical Research Site: Targeted Therapies 5b. GRANT NUMBER... therapy resistance/sensitivity, identification of new therapeutic targets through high quality genomic analyses, providing access to the highest quality

The yeast Hot1 transcription factor is critical for activating a single target gene, STL1

PubMed Central

Bai, Chen; Tesker, Masha; Engelberg, David

2015-01-01

Transcription factors are commonly activated by signal transduction cascades and induce expression of many genes. They therefore play critical roles in determining the cell's fate. The yeast Hog1 MAP kinase pathway is believed to control the transcription of hundreds of genes via several transcription factors. To identify the bona fide target genes of Hog1, we inducibly expressed the spontaneously active variant Hog1D170A+F318L in cells lacking the Hog1 activator Pbs2. This system allowed monitoring the effects of Hog1 by itself. Expression of Hog1D170A+F318L in pbs2∆ cells imposed induction of just 105 and suppression of only 26 transcripts by at least twofold. We looked for the Hog1-responsive element within the promoter of the most highly induced gene, STL1 (88-fold). A novel Hog1 responsive element (HoRE) was identified and shown to be the direct target of the transcription factor Hot1. Unexpectedly, we could not find this HoRE in any other yeast promoter. In addition, the only gene whose expression was abolished in hot1∆ cells was STL1. Thus Hot1 is essential for transcription of just one gene, STL1. Hot1 may represent a class of transcription factors that are essential for transcription of a very few genes or even just one. PMID:25904326

PILOT-SCALE INCINERATION OF PCB-CONTAMINATED SEDIMENTS FROM THE HOT SPOT OF THE NEW BEDFORD HARBOR SUPERFUND SITE

EPA Science Inventory

Testing was performed at the EPA's Incineration Research Facility (IRF) to determine the incinerability of contaminated marine sediment from the Hot Spot in the New Bedford Harbor Superfund Site. he contaminants at this site were PCBs, at concentration up to >200,000 mg/kb, and m...

TarPmiR: a new approach for microRNA target site prediction.

PubMed

Ding, Jun; Li, Xiaoman; Hu, Haiyan

2016-09-15

The identification of microRNA (miRNA) target sites is fundamentally important for studying gene regulation. There are dozens of computational methods available for miRNA target site prediction. Despite their existence, we still cannot reliably identify miRNA target sites, partially due to our limited understanding of the characteristics of miRNA target sites. The recently published CLASH (crosslinking ligation and sequencing of hybrids) data provide an unprecedented opportunity to study the characteristics of miRNA target sites and improve miRNA target site prediction methods. Applying four different machine learning approaches to the CLASH data, we identified seven new features of miRNA target sites. Combining these new features with those commonly used by existing miRNA target prediction algorithms, we developed an approach called TarPmiR for miRNA target site prediction. Testing on two human and one mouse non-CLASH datasets, we showed that TarPmiR predicted more than 74.2% of true miRNA target sites in each dataset. Compared with three existing approaches, we demonstrated that TarPmiR is superior to these existing approaches in terms of better recall and better precision. The TarPmiR software is freely available at http://hulab.ucf.edu/research/projects/miRNA/TarPmiR/ CONTACTS: haihu@cs.ucf.edu or xiaoman@mail.ucf.edu Supplementary data are available at Bioinformatics online. © The Author 2016. Published by Oxford University Press.

Collisionless absorption, hot electron generation, and energy scaling in intense laser-target interaction

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

Liseykina, T., E-mail: tatyana.tiseykina@uni-rostock.de; Institute of Computational Technologies SD RAS, Acad. Lavrentjev Ave. 6, 630090 Novosibirsk; Mulser, P.

2015-03-15

Among the various attempts to understand collisionless absorption of intense and superintense ultrashort laser pulses, a whole variety of models and hypotheses has been invented to describe the laser beam target interaction. In terms of basic physics, collisionless absorption is understood now as the interplay of the oscillating laser field with the space charge field produced by it in the plasma. A first approach to this idea is realized in Brunel's model the essence of which consists in the formation of an oscillating charge cloud in the vacuum in front of the target, therefore frequently addressed by the vague termmore » “vacuum heating.” The investigation of statistical ensembles of orbits shows that the absorption process is localized at the ion-vacuum interface and in the skin layer: Single electrons enter into resonance with the laser field thereby undergoing a phase shift which causes orbit crossing and braking of Brunel's laminar flow. This anharmonic resonance acts like an attractor for the electrons and leads to the formation of a Maxwellian tail in the electron energy spectrum. Most remarkable results of our investigations are the Brunel like spectral hot electron distribution at the relativistic threshold, the minimum of absorption at Iλ{sup 2}≅(0.3−1.2)×10{sup 21} Wcm{sup −2}μm{sup 2} in the plasma target with the electron density of n{sub e}λ{sup 2}∼10{sup 23}cm{sup −3}μm{sup 2}, the drastic reduction of the number of hot electrons in this domain and their reappearance in the highly relativistic domain, and strong coupling, beyond expectation, of the fast electron jets with the return current through Cherenkov emission of plasmons. The hot electron energy scaling shows a strong dependence on intensity in the moderately relativistic domain Iλ{sup 2}≅(10{sup 18}−10{sup 20}) Wcm{sup −2}μm{sup 2}, a scaling in vague accordance with current published estimates in the range Iλ{sup 2}≅(0.14−3.5)×10{sup 21} Wcm{sup �

Ribosomal DNA replication fork barrier and HOT1 recombination hot spot: shared sequences but independent activities.

PubMed

Ward, T R; Hoang, M L; Prusty, R; Lau, C K; Keil, R L; Fangman, W L; Brewer, B J

2000-07-01

In the ribosomal DNA of Saccharomyces cerevisiae, sequences in the nontranscribed spacer 3' of the 35S ribosomal RNA gene are important to the polar arrest of replication forks at a site called the replication fork barrier (RFB) and also to the cis-acting, mitotic hyperrecombination site called HOT1. We have found that the RFB and HOT1 activity share some but not all of their essential sequences. Many of the mutations that reduce HOT1 recombination also decrease or eliminate fork arrest at one of two closely spaced RFB sites, RFB1 and RFB2. A simple model for the juxtaposition of RFB and HOT1 sequences is that the breakage of strands in replication forks arrested at RFB stimulates recombination. Contrary to this model, we show here that HOT1-stimulated recombination does not require the arrest of forks at the RFB. Therefore, while HOT1 activity is independent of replication fork arrest, HOT1 and RFB require some common sequences, suggesting the existence of a common trans-acting factor(s).

Retention of ferrofluid aggregates at the target site during magnetic drug targeting

NASA Astrophysics Data System (ADS)

Asfer, Mohammed; Saroj, Sunil Kumar; Panigrahi, Pradipta Kumar

2017-08-01

The present study reports the retention dynamics of a ferrofluid aggregate localized at the target site inside a glass capillary (500 × 500 μm2 square cross section) against a bulk flow of DI water (Re = 0.16 and 0.016) during the process of magnetic drug targeting (MDT). The dispersion dynamics of iron oxide nanoparticles (IONPs) into bulk flow for different initial size of aggregate at the target site is reported using the brightfield visualization technique. The flow field around the aggregate during the retention is evaluated using the μPIV technique. IONPs at the outer boundary experience a higher shear force as compared to the magnetic force, resulting in dispersion of IONPs into the bulk flow downstream to the aggregate. The blockage effect and the roughness of the outer boundary of the aggregate resulting from chain like clustering of IONPs contribute to the flow recirculation at the downstream region of the aggregate. The entrapment of seeding particles inside the chain like clusters of IONPs at the outer boundary of the aggregate reduces the degree of roughness resulting in a streamlined aggregate at the target site at later time. The effect of blockage, structure of the aggregate, and disturbed flow such as recirculation around the aggregate are the primary factors, which must be investigated for the effectiveness of the MDT process for in vivo applications.

Prostate Cancer Clinical Consortium Clinical Research Site: Targeted Therapies

DTIC Science & Technology

2017-10-01

AWARD NUMBER: W81XWH-14-2-0159 TITLE: Prostate Cancer Clinical Consortium Clinical Research Site: Targeted Therapies PRINCIPAL INVESTIGATOR...Annual PREPARED FOR: U.S. Army Medical Research and Materiel Command Fort Detrick, Maryland 21702-5012 DISTRIBUTION STATEMENT: Approved for...AND SUBTITLE Prostate Cancer Clinical Consortium Clinical Research Site: Targeted Therapies 5a. CONTRACT NUMBER 5b. GRANT NUMBER 5c. PROGRAM ELEMENT

Target-mediated drug disposition model for drugs with two binding sites that bind to a target with one binding site.

PubMed

Gibiansky, Leonid; Gibiansky, Ekaterina

2017-10-01

The paper extended the TMDD model to drugs with two identical binding sites (2-1 TMDD). The quasi-steady-state (2-1 QSS), quasi-equilibrium (2-1 QE), irreversible binding (2-1 IB), and Michaelis-Menten (2-1 MM) approximations of the model were derived. Using simulations, the 2-1 QSS approximation was compared with the full 2-1 TMDD model. As expected and similarly to the standard TMDD for monoclonal antibodies (mAb), 2-1 QSS predictions were nearly identical to 2-1 TMDD predictions, except for times of fast changes following initiation of dosing, when equilibrium has not yet been reached. To illustrate properties of new equations and approximations, several variations of population PK data for mAbs with soluble (slow elimination of the complex) or membrane-bound (fast elimination of the complex) targets were simulated from a full 2-1 TMDD model and fitted to 2-1 TMDD models, to its approximations, and to the standard (1-1) QSS model. For a mAb with a soluble target, it was demonstrated that the 2-1 QSS model provided nearly identical description of the observed (simulated) free drug and total target concentrations, although there was some minor bias in predictions of unobserved free target concentrations. The standard QSS approximation also provided a good description of the observed data, but was not able to distinguish between free drug concentrations (with no target attached and both binding site free) and partially bound drug concentrations (with one of the binding sites occupied by the target). For a mAb with a membrane-bound target, the 2-1 MM approximation adequately described the data. The 2-1 QSS approximation converged 10 times faster than the full 2-1 TMDD, and its run time was comparable with the standard QSS model.

Targeted induction of meiotic double-strand breaks reveals chromosomal domain-dependent regulation of Spo11 and interactions among potential sites of meiotic recombination

PubMed Central

Fukuda, Tomoyuki; Kugou, Kazuto; Sasanuma, Hiroyuki; Shibata, Takehiko

2008-01-01

Meiotic recombination is initiated by programmed DNA double-strand break (DSB) formation mediated by Spo11. DSBs occur with frequency in chromosomal regions called hot domains but are seldom seen in cold domains. To obtain insights into the determinants of the distribution of meiotic DSBs, we examined the effects of inducing targeted DSBs during yeast meiosis using a UAS-directed form of Spo11 (Gal4BD-Spo11) and a meiosis-specific endonuclease, VDE (PI-SceI). Gal4BD-Spo11 cleaved its target sequence (UAS) integrated in hot domains but rarely in cold domains. However, Gal4BD-Spo11 did bind to UAS and VDE efficiently cleaved its recognition sequence in either context, suggesting that a cold domain is not a region of inaccessible or uncleavable chromosome structure. Importantly, self-association of Spo11 occurred at UAS in a hot domain but not in a cold domain, raising the possibility that Spo11 remains in an inactive intermediate state in cold domains. Integration of UAS adjacent to known DSB hotspots allowed us to detect competitive interactions among hotspots for activation. Moreover, the presence of VDE-introduced DSB repressed proximal hotspot activity, implicating DSBs themselves in interactions among hotspots. Thus, potential sites for Spo11-mediated DSB are subject to domain-specific and local competitive regulations during and after DSB formation. PMID:18096626

Generation and Transport of Hot Electrons in Cone-Wire Targets

NASA Astrophysics Data System (ADS)

Beg, Farhat

2009-11-01

We present results from a series of experiments where cone-wire targets in various configurations were employed both to assess hot electron coupling efficiency, and to reveal the source temperature of the hot electrons. Initial experiments were performed on the Vulcan petawatt laser at the Rutherford Appleton Laboratory and Titan laser at the Lawrence Livermore National Laboratory. Results with aluminum cones joined to Cu wires of diameters from 10 to 40 μm show that the laser coupling efficiency to electron energy within the wire is proportional to the cross sectional area of the wire. In addition, coupling into the wire was observed to decrease with the laser prepulse and cone-wall thickness. More recently, this study was extended, using the OMEGA EP laser. The resulting changes in coupling energy give indications of the scaling as we approach FI-relevant conditions. Requirements for FI scale fast ignition cone parameters: tip thickness, wall thickness, laser prepulse and laser pulse length, will be discussed. In collaboration with T. Yabuuchi, T. Ma, D. Higginson, H. Sawada, J. King, M.H. Key, K.U. Akli, Al Elsholz, D. Batani, H. Chen, R.R. Freeman, L. Gizzi, J. Green, S. Hatchett, D. Hey, P. Jaanimagi, J. Koch, K. L. Lancaster, D.Larson, A.J. MacKinnon, H. McLean, A. MacPhee, P.A. Norreys, P.K Patel, R. B. Stephens, W. Theobald, R. Town, M. Wei, S. Wilks, Roger Van Maren, B. Westover and L. VanWoerkom.

Cellular imaging by targeted assembly of hot-spot SERS and photoacoustic nanoprobes using split-fluorescent protein scaffolds.

PubMed

Köker, Tuğba; Tang, Nathalie; Tian, Chao; Zhang, Wei; Wang, Xueding; Martel, Richard; Pinaud, Fabien

2018-02-09

The in cellulo assembly of plasmonic nanomaterials into photo-responsive probes is of great interest for many bioimaging and nanophotonic applications but remains challenging with traditional nucleic acid scaffolds-based bottom-up methods. Here, we address this quandary using split-fluorescent protein (FP) fragments as molecular glue and switchable Raman reporters to assemble gold or silver plasmonic nanoparticles (NPs) into photonic clusters directly in live cells. When targeted to diffusing surface biomarkers in cancer cells, the NPs self-assemble into surface-enhanced Raman-scattering (SERS) nanoclusters having hot spots homogenously seeded by the reconstruction of full-length FPs. Within plasmonic hot spots, autocatalytic activation of the FP chromophore and near-field amplification of its Raman fingerprints enable selective and sensitive SERS imaging of targeted cells. This FP-driven assembly of metal colloids also yields enhanced photoacoustic signals, allowing the hybrid FP/NP nanoclusters to serve as contrast agents for multimodal SERS and photoacoustic microscopy with single-cell sensitivity.

Nuclease Target Site Selection for Maximizing On-target Activity and Minimizing Off-target Effects in Genome Editing

PubMed Central

Lee, Ciaran M; Cradick, Thomas J; Fine, Eli J; Bao, Gang

2016-01-01

The rapid advancement in targeted genome editing using engineered nucleases such as ZFNs, TALENs, and CRISPR/Cas9 systems has resulted in a suite of powerful methods that allows researchers to target any genomic locus of interest. A complementary set of design tools has been developed to aid researchers with nuclease design, target site selection, and experimental validation. Here, we review the various tools available for target selection in designing engineered nucleases, and for quantifying nuclease activity and specificity, including web-based search tools and experimental methods. We also elucidate challenges in target selection, especially in predicting off-target effects, and discuss future directions in precision genome editing and its applications. PMID:26750397

Hot-spot mix in ignition-scale inertial confinement fusion targets.

PubMed

Regan, S P; Epstein, R; Hammel, B A; Suter, L J; Scott, H A; Barrios, M A; Bradley, D K; Callahan, D A; Cerjan, C; Collins, G W; Dixit, S N; Döppner, T; Edwards, M J; Farley, D R; Fournier, K B; Glenn, S; Glenzer, S H; Golovkin, I E; Haan, S W; Hamza, A; Hicks, D G; Izumi, N; Jones, O S; Kilkenny, J D; Kline, J L; Kyrala, G A; Landen, O L; Ma, T; MacFarlane, J J; MacKinnon, A J; Mancini, R C; McCrory, R L; Meezan, N B; Meyerhofer, D D; Nikroo, A; Park, H-S; Ralph, J; Remington, B A; Sangster, T C; Smalyuk, V A; Springer, P T; Town, R P J

2013-07-26

Mixing of plastic ablator material, doped with Cu and Ge dopants, deep into the hot spot of ignition-scale inertial confinement fusion implosions by hydrodynamic instabilities is diagnosed with x-ray spectroscopy on the National Ignition Facility. The amount of hot-spot mix mass is determined from the absolute brightness of the emergent Cu and Ge K-shell emission. The Cu and Ge dopants placed at different radial locations in the plastic ablator show the ablation-front hydrodynamic instability is primarily responsible for hot-spot mix. Low neutron yields and hot-spot mix mass between 34(-13,+50)  ng and 4000(-2970,+17 160)  ng are observed.

Hot-spot mix in ignition-scale inertial confinement fusion targets

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

Regan, S. P.; Epstein, R.; Hammel, B. A.

Mixing of plastic ablator material, doped with Cu and Ge dopants, deep into the hot spot of ignition-scale inertial confinement fusion implosions by hydrodynamic instabilities is diagnosed with x-ray spectroscopy on the National Ignition Facility. The amount of hot-spot mix mass is determined from the absolute brightness of the emergent Cu and Ge K-shell emission. The Cu and Ge dopants placed at different radial locations in the plastic ablator show the ablation-front hydrodynamic instability is primarily responsible for hot-spot mix. As a result, low neutron yields and hot-spot mix mass between 34(–13,+50) ng and 4000(–2970,+17 160) ng are observed.

Hot-spot mix in ignition-scale inertial confinement fusion targets

DOE PAGES

Regan, S. P.; Epstein, R.; Hammel, B. A.; ...

2013-07-22

Mixing of plastic ablator material, doped with Cu and Ge dopants, deep into the hot spot of ignition-scale inertial confinement fusion implosions by hydrodynamic instabilities is diagnosed with x-ray spectroscopy on the National Ignition Facility. The amount of hot-spot mix mass is determined from the absolute brightness of the emergent Cu and Ge K-shell emission. The Cu and Ge dopants placed at different radial locations in the plastic ablator show the ablation-front hydrodynamic instability is primarily responsible for hot-spot mix. As a result, low neutron yields and hot-spot mix mass between 34(–13,+50) ng and 4000(–2970,+17 160) ng are observed.

Transport of high intensity laser-generated hot electrons in cone coupled wire targets

NASA Astrophysics Data System (ADS)

Beg, Farhat

2008-04-01

In this talk, we present results from a series of experiments where cone-wire targets were employed both to assess hot electron coupling efficiency, and to reveal the source temperature of the hot electrons. Experiments were performed on the petawatt laser at the Rutherford Appleton Laboratory. A 500J, 1ps laser (I ˜ 4 x 10^20 W/cm-2) was focused by an f/3 off-axis parabolic mirror into hollow aluminum cones joined at their tip to Cu wires of diameters from 10 to 40 μm. The three main diagnostics fielded were a copper Kalpha Bragg crystal imager, a single hit CCD camera spectrometer and a Highly Oriented Pyrolytic Graphite (HOPG) spectrometer. The resulting data were cross-calibrated to obtain the absolute Kalpha yield. Comparison of the axially diminishing absolute Cu Kα intensity with modeling shows that the penetration of the hot electrons is consistent with one dimensional ohmic potential limited transport (1/e length ˜ 100 μm). The laser coupling efficiency to electron energy within the wire is shown to be proportional to the cross sectional area of the wire, reaching 15% for 40 μm wires. We find that the hot electron temperature within the wire was <=750 keV, significantly lower than that predicted by the ponderomotive scaling. A comparison of the experimental results with 2D hybrid PIC simulations using e-PLAS code will be presented and relevance to Fast Ignition will be discussed at the meeting. *In collaboration with J.A. King, M.H. Key, K.U. Akli, R.R. Freeman, J. Green, S. P. Hatchett, D. Hey, P. Jaanimagi, J. Koch, K. L. Lancaster, T. Ma, A.J. MacKinnon, A. MacPhee, R. Mason, P.A. Norreys, P.K Patel, T. Phillips, R. Stephens, W. Theobald, R.P.J. Town, M. Wei, L. Van Woerkom, B. Zhang.

X-rays diagnostics of the hot electron energy distribution in the intense laser interaction with metal targets

NASA Astrophysics Data System (ADS)

Kostenko, O. F.; Andreev, N. E.; Rosmej, O. N.

2018-03-01

A two-temperature hot electron energy distribution has been revealed by modeling of bremsstrahlung emission, measured by the radiation attenuation and half-shade methods, and Kα emission from a massive silver cylinder irradiated by a subpicosecond s-polarized laser pulse with a peak intensity of about 2 × 1019 W/cm2. To deduce parameters of the hot electron spectrum, we have developed semi-analytical models of generation and measurements of the x-rays. The models are based on analytical expressions and tabulated data on electron stopping power as well as cross-sections of generation and absorption of the x-rays. The Kα emission from thin silver foils deposited on low-Z substrates, both conducting and nonconducting, has been used to verify the developed models and obtained hot electron spectrum. The obtained temperatures of the colder and hotter electron components are in agreement with the values predicted by kinetic simulations of the cone-guided approach to fast ignition [Chrisman et al., Phys. Plasmas 15, 056309 (2008)]. The temperature of the low-energy component of the accelerated electron spectrum is well below the ponderomotive scaling and Beg's law. We have obtained relatively low conversion efficiency of laser energy into the energy of hot electrons propagating through the solid target of about 2%. It is demonstrated that the assumption about a single-temperature hot electron energy distribution with the slope temperature described by the ponderomotive scaling relationship, without detailed analysis of the hot electron spectrum, can lead to strong overestimation of the laser-to-electron energy-conversion efficiency, in particular, the conversion efficiency of laser energy into the high-temperature component of the hot electron distribution.

Engineering synthetic TAL effectors with orthogonal target sites

PubMed Central

Garg, Abhishek; Lohmueller, Jason J.; Silver, Pamela A.; Armel, Thomas Z.

2012-01-01

The ability to engineer biological circuits that process and respond to complex cellular signals has the potential to impact many areas of biology and medicine. Transcriptional activator-like effectors (TALEs) have emerged as an attractive component for engineering these circuits, as TALEs can be designed de novo to target a given DNA sequence. Currently, however, the use of TALEs is limited by degeneracy in the site-specific manner by which they recognize DNA. Here, we propose an algorithm to computationally address this problem. We apply our algorithm to design 180 TALEs targeting 20 bp cognate binding sites that are at least 3 nt mismatches away from all 20 bp sequences in putative 2 kb human promoter regions. We generated eight of these synthetic TALE activators and showed that each is able to activate transcription from a targeted reporter. Importantly, we show that these proteins do not activate synthetic reporters containing mismatches similar to those present in the genome nor a set of endogenous genes predicted to be the most likely targets in vivo. Finally, we generated and characterized TALE repressors comprised of our orthogonal DNA binding domains and further combined them with shRNAs to accomplish near complete repression of target gene expression. PMID:22581776

Influence of argon pressure and current density on substrate temperature during magnetron sputtering of hot titanium target

NASA Astrophysics Data System (ADS)

Komlev, Anton A.; Minzhulina, Ekaterina A.; Smirnov, Vladislav V.; Shapovalov, Viktor I.

2018-01-01

The paper describes physical characteristics of the hot target sputtering process, which have not been known before. To switch a magnetron over to the hot target regime, a titanium disk of 1 mm thick with a 1-mm-gap was attached on a 4-mm-thick copper plate cooled by running water. A thermocouple sensor was used to investigate the thermal processes occurring in substrates. The study was performed at the discharge current density of 20-40 mA/cm2 and argon pressure of 3-7 mTorr. The accuracy of temperature measurement appeared to be within ± 5%, due the application of a chromel-copel thermocouple. The study reveals that under these conditions the heating curves have the inflection points positioned proportionally to the discharge current density and argon pressure on a time axis. The inflection point appears in the kinetic curves due to the finite value of the target heating time constant. The study shows that the substrate fixed temperature and substrate heating time constant depend on the argon pressure and relate to the current density by the polynomials of the first and second degrees, respectively. The influence of a target on the substrate heating kinetics is considered in an analytical description by the introduction of a multiplier in the form of an exponential function of time. The results of the research make a novel contribution to the field of the sputtering process.

Evolutionary transitions to new DNA methyltransferases through target site expansion and shrinkage.

PubMed

Rockah-Shmuel, Liat; Tawfik, Dan S

2012-12-01

DNA-binding and modifying proteins show high specificity but also exhibit a certain level of promiscuity. Such latent promiscuous activities comprise the starting points for new protein functions, but this hypothesis presents a paradox: a new activity can only evolve if it already exists. How then, do novel activities evolve? DNA methyltransferases, for example, are highly divergent in their target sites, but how transitions toward novel sites occur remains unknown. We performed laboratory evolution of the DNA methyltransferase M.HaeIII. We found that new target sites emerged primarily through expansion of the original site, GGCC, and the subsequent shrinkage of evolved expanded sites. Variants evolved for sites that are promiscuously methylated by M.HaeIII [GG((A)/(T))CC and GGCGCC] carried mutations in 'gate-keeper' residues. They could thereby methylate novel target sites such as GCGC and GGATCC that were neither selected for nor present in M.HaeIII. These 'generalist' intermediates were further evolved to obtain variants with novel target specificities. Our results demonstrate the ease by which new DNA-binding and modifying specificities evolve and the mechanism by which they occur at both the protein and DNA levels.

Remediating radium contaminated legacy sites: Advances made through machine learning in routine monitoring of "hot" particles.

PubMed

Varley, Adam; Tyler, Andrew; Smith, Leslie; Dale, Paul; Davies, Mike

2015-07-15

The extensive use of radium during the 20th century for industrial, military and pharmaceutical purposes has led to a large number of contaminated legacy sites across Europe and North America. Sites that pose a high risk to the general public can present expensive and long-term remediation projects. Often the most pragmatic remediation approach is through routine monitoring operating gamma-ray detectors to identify, in real-time, the signal from the most hazardous heterogeneous contamination (hot particles); thus facilitating their removal and safe disposal. However, current detection systems do not fully utilise all spectral information resulting in low detection rates and ultimately an increased risk to the human health. The aim of this study was to establish an optimised detector-algorithm combination. To achieve this, field data was collected using two handheld detectors (sodium iodide and lanthanum bromide) and a number of Monte Carlo simulated hot particles were randomly injected into the field data. This allowed for the detection rate of conventional deterministic (gross counts) and machine learning (neural networks and support vector machines) algorithms to be assessed. The results demonstrated that a Neural Network operated on a sodium iodide detector provided the best detection capability. Compared to deterministic approaches, this optimised detection system could detect a hot particle on average 10cm deeper into the soil column or with half of the activity at the same depth. It was also found that noise presented by internal contamination restricted lanthanum bromide for this application. Copyright © 2015. Published by Elsevier B.V.

Computational Predictions Provide Insights into the Biology of TAL Effector Target Sites

PubMed Central

Grau, Jan; Wolf, Annett; Reschke, Maik; Bonas, Ulla; Posch, Stefan; Boch, Jens

2013-01-01

Transcription activator-like (TAL) effectors are injected into host plant cells by Xanthomonas bacteria to function as transcriptional activators for the benefit of the pathogen. The DNA binding domain of TAL effectors is composed of conserved amino acid repeat structures containing repeat-variable diresidues (RVDs) that determine DNA binding specificity. In this paper, we present TALgetter, a new approach for predicting TAL effector target sites based on a statistical model. In contrast to previous approaches, the parameters of TALgetter are estimated from training data computationally. We demonstrate that TALgetter successfully predicts known TAL effector target sites and often yields a greater number of predictions that are consistent with up-regulation in gene expression microarrays than an existing approach, Target Finder of the TALE-NT suite. We study the binding specificities estimated by TALgetter and approve that different RVDs are differently important for transcriptional activation. In subsequent studies, the predictions of TALgetter indicate a previously unreported positional preference of TAL effector target sites relative to the transcription start site. In addition, several TAL effectors are predicted to bind to the TATA-box, which might constitute one general mode of transcriptional activation by TAL effectors. Scrutinizing the predicted target sites of TALgetter, we propose several novel TAL effector virulence targets in rice and sweet orange. TAL-mediated induction of the candidates is supported by gene expression microarrays. Validity of these targets is also supported by functional analogy to known TAL effector targets, by an over-representation of TAL effector targets with similar function, or by a biological function related to pathogen infection. Hence, these predicted TAL effector virulence targets are promising candidates for studying the virulence function of TAL effectors. TALgetter is implemented as part of the open-source Java library

Identification of a Non-Gatekeeper Hot Spot for Drug-Resistant Mutations in mTOR Kinase.

PubMed

Wu, Tzung-Ju; Wang, Xiaowen; Zhang, Yanjie; Meng, Linghua; Kerrigan, John E; Burley, Stephen K; Zheng, X F Steven

2015-04-21

Protein kinases are therapeutic targets for human cancer. However, "gatekeeper" mutations in tyrosine kinases cause acquired clinical resistance, limiting long-term treatment benefits. mTOR is a key cancer driver and drug target. Numerous small-molecule mTOR kinase inhibitors have been developed, with some already in human clinical trials. Given our clinical experience with targeted therapeutics, acquired drug resistance in mTOR is thought likely, but not yet documented. Herein, we describe identification of a hot spot (L2185) for drug-resistant mutations, which is distinct from the gatekeeper site, and a chemical scaffold refractory to drug-resistant mutations. We also provide new insights into mTOR kinase structure and function. The hot spot mutations are potentially useful as surrogate biomarkers for acquired drug resistance in ongoing clinical trials and future treatments and for the design of the next generation of mTOR-targeted drugs. Our study provides a foundation for further research into mTOR kinase function and targeting. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

Characteristics of Food Industry Web Sites and "Advergames" Targeting Children

ERIC Educational Resources Information Center

Culp, Jennifer; Bell, Robert A.; Cassady, Diana

2010-01-01

Objective: To assess the content of food industry Web sites targeting children by describing strategies used to prolong their visits and foster brand loyalty; and to document health-promoting messages on these Web sites. Design: A content analysis was conducted of Web sites advertised on 2 children's networks, Cartoon Network and Nickelodeon. A…

Target-classification approach applied to active UXO sites

NASA Astrophysics Data System (ADS)

Shubitidze, F.; Fernández, J. P.; Shamatava, Irma; Barrowes, B. E.; O'Neill, K.

2013-06-01

This study is designed to illustrate the discrimination performance at two UXO active sites (Oklahoma's Fort Sill and the Massachusetts Military Reservation) of a set of advanced electromagnetic induction (EMI) inversion/discrimination models which include the orthonormalized volume magnetic source (ONVMS), joint diagonalization (JD), and differential evolution (DE) approaches and whose power and flexibility greatly exceed those of the simple dipole model. The Fort Sill site is highly contaminated by a mix of the following types of munitions: 37-mm target practice tracers, 60-mm illumination mortars, 75-mm and 4.5'' projectiles, 3.5'', 2.36'', and LAAW rockets, antitank mine fuzes with and without hex nuts, practice MK2 and M67 grenades, 2.5'' ballistic windshields, M2A1-mines with/without bases, M19-14 time fuzes, and 40-mm practice grenades with/without cartridges. The site at the MMR site contains targets of yet different sizes. In this work we apply our models to EMI data collected using the MetalMapper (MM) and 2 × 2 TEMTADS sensors. The data for each anomaly are inverted to extract estimates of the extrinsic and intrinsic parameters associated with each buried target. (The latter include the total volume magnetic source or NVMS, which relates to size, shape, and material properties; the former includes location, depth, and orientation). The estimated intrinsic parameters are then used for classification performed via library matching and the use of statistical classification algorithms; this process yielded prioritized dig-lists that were submitted to the Institute for Defense Analyses (IDA) for independent scoring. The models' classification performance is illustrated and assessed based on these independent evaluations.

Computational design of trimeric influenza-neutralizing proteins targeting the hemagglutinin receptor binding site

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

Strauch, Eva-Maria; Bernard, Steffen M.; La, David

Many viral surface glycoproteins and cell surface receptors are homo-oligomers1, 2, 3, 4, and thus can potentially be targeted by geometrically matched homo-oligomers that engage all subunits simultaneously to attain high avidity and/or lock subunits together. The adaptive immune system cannot generally employ this strategy since the individual antibody binding sites are not arranged with appropriate geometry to simultaneously engage multiple sites in a single target homo-oligomer. We describe a general strategy for the computational design of homo-oligomeric protein assemblies with binding functionality precisely matched to homo-oligomeric target sites5, 6, 7, 8. In the first step, a small protein ismore » designed that binds a single site on the target. In the second step, the designed protein is assembled into a homo-oligomer such that the designed binding sites are aligned with the target sites. We use this approach to design high-avidity trimeric proteins that bind influenza A hemagglutinin (HA) at its conserved receptor binding site. The designed trimers can both capture and detect HA in a paper-based diagnostic format, neutralizes influenza in cell culture, and completely protects mice when given as a single dose 24 h before or after challenge with influenza.« less

Estimating Expressed Temperature and Fractional Area of Hot Lava at the Kilauea Vent with AVIRIS Spectral Measurements

NASA Technical Reports Server (NTRS)

Green, Robert O.

2001-01-01

Imaging spectroscopy offers a framework based in physics and chemistry for scientific investigation of a wide range of phenomena of interest in the Earth environment. In the scientific discipline of volcanology knowledge of lava temperature and distribution at the surface provides insight into the volcano status and subsurface processes. A remote sensing strategy to measure surface lava temperatures and distribution would support volcanology research. Hot targets such as molten lava emit spectral radiance as a function of temperature. A figure shows a series of Planck functions calculated radiance spectra for hot targets at different temperatures. A maximum Lambertian solar reflected radiance spectrum is shown as well. While similar in form, each hot target spectrum has a unique spectral shape and is distinct from the solar reflected radiance spectrum. Based on this temperature-dependent signature, imaging spectroscopy provides an innovative approach for the remote-sensing-based measurement of lava temperature. A natural site for investigation of the measurement of lava temperature is the Big Island of Hawaii where molten lava from the Kilauea vent is present at the surface. In the past, Airborne Visible/Infrared Imaging Spectrometer (AVIRIS) data sets have been used for the analysis of hot volcanic targets and hot burning fires. The research presented here builds upon and extends this earlier work. The year 2000 Hawaii AVIRIS data set has been analyzed to derive lava temperatures taking into account factors of fractional fill, solar reflected radiance, and atmospheric attenuation of the surface emitted radiance. The measurements, analyses, and current results for this research are presented here.

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

Petrologic considerations for hot dry rock geothermal site selection in the Clear Lake Region, California

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

Stimac, J.; Goff, F.; Hearn, B.C. Jr.

1992-01-01

The Clear Lake area is well known for anomalous heat flow, thermal springs, hydrothermal mineral deposits, and Quaternary volcanism. These factors, along with the apparent lack of a large reservoir of geothermal fluid north of Collayomi fault make the Clear Lake area an attractive target for hot dry rock (HDR) geothermal development. Petrologic considerations provide some constraints on site selection for HDR development. Spatial and temporal trends in volcanism in the Coast Ranges indicate that magmatism has migrated to the north with time, paralleling passage of the Mendocino triple junction and propagation of the San Andreas fault. Volcanism in themore » region may have resulted from upwelling of hot asthenosphere along the southern margin of the subducted segment of the Gorda plate. Spatial and temporal trends of volcanism within the Clear Lake volcanic field are similar to larger-scale trends of Neogene volcanism in the Cost Ranges. Volcanism (especially for silicic compositions) shows a general migration to the north over the {approximately}2 Ma history of the field, with the youngest two silicic centers located at Mt. Konocti and Borax Lake. The Mt. Konocti system (active from {approximately} 0.6 to 0.3 Ma) was large and long-lived, whereas the Borax Lake system is much smaller but younger (0.09 Ma). Remnants of silicic magma bodies under Mt. Konocti may be in the latter stages of cooling, whereas a magma body centered under Borax Lake may be in the early stages of development. The existence of an upper crustal silicic magma body of under Borax Lake has yet to be demonstrated by passive geophysics, however, subsurface temperatures in the area as high (> 200{degrees}C at 2000 m) as those beneath the Mt. Konocti area. Based on petrologic considerations alone, the Mt. Konocti-Borax Lake area appears to be the most logical choice for HDR geothermal development in the region.« less

Comprehensive modeling of microRNA targets predicts functional non-conserved and non-canonical sites.

PubMed

Betel, Doron; Koppal, Anjali; Agius, Phaedra; Sander, Chris; Leslie, Christina

2010-01-01

mirSVR is a new machine learning method for ranking microRNA target sites by a down-regulation score. The algorithm trains a regression model on sequence and contextual features extracted from miRanda-predicted target sites. In a large-scale evaluation, miRanda-mirSVR is competitive with other target prediction methods in identifying target genes and predicting the extent of their downregulation at the mRNA or protein levels. Importantly, the method identifies a significant number of experimentally determined non-canonical and non-conserved sites.

Hot conditioning equipment conceptual design report

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

Bradshaw, F.W., Westinghouse Hanford

1996-08-06

This report documents the conceptual design of the Hot Conditioning System Equipment. The Hot conditioning System will consist of two separate designs: the Hot Conditioning System Equipment; and the Hot Conditioning System Annex. The Hot Conditioning System Equipment Design includes the equipment such as ovens, vacuum pumps, inert gas delivery systems, etc.necessary to condition spent nuclear fuel currently in storage in the K Basins of the Hanford Site. The Hot Conditioning System Annex consists of the facility of house the Hot Conditioning System. The Hot Conditioning System will be housed in an annex to the Canister Storage Building. The Hotmore » Conditioning System will consist of pits in the floor which contain ovens in which the spent nuclear will be conditioned prior to interim storage.« less

Target Site Recognition by a Diversity-Generating Retroelement

PubMed Central

Guo, Huatao; Tse, Longping V.; Nieh, Angela W.; Czornyj, Elizabeth; Williams, Steven; Oukil, Sabrina; Liu, Vincent B.; Miller, Jeff F.

2011-01-01

Diversity-generating retroelements (DGRs) are in vivo sequence diversification machines that are widely distributed in bacterial, phage, and plasmid genomes. They function to introduce vast amounts of targeted diversity into protein-encoding DNA sequences via mutagenic homing. Adenine residues are converted to random nucleotides in a retrotransposition process from a donor template repeat (TR) to a recipient variable repeat (VR). Using the Bordetella bacteriophage BPP-1 element as a prototype, we have characterized requirements for DGR target site function. Although sequences upstream of VR are dispensable, a 24 bp sequence immediately downstream of VR, which contains short inverted repeats, is required for efficient retrohoming. The inverted repeats form a hairpin or cruciform structure and mutational analysis demonstrated that, while the structure of the stem is important, its sequence can vary. In contrast, the loop has a sequence-dependent function. Structure-specific nuclease digestion confirmed the existence of a DNA hairpin/cruciform, and marker coconversion assays demonstrated that it influences the efficiency, but not the site of cDNA integration. Comparisons with other phage DGRs suggested that similar structures are a conserved feature of target sequences. Using a kanamycin resistance determinant as a reporter, we found that transplantation of the IMH and hairpin/cruciform-forming region was sufficient to target the DGR diversification machinery to a heterologous gene. In addition to furthering our understanding of DGR retrohoming, our results suggest that DGRs may provide unique tools for directed protein evolution via in vivo DNA diversification. PMID:22194701

Near Surface Swimming of Salmonella Typhimurium Explains Target-Site Selection and Cooperative Invasion

PubMed Central

Kreibich, Saskia; Vonaesch, Pascale; Andritschke, Daniel; Rout, Samuel; Weidner, Kerstin; Sormaz, Milos; Songhet, Pascal; Horvath, Peter; Chabria, Mamta; Vogel, Viola; Spori, Doris M.; Jenny, Patrick; Hardt, Wolf-Dietrich

2012-01-01

Targeting of permissive entry sites is crucial for bacterial infection. The targeting mechanisms are incompletely understood. We have analyzed target-site selection by S. Typhimurium. This enteropathogenic bacterium employs adhesins (e.g. fim) and the type III secretion system 1 (TTSS-1) for host cell binding, the triggering of ruffles and invasion. Typically, S. Typhimurium invasion is focused on a subset of cells and multiple bacteria invade via the same ruffle. It has remained unclear how this is achieved. We have studied target-site selection in tissue culture by time lapse microscopy, movement pattern analysis and modeling. Flagellar motility (but not chemotaxis) was required for reaching the host cell surface in vitro. Subsequently, physical forces trapped the pathogen for ∼1.5–3 s in “near surface swimming”. This increased the local pathogen density and facilitated “scanning” of the host surface topology. We observed transient TTSS-1 and fim-independent “stopping” and irreversible TTSS-1-mediated docking, in particular at sites of prominent topology, i.e. the base of rounded-up cells and membrane ruffles. Our data indicate that target site selection and the cooperative infection of membrane ruffles are attributable to near surface swimming. This mechanism might be of general importance for understanding infection by flagellated bacteria. PMID:22911370

Initial basalt target site selection evaluation for the Mars penetrator drop test

NASA Technical Reports Server (NTRS)

Bunch, T. E.; Quaide, W. L.; Polkowski, G.

1976-01-01

Potential basalt target sites for an air drop penetrator test were described and the criteria involved in site selection were discussed. A summary of the background field geology and recommendations for optimum sites are also presented.

Shift in the Microbial Ecology of a Hospital Hot Water System following the Introduction of an On-Site Monochloramine Disinfection System

PubMed Central

Baron, Julianne L.; Vikram, Amit; Duda, Scott; Stout, Janet E.; Bibby, Kyle

2014-01-01

Drinking water distribution systems, including premise plumbing, contain a diverse microbiological community that may include opportunistic pathogens. On-site supplemental disinfection systems have been proposed as a control method for opportunistic pathogens in premise plumbing. The majority of on-site disinfection systems to date have been installed in hospitals due to the high concentration of opportunistic pathogen susceptible occupants. The installation of on-site supplemental disinfection systems in hospitals allows for evaluation of the impact of on-site disinfection systems on drinking water system microbial ecology prior to widespread application. This study evaluated the impact of supplemental monochloramine on the microbial ecology of a hospital’s hot water system. Samples were taken three months and immediately prior to monochloramine treatment and monthly for the first six months of treatment, and all samples were subjected to high throughput Illumina 16S rRNA region sequencing. The microbial community composition of monochloramine treated samples was dramatically different than the baseline months. There was an immediate shift towards decreased relative abundance of Betaproteobacteria, and increased relative abundance of Firmicutes, Alphaproteobacteria, Gammaproteobacteria, Cyanobacteria and Actinobacteria. Following treatment, microbial populations grouped by sampling location rather than sampling time. Over the course of treatment the relative abundance of certain genera containing opportunistic pathogens and genera containing denitrifying bacteria increased. The results demonstrate the driving influence of supplemental disinfection on premise plumbing microbial ecology and suggest the value of further investigation into the overall effects of premise plumbing disinfection strategies on microbial ecology and not solely specific target microorganisms. PMID:25033448

Shift in the microbial ecology of a hospital hot water system following the introduction of an on-site monochloramine disinfection system.

PubMed

Baron, Julianne L; Vikram, Amit; Duda, Scott; Stout, Janet E; Bibby, Kyle

2014-01-01

Drinking water distribution systems, including premise plumbing, contain a diverse microbiological community that may include opportunistic pathogens. On-site supplemental disinfection systems have been proposed as a control method for opportunistic pathogens in premise plumbing. The majority of on-site disinfection systems to date have been installed in hospitals due to the high concentration of opportunistic pathogen susceptible occupants. The installation of on-site supplemental disinfection systems in hospitals allows for evaluation of the impact of on-site disinfection systems on drinking water system microbial ecology prior to widespread application. This study evaluated the impact of supplemental monochloramine on the microbial ecology of a hospital's hot water system. Samples were taken three months and immediately prior to monochloramine treatment and monthly for the first six months of treatment, and all samples were subjected to high throughput Illumina 16S rRNA region sequencing. The microbial community composition of monochloramine treated samples was dramatically different than the baseline months. There was an immediate shift towards decreased relative abundance of Betaproteobacteria, and increased relative abundance of Firmicutes, Alphaproteobacteria, Gammaproteobacteria, Cyanobacteria and Actinobacteria. Following treatment, microbial populations grouped by sampling location rather than sampling time. Over the course of treatment the relative abundance of certain genera containing opportunistic pathogens and genera containing denitrifying bacteria increased. The results demonstrate the driving influence of supplemental disinfection on premise plumbing microbial ecology and suggest the value of further investigation into the overall effects of premise plumbing disinfection strategies on microbial ecology and not solely specific target microorganisms.

Submerged RadBall® deployments in Hanford Site hot cells containing 137CsCl capsules.

PubMed

Farfán, Eduardo B; Coleman, J Rusty; Stanley, Steven; Adamovics, John; Oldham, Mark; Thomas, Andrew

2012-07-01

The overall objective of this study was to demonstrate that a new technology, known as RadBall®, could locate submerged radiological hazards. RadBall® is a novel, passive, radiation detection device that provides a 3-D visualization of radiation from areas where measurements have not been previously possible due to lack of access or extremely high radiation doses. This technology has been under development during recent years, and all of its previous tests have included dry deployments. This study involved, for the first time, underwater RadBall® deployments in hot cells containing 137CsCl capsules at the U.S. Department of Energy's Hanford Site. RadBall® can be used to characterize a contaminated room, hot cell, or glovebox by providing the locations of the radiation sources and hazards, identifying the radionuclides present within the cell, and determining the radiation sources' strength (e.g., intensities or dose rates). These parameters have been previously determined for dry deployments; however, only the location of radiation sources and hazards can be determined for an underwater RadBall® deployment. The results from this study include 3-D images representing the location of the radiation sources within the Hanford Site cells. Due to RadBall®'s unique deployability and non-electrical nature, this technology shows significant promise for future characterization of radiation hazards prior to and during the decommissioning of contaminated nuclear facilities.

Mathematical description of drug-target interactions: application to biologics that bind to targets with two binding sites.

PubMed

Gibiansky, Leonid; Gibiansky, Ekaterina

2018-02-01

The emerging discipline of mathematical pharmacology occupies the space between advanced pharmacometrics and systems biology. A characteristic feature of the approach is application of advance mathematical methods to study the behavior of biological systems as described by mathematical (most often differential) equations. One of the early application of mathematical pharmacology (that was not called this name at the time) was formulation and investigation of the target-mediated drug disposition (TMDD) model and its approximations. The model was shown to be remarkably successful, not only in describing the observed data for drug-target interactions, but also in advancing the qualitative and quantitative understanding of those interactions and their role in pharmacokinetic and pharmacodynamic properties of biologics. The TMDD model in its original formulation describes the interaction of the drug that has one binding site with the target that also has only one binding site. Following the framework developed earlier for drugs with one-to-one binding, this work aims to describe a rigorous approach for working with similar systems and to apply it to drugs that bind to targets with two binding sites. The quasi-steady-state, quasi-equilibrium, irreversible binding, and Michaelis-Menten approximations of the model are also derived. These equations can be used, in particular, to predict concentrations of the partially bound target (RC). This could be clinically important if RC remains active and has slow internalization rate. In this case, introduction of the drug aimed to suppress target activity may lead to the opposite effect due to RC accumulation.

Sedimentation in Hot Creek in vicinity of Hot Creek Fish Hatchery, Mono County, California

USGS Publications Warehouse

Burkham, D.E.

1978-01-01

An accumulation of fine-grained sediment in Hot Creek downstream from Hot Creek Fish Hatchery, Mono County, Calif., created concern that the site may be deteriorating as a habitat for trout. The accumulation is a phenomenon that probably occurs naturally in the problem reach. Fluctuation in the weather probably is the basic cause of the deposition of fine-grained sediment that has occurred since about 1970. Man 's activities and the Hot Creek Fish Hatchery may have contributed to the problem; the significance of these factors, however, probably was magnified because of drought conditions in 1975-77. (Woodard-USGS)

29 CFR 1915.503 - Precautions for hot work.

Code of Federal Regulations, 2013 CFR

2013-07-01

... 29 Labor 7 2013-07-01 2013-07-01 false Precautions for hot work. 1915.503 Section 1915.503 Labor... Employment § 1915.503 Precautions for hot work. (a) General requirements—(1) Designated Areas. The employer may designate areas for hot work in sites such as vessels, vessel sections, fabricating shops, and...

29 CFR 1915.503 - Precautions for hot work.

Code of Federal Regulations, 2012 CFR

2012-07-01

... 29 Labor 7 2012-07-01 2012-07-01 false Precautions for hot work. 1915.503 Section 1915.503 Labor... Employment § 1915.503 Precautions for hot work. (a) General requirements—(1) Designated Areas. The employer may designate areas for hot work in sites such as vessels, vessel sections, fabricating shops, and...

29 CFR 1915.503 - Precautions for hot work.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 29 Labor 7 2011-07-01 2011-07-01 false Precautions for hot work. 1915.503 Section 1915.503 Labor... Employment § 1915.503 Precautions for hot work. (a) General requirements—(1) Designated Areas. The employer may designate areas for hot work in sites such as vessels, vessel sections, fabricating shops, and...

29 CFR 1915.503 - Precautions for hot work.

Code of Federal Regulations, 2014 CFR

2014-07-01

... 29 Labor 7 2014-07-01 2014-07-01 false Precautions for hot work. 1915.503 Section 1915.503 Labor... Employment § 1915.503 Precautions for hot work. (a) General requirements—(1) Designated Areas. The employer may designate areas for hot work in sites such as vessels, vessel sections, fabricating shops, and...

29 CFR 1915.503 - Precautions for hot work.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 29 Labor 7 2010-07-01 2010-07-01 false Precautions for hot work. 1915.503 Section 1915.503 Labor... Employment § 1915.503 Precautions for hot work. (a) General requirements—(1) Designated Areas. The employer may designate areas for hot work in sites such as vessels, vessel sections, fabricating shops, and...

Geostatistical risk estimation at waste disposal sites in the presence of hot spots.

PubMed

Komnitsas, Kostas; Modis, Kostas

2009-05-30

The present paper aims to estimate risk by using geostatistics at the wider coal mining/waste disposal site of Belkovskaya, Tula region, in Russia. In this area the presence of hot spots causes a spatial trend in the mean value of the random field and a non-Gaussian data distribution. Prior to application of geostatistics, subtraction of trend and appropriate smoothing and transformation of the data into a Gaussian form were carried out; risk maps were then generated for the wider study area in order to assess the probability of exceeding risk thresholds. Finally, the present paper discusses the need for homogenization of soil risk thresholds regarding hazardous elements that will enhance reliability of risk estimation and enable application of appropriate rehabilitation actions in contaminated areas.

Computational Prediction of Hot Spot Residues

PubMed Central

Morrow, John Kenneth; Zhang, Shuxing

2013-01-01

Most biological processes involve multiple proteins interacting with each other. It has been recently discovered that certain residues in these protein-protein interactions, which are called hot spots, contribute more significantly to binding affinity than others. Hot spot residues have unique and diverse energetic properties that make them challenging yet important targets in the modulation of protein-protein complexes. Design of therapeutic agents that interact with hot spot residues has proven to be a valid methodology in disrupting unwanted protein-protein interactions. Using biological methods to determine which residues are hot spots can be costly and time consuming. Recent advances in computational approaches to predict hot spots have incorporated a myriad of features, and have shown increasing predictive successes. Here we review the state of knowledge around protein-protein interactions, hot spots, and give an overview of multiple in silico prediction techniques of hot spot residues. PMID:22316154

An approach for addressing hard-to-detect hot spots.

PubMed

Abelquist, Eric W; King, David A; Miller, Laurence F; Viars, James A

2013-05-01

The Multi-Agency Radiation Survey and Site Investigation Manual (MARSSIM) survey approach is comprised of systematic random sampling coupled with radiation scanning to assess acceptability of potential hot spots. Hot spot identification for some radionuclides may not be possible due to the very weak gamma or x-ray radiation they emit-these hard-to-detect nuclides are unlikely to be identified by field scans. Similarly, scanning technology is not yet available for chemical contamination. For both hard-to-detect nuclides and chemical contamination, hot spots are only identified via volumetric sampling. The remedial investigation and cleanup of sites under the Comprehensive Environmental Response, Compensation, and Liability Act typically includes the collection of samples over relatively large exposure units, and concentration limits are applied assuming the contamination is more or less uniformly distributed. However, data collected from contaminated sites demonstrate contamination is often highly localized. These highly localized areas, or hot spots, will only be identified if sample densities are high or if the environmental characterization program happens to sample directly from the hot spot footprint. This paper describes a Bayesian approach for addressing hard-to-detect nuclides and chemical hot spots. The approach begins using available data (e.g., as collected using the standard approach) to predict the probability that an unacceptable hot spot is present somewhere in the exposure unit. This Bayesian approach may even be coupled with the graded sampling approach to optimize hot spot characterization. Once the investigator concludes that the presence of hot spots is likely, then the surveyor should use the data quality objectives process to generate an appropriate sample campaign that optimizes the identification of risk-relevant hot spots.

Time-resolved K α spectroscopy measurements of hot-electron equilibration dynamics in thin-foil solid targets: collisional and collective effects

NASA Astrophysics Data System (ADS)

Nilson, P. M.; Solodov, A. A.; Davies, J. R.; Theobald, W.; Mileham, C.; Stoeckl, C.; Begishev, I. A.; Zuegel, J. D.; Froula, D. H.; Betti, R.; Meyerhofer, D. D.

2015-11-01

Time-resolved K α spectroscopy measurements from high-intensity laser interactions with thin-foil solid targets are reviewed. Thin Cu foils were irradiated with 1-10 J, 1 ps pulses at focused intensities from 1018 to 1019 W cm-2. The experimental data show K α -emission pulse widths from 3 to 6 ps, increasing with laser intensity. The time-resolved K α -emission data are compared to a hot-electron transport and K α -production model that includes collisional electron-energy coupling, resistive heating, and electromagnetic field effects. The experimental data show good agreement with the model when a reduced ponderomotive scaling is used to describe the initial mean hot-electron energy over the relevant intensity range.

The impact of target site accessibility on the design of effective siRNAs.

PubMed

Tafer, Hakim; Ameres, Stefan L; Obernosterer, Gregor; Gebeshuber, Christoph A; Schroeder, Renée; Martinez, Javier; Hofacker, Ivo L

2008-05-01

Small-interfering RNAs (siRNAs) assemble into RISC, the RNA-induced silencing complex, which cleaves complementary mRNAs. Despite their fluctuating efficacy, siRNAs are widely used to assess gene function. Although this limitation could be ascribed, in part, to variations in the assembly and activation of RISC, downstream events in the RNA interference (RNAi) pathway, such as target site accessibility, have so far not been investigated extensively. In this study we present a comprehensive analysis of target RNA structure effects on RNAi by computing the accessibility of the target site for interaction with the siRNA. Based on our observations, we developed a novel siRNA design tool, RNAxs, by combining known siRNA functionality criteria with target site accessibility. We calibrated our method on two data sets comprising 573 siRNAs for 38 genes, and tested it on an independent set of 360 siRNAs targeting four additional genes. Overall, RNAxs proves to be a robust siRNA selection tool that substantially improves the prediction of highly efficient siRNAs.

Environmental studies conducted at the Fenton Hill Hot Dry Rock geothermal development site

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

Miera, F.R. Jr.; Langhorst, G.; McEllin, S.

1984-05-01

An environmental investigation of Hot Dry Rock (HDR) geothermal development was conducted at Fenton Hill, New Mexico, during 1976-1979. Activities at the Fenton Hill Site included an evaluation of baseline data for biotic and abiotic ecosystem components. Identification of contaminants produced by HDR processes that had the potential for reaching the surrounding environment is also discussed. Three dominant vegetative communities were identified in the vicinity of the site. These included grass-forb, aspen, and mixed conifer communities. The grass-forb area was identified as having the highest number of species encountered, with Phleum pratense and Dactylis glomerata being the dominant grass species.more » Frequency of occurrence and mean coverage values are also given for other species in the three main vegetative complexes. Live trapping of small mammals was conducted to determine species composition, densities, population, and diversity estimates for this component of the ecosystem. The data indicate that Peromyscus maniculatus was the dominant species across all trapping sites during the study. Comparisons of relative density of small mammals among the various trapping sites show the grass-forb vegetative community to have had the highest overall density. Comparisons of small mammal diversity for the three main vegetative complexes indicate that the aspen habitat had the highest diversity and the grass-forb habitat had the lowest. Analyses of waste waters from the closed circulation loop indicate that several trace contaminants (e.g., arsenic, cadmium, fluoride, boron, and lithium) were present at concentrations greater than those reported for surface waters of the region.« less

Targeted Removal of Ant Colonies in Ecological Experiments, Using Hot Water

PubMed Central

Tschinkel, Walter R.; King, Joshua R.

2007-01-01

Ecological experiments on fire ants cannot, or should not, use poison baits to eliminate the fire ants because such baits are not specific to fire ants, or even to ants. Hot water is an extremely effective and specific killing agent for fire ant colonies, but producing large amounts of hot water in the field, and making the production apparatus mobile have been problematical. The construction and use of a charcoal-fired kiln made from a 55-gal. oil drum lined with a sand-fireclay mixture is described. An automobile heater fan powered from a 12-v battery provided a draft. Dual bilge pumps pumped water from a large tank through a long coil of copper tubing within the kiln to produce 4 to 5 l. of hot water per min. The hot water was collected in 20 l. buckets and poured into fire ant nests previously opened by piercing with a stick. The entire assembly was transported in and operated from the back of a pickup truck. Five experimental plots containing 32 to 38 colonies of the fire ant, Solenopsis invicta, Buren (Hymenoptera: Formicidae), were treated with hot water over a period of two years. All colonies on the treatment plots were treated twice with hot water early in 2004, reducing their numbers to zero. However new colonies were formed, and mature colonies expanded into the plots. A third treatment was made in the spring of 2005, after which fire ant populations were suppressed for over a year. Whereas the 5 control plots contained a total of 166 mostly large colonies, the 5 treatment plots contained no live colonies at all. Averaged over a two-year period, a 70% reduction in total number of colonies was achieved (P < 0.001) on the treatment plots, and a 93% reduction of large, mature colonies. Over this same time span, the number of colonies in control plots remained stable. The reduction in colony numbers on the treatment plots was reflected in the pitfall trap samples that recorded a 60% reduction in fire ants. PMID:20233079

Targeted removal of ant colonies in ecological experiments, using hot water.

PubMed

Tschinkel, Walter R; King, Joshua R

2007-01-01

Ecological experiments on fire ants cannot, or should not, use poison baits to eliminate the fire ants because such baits are not specific to fire ants, or even to ants. Hot water is an extremely effective and specific killing agent for fire ant colonies, but producing large amounts of hot water in the field, and making the production apparatus mobile have been problematical. The construction and use of a charcoal-fired kiln made from a 55-gal. oil drum lined with a sand-fireclay mixture is described. An automobile heater fan powered from a 12-v battery provided a draft. Dual bilge pumps pumped water from a large tank through a long coil of copper tubing within the kiln to produce 4 to 5 l. of hot water per min. The hot water was collected in 20 l. buckets and poured into fire ant nests previously opened by piercing with a stick. The entire assembly was transported in and operated from the back of a pickup truck. Five experimental plots containing 32 to 38 colonies of the fire ant, Solenopsis invicta, Buren (Hymenoptera: Formicidae), were treated with hot water over a period of two years. All colonies on the treatment plots were treated twice with hot water early in 2004, reducing their numbers to zero. However new colonies were formed, and mature colonies expanded into the plots. A third treatment was made in the spring of 2005, after which fire ant populations were suppressed for over a year. Whereas the 5 control plots contained a total of 166 mostly large colonies, the 5 treatment plots contained no live colonies at all. Averaged over a two-year period, a 70% reduction in total number of colonies was achieved (P < 0.001) on the treatment plots, and a 93% reduction of large, mature colonies. Over this same time span, the number of colonies in control plots remained stable. The reduction in colony numbers on the treatment plots was reflected in the pitfall trap samples that recorded a 60% reduction in fire ants.

Recovery of perennial vegetation in military target sites in the eastern Mohave Desert, Arizona

USGS Publications Warehouse

Steiger, John W.; Webb, Robert H.

2000-01-01

The effect of the age of geomorphic surfaces on the recovery of desert vegetation in military target sites was studied in the Mohave and Cerbat Mountains of northwestern Arizona. The target sites were cleared of all vegetation during military exercises in 1942-1943 and have not been subsequently disturbed. The degree of recovery was measured by calculating percentage-similarity (PS) and correlation-coefficient indices on the basis of differences in cover, density, and volume of species growing in and out of each target site. PS values, ranging from 22.7 to 95.1 percent (100 percent = identical composition), indicate a wide range of recovery that is partially controlled by the edaphic properties of the geomorphic surfaces. Statistical analyses show a strong pattern that indicates a greater variability in the degree of recovery for sites on older surfaces than on younger surfaces and a weak pattern that indicates an inverse relation between the degree of recovery and geomorphic age. Comparisons of the different effects of target site construction on the edaphic characteristics of each target site provides an explanation for these patterns and suggests the soil properties critical to the recovery process. Statistically significant negative or positive response to disturbance for most species are independent of the age of the geomorphic surfaces; however, there is strong evidence for a shift in response for the common perennial species Acamptopappus sphaerocephalus, and to a lesser extent, Salazaria mexicana, Encelia farinosa, and Coldenia canescens, among different geomorphic surfaces.

DECOMMISSIONING OF HOT CELL FACILITIES AT THE BATTELLE COLUMBUS LABORATORIES

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

Weaver, Patrick; Henderson, Glenn; Erickson, Peter

2003-02-27

Battelle Columbus Laboratories (BCL), located in Columbus, Ohio, must complete decontamination and decommissioning activities for nuclear research buildings and grounds at its West Jefferson Facilities by 2006, as mandated by Congress. This effort includes decommissioning several hot cells located in the Hot Cell Laboratory (Building JN-1). JN-1 was originally constructed in 1955, and a hot cell/high bay addition was built in the mid 1970s. For over 30 years, BCL used these hot cell facilities to conduct research for the nuclear power industry and several government agencies, including the U.S. Navy, U.S. Army, U.S. Air Force, and the U.S. Department ofmore » Energy. As a result of this research, the JN-1 hot cells became highly contaminated with mixed fission and activation products, as well as fuel residues. In 1998, the Battelle Columbus Laboratories Decommissioning Project (BCLDP) began efforts to decommission JN-1 with the goal of remediating the site to levels of residual contamination allowing future use without radiological restrictions. This goal requires that each hot cell be decommissioned to a state where it can be safely demolished and transported to an off-site disposal facility. To achieve this, the BCLDP uses a four-step process for decommissioning each hot cell: (1) Source Term Removal; (2) Initial (i.e., remote) Decontamination; (3) Utility Removal; and (4) Final (i.e., manual) Decontamination/Stabilization. To date, this process has been successfully utilized on 13 hot cells within JN-1, with one hot cell remaining to be decommissioned. This paper will provide a case study of the hot cell decommissioning being conducted by the BCLDP. Discussed will be the methods used to achieve the goals of each of the hot cell decommissioning stages and the lessons learned that could be applied at other sites where hot cells need to be decommissioned.« less

Engineering Factor Xa Inhibitor with Multiple Platelet-Binding Sites Facilitates its Platelet Targeting

NASA Astrophysics Data System (ADS)

Zhu, Yuanjun; Li, Ruyi; Lin, Yuan; Shui, Mengyang; Liu, Xiaoyan; Chen, Huan; Wang, Yinye

2016-07-01

Targeted delivery of antithrombotic drugs centralizes the effects in the thrombosis site and reduces the hemorrhage side effects in uninjured vessels. We have recently reported that the platelet-targeting factor Xa (FXa) inhibitors, constructed by engineering one Arg-Gly-Asp (RGD) motif into Ancylostoma caninum anticoagulant peptide 5 (AcAP5), can reduce the risk of systemic bleeding than non-targeted AcAP5 in mouse arterial injury model. Increasing the number of platelet-binding sites of FXa inhibitors may facilitate their adhesion to activated platelets, and further lower the bleeding risks. For this purpose, we introduced three RGD motifs into AcAP5 to generate a variant NR4 containing three platelet-binding sites. NR4 reserved its inherent anti-FXa activity. Protein-protein docking showed that all three RGD motifs were capable of binding to platelet receptor αIIbβ3. Molecular dynamics simulation demonstrated that NR4 has more opportunities to interact with αIIbβ3 than single-RGD-containing NR3. Flow cytometry analysis and rat arterial thrombosis model further confirmed that NR4 possesses enhanced platelet targeting activity. Moreover, NR4-treated mice showed a trend toward less tail bleeding time than NR3-treated mice in carotid artery endothelium injury model. Therefore, our data suggest that engineering multiple binding sites in one recombinant protein is a useful tool to improve its platelet-targeting efficiency.

Hot Spots in a Network of Functional Sites

PubMed Central

Ozbek, Pemra; Soner, Seren; Haliloglu, Turkan

2013-01-01

It is of significant interest to understand how proteins interact, which holds the key phenomenon in biological functions. Using dynamic fluctuations in high frequency modes, we show that the Gaussian Network Model (GNM) predicts hot spot residues with success rates ranging between S 8–58%, C 84–95%, P 5–19% and A 81–92% on unbound structures and S 8–51%, C 97–99%, P 14–50%, A 94–97% on complex structures for sensitivity, specificity, precision and accuracy, respectively. High specificity and accuracy rates with a single property on unbound protein structures suggest that hot spots are predefined in the dynamics of unbound structures and forming the binding core of interfaces, whereas the prediction of other functional residues with similar dynamic behavior explains the lower precision values. The latter is demonstrated with the case studies; ubiquitin, hen egg-white lysozyme and M2 proton channel. The dynamic fluctuations suggest a pseudo network of residues with high frequency fluctuations, which could be plausible for the mechanism of biological interactions and allosteric regulation. PMID:24023934

Hot spot formation and stagnation properties in simulations of direct-drive NIF implosions

NASA Astrophysics Data System (ADS)

Schmitt, Andrew J.; Obenschain, Stephen P.

2016-05-01

We investigate different proposed methods of increasing the hot spot energy and radius in inertial confinement fusion implosions. In particular, shock mistiming (preferentially heating the inner edge of the target's fuel) and increasing the initial vapor gas density are investigated as possible control mechanisms. We find that only the latter is effective in substantially increasing the hot spot energy and dimensions while achieving ignition. In all cases an increase in the hot spot energy is accompanied by a decrease in the hot spot energy density (pressure) and both the yield and the gain of the target drop substantially. 2D simulations of increased vapor density targets predict an increase in the robustness of the target with respect to surface perturbations but are accompanied by significant yield degradation.

Characteristics of food industry web sites and "advergames" targeting children.

PubMed

Culp, Jennifer; Bell, Robert A; Cassady, Diana

2010-01-01

To assess the content of food industry Web sites targeting children by describing strategies used to prolong their visits and foster brand loyalty; and to document health-promoting messages on these Web sites. A content analysis was conducted of Web sites advertised on 2 children's networks, Cartoon Network and Nickelodeon. A total of 290 Web pages and 247 unique games on 19 Internet sites were examined. Games, found on 81% of Web sites, were the most predominant promotion strategy used. All games had at least 1 brand identifier, with logos being most frequently used. On average Web sites contained 1 "healthful" message for every 45 exposures to brand identifiers. Food companies use Web sites to extend their television advertising to promote brand loyalty among children. These sites almost exclusively promoted food items high in sugar and fat. Health professionals need to monitor food industry marketing practices used in "new media." Published by Elsevier Inc.

Protein-protein interface analysis and hot spots identification for chemical ligand design.

PubMed

Chen, Jing; Ma, Xiaomin; Yuan, Yaxia; Pei, Jianfeng; Lai, Luhua

2014-01-01

Rational design for chemical compounds targeting protein-protein interactions has grown from a dream to reality after a decade of efforts. There are an increasing number of successful examples, though major challenges remain in the field. In this paper, we will first give a brief review of the available methods that can be used to analyze protein-protein interface and predict hot spots for chemical ligand design. New developments of binding sites detection, ligandability and hot spots prediction from the author's group will also be described. Pocket V.3 is an improved program for identifying hot spots in protein-protein interface using only an apo protein structure. It has been developed based on Pocket V.2 that can derive receptor-based pharmacophore model for ligand binding cavity. Given similarities and differences between the essence of pharmacophore and hot spots for guiding design of chemical compounds, not only energetic but also spatial properties of protein-protein interface are used in Pocket V.3 for dealing with protein-protein interface. In order to illustrate the capability of Pocket V.3, two datasets have been used. One is taken from ASEdb and BID having experimental alanine scanning results for testing hot spots prediction. The other is taken from the 2P2I database containing complex structures of protein-ligand binding at the original protein-protein interface for testing hot spots application in ligand design.

Mitigating road mortality of diamond-backed terrapins (Malaclemy's terrapin) with hybrid barriers at crossing hot spots

USGS Publications Warehouse

Crawford, Brian A.; Moore, Clinton; Norton, Terry M.; Maerz, John C.

2017-01-01

Roads represent a pervasive feature on most landscapes that can pose multiple threats to wildlife populations and substantial challenges for management. To be effective, management strategies must often target where threats are most concentrated. Road mortality and nest predation are well-documented threats to Diamond-backed Terrapins (Malaclemys terrapin) across the majority of their range, including the 8.7-km causeway to Jekyll Island, Georgia, USA, where both are predicted to contribute to population declines if left unmitigated. From 2009 to 2014, we used intensive road surveying to identify spatial peaks (hot spots) of terrapin crossing activity and road mortality and exploit these as targets for management. In 2011, we deployed a hybrid barrier composed of nest boxes, which were designed to prevent terrapins from accessing the road and mitigate nest predation, at one hot spot while leaving two other hot spots unmanaged. We evaluated the impact of the barrier on terrapin emergences on the causeway under a Before-After-Control-Impact (BACI) design, and a companion study evaluated the effects of nest boxes on nest predation rates. We estimated a 57% reduction in annual terrapin emergences at the barrier site compared to no measurable change at control hot spots. Our findings support the use of hybrid barriers for simultaneously addressing road mortality and nest predation for other terrapin populations at risk to these threats. Our approach highlights the need to design feasible but robust management strategies that target spatial peaks of road mortality while addressing additional threats contributing to population declines of terrapins and other species.

Time-resolved K α spectroscopy measurements of hot-electron equilibration dynamics in thin-foil solid targets: Collisional and collective effects

DOE PAGES

Nilson, P. M.; Solodov, A. A.; Davies, J. R.; ...

2015-09-25

Time-resolved K α spectroscopy measurements from high-intensity laser interactions with thin-foil solid targets are reviewed. Thin Cu foils were irradiated with 1- to 10-J, 1-ps pulses at focused intensities from 10 18 to 10 19 W/cm 2. The experimental data show K α-emission pulse widths from 3 to 6 ps, increasing with laser intensity. The time-resolved K α-emission data are compared to a hot-electron transport and K α-production model that includes collisional electron-energy coupling, resistive heating, and electromagnetic field effects. The experimental data show good agreement with the model when a reduced ponderomotive scaling is used to describe the initialmore » mean hot-electron energy over the relevant intensity range.« less

Widespread occurrence of both metabolic and target-site herbicide resistance mechanisms in Lolium rigidum populations.

PubMed

Han, Heping; Yu, Qin; Owen, Mechelle J; Cawthray, Gregory R; Powles, Stephen B

2016-02-01

Lolium rigidum populations in Australia and globally have demonstrated rapid and widespread evolution of resistance to acetyl coenzyme A carboxylase (ACCase)-inhibiting and acetolactate synthase (ALS)-inhibiting herbicides. Thirty-three resistant L. rigidum populations, randomly collected from crop fields in a most recent resistance survey, were analysed for non-target-site diclofop metabolism and all known target-site ACCase gene resistance-endowing mutations. The HPLC profile of [(14) C]-diclofop-methyl in vivo metabolism revealed that 79% of these resistant L. rigidum populations showed enhanced capacity for diclofop acid metabolism (metabolic resistance). ACCase gene sequencing identified that 91% of the populations contain plants with ACCase resistance mutation(s). Importantly, 70% of the populations exhibit both non-target-site metabolic resistance and target-site ACCase mutations. This work demonstrates that metabolic herbicide resistance is commonly occurring in L. rigidum, and coevolution of both metabolic resistance and target-site resistance is an evolutionary reality. Metabolic herbicide resistance can potentially endow resistance to many herbicides and poses a threat to herbicide sustainability and thus crop production, calling for major research and management efforts. © 2015 Society of Chemical Industry.

Computational prediction of protein hot spot residues.

PubMed

Morrow, John Kenneth; Zhang, Shuxing

2012-01-01

Most biological processes involve multiple proteins interacting with each other. It has been recently discovered that certain residues in these protein-protein interactions, which are called hot spots, contribute more significantly to binding affinity than others. Hot spot residues have unique and diverse energetic properties that make them challenging yet important targets in the modulation of protein-protein complexes. Design of therapeutic agents that interact with hot spot residues has proven to be a valid methodology in disrupting unwanted protein-protein interactions. Using biological methods to determine which residues are hot spots can be costly and time consuming. Recent advances in computational approaches to predict hot spots have incorporated a myriad of features, and have shown increasing predictive successes. Here we review the state of knowledge around protein-protein interactions, hot spots, and give an overview of multiple in silico prediction techniques of hot spot residues.

Target sites for the transposition of rat long interspersed repeated DNA elements (LINEs) are not random.

PubMed Central

Furano, A V; Somerville, C C; Tsichlis, P N; D'Ambrosio, E

1986-01-01

The long interspersed repeated DNA family of rats (LINE or L1Rn family) contains about 40,000 6.7-kilobase (kb) long members (1). LINE members may be currently mobile since their presence or absence causes allelic variation at three single copy loci (2, 3): insulin 1, Moloney leukemia virus integration 2 (Mlvi-2) (4), and immunoglobulin heavy chain (Igh). To characterize target sites for LINE insertion, we compared the DNA sequences of the unoccupied Mlvi-2 target site, its LINE-containing allele, and several other LINE-containing sites. Although not homologous overall, the target sites share three characteristics: First, depending on the site, they are from 68% to 86% (A+T) compared to 58% (A+T) for total rat DNA (5). Depending on the site, a 7- to 15-bp target site sequence becomes duplicated and flanks the inserted LINE member. The second is a version (0 or 1 mismatch) of the hexanucleotide, TACTCA, which is also present in the LINE member, in a highly conserved region located just before the A-rich right end of the LINE member. The third is a stretch of alternating purine/pyrimidine (PQ). The A-rich right ends of different LINE members vary in length and composition, and the sequence of a particularly long one suggests that it contains the A-rich target site from a previous transposition. PMID:3012480

RNase L targets distinct sites in influenza A virus RNAs.

PubMed

Cooper, Daphne A; Banerjee, Shuvojit; Chakrabarti, Arindam; García-Sastre, Adolfo; Hesselberth, Jay R; Silverman, Robert H; Barton, David J

2015-03-01

Influenza A virus (IAV) infections are influenced by type 1 interferon-mediated antiviral defenses and by viral countermeasures to these defenses. When IAV NS1 protein is disabled, RNase L restricts virus replication; however, the RNAs targeted for cleavage by RNase L under these conditions have not been defined. In this study, we used deep-sequencing methods to identify RNase L cleavage sites within host and viral RNAs from IAV PR8ΔNS1-infected A549 cells. Short hairpin RNA knockdown of RNase L allowed us to distinguish between RNase L-dependent and RNase L-independent cleavage sites. RNase L-dependent cleavage sites were evident at discrete locations in IAV RNA segments (both positive and negative strands). Cleavage in PB2, PB1, and PA genomic RNAs suggests that viral RNPs are susceptible to cleavage by RNase L. Prominent amounts of cleavage mapped to specific regions within IAV RNAs, including some areas of increased synonymous-site conservation. Among cellular RNAs, RNase L-dependent cleavage was most frequent at precise locations in rRNAs. Our data show that RNase L targets specific sites in both host and viral RNAs to restrict influenza virus replication when NS1 protein is disabled. RNase L is a critical component of interferon-regulated and double-stranded-RNA-activated antiviral host responses. We sought to determine how RNase L exerts its antiviral activity during influenza virus infection. We enhanced the antiviral activity of RNase L by disabling a viral protein, NS1, that inhibits the activation of RNase L. Then, using deep-sequencing methods, we identified the host and viral RNAs targeted by RNase L. We found that RNase L cleaved viral RNAs and rRNAs at very precise locations. The direct cleavage of IAV RNAs by RNase L highlights an intimate battle between viral RNAs and an antiviral endonuclease. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

Propagation in compressed matter of hot electrons created by short intense lasers

NASA Astrophysics Data System (ADS)

Batani, D.; Bernardinello, A.; Masella, V.; Pisani, F.; Koenig, M.; Krishnan, J.; Benuzzi, A.; Ellwi, S.; Hall, T.; Norreys, P.; Djaoui, A.; Neely, D.; Rose, S.; Fews, P.; Key, M.

1998-02-01

We performed the first experimental study of propagation in compressed matter of hot electrons created by a short pulse intense laser. The experiment has been carried out with the VULCAN laser at Rutherford compressing plastic targets with two ns laser beams at an intensity ⩾1014W/cm2. A CPA beam with an intensity ⩾1016W/cm2 irradiated the rear side of the target and created hot electrons propagating through the compressed matter. K-α emission was used as diagnostics of hot electron penetration by putting a chloride plastic layer inside the target.

PAM multiplicity marks genomic target sites as inhibitory to CRISPR-Cas9 editing.

PubMed

Malina, Abba; Cameron, Christopher J F; Robert, Francis; Blanchette, Mathieu; Dostie, Josée; Pelletier, Jerry

2015-12-08

In CRISPR-Cas9 genome editing, the underlying principles for selecting guide RNA (gRNA) sequences that would ensure for efficient target site modification remain poorly understood. Here we show that target sites harbouring multiple protospacer adjacent motifs (PAMs) are refractory to Cas9-mediated repair in situ. Thus we refine which substrates should be avoided in gRNA design, implicating PAM density as a novel sequence-specific feature that inhibits in vivo Cas9-driven DNA modification.

PAM multiplicity marks genomic target sites as inhibitory to CRISPR-Cas9 editing

PubMed Central

Malina, Abba; Cameron, Christopher J. F.; Robert, Francis; Blanchette, Mathieu; Dostie, Josée; Pelletier, Jerry

2015-01-01

In CRISPR-Cas9 genome editing, the underlying principles for selecting guide RNA (gRNA) sequences that would ensure for efficient target site modification remain poorly understood. Here we show that target sites harbouring multiple protospacer adjacent motifs (PAMs) are refractory to Cas9-mediated repair in situ. Thus we refine which substrates should be avoided in gRNA design, implicating PAM density as a novel sequence-specific feature that inhibits in vivo Cas9-driven DNA modification. PMID:26644285

The hot pepper (Capsicum annuum) microRNA transcriptome reveals novel and conserved targets: a foundation for understanding MicroRNA functional roles in hot pepper.

PubMed

Hwang, Dong-Gyu; Park, June Hyun; Lim, Jae Yun; Kim, Donghyun; Choi, Yourim; Kim, Soyoung; Reeves, Gregory; Yeom, Seon-In; Lee, Jeong-Soo; Park, Minkyu; Kim, Seungill; Choi, Ik-Young; Choi, Doil; Shin, Chanseok

2013-01-01

MicroRNAs (miRNAs) are a class of non-coding RNAs approximately 21 nt in length which play important roles in regulating gene expression in plants. Although many miRNA studies have focused on a few model plants, miRNAs and their target genes remain largely unknown in hot pepper (Capsicum annuum), one of the most important crops cultivated worldwide. Here, we employed high-throughput sequencing technology to identify miRNAs in pepper extensively from 10 different libraries, including leaf, stem, root, flower, and six developmental stage fruits. Based on a bioinformatics pipeline, we successfully identified 29 and 35 families of conserved and novel miRNAs, respectively. Northern blot analysis was used to validate further the expression of representative miRNAs and to analyze their tissue-specific or developmental stage-specific expression patterns. Moreover, we computationally predicted miRNA targets, many of which were experimentally confirmed using 5' rapid amplification of cDNA ends analysis. One of the validated novel targets of miR-396 was a domain rearranged methyltransferase, the major de novo methylation enzyme, involved in RNA-directed DNA methylation in plants. This work provides the first reliable draft of the pepper miRNA transcriptome. It offers an expanded picture of pepper miRNAs in relation to other plants, providing a basis for understanding the functional roles of miRNAs in pepper.

Hot-spot mix in ignition-scale implosions on the NIF [Hot-spot mix in ignition-scale implosions on the National Ignition Facility (NIF)

DOE PAGES

Regan, S. P.; Epstein, R.; Hammel, B. A.; ...

2012-03-30

Ignition of an inertial confinement fusion (ICF) target depends on the formation of a central hot spot with sufficient temperature and areal density. Radiative and conductive losses from the hot spot can be enhanced by hydrodynamic instabilities. The concentric spherical layers of current National Ignition Facility (NIF) ignition targets consist of a plastic ablator surrounding 2 a thin shell of cryogenic thermonuclear fuel (i.e., hydrogen isotopes), with fuel vapor filling the interior volume. The Rev. 5 ablator is doped with Ge to minimize preheat of the ablator closest to the DT ice caused by Au M-band emission from the hohlraummore » x-ray drive. Richtmyer–Meshkov and Rayleigh–Taylor hydrodynamic instabilities seeded by high-mode (50 < t < 200) ablator-surface perturbations can cause Ge-doped ablator to mix into the interior of the shell at the end of the acceleration phase. As the shell decelerates, it compresses the fuel vapor, forming a hot spot. K-shell line emission from the ionized Ge that has penetrated into the hot spot provides an experimental signature of hot-spot mix. The Ge emission from tritium–hydrogen–deuterium (THD) and DT cryogenic targets and gas-filled plastic shell capsules, which replace the THD layer with a massequivalent CH layer, was examined. The inferred amount of hot-spot mix mass, estimated from the Ge K-shell line brightness using a detailed atomic physics code, is typically below the 75 ng allowance for hot-spot mix. Furthermore, predictions of a simple mix model, based on linear growth of the measured surface-mass modulations, are consistent with the experimental results.« less

Hot-spot mix in ignition-scale implosions on the NIF [Hot-spot mix in ignition-scale implosions on the National Ignition Facility (NIF)

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

Regan, S. P.; Epstein, R.; Hammel, B. A.

Ignition of an inertial confinement fusion (ICF) target depends on the formation of a central hot spot with sufficient temperature and areal density. Radiative and conductive losses from the hot spot can be enhanced by hydrodynamic instabilities. The concentric spherical layers of current National Ignition Facility (NIF) ignition targets consist of a plastic ablator surrounding 2 a thin shell of cryogenic thermonuclear fuel (i.e., hydrogen isotopes), with fuel vapor filling the interior volume. The Rev. 5 ablator is doped with Ge to minimize preheat of the ablator closest to the DT ice caused by Au M-band emission from the hohlraummore » x-ray drive. Richtmyer–Meshkov and Rayleigh–Taylor hydrodynamic instabilities seeded by high-mode (50 < t < 200) ablator-surface perturbations can cause Ge-doped ablator to mix into the interior of the shell at the end of the acceleration phase. As the shell decelerates, it compresses the fuel vapor, forming a hot spot. K-shell line emission from the ionized Ge that has penetrated into the hot spot provides an experimental signature of hot-spot mix. The Ge emission from tritium–hydrogen–deuterium (THD) and DT cryogenic targets and gas-filled plastic shell capsules, which replace the THD layer with a massequivalent CH layer, was examined. The inferred amount of hot-spot mix mass, estimated from the Ge K-shell line brightness using a detailed atomic physics code, is typically below the 75 ng allowance for hot-spot mix. Furthermore, predictions of a simple mix model, based on linear growth of the measured surface-mass modulations, are consistent with the experimental results.« less

Construction of a directed hammerhead ribozyme library: towards the identification of optimal target sites for antisense-mediated gene inhibition.

PubMed Central

Pierce, M L; Ruffner, D E

1998-01-01

Antisense-mediated gene inhibition uses short complementary DNA or RNA oligonucleotides to block expression of any mRNA of interest. A key parameter in the success or failure of an antisense therapy is the identification of a suitable target site on the chosen mRNA. Ultimately, the accessibility of the target to the antisense agent determines target suitability. Since accessibility is a function of many complex factors, it is currently beyond our ability to predict. Consequently, identification of the most effective target(s) requires examination of every site. Towards this goal, we describe a method to construct directed ribozyme libraries against any chosen mRNA. The library contains nearly equal amounts of ribozymes targeting every site on the chosen transcript and the library only contains ribozymes capable of binding to that transcript. Expression of the ribozyme library in cultured cells should allow identification of optimal target sites under natural conditions, subject to the complexities of a fully functional cell. Optimal target sites identified in this manner should be the most effective sites for therapeutic intervention. PMID:9801305

Pre-cometary ice composition from hot core chemistry.

PubMed

Tornow, Carmen; Kührt, Ekkehard; Motschmann, Uwe

2005-10-01

Pre-cometary ice located around star-forming regions contains molecules that are pre-biotic compounds or pre-biotic precursors. Molecular line surveys of hot cores provide information on the composition of the ice since it sublimates near these sites. We have combined a hydrostatic hot core model with a complex network of chemical reactions to calculate the time-dependent abundances of molecules, ions, and radicals. The model considers the interaction between the ice and gas phase. It is applied to the Orion hot core where high-mass star formation occurs, and to the solar-mass binary protostar system IRAS 16293-2422. Our calculations show that at the end of the hot core phase both star-forming sites produce the same prebiotic CN-bearing molecules. However, in the Orion hot core these molecules are formed in larger abundances. A comparison of the calculated values with the abundances derived from the observed line data requires a chemically unprocessed molecular cloud as the initial state of hot core evolution. Thus, it appears that these objects are formed at a much younger cloud stage than previously thought. This implies that the ice phase of the young clouds does not contain CN-bearing molecules in large abundances before the hot core has been formed. The pre-biotic molecules synthesized in hot cores cause a chemical enrichment in the gas phase and in the pre-cometary ice. This enrichment is thought to be an important extraterrestrial aspect of the formation of life on Earth and elsewhere.

Catalog of known hot springs and thermal place names for Honduras

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

Finch, R.C.

Thermal place names were compiled from all 1:50,000 topographic quadrangle maps for the Republic of Honduras as of July 1986, from other published maps, and from several sources of unpublished data. Known hot spring sites include those visited by Empresa Nacional de Energia Electrica (Honduras) geologists, sites visited by Los Alamos geologists in 1985, and other sites known to R.C. Finch. The number of known hot spring sites in Honduras with temperatures >30/sup 0/C is 125. In addition, 56 thermal sites are suspected on the basis of thermal place names. The total number of geothermal sites, known and suspected, ismore » 181.« less

A Hot-Spot Motif Characterizes the Interface between a Designed Ankyrin-Repeat Protein and Its Target Ligand

PubMed Central

Cheung, Luthur Siu-Lun; Kanwar, Manu; Ostermeier, Marc; Konstantopoulos, Konstantinos

2012-01-01

Nonantibody scaffolds such as designed ankyrin repeat proteins (DARPins) can be rapidly engineered to detect diverse target proteins with high specificity and offer an attractive alternative to antibodies. Using molecular simulations, we predicted that the binding interface between DARPin off7 and its ligand (maltose binding protein; MBP) is characterized by a hot-spot motif in which binding energy is largely concentrated on a few amino acids. To experimentally test this prediction, we fused MBP to a transmembrane domain to properly orient the protein into a polymer-cushioned lipid bilayer, and characterized its interaction with off7 using force spectroscopy. Using this, to our knowledge, novel technique along with surface plasmon resonance, we validated the simulation predictions and characterized the effects of select mutations on the kinetics of the off7-MBP interaction. Our integrated approach offers scientific insights on how the engineered protein interacts with the target molecule. PMID:22325262

Hot-electron surface retention in intense short-pulse laser-matter interactions.

PubMed

Mason, R J; Dodd, E S; Albright, B J

2005-07-01

Implicit hybrid plasma simulations predict that a significant fraction of the energy deposited into hot electrons can be retained near the surface of targets with steep density gradients illuminated by intense short-pulse lasers. This retention derives from the lateral transport of heated electrons randomly emitted in the presence of spontaneous magnetic fields arising near the laser spot, from geometric effects associated with a small hot-electron source, and from E fields arising in reaction to the ponderomotive force. Below the laser spot hot electrons are axially focused into a target by the B fields, and can filament in moderate Z targets by resistive Weibel-like instability, if the effective background electron temperature remains sufficiently low. Carefully engineered use of such retention in conjunction with ponderomotive density profile steepening could result in a reduced hot-electron range that aids fast ignition. Alternatively, such retention may disturb a deeper deposition needed for efficient radiography and backside fast ion generation.

An integrated CRISPR Bombyx mori genome editing system with improved efficiency and expanded target sites.

PubMed

Ma, Sanyuan; Liu, Yue; Liu, Yuanyuan; Chang, Jiasong; Zhang, Tong; Wang, Xiaogang; Shi, Run; Lu, Wei; Xia, Xiaojuan; Zhao, Ping; Xia, Qingyou

2017-04-01

Genome editing enabled unprecedented new opportunities for targeted genomic engineering of a wide variety of organisms ranging from microbes, plants, animals and even human embryos. The serial establishing and rapid applications of genome editing tools significantly accelerated Bombyx mori (B. mori) research during the past years. However, the only CRISPR system in B. mori was the commonly used SpCas9, which only recognize target sites containing NGG PAM sequence. In the present study, we first improve the efficiency of our previous established SpCas9 system by 3.5 folds. The improved high efficiency was also observed at several loci in both BmNs cells and B. mori embryos. Then to expand the target sites, we showed that two newly discovered CRISPR system, SaCas9 and AsCpf1, could also induce highly efficient site-specific genome editing in BmNs cells, and constructed an integrated CRISPR system. Genome-wide analysis of targetable sites was further conducted and showed that the integrated system cover 69,144,399 sites in B. mori genome, and one site could be found in every 6.5 bp. The efficiency and resolution of this CRISPR platform will probably accelerate both fundamental researches and applicable studies in B. mori, and perhaps other insects. Copyright © 2017 Elsevier Ltd. All rights reserved.

Diverse Actions and Target-Site Selectivity of Neonicotinoids: Structural Insights

PubMed Central

Matsuda, Kazuhiko; Kanaoka, Satoshi; Akamatsu, Miki; Sattelle, David B.

2009-01-01

The nicotinic acetylcholine receptors (nAChRs) are targets for human and veterinary medicines as well as insecticides. Subtype-selectivity among the diverse nAChR family members is important for medicines targeting particular disorders, and pest-insect selectivity is essential for the development of safer, environmentally acceptable insecticides. Neonicotinoid insecticides selectively targeting insect nAChRs have important applications in crop protection and animal health. Members of this class exhibit strikingly diverse actions on their nAChR targets. Here we review the chemistry and diverse actions of neonicotinoids on insect and mammalian nAChRs. Electrophysiological studies on native nAChRs and on wild-type and mutagenized recombinant nAChRs have shown that basic residues particular to loop D of insect nAChRs are likely to interact electrostatically with the nitro group of neonicotinoids. In 2008, the crystal structures were published showing neonicotinoids docking into the acetylcholine binding site of molluscan acetylcholine binding proteins with homology to the ligand binding domain (LBD) of nAChRs. The crystal structures showed that 1) glutamine in loop D, corresponding to the basic residues of insect nAChRs, hydrogen bonds with the NO2 group of imidacloprid and 2) neonicotinoid-unique stacking and CH-π bonds at the LBD. A neonicotinoid-resistant strain obtained by laboratory-screening has been found to result from target site mutations, and possible reasons for this are also suggested by the crystal structures. The prospects of designing neonicotinoids that are safe not only for mammals but also for beneficial insects such as honey bees (Apis mellifera) are discussed in terms of interactions with non-α nAChR subunits. PMID:19321668

Measurements of hot-electron temperature in laser-irradiated plasmas

DOE PAGES

Solodov, A. A.; Yaakobi, B.; Edgell, D. H.; ...

2016-10-26

In a recently published work 1–3 we reported on measuring the total energy of hot electrons produced by the interaction of a nanosecond laser with planar CH-coated molybdenum targets, using the Mo K α emission. The temperature of the hot electrons in that work was determined by the high-energy bremsstrahlung [hard x-ray (HXR)] spectrum measured by a three-channel fluorescence-photomultiplier detector (HXRD). In the present work, we replaced the HXRD with a nine-channel image-plate (IP)–based detector (HXIP). For the same conditions (irradiance of the order of 10 14 W/cm 2; 2-ns pulses) the measured temperatures are consistently lower than those measuredmore » by the HXRD (by a factor ~1.5 to 1.7). In addition, we supplemented this measurement with three experiments that measure the hot-electron temperature using K α line-intensity ratios from high-Z target layers, independent of the HXR emission. These experiments yielded temperatures that were consistent with those measured by the HXIP. We showed that the thermal x-ray radiation must be included in the derivation of total energy in hot electrons (E hot), and that this makes E hot only weakly dependent on hot-electron temperature. For a given x-ray emission in inertial confinement fusion compression experiments, this result would lead to a higher total energy in hot electrons, but the preheat of the compressed fuel may be lower because of the reduced hot-electron range.« less

Measurements of hot-electron temperature in laser-irradiated plasmas

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

Solodov, A. A.; Yaakobi, B.; Edgell, D. H.

In a recently published work 1–3 we reported on measuring the total energy of hot electrons produced by the interaction of a nanosecond laser with planar CH-coated molybdenum targets, using the Mo K α emission. The temperature of the hot electrons in that work was determined by the high-energy bremsstrahlung [hard x-ray (HXR)] spectrum measured by a three-channel fluorescence-photomultiplier detector (HXRD). In the present work, we replaced the HXRD with a nine-channel image-plate (IP)–based detector (HXIP). For the same conditions (irradiance of the order of 10 14 W/cm 2; 2-ns pulses) the measured temperatures are consistently lower than those measuredmore » by the HXRD (by a factor ~1.5 to 1.7). In addition, we supplemented this measurement with three experiments that measure the hot-electron temperature using K α line-intensity ratios from high-Z target layers, independent of the HXR emission. These experiments yielded temperatures that were consistent with those measured by the HXIP. We showed that the thermal x-ray radiation must be included in the derivation of total energy in hot electrons (E hot), and that this makes E hot only weakly dependent on hot-electron temperature. For a given x-ray emission in inertial confinement fusion compression experiments, this result would lead to a higher total energy in hot electrons, but the preheat of the compressed fuel may be lower because of the reduced hot-electron range.« less

E2F1 somatic mutation within miRNA target site impairs gene regulation in colorectal cancer.

PubMed

Lopes-Ramos, Camila M; Barros, Bruna P; Koyama, Fernanda C; Carpinetti, Paola A; Pezuk, Julia; Doimo, Nayara T S; Habr-Gama, Angelita; Perez, Rodrigo O; Parmigiani, Raphael B

2017-01-01

Genetic studies have largely concentrated on the impact of somatic mutations found in coding regions, and have neglected mutations outside of these. However, 3' untranslated regions (3' UTR) mutations can also disrupt or create miRNA target sites, and trigger oncogene activation or tumor suppressor inactivation. We used next-generation sequencing to widely screen for genetic alterations within predicted miRNA target sites of oncogenes associated with colorectal cancer, and evaluated the functional impact of a new somatic mutation. Target sequencing of 47 genes was performed for 29 primary colorectal tumor samples. For 71 independent samples, Sanger methodology was used to screen for E2F1 mutations in miRNA predicted target sites, and the functional impact of these mutations was evaluated by luciferase reporter assays. We identified germline and somatic alterations in E2F1. Of the 100 samples evaluated, 3 had germline alterations at the MIR205-5p target site, while one had a somatic mutation at MIR136-5p target site. E2F1 gene expression was similar between normal and tumor tissues bearing the germline alteration; however, expression was increased 4-fold in tumor tissue that harbored a somatic mutation compared to that in normal tissue. Luciferase reporter assays revealed both germline and somatic alterations increased E2F1 activity relative to wild-type E2F1. We demonstrated that somatic mutation within E2F1:MIR136-5p target site impairs miRNA-mediated regulation and leads to increased gene activity. We conclude that somatic mutations that disrupt miRNA target sites have the potential to impact gene regulation, highlighting an important mechanism of oncogene activation.

A fluorescence anisotropy assay to discover and characterize ligands targeting the maytansine site of tubulin.

PubMed

Menchon, Grégory; Prota, Andrea E; Lucena-Agell, Daniel; Bucher, Pascal; Jansen, Rolf; Irschik, Herbert; Müller, Rolf; Paterson, Ian; Díaz, J Fernando; Altmann, Karl-Heinz; Steinmetz, Michel O

2018-05-29

Microtubule-targeting agents (MTAs) like taxol and vinblastine are among the most successful chemotherapeutic drugs against cancer. Here, we describe a fluorescence anisotropy-based assay that specifically probes for ligands targeting the recently discovered maytansine site of tubulin. Using this assay, we have determined the dissociation constants of known maytansine site ligands, including the pharmacologically active degradation product of the clinical antibody-drug conjugate trastuzumab emtansine. In addition, we discovered that the two natural products spongistatin-1 and disorazole Z with established cellular potency bind to the maytansine site on β-tubulin. The high-resolution crystal structures of spongistatin-1 and disorazole Z in complex with tubulin allowed the definition of an additional sub-site adjacent to the pocket shared by all maytansine-site ligands, which could be exploitable as a distinct, separate target site for small molecules. Our study provides a basis for the discovery and development of next-generation MTAs for the treatment of cancer.

Novel and viable acetylcholinesterase target site for developing effective and environmentally safe insecticides.

PubMed

Pang, Yuan-Ping; Brimijoin, Stephen; Ragsdale, David W; Zhu, Kun Yan; Suranyi, Robert

2012-04-01

Insect pests are responsible for human suffering and financial losses worldwide. New and environmentally safe insecticides are urgently needed to cope with these serious problems. Resistance to current insecticides has resulted in a resurgence of insect pests, and growing concerns about insecticide toxicity to humans discourage the use of insecticides for pest control. The small market for insecticides has hampered insecticide development; however, advances in genomics and structural genomics offer new opportunities to develop insecticides that are less dependent on the insecticide market. This review summarizes the literature data that support the hypothesis that an insect-specific cysteine residue located at the opening of the acetylcholinesterase active site is a promising target site for developing new insecticides with reduced off-target toxicity and low propensity for insect resistance. These data are used to discuss the differences between targeting the insect-specific cysteine residue and targeting the ubiquitous catalytic serine residue of acetylcholinesterase from the perspective of reducing off-target toxicity and insect resistance. Also discussed is the prospect of developing cysteine-targeting anticholinesterases as effective and environmentally safe insecticides for control of disease vectors, crop damage, and residential insect pests within the financial confines of the present insecticide market.

Influence of quasi-specific sites on kinetics of target DNA search by a sequence-specific DNA-binding protein.

PubMed

Kemme, Catherine A; Esadze, Alexandre; Iwahara, Junji

2015-11-10

Functions of transcription factors require formation of specific complexes at particular sites in cis-regulatory elements of genes. However, chromosomal DNA contains numerous sites that are similar to the target sequences recognized by transcription factors. The influence of such "quasi-specific" sites on functions of the transcription factors is not well understood at present by experimental means. In this work, using fluorescence methods, we have investigated the influence of quasi-specific DNA sites on the efficiency of target location by the zinc finger DNA-binding domain of the inducible transcription factor Egr-1, which recognizes a 9 bp sequence. By stopped-flow assays, we measured the kinetics of Egr-1's association with a target site on 143 bp DNA in the presence of various competitor DNAs, including nonspecific and quasi-specific sites. The presence of quasi-specific sites on competitor DNA significantly decelerated the target association by the Egr-1 protein. The impact of the quasi-specific sites depended strongly on their affinity, their concentration, and the degree of their binding to the protein. To quantitatively describe the kinetic impact of the quasi-specific sites, we derived an analytical form of the apparent kinetic rate constant for the target association and used it for fitting to the experimental data. Our kinetic data with calf thymus DNA as a competitor suggested that there are millions of high-affinity quasi-specific sites for Egr-1 among the 3 billion bp of genomic DNA. This study quantitatively demonstrates that naturally abundant quasi-specific sites on DNA can considerably impede the target search processes of sequence-specific DNA-binding proteins.

Influence of Quasi-Specific Sites on Kinetics of Target DNA Search by a Sequence-Specific DNA-Binding Protein

PubMed Central

2015-01-01

Functions of transcription factors require formation of specific complexes at particular sites in cis-regulatory elements of genes. However, chromosomal DNA contains numerous sites that are similar to the target sequences recognized by transcription factors. The influence of such “quasi-specific” sites on functions of the transcription factors is not well understood at present by experimental means. In this work, using fluorescence methods, we have investigated the influence of quasi-specific DNA sites on the efficiency of target location by the zinc finger DNA-binding domain of the inducible transcription factor Egr-1, which recognizes a 9 bp sequence. By stopped-flow assays, we measured the kinetics of Egr-1’s association with a target site on 143 bp DNA in the presence of various competitor DNAs, including nonspecific and quasi-specific sites. The presence of quasi-specific sites on competitor DNA significantly decelerated the target association by the Egr-1 protein. The impact of the quasi-specific sites depended strongly on their affinity, their concentration, and the degree of their binding to the protein. To quantitatively describe the kinetic impact of the quasi-specific sites, we derived an analytical form of the apparent kinetic rate constant for the target association and used it for fitting to the experimental data. Our kinetic data with calf thymus DNA as a competitor suggested that there are millions of high-affinity quasi-specific sites for Egr-1 among the 3 billion bp of genomic DNA. This study quantitatively demonstrates that naturally abundant quasi-specific sites on DNA can considerably impede the target search processes of sequence-specific DNA-binding proteins. PMID:26502071

Design package for solar domestic hot water system

NASA Technical Reports Server (NTRS)

1980-01-01

The initial design of a solar domestic hot water system is considered. The system performance specification and detailed design drawings are included. The hot water systems consist of the following subsystems: collector, storage, control, transport, auxiliary energy, and government-furnished site data acquisition. The two systems are installed at Tempe, Arizona, and San Diego, California.

Effect of Escitalopram on Hot Flash Interference: A Randomized, Controlled Trial

PubMed Central

Carpenter, Janet S.; Guthrie, Katherine A.; Larson, Joseph C.; Freeman, Ellen W.; Joffe, Hadine; Reed, Susan D.; Ensrud, Kristine E.; LaCroix, Andrea Z.

2012-01-01

Objectives To estimate the effect of escitalopram 10–20 mg/day versus placebo for reducing hot flash interference in daily life and understand correlates and predictors of reductions in hot flash interference, a key measure of quality of life. Design Multi-site, randomized, double-blind, placebo-controlled clinical trial. Patients 205 midlife women (46% African-American) who met criteria participated. Setting MsFLASH clinical sites in Boston, Indianapolis, Oakland, and Philadelphia. Intervention After baseline, women were randomized to 1 pill of escitalopram 10 mg/day (n=104) or placebo (n=101) with follow-up at 4- and 8-weeks. At week 4, those not achieving 50% fewer hot flashes were increased to 2 pills daily (20 mg/day or 2 placebo pills). Main outcome measures The Hot Flash Related Daily Interference Scale; Correlates were variables from hot flash diaries; Predictors were baseline demographics, clinical variables, depression, anxiety, sleep quality, and hot flashes. Results Compared to placebo, escitalopram significantly reduced hot flash interference by 6.0 points at week 4 and 3.4 points at week 8 more than placebo (p=0.012). Reductions in hot flash interference correlated with changes in hot flash diary variables. However, baseline variables did not significantly predict reductions in hot flash interference. Conclusions Escitalopram 10–20mg/day for 8 weeks improves women’s quality of life and this benefit did not vary by demographic, clinical, mood, sleep, or hot flash variables. PMID:22480818

Renton's Quendall Terminals on List of EPA Superfund Sites Targeted for Immediate, Intense Attention

EPA Pesticide Factsheets

EPA released the list of Superfund sites that Administrator Pruitt has targeted for intense and immediate attention, including the Quendall Terminals Site, a former creosote facility on the shore of Lake Washington in Renton, Washington.

Optimum hot electron production with low-density foams for laser fusion by fast ignition.

PubMed

Lei, A L; Tanaka, K A; Kodama, R; Kumar, G R; Nagai, K; Norimatsu, T; Yabuuchi, T; Mima, K

2006-06-30

We propose a foam cone-in-shell target design aiming at optimum hot electron production for the fast ignition. A thin low-density foam is proposed to cover the inner tip of a gold cone inserted in a fuel shell. An intense laser is then focused on the foam to generate hot electrons for the fast ignition. Element experiments demonstrate increased laser energy coupling efficiency into hot electrons without increasing the electron temperature and beam divergence with foam coated targets in comparison with solid targets. This may enhance the laser energy deposition in the compressed fuel plasma.

Induced Seismicity at the UK "Hot Dry Rock" Test Site for Geothermal Energy Production

NASA Astrophysics Data System (ADS)

Li, Xun; Main, Ian; Jupe, Andrew

2018-03-01

In enhanced geothermal systems (EGS), fluid is injected at high pressure in order to stimulate fracturing and/or fluid flow through otherwise relatively impermeable underlying hot rocks to generate power and/or heat. The stimulation induces micro-earthquakes whose precise triggering mechanism and relationship to new and pre-existing fracture networks are still the subject of some debate. Here we analyse the dataset for induced micro-earthquakes at the UK "hot dry rock" experimental geothermal site (Rosemanowes, Cornwall). We quantify the evolution of several metrics used to characterise induced seismicity, including the seismic strain partition factor and the "seismogenic index". The results show a low strain partition factor of 0.01% and a low seismogenenic index indicating that aseismic processes dominate. We also analyse the spatio-temporal distribution of hypocentres, using simple models for the evolution of hydraulic diffusivity by (a) isotropic and (b) anisotropic pore-pressure relaxation. The principal axes of the diffusivity or permeability tensor inferred from the spatial distribution of earthquake foci are aligned parallel to the present-day stress field, although the maximum permeability is vertical, whereas the maximum principal stress is horizontal. Our results are consistent with a triggering mechanism that involves (a) seismic shear slip along optimally-oriented pre-existing fractures, (b) a large component of aseismic slip with creep (c) activation of tensile fractures as hydraulic conduits created by both the present-day stress field and by the induced shear slip, both exploiting pre-existing joint sets exposed in borehole data.

Induced seismicity at the UK `hot dry rock' test site for geothermal energy production

NASA Astrophysics Data System (ADS)

Li, Xun; Main, Ian; Jupe, Andrew

2018-07-01

In enhanced geothermal systems (EGS), fluid is injected at high pressure in order to stimulate fracturing and/or fluid flow through otherwise relatively impermeable underlying hot rocks to generate power and/or heat. The stimulation induces microearthquakes whose precise triggering mechanism and relationship to new and pre-existing fracture networks are still the subject of some debate. Here, we analyse the data set for induced microearthquakes at the UK `hot dry rock' experimental geothermal site (Rosemanowes, Cornwall). We quantify the evolution of several metrics used to characterise induced seismicity, including the seismic strain partition factor and the `seismogenic index'. The results show a low strain partition factor of 0.01 per cent and a low seismogenic index indicating that aseismic processes dominate. We also analyse the spatio-temporal distribution of hypocentres, using simple models for the evolution of hydraulic diffusivity by (1) isotropic and (2) anisotropic pore-pressure relaxation. The principal axes of the diffusivity or permeability tensor inferred from the spatial distribution of earthquake foci are aligned parallel to the present-day stress field, although the maximum permeability is vertical, whereas the maximum principal stress is horizontal. Our results are consistent with a triggering mechanism that involves (1) seismic shear slip along optimally oriented pre-existing fractures, (2) a large component of aseismic slip with creep and (3) activation of tensile fractures as hydraulic conduits created by both the present-day stress field and by the induced shear slip, both exploiting pre-existing joint sets exposed in borehole data.

Novel and Viable Acetylcholinesterase Target Site for Developing Effective and Environmentally Safe Insecticides

PubMed Central

Pang, Yuan-Ping; Brimijoin, Stephen; Ragsdale, David W; Zhu, Kun Yan; Suranyi, Robert

2012-01-01

Insect pests are responsible for human suffering and financial losses worldwide. New and environmentally safe insecticides are urgently needed to cope with these serious problems. Resistance to current insecticides has resulted in a resurgence of insect pests, and growing concerns about insecticide toxicity to humans discourage the use of insecticides for pest control. The small market for insecticides has hampered insecticide development; however, advances in genomics and structural genomics offer new opportunities to develop insecticides that are less dependent on the insecticide market. This review summarizes the literature data that support the hypothesis that an insect-specific cysteine residue located at the opening of the acetylcholinesterase active site is a promising target site for developing new insecticides with reduced off-target toxicity and low propensity for insect resistance. These data are used to discuss the differences between targeting the insect-specific cysteine residue and targeting the ubiquitous catalytic serine residue of acetylcholinesterase from the perspective of reducing off-target toxicity and insect resistance. Also discussed is the prospect of developing cysteine-targeting anticholinesterases as effective and environmentally safe insecticides for control of disease vectors, crop damage, and residential insect pests within the financial confines of the present insecticide market. PMID:22280344

Prototype solar heating and cooling systems including potable hot water

NASA Technical Reports Server (NTRS)

1978-01-01

Progress is reviewed in the development, delivery, and support of two prototype solar heating and cooling systems including potable hot water. The system consisted of the following subsystems: collector, auxiliary heating, potable hot water, storage, control, transport, and government-furnished site data acquisition.

Criticality and Induction Time of Hot Spots in Detonating Heterogeneous Explosives

NASA Astrophysics Data System (ADS)

Hill, Larry

2017-06-01

Detonation reaction in physically heterogeneous explosives is-to an extent that depends on multiple material attributes-likewise heterogeneous. Like all heterogeneous reaction, detonation heterogeneous reaction begins at nucleation sites, which, in this case, comprise localized regions of higher-than-average temperature-so-called hot spots. Burning grows at, and then spreads from these nucleation sites, via reactive-thermal (R-T) waves, to consume the interstitial material. Not all hot spots are consequential, but only those that are 1) supercritical, and 2) sufficiently so as to form R-T waves before being consumed by those already emanating from neighboring sites. I explore aspects of these two effects by deriving simple formulae for hot spot criticality and the induction time of supercritical hot spots. These results serve to illustrate the non-intuitive, yet mathematically simplifying, effects of extreme dependence of reaction rate upon temperature. They can play a role in the development of better reactive burn models, for which we seek to homogenize the essentials of heterogeneous detonation reaction without introducing spurious complexity. Work supported by the US Dept. of Energy.

Multi-level hot zone identification for pedestrian safety.

PubMed

Lee, Jaeyoung; Abdel-Aty, Mohamed; Choi, Keechoo; Huang, Helai

2015-03-01

According to the National Highway Traffic Safety Administration (NHTSA), while fatalities from traffic crashes have decreased, the proportion of pedestrian fatalities has steadily increased from 11% to 14% over the past decade. This study aims at identifying two zonal levels factors. The first is to identify hot zones at which pedestrian crashes occurs, while the second are zones where crash-involved pedestrians came from. Bayesian Poisson lognormal simultaneous equation spatial error model (BPLSESEM) was estimated and revealed significant factors for the two target variables. Then, PSIs (potential for safety improvements) were computed using the model. Subsequently, a novel hot zone identification method was suggested to combine both hot zones from where vulnerable pedestrians originated with hot zones where many pedestrian crashes occur. For the former zones, targeted safety education and awareness campaigns can be provided as countermeasures whereas area-wide engineering treatments and enforcement may be effective safety treatments for the latter ones. Thus, it is expected that practitioners are able to suggest appropriate safety treatments for pedestrian crashes using the method and results from this study. Copyright © 2015 Elsevier Ltd. All rights reserved.

Observations of IO hot-spots at coastal sites with the combination of a mobile CE- and LP- DOAS

NASA Astrophysics Data System (ADS)

Pöhler, D.; Horbanski, M.; Schmitt, S.; Anthofer, M.; Tschritter, J.; Platt, U.

2012-04-01

Reactive iodine species are emitted by seaweed in the intertidal zone of coastal sites during low tide. Beside their oxidation to iodine oxide (IO) and reduction of ozone, they act as precursors for particle formation and therefore have a potential impact on climate. A correlation between iodine oxide and particle formation could be observed in several field studies. However, modelling studies suggest that the so far observed mixing ratios of iodine oxide are too low to explain the observed particle formation. This may be caused by the so far applied measurement techniques which either average over a long measurement path of several km (LP-DOAS) or by immobile in-situ techniques (LIF or BB-CEAS) located typically few 10-100m of the intertidal area. Thus both techniques could not observe local "hot-spots", locations with locally elevated IO levels above the background with small spatial extend (e.g. above a source). We present a new developed Cavity Enhanced Differential Optical Absorption Spectroscopy (CE- DOAS) instrument for the direct identification of IO down to 1ppt. This technique gives the possibility to achieve long absorption light paths in a compact setup (<2.0m) and thus apply the DOAS principle to in-situ measurements. The resonator of the cavity is formed by two high reflective mirrors in the spectral window from 430-460nm. To avoid any interference of reactive iodine compounds with tubes, walls or filters, the resonator is open similar to a LP-DOAS setup. A blue LED is used as light source. The total instrument setup is relatively light (25kg) and can easily be located at different locations. Hence it is possible to setup this instrument directly over the macro algae in the intertidal area during low tide to investigate the IO spatial distribution and "hot-spots". As IO concentrations vary strongly due to different meteorological parameters, the CE-DOAS measurements are combined with LP-DOAS in the same area. Thus the combination allows deriving a

Rotifer rDNA-specific R9 retrotransposable elements generate an exceptionally long target site duplication upon insertion.

PubMed

Gladyshev, Eugene A; Arkhipova, Irina R

2009-12-15

Ribosomal DNA genes in many eukaryotes contain insertions of non-LTR retrotransposable elements belonging to the R2 clade. These elements persist in the host genomes by inserting site-specifically into multicopy target sites, thereby avoiding random disruption of single-copy host genes. Here we describe R9 retrotransposons from the R2 clade in the 28S RNA genes of bdelloid rotifers, small freshwater invertebrate animals best known for their long-term asexuality and for their ability to survive repeated cycles of desiccation and rehydration. While the structural organization of R9 elements is highly similar to that of other members of the R2 clade, they are characterized by two distinct features: site-specific insertion into a previously unreported target sequence within the 28S gene, and an unusually long target site duplication of 126 bp. We discuss the implications of these findings in the context of bdelloid genome organization and the mechanisms of target-primed reverse transcription.

Intensification of hot extremes in the United States

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

Diffenbaugh, Noah; Ashfaq, Moetasim

Governments are currently considering policies that will limit greenhouse gas concentrations, including negotiation of an international treaty to replace the expiring Kyoto Protocol. Existing mitigation targets have arisen primarily from political negotiations, and the ability of such policies to avoid dangerous impacts is still uncertain. Using a large suite of climate model experiments, we find that substantial intensification of hot extremes could occur within the next 3 decades, below the 2 C global warming target currently being considered by policy makers. We also find that the intensification of hot extremes is associated with a shift towards more anticyclonic atmospheric circulationmore » during the warm season, along with warm-season drying over much of the U.S. The possibility that intensification of hot extremes could result from relatively small increases in greenhouse gas concentrations suggests that constraining global warming to 2 C may not be sufficient to avoid dangerous climate change.« less

Drilling confirms hot-spot origins

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

Not Available

1978-02-01

Eleven holes were drilled at 4 sites in the Emperor Seamount chain in order to test the hot-spot hypothesis of the origin of the Hawaiian and Emperor chains and several important corollaries. Basalt was penetrated at 3 sites, and the paleontological ages of the lowest sediments above basalt are consistent with a linear geochron connecting the ages of Meiji Seamount to the north, and Koko and Yuryaku seamounts to the south. The chemical composition of the upper 4 basalt flow units cored at Ojin Seamount indicates that they are typical Hawaiites. A sample of tholeiite was recovered from the bottommore » of the hole. The lava flows from Ojin, Nintoku, and Suiko have natural remanent magnetization that is relatively stable to alternating field demagnetization, as expected of oceanic-island basalts. Many of the basalts at all 3 sites have highly vesicular and oxidized flow tops and bottoms. Observations indicate that the flows were erupted subaerially, and that Ojin, Nintoku, and Suiko volcanoes once stood well above sea level. In a general way, the hot-spot origin of the Emperor Seamount chain was confirmed. (JGB)« less

Preliminary design package for Sunspot Domestic Hot Water Heating System

NASA Technical Reports Server (NTRS)

1976-01-01

The design review includes a drawing list, auto-control logic, measurement definitions, and other document pertaining to the solar heated prototype hot water systems and two heat exchangers. The hot water systems consist of the following subsystems: collector, storage, control transport, auxiliary energy, and site data acquisition.

Suppression of Aedes albopictus, the Asian tiger mosquito, using a 'hot spot' approach.

PubMed

Unlu, Isik; Klingler, Kim; Indelicato, Nicholas; Faraji, Ary; Strickman, Daniel

2016-07-01

Recent changes in climate and human behavior have led to dramatic increases in the abundance and geographic expansion of invasive mosquito vectors such as Aedes albopictus. Although source reduction has been shown to be effective in reducing mosquito populations, thousands of backyards need to be inspected during door-to-door campaigns, which is labor intensive and expensive. We identified 'hot spots' as high (five or more female or male Ae. albopictus) adult mosquito populations at very focal locations. We tested whether hot spot source reduction efforts were effective in reducing mosquito populations in the early summer season (June to July). Analysis of historical data from the study sites indicated the proportion of hot spots in the control site relative to the intervention site was much greater in 2011, when hot spot treatments were applied to the intervention site, than in 2012, 2013 and 2014 combined, when no sites were treated [OR (95% CI) = 3.9 (1.8, 8.5), Z = 3.39, P < 0.001). Hot spot treatments can be incorporated into existing integrated mosquito management programs to increase effectiveness while reducing the time, cost and effort spent on methods such as door-to-door source reduction. Published 2015. This article is a U.S. Government work and is in the public domain in the USA. Published 2015. This article is a U.S. Government work and is in the public domain in the USA.

Hot Deformation Behavior of Hot-Extruded AA7175 Through Hot Torsion Tests.

PubMed

Lee, Se-Yeon; Jung, Taek-Kyun; Son, Hyeon-Woo; Kim, Sang-Wook; Son, Kwang-Tae; Choi, Ho-Joon; Oh, Sang-Ho; Lee, Ji-Woon; Hyun, Soong-Keun

2018-03-01

The hot deformation behavior of hot-extruded AA7175 was investigated with flow curves and processing maps through hot torsion tests. The flow curves and the deformed microstructures revealed that dynamic recrystallization (DRX) occurred in the hot-extruded AA7175 during hot working. The failure strain was highest at medium temperature. This was mainly influenced by the dynamic precipitation of fine rod-shaped MgZn2. The processing map determined the optimal deformation condition for the alloy during hot working.

A mathematical model of single target site location by Brownian movement in subcellular compartments.

PubMed

Kuthan, Hartmut

2003-03-07

The location of distinct sites is mandatory for many cellular processes. In the subcompartments of the cell nucleus, only very small numbers of diffusing macromolecules and specific target sites of some types may be present. In this case, we are faced with the Brownian movement of individual macromolecules and their "random search" for single/few specific target sites, rather than bulk-averaged diffusion and multiple sites. In this article, I consider the location of a distant central target site, e.g. a globular protein, by individual macromolecules executing unbiased (i.e. drift-free) random walks in a spherical compartment. For this walk-and-capture model, the closed-form analytic solution of the first passage time probability density function (p.d.f.) has been obtained as well as the first and second moment. In the limit of a large ratio of the radii of the spherical diffusion space and central target, well-known relations for the variance and the first two moments for the exponential p.d.f. were found to hold with high accuracy. These calculations reinforce earlier numerical results and Monte Carlo simulations. A major implication derivable from the model is that non-directed random movement is an effective means for locating single sites in submicron-sized compartments, even when the diffusion coefficients are comparatively small and the diffusing species are present in one copy only. These theoretical conclusions are underscored numerically for effective diffusion constants ranging from 0.5 to 10.0 microm(2) s(-1), which have been reported for a couple of nuclear proteins in their physiological environment. Spherical compartments of submicron size are, for example, the Cajal bodies (size: 0.1-1.0 microm), which are present in 1-5 copies in the cell nucleus. Within a small Cajal body of radius 0.1 microm a single diffusing protein molecule (with D=0.5 microm(2) s(-1)) would encounter a medium-sized protein of radius 2.5 nm within 1 s with a probability near

Engineered Proteins Program Mammalian Cells to Target Inflammatory Disease Sites.

PubMed

Qudrat, Anam; Mosabbir, Abdullah Al; Truong, Kevin

2017-06-22

Disease sites in atherosclerosis and cancer feature cell masses (e.g., plaques/tumors), a low pH extracellular microenvironment, and various pro-inflammatory cytokines such as tumor necrosis factor α (TNFα). The ability to engineer a cell to seek TNFα sources allows for targeted therapeutic delivery. To accomplish this, here we introduced a system of proteins: an engineered TNFα chimeric receptor (named TNFR1chi), a previously engineered Ca 2+ -activated RhoA (named CaRQ), vesicular stomatitis virus glycoprotein G (VSVG), and thymidine kinase. Upon binding TNFα, TNFR1chi generates a Ca 2+ signal that in turn activates CaRQ-mediated non-apoptotic blebs that allow migration toward the TNFα source. Next, the addition of VSVG, upon low pH induction, causes membrane fusion of the engineered and TNFα source cells. Finally, after ganciclovir treatment cells undergo death via the thymidine kinase suicide mechanism. Hence, we assembled a system of proteins that forms the basis of engineering a cell to target inflammatory disease sites characterized by TNFα secretion and a low-pH microenvironment. Copyright © 2017 Elsevier Ltd. All rights reserved.

Energy transfer dynamics in strongly inhomogeneous hot-dense-matter systems

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

Stillman, C. R.; Nilson, P. M.; Sefkow, A. B.

Direct measurements of energy transfer across steep density and temperature gradients in a hot-dense-matter system are presented. Hot dense plasma conditions were generated by high-intensity laser irradiation of a thin-foil target containing a buried metal layer. Energy transfer to the layer was measured using picosecond time-resolved x-ray emission spectroscopy. Here, the data show two x-ray flashes in time. Fully explicit, coupled particle-in-cell and collisional-radiative atomic kinetics model predictions reproduce these observations, connecting the two x-ray flashes with staged radial energy transfer within the target.

Energy transfer dynamics in strongly inhomogeneous hot-dense-matter systems

DOE PAGES

Stillman, C. R.; Nilson, P. M.; Sefkow, A. B.; ...

2018-06-25

Direct measurements of energy transfer across steep density and temperature gradients in a hot-dense-matter system are presented. Hot dense plasma conditions were generated by high-intensity laser irradiation of a thin-foil target containing a buried metal layer. Energy transfer to the layer was measured using picosecond time-resolved x-ray emission spectroscopy. Here, the data show two x-ray flashes in time. Fully explicit, coupled particle-in-cell and collisional-radiative atomic kinetics model predictions reproduce these observations, connecting the two x-ray flashes with staged radial energy transfer within the target.

Centredale Manor Superfund Site in Rhode Island included on EPA List of Targeted for Immediate Attention

EPA Pesticide Factsheets

Today, the U.S. Environmental Protection Agency released the list of Superfund sites that Administrator Pruitt has targeted for immediate and intense attention. The Centredale Manor Restoration Project superfund site is one of the 21 sites on the list.

Spy: a new group of eukaryotic DNA transposons without target site duplications.

PubMed

Han, Min-Jin; Xu, Hong-En; Zhang, Hua-Hao; Feschotte, Cédric; Zhang, Ze

2014-06-24

Class 2 or DNA transposons populate the genomes of most eukaryotes and like other mobile genetic elements have a profound impact on genome evolution. Most DNA transposons belong to the cut-and-paste types, which are relatively simple elements characterized by terminal-inverted repeats (TIRs) flanking a single gene encoding a transposase. All eukaryotic cut-and-paste transposons so far described are also characterized by target site duplications (TSDs) of host DNA generated upon chromosomal insertion. Here, we report a new group of evolutionarily related DNA transposons called Spy, which also include TIRs and DDE motif-containing transposase but surprisingly do not create TSDs upon insertion. Instead, Spy transposons appear to transpose precisely between 5'-AAA and TTT-3' host nucleotides, without duplication or modification of the AAATTT target sites. Spy transposons were identified in the genomes of diverse invertebrate species based on transposase homology searches and structure-based approaches. Phylogenetic analyses indicate that Spy transposases are distantly related to IS5, ISL2EU, and PIF/Harbinger transposases. However, Spy transposons are distinct from these and other DNA transposon superfamilies by their lack of TSD and their target site preference. Our findings expand the known diversity of DNA transposons and reveal a new group of eukaryotic DDE transposases with unusual catalytic properties. © The Author(s) 2014. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.

Unusual target site disruption by the rare-cutting HNH restriction endonuclease PacI

PubMed Central

Shen, Betty; Heiter, Daniel F.; Chan, Siu-Hong; Wang, Hua; Xu, Shuang-Yong; Morgan, Richard D.; Wilson, Geoffrey G.; Stoddard, Barry L.

2010-01-01

The crystal structure of the rare-cutting HNH restriction endonuclease PacI in complex with its eight base pair target recognition sequence 5'-TTAATTAA-3' has been determined to 1.9 Å resolution. The enzyme forms an extended homodimer, with each subunit containing two zinc-bound motifs surrounding a ββα-metal catalytic site. The latter is unusual in that a tyrosine residue likely initiates strand-cleavage. PacI dramatically distorts its target sequence from Watson-Crick duplex DNA basepairing, with every base separated from its original partner. Two bases on each strand are unpaired, four are engaged in non-canonical A:A and T:T base pairs, and the remaining two bases are matched with new Watson-Crick partners. This represents a highly unusual DNA binding mechanism for a restriction endonuclease, and implies that initial recognition of the target site might involve significantly different contacts from those visualized in the DNA-bound cocrystal structures. PMID:20541511

Evaluation of hot in-place recycle.

DOT National Transportation Integrated Search

2010-06-01

This report documents the construction of hot in-place recycled (HIPR) pavement on SR 542. : HIPR is a process by which rehabilitation of the existing HMA pavement occurs on site in one : operation. HIPR project selection, mix design, construction an...

Rapid development of stable transgene CHO cell lines by CRISPR/Cas9-mediated site-specific integration into C12orf35.

PubMed

Zhao, Menglin; Wang, Jiaxian; Luo, Manyu; Luo, Han; Zhao, Meiqi; Han, Lei; Zhang, Mengxiao; Yang, Hui; Xie, Yueqing; Jiang, Hua; Feng, Lei; Lu, Huili; Zhu, Jianwei

2018-07-01

Chinese hamster ovary (CHO) cells are the most widely used mammalian hosts for recombinant protein production. However, by conventional random integration strategy, development of a high-expressing and stable recombinant CHO cell line has always been a difficult task due to the heterogenic insertion and its caused requirement of multiple rounds of selection. Site-specific integration of transgenes into CHO hot spots is an ideal strategy to overcome these challenges since it can generate isogenic cell lines with consistent productivity and stability. In this study, we investigated three sites with potential high transcriptional activities: C12orf35, HPRT, and GRIK1, to determine the possible transcriptional hot spots in CHO cells, and further construct a reliable site-specific integration strategy to develop recombinant cell lines efficiently. Genes encoding representative proteins mCherry and anti-PD1 monoclonal antibody were targeted into these three loci respectively through CRISPR/Cas9 technology. Stable cell lines were generated successfully after a single round of selection. In comparison with a random integration control, all the targeted integration cell lines showed higher productivity, among which C12orf35 locus was the most advantageous in both productivity and cell line stability. Binding affinity and N-glycan analysis of the antibody revealed that all batches of product were of similar quality independent on integrated sites. Deep sequencing demonstrated that there was low level of off-target mutations caused by CRISPR/Cas9, but none of them contributed to the development process of transgene cell lines. Our results demonstrated the feasibility of C12orf35 as the target site for exogenous gene integration, and strongly suggested that C12orf35 targeted integration mediated by CRISPR/Cas9 is a reliable strategy for the rapid development of recombinant CHO cell lines.

Hydrologic data collected in the vicinity of the proposed gamma-ray and neutrino detector site, Hot Spring County, Arkansas, 1988-89

USGS Publications Warehouse

Fitzpatrick, D.J.; Westerfield, P.W.

1990-01-01

An abandoned barite mine in Hot Spring County, Arkansas, has been selected as the location for a proposed gamma-ray and neutrino detector site. As part of the hydrologic evaluation of the site, the U.S. Geological Survey in cooperation with the Arkansas Geological Commission collected hydrologic data at selected locations in the vicinity of the abandoned barite mine. Data collected as part of the project included water quality, pond-evaluation, and precipitation data within the abandoned barite mine and flow and water quality data at selected sites in the vicinity of the mine. Water quality samples from within the abandoned mine were collected at three locations in the pond at selected depths. These data included field measurements of specific conductance, pH, water temperature, dissolved oxygen, major ions, and trace metals. Major ion and trace-metal samples were collected at six stream sites, one lake site, and two wastewater pond sites. Pond elevation and precipitation data from within the abandoned barite mine were measured during the period between July 1, 1988 and June 30, 1989. Twevle discharge measurements during the period between June 21, 1988, and June 26, 1989, were collected at six sites in the vicinity of the abandoned barite mine. (USGS)

Analysis on establishing Chang'E-3 landing site as a reflectance calibration target

NASA Astrophysics Data System (ADS)

Liu, Bin; Fu, Xiaohui; Zeng, Xingguo; Yao, Meijuan; Zhang, Hongbo; Su, Yan; Zhao, Shu; Xue, Xiping; Li, Chunlai; Zou, Yongliao

2015-04-01

Recent lunar orbital observations suggested that the surface reflectance calculated based on the Apollo 16 standard area and Apollo 16 sample laboratory measurement is significantly different from its true value [1-3], one reason is the composition and maturity differences between the 62231 sampling site and the Apollo 16 standard site existed, the other reason is the physical properties of the returned lunar sample, such as porosity, have been changed during the sampling operations. So more new standard targets on the Moon, besides the widely used Apollo 16 area, are needed for imaging spectrometers on lunar missions to improve their reflectance calibration accuracies. The Chang'E-3 VIS/NIR Imaging Spectrometer (VNIS), which is just fixed at the front of the Yutu rover [4], equipped with a white spectralon panel as reflectance calibration standard, can perform in situ multispectral observations around the Chang'E-3 landing site without altering the physical and mineralogical natures of lunar soils. Therefore, it provides an opportunity to establish a new reliable standard target for in-flight reflectance calibration. The reflectance calibration target should be compositional homogeneous, the topography of which must be flat, and the reflectance should be identical with no nearby units of other different materials. As we have known, Chang'e-3 probe landed on the Mare Imbrium basin in the east part of Sinus Iridum, the landing site is relatively flat at a spatial coverage of ~660km2, and this region belongs to Eratosthenian low-Ti/high-Ti mare basalts [5-6]. According to much higher resolution topography data, elemental data and reflectance data of Chang'E-2 and Chang'E-3[7-8], we preliminary analyse the possibility on establishing Chang'E-3 landing site as a reflectance calibration target. Firstly, the overall terrain of the 4 km×4 km area around the landing site is flat, but there are still three bigger craters existed. Secondly, the composition on Chang'E-3

Observations of hot stars and eclipsing binaries with FRESIP

NASA Technical Reports Server (NTRS)

Gies, Douglas R.

1994-01-01

The FRESIP project offers an unprecedented opportunity to study pulsations in hot stars (which vary on time scales of a day) over a several year period. The photometric data will determine what frequencies are present, how or if the amplitudes change with time, and whether there is a connection between pulsation and mass loss episodes. It would initiate a new field of asteroseismology studies of hot star interiors. A search should be made for selected hot stars for inclusion in the list of project targets. Many of the primary solar mass targets will be eclipsing binaries, and I present estimates of their frequency and typical light curves. The photometric data combined with follow up spectroscopy and interferometric observations will provide fundamental data on these stars. The data will provide definitive information on the mass ratio distribution of solar-mass binaries (including the incidence of brown dwarf companions) and on the incidence of planets in binary systems.

Deletion of exons 3-9 encompassing a mutational hot spot in the DMD gene presents an asymptomatic phenotype, indicating a target region for multiexon skipping therapy.

PubMed

Nakamura, Akinori; Fueki, Noboru; Shiba, Naoko; Motoki, Hirohiko; Miyazaki, Daigo; Nishizawa, Hitomi; Echigoya, Yusuke; Yokota, Toshifumi; Aoki, Yoshitsugu; Takeda, Shin'ichi

2016-07-01

Few cases of dystrophinopathy show an asymptomatic phenotype with mutations in the 5' (exons 3-7) hot spot in the Duchenne muscular dystrophy (DMD) gene. Our patient showed increased serum creatine kinase levels at 12 years of age. A muscle biopsy at 15 years of age led to a diagnosis of Becker muscular dystrophy. The patient showed a slight decrease in cardiac function at the age of 21 years and was administered a β-blocker, but there was no muscle involvement even at the age of 27 years. A deletion of exons 3-9 encompassing a mutational hot spot in the DMD gene was detected, and dystrophin protein expression was ∼15% that of control level. We propose that in-frame deletion of exons 3-9 may produce a functional protein, and that multiexon skipping therapy targeting these exons may be feasible for severe dystrophic patients with a mutation in the 5' hot spot of the DMD gene.

Prototype solar heating and cooling systems including potable hot water

NASA Technical Reports Server (NTRS)

1978-01-01

These combined quarterly reports summarize the activities from November 1977 through September 1978, and over the progress made in the development, delivery and support of two prototype solar heating and cooling systems including potable hot water. The system consists of the following subsystems: solar collector, auxiliary heating, potable hot water, storage, control, transport, and government-furnished site data acquisition.

Immunological Reactivity Using Monoclonal and Polyclonal Antibodies of Autoimmune Thyroid Target Sites with Dietary Proteins

PubMed Central

Herbert, Martha

2017-01-01

Many hypothyroid and autoimmune thyroid patients experience reactions with specific foods. Additionally, food interactions may play a role in a subset of individuals who have difficulty finding a suitable thyroid hormone dosage. Our study was designed to investigate the potential role of dietary protein immune reactivity with thyroid hormones and thyroid axis target sites. We identified immune reactivity between dietary proteins and target sites on the thyroid axis that includes thyroid hormones, thyroid receptors, enzymes, and transport proteins. We also measured immune reactivity of either target specific monoclonal or polyclonal antibodies for thyroid-stimulating hormone (TSH) receptor, 5′deiodinase, thyroid peroxidase, thyroglobulin, thyroxine-binding globulin, thyroxine, and triiodothyronine against 204 purified dietary proteins commonly consumed in cooked and raw forms. Dietary protein determinants included unmodified (raw) and modified (cooked and roasted) foods, herbs, spices, food gums, brewed beverages, and additives. There were no dietary protein immune reactions with TSH receptor, thyroid peroxidase, and thyroxine-binding globulin. However, specific antigen-antibody immune reactivity was identified with several purified food proteins with triiodothyronine, thyroxine, thyroglobulin, and 5′deiodinase. Laboratory analysis of immunological cross-reactivity between thyroid target sites and dietary proteins is the initial step necessary in determining whether dietary proteins may play a potential immunoreactive role in autoimmune thyroid disease. PMID:28894619

Preliminary design package for solar heating and hot water system

NASA Technical Reports Server (NTRS)

1976-01-01

Two prototype solar heating and hot water systems for use in single-family dwellings or commercial buildings were designed. Subsystems included are: collector, storage, transport, hot water, auxiliary energy, and government-furnished site data acquisition. The systems are designed for Yosemite, California, and Pueblo, Colorado. The necessary information to evaluate the preliminary design for these solar heating and hot water systems is presented. Included are a proposed instrumentation plan, a training program, hazard analysis, preliminary design drawings, and other information about the design of the system.

Searching target sites on DNA by proteins: Role of DNA dynamics under confinement

PubMed Central

Mondal, Anupam; Bhattacherjee, Arnab

2015-01-01

DNA-binding proteins (DBPs) rapidly search and specifically bind to their target sites on genomic DNA in order to trigger many cellular regulatory processes. It has been suggested that the facilitation of search dynamics is achieved by combining 3D diffusion with one-dimensional sliding and hopping dynamics of interacting proteins. Although, recent studies have advanced the knowledge of molecular determinants that affect one-dimensional search efficiency, the role of DNA molecule is poorly understood. In this study, by using coarse-grained simulations, we propose that dynamics of DNA molecule and its degree of confinement due to cellular crowding concertedly regulate its groove geometry and modulate the inter-communication with DBPs. Under weak confinement, DNA dynamics promotes many short, rotation-decoupled sliding events interspersed by hopping dynamics. While this results in faster 1D diffusion, associated probability of missing targets by jumping over them increases. In contrast, strong confinement favours rotation-coupled sliding to locate targets but lacks structural flexibility to achieve desired specificity. By testing under physiological crowding, our study provides a plausible mechanism on how DNA molecule may help in maintaining an optimal balance between fast hopping and rotation-coupled sliding dynamics, to locate target sites rapidly and form specific complexes precisely. PMID:26400158

CRISPRdirect: software for designing CRISPR/Cas guide RNA with reduced off-target sites

PubMed Central

Naito, Yuki; Hino, Kimihiro; Bono, Hidemasa; Ui-Tei, Kumiko

2015-01-01

Summary: CRISPRdirect is a simple and functional web server for selecting rational CRISPR/Cas targets from an input sequence. The CRISPR/Cas system is a promising technique for genome engineering which allows target-specific cleavage of genomic DNA guided by Cas9 nuclease in complex with a guide RNA (gRNA), that complementarily binds to a ∼20 nt targeted sequence. The target sequence requirements are twofold. First, the 5′-NGG protospacer adjacent motif (PAM) sequence must be located adjacent to the target sequence. Second, the target sequence should be specific within the entire genome in order to avoid off-target editing. CRISPRdirect enables users to easily select rational target sequences with minimized off-target sites by performing exhaustive searches against genomic sequences. The server currently incorporates the genomic sequences of human, mouse, rat, marmoset, pig, chicken, frog, zebrafish, Ciona, fruit fly, silkworm, Caenorhabditis elegans, Arabidopsis, rice, Sorghum and budding yeast. Availability: Freely available at http://crispr.dbcls.jp/. Contact: y-naito@dbcls.rois.ac.jp Supplementary information: Supplementary data are available at Bioinformatics online. PMID:25414360

Targeted Metagenomic Survey of the Fe-Cycling Microbial Community at Chocolate Pots Hot Springs, Yellowstone National Park

NASA Astrophysics Data System (ADS)

Fortney, N. W.; He, S.; Kulkarni, A.; Friedrich, M. W.; Boyd, E. S.; Roden, E. E.

2016-12-01

Chocolate Pots hot springs (CP) is a circumneutral pH, Fe-rich geothermal feature located in Yellowstone National Park. Fe-based metabolic processes are deeply rooted in the tree of life and studying environments like CP are important for us to study to gain insight into ancient Earth ecosystems. Recently identified features on Mars are indicative of near-surface hydrothermal environments and studies of modern Earth systems like CP allow us a glimpse into how life may have potentially arisen on other rocky worlds. Previous enrichment culture studies of the microbial community present at CP identified close relatives of dissimilatory Fe-reducing bacteria (DIRB), including Geobacter metallireducens and Melioribacter roseus. However, the question still remains as to the composition and activity of the microbial community in situ. Here we used 13C stable isotope probing to gain an understanding of the Fe cycling microbial community at CP. Fe-Si oxide sediments collected from near the hot spring vent were incubated under in situ conditions and amended with 13C-acetate or -bicarbonate to target DIRB and Fe-oxidizing bacteria, respectively. 16S rRNA gene amplicon libraries along with shotgun metagenomic libraries were obtained from both sets of incubations. Differential read coverage mapping of metagenomic reads identified a set of taxonomic bins that showed a response to the incubation treatments. We searched the Fe-reducing incubation bins for homologues of genes involved in known extracellular electron transfer (EET) systems such as Pcc and MtrAB, as well as putative porins proximal to multiheme cytochrome c genes. We also searched bins from the Fe-oxidizing incubations for these EET systems in addition to homologues of the outer membrane cytochrome c Cyc2. The Fe-oxidizing bins were also examined for genes encoding RuBisCo to identify potential chemolithoautotrophs. Our targeted metagenomic analysis will identify which organisms are likely to be part of an active Fe

FRIENDS OF HOT JUPITERS. II. NO CORRESPONDENCE BETWEEN HOT-JUPITER SPIN-ORBIT MISALIGNMENT AND THE INCIDENCE OF DIRECTLY IMAGED STELLAR COMPANIONS

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

Ngo, Henry; Knutson, Heather A.; Hinkley, Sasha

Multi-star systems are common, yet little is known about a stellar companion's influence on the formation and evolution of planetary systems. For instance, stellar companions may have facilitated the inward migration of hot Jupiters toward to their present day positions. Many observed short-period gas giant planets also have orbits that are misaligned with respect to their star's spin axis, which has also been attributed to the presence of a massive outer companion on a non-coplanar orbit. We present the results of a multi-band direct imaging survey using Keck NIRC2 to measure the fraction of short-period gas giant planets found inmore » multi-star systems. Over three years, we completed a survey of 50 targets ('Friends of Hot Jupiters') with 27 targets showing some signature of multi-body interaction (misaligned or eccentric orbits) and 23 targets in a control sample (well-aligned and circular orbits). We report the masses, projected separations, and confirmed common proper motion for the 19 stellar companions found around 17 stars. Correcting for survey incompleteness, we report companion fractions of 48% ± 9%, 47% ± 12%, and 51% ± 13% in our total, misaligned/eccentric, and control samples, respectively. This total stellar companion fraction is 2.8σ larger than the fraction of field stars with companions approximately 50-2000 AU. We observe no correlation between misaligned/eccentric hot Jupiter systems and the incidence of stellar companions. Combining this result with our previous radial velocity survey, we determine that 72% ± 16% of hot Jupiters are part of multi-planet and/or multi-star systems.« less

Vegetation and the importance of insecticide-treated target siting for control of Glossina fuscipes fuscipes.

PubMed

Esterhuizen, Johan; Njiru, Basilio; Vale, Glyn A; Lehane, Michael J; Torr, Stephen J

2011-09-01

Control of tsetse flies using insecticide-treated targets is often hampered by vegetation re-growth and encroachment which obscures a target and renders it less effective. Potentially this is of particular concern for the newly developed small targets (0.25 high × 0.5 m wide) which show promise for cost-efficient control of Palpalis group tsetse flies. Consequently the performance of a small target was investigated for Glossina fuscipes fuscipes in Kenya, when the target was obscured following the placement of vegetation to simulate various degrees of natural bush encroachment. Catches decreased significantly only when the target was obscured by more than 80%. Even if a small target is underneath a very low overhanging bush (0.5 m above ground), the numbers of G. f. fuscipes decreased by only about 30% compared to a target in the open. We show that the efficiency of the small targets, even in small (1 m diameter) clearings, is largely uncompromised by vegetation re-growth because G. f. fuscipes readily enter between and under vegetation. The essential characteristic is that there should be some openings between vegetation. This implies that for this important vector of HAT, and possibly other Palpalis group flies, a smaller initial clearance zone around targets can be made and longer interval between site maintenance visits is possible both of which will result in cost savings for large scale operations. We also investigated and discuss other site features e.g. large solid objects and position in relation to the water's edge in terms of the efficacy of the small targets.

Hot spot-based design of small-molecule inhibitors for protein-protein interactions.

PubMed

Guo, Wenxing; Wisniewski, John A; Ji, Haitao

2014-06-01

Protein-protein interactions (PPIs) are important targets for the development of chemical probes and therapeutic agents. From the initial discovery of the existence of hot spots at PPI interfaces, it has been proposed that hot spots might provide the key for developing small-molecule PPI inhibitors. However, there has been no review on the ways in which the knowledge of hot spots can be used to achieve inhibitor design, nor critical examination of successful examples. This Digest discusses the characteristics of hot spots and the identification of druggable hot spot pockets. An analysis of four examples of hot spot-based design reveals the importance of this strategy in discovering potent and selective PPI inhibitors. A general procedure for hot spot-based design of PPI inhibitors is outlined. Copyright © 2014 Elsevier Ltd. All rights reserved.

Detection of Hot Halo Gets Theory Out of Hot Water

NASA Astrophysics Data System (ADS)

2006-02-01

Scientists using NASA's Chandra X-ray Observatory have detected an extensive halo of hot gas around a quiescent spiral galaxy. This discovery is evidence that galaxies like our Milky Way are still accumulating matter from the gradual inflow of intergalactic gas. "What we are likely witnessing here is the ongoing galaxy formation process," said Kristian Pedersen of the University of Copenhagen, Denmark, and lead author of a report on the discovery. Chandra observations show that the hot halo extends more than 60,000 light years on either side of the disk of the galaxy known as NGC 5746. The detection of such a large halo alleviates a long-standing problem for the theory of galaxy formation. Spiral galaxies are thought to form from enormous clouds of intergalactic gas that collapse to form giant, spinning disks of stars and gas. Chandra X-ray Image of NGC 5746 Chandra X-ray Image of NGC 5746 One prediction of this theory is that large spiral galaxies should be immersed in halos of hot gas left over from the galaxy formation process. Hot gas has been detected around spiral galaxies in which vigorous star formation is ejecting matter from the galaxy, but until now hot halos due to infall of intergalactic matter have not been detected. "Our observations solve the mystery of the missing hot halos around spiral galaxies," said Pedersen. "The halos exist, but are so faint that an extremely sensitive telescope such as Chandra is needed to detect them." DSS Optical Image of NGC 5746 DSS Optical Image of NGC 5746 NGC 5746 is a massive spiral galaxy about a 100 million light years from Earth. Its disk of stars and gas is viewed almost edge-on. The galaxy shows no signs of unusual star formation, or energetic activity from its nuclear region, making it unlikely that the hot halo is produced by gas flowing out of the galaxy. "We targeted NGC 5746 because we thought its distance and orientation would give us the best chance to detect a hot halo caused by the infall of

Simulations of electron transport and ignition for direct-drive fast-ignition targets

NASA Astrophysics Data System (ADS)

Solodov, A. A.; Anderson, K. S.; Betti, R.; Gotcheva, V.; Myatt, J.; Delettrez, J. A.; Skupsky, S.; Theobald, W.; Stoeckl, C.

2008-11-01

The performance of high-gain, fast-ignition fusion targets is investigated using one-dimensional hydrodynamic simulations of implosion and two-dimensional (2D) hybrid fluid-particle simulations of hot-electron transport, ignition, and burn. The 2D/3D hybrid-particle-in-cell code LSP [D. R. Welch et al., Nucl. Instrum. Methods Phys. Res. A 464, 134 (2001)] and the 2D fluid code DRACO [P. B. Radha et al., Phys. Plasmas 12, 056307 (2005)] are integrated to simulate the hot-electron transport and heating for direct-drive fast-ignition targets. LSP simulates the transport of hot electrons from the place where they are generated to the dense fuel core where their energy is absorbed. DRACO includes the physics required to simulate compression, ignition, and burn of fast-ignition targets. The self-generated resistive magnetic field is found to collimate the hot-electron beam, increase the coupling efficiency of hot electrons with the target, and reduce the minimum energy required for ignition. Resistive filamentation of the hot-electron beam is also observed. The minimum energy required for ignition is found for hot electrons with realistic angular spread and Maxwellian energy-distribution function.

Effects of Long- and Intermediate-Wavelength Nonuniformities on Hot-Spot Energetics of Hydrodynamic Equivalent Targets

NASA Astrophysics Data System (ADS)

Bose, A.; Betti, R.; Woo, K. M.; Christopherson, A. R.; Shvarts, D.

2015-11-01

The impact of intermediate- and low-mode nonuniformities on the performance of inertial confinement fusion (ICF) implosions is investigated by a detailed study of hot-spot energetics. It is found that low- (1 ~ 2) and intermediate-mode (1 >= 10) asymmetries affect the hot-spot hydrodynamics in very different ways. It is observed that for low-mode asymmetries, the fusion yield decreases because of a significant reduction in hot-spot pressure while the neutron-averaged hot-spot volume remains comparable to that of unperturbed (clean) simulations. On the other hand, implosions with moderate-amplitude, intermediate-wavelength modes, which are amplified by the Rayleigh-Taylor instability (RTI), exhibit a fusion-yield degradation primarily caused by a reduction in the burn volume without significant degradation of the pressure. For very large amplitudes, the intermediate modes show a ``secondary piston effect,'' where the converging RTI spikes compress a much smaller volume, allowing for a secondary conversion of the shell's kinetic energy to internal energy at a central region. Understanding the effects of nonuniformities on the hot-spot energetics provides valuable insight in determining the causes of performance degradation in current ICF experiments. This material is based upon work supported by the Department of Energy National Nuclear Security Administration under Award Number DE-NA0001944 and DE-FC02-04ER54789 (Fusion Science Center).

Solar 'hot spots' are still hot

NASA Technical Reports Server (NTRS)

Bai, Taeil

1990-01-01

Longitude distributions of solar flares are not random but show evidence for active zones (or hot spots) where flares are concentrated. According to a previous study, two hot spots in the northern hemisphere, which rotate with a synodic period of about 26.72 days, produced the majority of major flares, during solar cycles 20 and 21. The more prominent of these two hot spots is found to be still active during the rising part of cycle 22, producing the majority of northern hemisphere major flares. The synodic rotation period of this hot spot is 26.727 + or - 0.007 days. There is also evidence for hot spots in the southern hemisphere. Two hot spots separated by 180 deg are found to rotate with a period of 29.407 days, with one of them having persisted in the same locations during cycles 19-22 and the other, during cycles 20-22.

Abdominal adiposity and hot flashes among midlife women.

PubMed

Thurston, Rebecca C; Sowers, MaryFran R; Sutton-Tyrrell, Kim; Everson-Rose, Susan A; Lewis, Tené T; Edmundowicz, Daniel; Matthews, Karen A

2008-01-01

Two competing hypotheses suggest how adiposity may affect menopausal hot flashes. The "thin hypothesis" asserts that aromatization of androgens to estrogens in body fat should be associated with decreased hot flashes. Conversely, thermoregulatory models argue that body fat should be associated with increased hot flashes. The study objective was to examine associations between abdominal adiposity and hot flashes, including the role of reproductive hormones in these associations. The Study of Women's Health Across the Nation Heart Study (2001-2003) is an ancillary study to the Study of Women's Health Across the Nation, a community-based cohort study. Participants were 461 women (35% African American, 65% white) ages 45 to 58 years with an intact uterus and at least one ovary. Measures included a computed tomography scan to assess abdominal adiposity; reported hot flashes over the previous 2 weeks; and a blood sample for measurement of follicle-stimulating hormone, estradiol, and sex hormone-binding globulin-adjusted estradiol (free estradiol index). Associations were evaluated within multivariable logistic and linear regression models. Every 1-SD increase in total (odds ratio [OR]=1.28; 95% CI: 1.06-1.55) and subcutaneous (OR=1.30; 95% CI: 1.07-1.58) abdominal adiposity was associated with increased odds of hot flashes in age- and site-adjusted models. Visceral adiposity was not associated with hot flashes. Associations were not reduced when models included reproductive hormone concentrations. Increased abdominal adiposity, particularly subcutaneous adiposity, is associated with increased odds of hot flashes, favoring thermoregulatory models of hot flashes. Body fat may not protect women from hot flashes as once thought.

Role of target thickness in proton acceleration from near-critical mass-limited plasmas

NASA Astrophysics Data System (ADS)

Kuri, Deep Kumar; Das, Nilakshi; Patel, Kartik

2017-07-01

The role played by the target thickness in generating high energetic protons by a circularly polarized laser from near-critical mass-limited targets (MLT) has been investigated with the help of three-dimensional (3D) particle-in-cell (PIC) simulations. The radiation pressure accelerates protons from the front side of the target. Due to hole boring, the target front side gets deformed resulting in a change in the effective angle of incidence which causes vacuum heating and hence generates hot electrons. These hot electrons travel through the target at an angle with the laser axis and hence get more diverged along transverse directions for large target thickness. The hot electrons form sheath fields on the target rear side which accelerates protons via target normal sheath acceleration (TNSA). It is observed that the collimation of radiation pressure accelerated protons gets degraded on reaching the target rear side due to TNSA. The effect of transverse hot electron recirculations gets suppressed and the energetic protons get highly collimated on decreasing target thickness as the radiation pressure acceleration (RPA) starts dominating the acceleration process.

Use of NDT equipment for construction quality control of hot mix asphalt pavements

DOT National Transportation Integrated Search

2006-08-01

The focus of the study has been to evaluate the utility of seismic methods in the quality management of the hot mix asphalt layers. Procedures are presented to measure the target field moduli of hot mix asphalt (HMA) with laboratory seismic methods, ...

Use of Spatial Epidemiology and Hot Spot Analysis to Target Women Eligible for Prenatal Women, Infants, and Children Services

PubMed Central

Krawczyk, Christopher; Gradziel, Pat; Geraghty, Estella M.

2014-01-01

Objectives. We used a geographic information system and cluster analyses to determine locations in need of enhanced Special Supplemental Nutrition Program for Women, Infants, and Children (WIC) Program services. Methods. We linked documented births in the 2010 California Birth Statistical Master File with the 2010 data from the WIC Integrated Statewide Information System. Analyses focused on the density of pregnant women who were eligible for but not receiving WIC services in California’s 7049 census tracts. We used incremental spatial autocorrelation and hot spot analyses to identify clusters of WIC-eligible nonparticipants. Results. We detected clusters of census tracts with higher-than-expected densities, compared with the state mean density of WIC-eligible nonparticipants, in 21 of 58 (36.2%) California counties (P < .05). In subsequent county-level analyses, we located neighborhood-level clusters of higher-than-expected densities of eligible nonparticipants in Sacramento, San Francisco, Fresno, and Los Angeles Counties (P < .05). Conclusions. Hot spot analyses provided a rigorous and objective approach to determine the locations of statistically significant clusters of WIC-eligible nonparticipants. Results helped inform WIC program and funding decisions, including the opening of new WIC centers, and offered a novel approach for targeting public health services. PMID:24354821

Two-Plasmon Decay Mitigation in Direct-Drive Inertial-Confinement-Fusion Experiments Using Multilayer Targets.

PubMed

Follett, R K; Delettrez, J A; Edgell, D H; Goncharov, V N; Henchen, R J; Katz, J; Michel, D T; Myatt, J F; Shaw, J; Solodov, A A; Stoeckl, C; Yaakobi, B; Froula, D H

2016-04-15

Multilayer direct-drive inertial-confinement-fusion targets are shown to significantly reduce two-plasmon decay (TPD) driven hot-electron production while maintaining high hydrodynamic efficiency. Implosion experiments on the OMEGA laser used targets with silicon layered between an inner beryllium and outer silicon-doped plastic ablator. A factor-of-5 reduction in hot-electron generation (>50  keV) was observed in the multilayer targets relative to pure CH targets. Three-dimensional simulations of the TPD-driven hot-electron production using a laser-plasma interaction code (lpse) that includes nonlinear and kinetic effects show good agreement with the measurements. The simulations suggest that the reduction in hot-electron production observed in the multilayer targets is primarily caused by increased electron-ion collisional damping.

Diversity and Distribution of Thermophilic Bacteria in Hot Springs of Pakistan.

PubMed

Amin, Arshia; Ahmed, Iftikhar; Salam, Nimaichand; Kim, Byung-Yong; Singh, Dharmesh; Zhi, Xiao-Yang; Xiao, Min; Li, Wen-Jun

2017-07-01

Chilas and Hunza areas, located in the Main Mantle Thrust and Main Karakoram Thrust of the Himalayas, host a range of geochemically diverse hot springs. This Himalayan geothermal region encompassed hot springs ranging in temperature from 60 to 95 °C, in pH from 6.2 to 9.4, and in mineralogy from bicarbonates (Tato Field), sulfates (Tatta Pani) to mixed type (Murtazaabad). Microbial community structures in these geothermal springs remained largely unexplored to date. In this study, we report a comprehensive, culture-independent survey of microbial communities in nine samples from these geothermal fields by employing a bar-coded pyrosequencing technique. The bacterial phyla Proteobacteria and Chloroflexi were dominant in all samples from Tato Field, Tatta Pani, and Murtazaabad. The community structures however depended on temperature, pH, and physicochemical parameters of the geothermal sites. The Murtazaabad hot springs with relatively higher temperature (90-95 °C) favored the growth of phylum Thermotogae, whereas the Tatta Pani thermal spring site TP-H3-b (60 °C) favored the phylum Proteobacteria. At sites with low silica and high temperature, OTUs belonging to phylum Chloroflexi were dominant. Deep water areas of the Murtazaabad hot springs favored the sulfur-reducing bacteria. About 40% of the total OTUs obtained from these samples were unclassified or uncharacterized, suggesting the presence of many undiscovered and unexplored microbiota. This study has provided novel insights into the nature of ecological interactions among important taxa in these communities, which in turn will help in determining future study courses in these sites.

Modeling deflagration waves out of hot spots

NASA Astrophysics Data System (ADS)

Partom, Yehuda

2017-01-01

It is widely accepted that shock initiation and detonation of heterogeneous explosives comes about by a two-step process known as ignition and growth. In the first step a shock sweeping through an explosive cell (control volume) creates hot spots that become ignition sites. In the second step, deflagration waves (or burn waves) propagate out of those hot spots and transform the reactant in the cell into reaction products. The macroscopic (or average) reaction rate of the reactant in the cell depends on the speed of those deflagration waves and on the average distance between neighboring hot spots. Here we simulate the propagation of deflagration waves out of hot spots on the mesoscale in axial symmetry using a 2D hydrocode, to which we add heat conduction and bulk reaction. The propagation speed of the deflagration waves may depend on both pressure and temperature. It depends on pressure for quasistatic loading near ambient temperature, and on temperature at high temperatures resulting from shock loading. From the simulation we obtain deflagration fronts emanating out of the hot spots. For 8 to 13 GPa shocks, the emanating fronts propagate as deflagration waves to consume the explosive between hot spots. For higher shock levels deflagration waves may interact with the sweeping shock to become detonation waves on the mesoscale. From the simulation results we extract average deflagration wave speeds.

Avalanche multiplication and impact ionization in amorphous selenium photoconductive target

NASA Astrophysics Data System (ADS)

Park, Wug-Dong; Tanioka, Kenkichi

2014-03-01

The avalanche multiplication factor and the hole ionization coefficient in the amorphous selenium (a-Se) high-gain avalanche rushing amorphous photoconductor (HARP) target depend on the electric field. The phenomenon of avalanche multiplication and impact ionization in the 0.4-µm-thick a-Se HARP target is investigated. The hot carrier energy in the 0.4-µm-thick a-Se HARP target increases linearly as the target voltage increases. The energy relaxation length of hot carriers in the a-Se photoconductor of the 0.4-µm-thick HARP target saturates as the electric field increases. The average energy Eav of a hot carrier and the energy relaxation length λE in the a-Se photoconductor of the 0.4-µm-thick HARP target at 1 × 108 V/m were 0.25 eV and 2.5 nm, respectively. In addition, the hole ionization coefficient β and the avalanche multiplication factor M are derived as a function of the electric field, the average energy of a hot carrier, and the impact ionization energy. The experimental hole ionization coefficient β and the avalanche multiplication factor M in the 0.4-µm-thick a-Se HARP target agree with the theoretical results.

Protecting Important Sites for Biodiversity Contributes to Meeting Global Conservation Targets

PubMed Central

Butchart, Stuart H. M.; Scharlemann, Jörn P. W.; Evans, Mike I.; Quader, Suhel; Aricò, Salvatore; Arinaitwe, Julius; Balman, Mark; Bennun, Leon A.; Bertzky, Bastian; Besançon, Charles; Boucher, Timothy M.; Brooks, Thomas M.; Burfield, Ian J.; Burgess, Neil D.; Chan, Simba; Clay, Rob P.; Crosby, Mike J.; Davidson, Nicholas C.; De Silva, Naamal; Devenish, Christian; Dutson, Guy C. L.; Fernández, David F. Día z; Fishpool, Lincoln D. C.; Fitzgerald, Claire; Foster, Matt; Heath, Melanie F.; Hockings, Marc; Hoffmann, Michael; Knox, David; Larsen, Frank W.; Lamoreux, John F.; Loucks, Colby; May, Ian; Millett, James; Molloy, Dominic; Morling, Paul; Parr, Mike; Ricketts, Taylor H.; Seddon, Nathalie; Skolnik, Benjamin; Stuart, Simon N.; Upgren, Amy; Woodley, Stephen

2012-01-01

Protected areas (PAs) are a cornerstone of conservation efforts and now cover nearly 13% of the world's land surface, with the world's governments committed to expand this to 17%. However, as biodiversity continues to decline, the effectiveness of PAs in reducing the extinction risk of species remains largely untested. We analyzed PA coverage and trends in species' extinction risk at globally significant sites for conserving birds (10,993 Important Bird Areas, IBAs) and highly threatened vertebrates and conifers (588 Alliance for Zero Extinction sites, AZEs) (referred to collectively hereafter as ‘important sites’). Species occurring in important sites with greater PA coverage experienced smaller increases in extinction risk over recent decades: the increase was half as large for bird species with>50% of the IBAs at which they occur completely covered by PAs, and a third lower for birds, mammals and amphibians restricted to protected AZEs (compared with unprotected or partially protected sites). Globally, half of the important sites for biodiversity conservation remain unprotected (49% of IBAs, 51% of AZEs). While PA coverage of important sites has increased over time, the proportion of PA area covering important sites, as opposed to less important land, has declined (by 0.45–1.14% annually since 1950 for IBAs and 0.79–1.49% annually for AZEs). Thus, while appropriately located PAs may slow the rate at which species are driven towards extinction, recent PA network expansion has under-represented important sites. We conclude that better targeted expansion of PA networks would help to improve biodiversity trends. PMID:22457717

Microbial community analysis of a coastal hot spring in Kagoshima, Japan, using molecular- and culture-based approaches.

PubMed

Nishiyama, Minako; Yamamoto, Shuichi; Kurosawa, Norio

2013-08-01

Ibusuki hot spring is located on the coastline of Kagoshima Bay, Japan. The hot spring water is characterized by high salinity, high temperature, and neutral pH. The hot spring is covered by the sea during high tide, which leads to severe fluctuations in several environmental variables. A combination of molecular- and culture-based techniques was used to determine the bacterial and archaeal diversity of the hot spring. A total of 48 thermophilic bacterial strains were isolated from two sites (Site 1: 55.6°C; Site 2: 83.1°C) and they were categorized into six groups based on their 16S rRNA gene sequence similarity. Two groups (including 32 isolates) demonstrated low sequence similarity with published species, suggesting that they might represent novel taxa. The 148 clones from the Site 1 bacterial library included 76 operational taxonomy units (OTUs; 97% threshold), while 132 clones from the Site 2 bacterial library included 31 OTUs. Proteobacteria, Bacteroidetes, and Firmicutes were frequently detected in both clone libraries. The clones were related to thermophilic, mesophilic and psychrophilic bacteria. Approximately half of the sequences in bacterial clone libraries shared <92% sequence similarity with their closest sequences in a public database, suggesting that the Ibusuki hot spring may harbor a unique and novel bacterial community. By contrast, 77 clones from the Site 2 archaeal library contained only three OTUs, most of which were affiliated with Thaumarchaeota.

Repopulation of calibrations with samples from the target site: effect of the size of the calibration.

NASA Astrophysics Data System (ADS)

Guerrero, C.; Zornoza, R.; Gómez, I.; Mataix-Solera, J.; Navarro-Pedreño, J.; Mataix-Beneyto, J.; García-Orenes, F.

2009-04-01

Near infrared (NIR) reflectance spectroscopy offers important advantages because is a non-destructive technique, the pre-treatments needed in samples are minimal, and the spectrum of the sample is obtained in less than 1 minute without the needs of chemical reagents. For these reasons, NIR is a fast and cost-effective method. Moreover, NIR allows the analysis of several constituents or parameters simultaneously from the same spectrum once it is obtained. For this, a needed steep is the development of soil spectral libraries (set of samples analysed and scanned) and calibrations (using multivariate techniques). The calibrations should contain the variability of the target site soils in which the calibration is to be used. Many times this premise is not easy to fulfil, especially in libraries recently developed. A classical way to solve this problem is through the repopulation of libraries and the subsequent recalibration of the models. In this work we studied the changes in the accuracy of the predictions as a consequence of the successive addition of samples to repopulation. In general, calibrations with high number of samples and high diversity are desired. But we hypothesized that calibrations with lower quantities of samples (lower size) will absorb more easily the spectral characteristics of the target site. Thus, we suspect that the size of the calibration (model) that will be repopulated could be important. For this reason we also studied this effect in the accuracy of predictions of the repopulated models. In this study we used those spectra of our library which contained data of soil Kjeldahl Nitrogen (NKj) content (near to 1500 samples). First, those spectra from the target site were removed from the spectral library. Then, different quantities of samples of the library were selected (representing the 5, 10, 25, 50, 75 and 100% of the total library). These samples were used to develop calibrations with different sizes (%) of samples. We used partial least

Prototype solar heating and hot water system

NASA Technical Reports Server (NTRS)

1977-01-01

Progress is reported in the development of a solar heating and hot water system which uses a pyramidal optics solar concentrator for heating, and consists of the following subsystems: collector, control, transport, and site data acquisition. Improvements made in the components and subsystems are discussed.

An environmental survey of Serpentine Hot Springs: Geology, hydrology, geochemistry, and microbiology

USGS Publications Warehouse

Nordstrom, D. Kirk; Hasselbach, Linda; Ingebritsen, Steven E.; Skorupa, Dana; McCleskey, R. Blaine; McDermott, Timothy R.

2015-01-01

Serpentine Hot Springs is the most visited site in the Bering Land Bridge National Preserve. The hot springs have traditionally been used by the Native people of the Seward Peninsula for religious, medicinal and spiritual purposes and continue to be used in many of the same ways by Native people today. The hot springs are also popular with non-Native users from Nome and other communities, recreational users and pilots from out of the area, and hunters and hikers.

Targeting Alpha5 Beta1 Integrin to Prevent Metastatic Breast Cancer Cell Invasion: PhScN Target Site Definition and Plasma Stability

DTIC Science & Technology

2015-11-01

increased PhScN potency as a result of preventing endoproteolytic degradation. Finally, the in vivo lung extravasation and colonization data, as well as...successful colonization are late stages in breast cancer progression that are ultimately fatal. Hence, prevention of extravasation which leads to colony...Award Number: TITLE: “Targeting Alpha5 Beta1 Integrin to Prevent Metastatic Breast Cancer Cell Invasion: PhScN Target Site Definition and Plasma

Prediction of hot spots in protein interfaces using a random forest model with hybrid features.

PubMed

Wang, Lin; Liu, Zhi-Ping; Zhang, Xiang-Sun; Chen, Luonan

2012-03-01

Prediction of hot spots in protein interfaces provides crucial information for the research on protein-protein interaction and drug design. Existing machine learning methods generally judge whether a given residue is likely to be a hot spot by extracting features only from the target residue. However, hot spots usually form a small cluster of residues which are tightly packed together at the center of protein interface. With this in mind, we present a novel method to extract hybrid features which incorporate a wide range of information of the target residue and its spatially neighboring residues, i.e. the nearest contact residue in the other face (mirror-contact residue) and the nearest contact residue in the same face (intra-contact residue). We provide a novel random forest (RF) model to effectively integrate these hybrid features for predicting hot spots in protein interfaces. Our method can achieve accuracy (ACC) of 82.4% and Matthew's correlation coefficient (MCC) of 0.482 in Alanine Scanning Energetics Database, and ACC of 77.6% and MCC of 0.429 in Binding Interface Database. In a comparison study, performance of our RF model exceeds other existing methods, such as Robetta, FOLDEF, KFC, KFC2, MINERVA and HotPoint. Of our hybrid features, three physicochemical features of target residues (mass, polarizability and isoelectric point), the relative side-chain accessible surface area and the average depth index of mirror-contact residues are found to be the main discriminative features in hot spots prediction. We also confirm that hot spots tend to form large contact surface areas between two interacting proteins. Source data and code are available at: http://www.aporc.org/doc/wiki/HotSpot.

Micron-scale mapping of megagauss magnetic fields using optical polarimetry to probe hot electron transport in petawatt-class laser-solid interactions.

PubMed

Chatterjee, Gourab; Singh, Prashant Kumar; Robinson, A P L; Blackman, D; Booth, N; Culfa, O; Dance, R J; Gizzi, L A; Gray, R J; Green, J S; Koester, P; Kumar, G Ravindra; Labate, L; Lad, Amit D; Lancaster, K L; Pasley, J; Woolsey, N C; Rajeev, P P

2017-08-21

The transport of hot, relativistic electrons produced by the interaction of an intense petawatt laser pulse with a solid has garnered interest due to its potential application in the development of innovative x-ray sources and ion-acceleration schemes. We report on spatially and temporally resolved measurements of megagauss magnetic fields at the rear of a 50-μm thick plastic target, irradiated by a multi-picosecond petawatt laser pulse at an incident intensity of ~10 20 W/cm 2 . The pump-probe polarimetric measurements with micron-scale spatial resolution reveal the dynamics of the magnetic fields generated by the hot electron distribution at the target rear. An annular magnetic field profile was observed ~5 ps after the interaction, indicating a relatively smooth hot electron distribution at the rear-side of the plastic target. This is contrary to previous time-integrated measurements, which infer that such targets will produce highly structured hot electron transport. We measured large-scale filamentation of the hot electron distribution at the target rear only at later time-scales of ~10 ps, resulting in a commensurate large-scale filamentation of the magnetic field profile. Three-dimensional hybrid simulations corroborate our experimental observations and demonstrate a beam-like hot electron transport at initial time-scales that may be attributed to the local resistivity profile at the target rear.

Update on the KELT Transit Survey: Hot Planets around Hot, Bright Stars

NASA Astrophysics Data System (ADS)

Gaudi, B. Scott; KELT Collaboration

2017-01-01

The KELT Transit Survey consists of a pair of small-aperture, wide-angle automated telescope located at Winer Observatory in Sonoita, Arizona and the South African Astronomical Observatory (SAAO) in Sutherland, South Africa. Together, they are surveying roughly 60% of the sky for transiting planets. By virtue of their small apertures (42 mm) and large fields-of-view (26 degrees x 26 degrees), KELT is most sensitive to hot Jupiters transiting relatively bright (V~8-11), and thus relatively hot stars. Roughly half of the dwarf stars targeted by KELT are hotter than 6250K; such stars pose novel challenges, but also provide unique opportunities. I will provide an update on the most recent companions discovered by KELT, focusing in detail on a few particularly interesting systems. KELT is a joint collaboration between the Ohio State University, Vanderbilt University, and Lehigh University. This work was partially supported by NSF CAREER grant AST-1056524.

Genome-wide identification and characterisation of HOT regions in the human genome.

PubMed

Li, Hao; Liu, Feng; Ren, Chao; Bo, Xiaochen; Shu, Wenjie

2016-09-15

HOT (high-occupancy target) regions, which are bound by a surprisingly large number of transcription factors, are considered to be among the most intriguing findings of recent years. An improved understanding of the roles that HOT regions play in biology would be afforded by knowing the constellation of factors that constitute these domains and by identifying HOT regions across the spectrum of human cell types. We characterised and validated HOT regions in embryonic stem cells (ESCs) and produced a catalogue of HOT regions in a broad range of human cell types. We found that HOT regions are associated with genes that control and define the developmental processes of the respective cell and tissue types. We also showed evidence of the developmental persistence of HOT regions at primitive enhancers and demonstrate unique signatures of HOT regions that distinguish them from typical enhancers and super-enhancers. Finally, we performed a dynamic analysis to reveal the dynamical regulation of HOT regions upon H1 differentiation. Taken together, our results provide a resource for the functional exploration of HOT regions and extend our understanding of the key roles of HOT regions in development and differentiation.

Two-plasmon decay mitigation in direct-drive inertial-confinement-fusion experiments using multilayer targets

DOE PAGES

Follett, R. K.; Delettrez, J. A.; Edgell, D. H.; ...

2016-04-15

Multilayer direct-drive inertial-confinement-fusion (ICF) targets are shown to significantly reduce two-plasmon-decay (TPD) driven hot-electron production while maintaining high hydrodynamic efficiency. Implosion experiments on the OMEGA Laser used targets with silicon layered between an inner beryllium and outer silicon-doped plastic ablator. A factor of five reduction in hot-electron generation (> 50 keV) was observed in the multilayer targets relative to pure CH targets. Three-dimensional simulations of the TPD driven hot-electron production using a laser-plasma interaction code (LPSE) that includes nonlinear and kinetic effects show excellent agreement with the measurements. As a result, the simulations suggest that the reduction in hot-electron productionmore » observed in the multilayer targets is primarily due to increased electron-ion collisional damping.« less

Outreach for Outreach: Targeting social media audiences to promote a NASA kids’ web site

NASA Astrophysics Data System (ADS)

Pham, C. C.

2009-12-01

The Space Place is a successful NASA web site that benefits upper elementary school students and educators by providing games, activities, and resources to stimulate interest in science, technology, engineering, and mathematics, as well as to inform the audience of NASA’s contributions. As online social networking grows to be a central component of modern communication, The Space Place has explored the benefits of integrating social networks with the web site to increase awareness of materials the web site offers. This study analyzes the capabilities of social networks, and specifically the demographics of Twitter and Facebook. It then compares these results with the content, audience, and perceived demographics of The Space Place web site. Based upon the demographic results, we identified a target constituency that would benefit from the integration of social networks into The Space Place web site. As a result of this study, a Twitter feed has been established that releases a daily tweet from The Space Place. In addition, a Facebook page has been created to showcase new content and prompt interaction among fans of The Space Place. Currently, plans are under way to populate the Space Place Facebook page. Each social network has been utilized in an effort to spark excitement about the content on The Space Place, as well as to attract followers to the main NASA Space Place web site. To pursue this idea further, a plan has been developed to promote NASA Space Place’s social media tools among the target audience.

Molecular Characterization of Monoclonal Antibodies that Inhibit Acetylcholinesterase by Targeting the Peripheral Site and Backdoor Region

PubMed Central

Essono, Sosthène; Mondielli, Grégoire; Lamourette, Patricia; Boquet, Didier; Grassi, Jacques; Marchot, Pascale

2013-01-01

The inhibition properties and target sites of monoclonal antibodies (mAbs) Elec403, Elec408 and Elec410, generated against Electrophorus electricus acetylcholinesterase (AChE), have been defined previously using biochemical and mutagenesis approaches. Elec403 and Elec410, which bind competitively with each other and with the peptidic toxin inhibitor fasciculin, are directed toward distinctive albeit overlapping epitopes located at the AChE peripheral anionic site, which surrounds the entrance of the active site gorge. Elec408, which is not competitive with the other two mAbs nor fasciculin, targets a second epitope located in the backdoor region, distant from the gorge entrance. To characterize the molecular determinants dictating their binding site specificity, we cloned and sequenced the mAbs; generated antigen-binding fragments (Fab) retaining the parental inhibition properties; and explored their structure-function relationships using complementary x-ray crystallography, homology modeling and flexible docking approaches. Hypermutation of one Elec403 complementarity-determining region suggests occurrence of antigen-driven selection towards recognition of the AChE peripheral site. Comparative analysis of the 1.9Å-resolution structure of Fab408 and of theoretical models of its Fab403 and Fab410 congeners evidences distinctive surface topographies and anisotropic repartitions of charges, consistent with their respective target sites and inhibition properties. Finally, a validated, data-driven docking model of the Fab403-AChE complex suggests a mode of binding at the PAS that fully correlates with the functional data. This comprehensive study documents the molecular peculiarities of Fab403 and Fab410, as the largest peptidic inhibitors directed towards the peripheral site, and those of Fab408, as the first inhibitor directed toward the backdoor region of an AChE and a unique template for the design of new, specific modulators of AChE catalysis. PMID:24146971

Casein Kinase II Regulation of the Hot1 Transcription Factor Promotes Stochastic Gene Expression*

PubMed Central

Burns, Laura T.; Wente, Susan R.

2014-01-01

In Saccharomyces cerevisiae, Hog1 MAPK is activated and induces a transcriptional program in response to hyperosmotic stress. Several Hog1-responsive genes exhibit stochastic transcription, resulting in cell-to-cell variability in mRNA and protein levels. However, the mechanisms governing stochastic gene activity are not fully defined. Here we uncover a novel role for casein kinase II (CK2) in the cellular response to hyperosmotic stress. CK2 interacts with and phosphorylates the Hot1 transcription factor; however, Hot1 phosphorylation is not sufficient for controlling the stochastic response. The CK2 protein itself is required to negatively regulate mRNA expression of Hot1-responsive genes and Hot1 enrichment at target promoters. Single-cell gene expression analysis reveals altered activation of Hot1-targeted STL1 in ck2 mutants, resulting in a bimodal to unimodal shift in expression. Together, this work reveals a novel CK2 function during the hyperosmotic stress response that promotes cell-to-cell variability in gene expression. PMID:24817120

Targeting Alpha5 Beta1 Integrin to Prevent Metastatic Breast Cancer Cell Invasion: PhScN Target Site Definition and Plasma Stability

DTIC Science & Technology

2015-11-01

systemic therapy to prevent breast cancer bone colony progression. Figure 6. Colocalization of Ac-PhscNGGK-Bio with DiI in lung– extravasated SUM149PT cells...breast cancer progression that are ultimately fatal. Hence, prevention of extravasation which leads to colony formation would increase life...1 Award Number: W81XWH-12-1-0097 TITLE: “Targeting Alpha5 Beta1 Integrin to Prevent Metastatic Breast Cancer Cell Invasion: PhScN Target Site

Urogenital schistosomiasis transmission on Unguja Island, Zanzibar: characterisation of persistent hot-spots.

PubMed

Pennance, Tom; Person, Bobbie; Muhsin, Mtumweni Ali; Khamis, Alipo Naim; Muhsin, Juma; Khamis, Iddi Simba; Mohammed, Khalfan Abdallah; Kabole, Fatma; Rollinson, David; Knopp, Stefanie

2016-12-16

Elimination of urogenital schistosomiasis transmission is a priority for the Zanzibar Ministry of Health. Preventative chemotherapy together with additional control interventions have successfully alleviated much of the disease burden. However, a persistently high Schistosoma haematobium prevalence is found in certain areas. Our aim was to characterise and evaluate these persistent "hot-spots" of transmission and reinfection in comparison with low-prevalence areas, to support the intervention planning for schistosomiasis elimination in Zanzibar. Prevalences of S. haematobium were annually determined by a single urine filtration in schoolchildren from 45 administrative areas (shehias) in Unguja in 2012, 2013 and 2014. Coverage data for biannual treatment with praziquantel were available from ministerial databases and internal surveys. Among the 45 shehias, five hot-spot (≥ 15 % prevalence) and two low-prevalence (≤ 5 %) shehias were identified and surveyed in mid-2014. Human-water contact sites (HWCSs) and the presence of S. haematobium-infected and uninfected Bulinus globosus, as well as safe water sources (SWSs) and their reliability in terms of water availability were determined and mapped. We found no major difference in the treatment coverage between persistent hot-spot and low-prevalence shehias. On average, there were considerably more HWCSs containing B. globosus in hot-spot than in low-prevalence shehias (n = 8 vs n = 2) and also more HWCSs containing infected B. globosus (n = 2 vs n = 0). There was no striking difference in the average abundance of SWSs in hot-spot and low-prevalence shehias (n = 45 vs n = 38) and also no difference when considering SWSs with a constant water supply (average: 62 % vs 62 %). The average number of taps with a constant water supply, however, was lower in hot-spot shehias (n = 7 vs n = 14). Average distances from schools to the nearest HWCS were considerably shorter in hot-spot shehias

The control of hot-electron preheat in shock-ignition implosions

NASA Astrophysics Data System (ADS)

Trela, J.; Theobald, W.; Anderson, K. S.; Batani, D.; Betti, R.; Casner, A.; Delettrez, J. A.; Frenje, J. A.; Glebov, V. Yu.; Ribeyre, X.; Solodov, A. A.; Stoeckl, M.; Stoeckl, C.

2018-05-01

In the shock-ignition scheme for inertial confinement fusion, hot electrons resulting from laser-plasma instabilities can play a major role during the late stage of the implosion. This article presents the results of an experiment performed on OMEGA in the so-called "40 + 20 configuration." Using a recent calibration of the time-resolved hard x-ray diagnostic, the hot electrons' temperature and total energy were measured. One-dimensional radiation-hydrodynamic simulations have been performed that include hot electrons and are in agreement with the measured neutron-rate-averaged areal density. For an early spike launch, both experiment and simulations show the detrimental effect of hot electrons on areal density and neutron yield. For a later spike launch, this effect is minimized because of a higher compression of the target.

Kepler constraints on planets near hot Jupiters

PubMed Central

Steffen, Jason H.; Ragozzine, Darin; Fabrycky, Daniel C.; Carter, Joshua A.; Ford, Eric B.; Holman, Matthew J.; Rowe, Jason F.; Welsh, William F.; Borucki, William J.; Boss, Alan P.; Ciardi, David R.; Quinn, Samuel N.

2012-01-01

We present the results of a search for planetary companions orbiting near hot Jupiter planet candidates (Jupiter-size candidates with orbital periods near 3 d) identified in the Kepler data through its sixth quarter of science operations. Special emphasis is given to companions between the 2∶1 interior and exterior mean-motion resonances. A photometric transit search excludes companions with sizes ranging from roughly two-thirds to five times the size of the Earth, depending upon the noise properties of the target star. A search for dynamically induced deviations from a constant period (transit timing variations) also shows no significant signals. In contrast, comparison studies of warm Jupiters (with slightly larger orbits) and hot Neptune-size candidates do exhibit signatures of additional companions with these same tests. These differences between hot Jupiters and other planetary systems denote a distinctly different formation or dynamical history. PMID:22566651

Kepler constraints on planets near hot Jupiters.

PubMed

Steffen, Jason H; Ragozzine, Darin; Fabrycky, Daniel C; Carter, Joshua A; Ford, Eric B; Holman, Matthew J; Rowe, Jason F; Welsh, William F; Borucki, William J; Boss, Alan P; Ciardi, David R; Quinn, Samuel N

2012-05-22

We present the results of a search for planetary companions orbiting near hot Jupiter planet candidates (Jupiter-size candidates with orbital periods near 3 d) identified in the Kepler data through its sixth quarter of science operations. Special emphasis is given to companions between the 21 interior and exterior mean-motion resonances. A photometric transit search excludes companions with sizes ranging from roughly two-thirds to five times the size of the Earth, depending upon the noise properties of the target star. A search for dynamically induced deviations from a constant period (transit timing variations) also shows no significant signals. In contrast, comparison studies of warm Jupiters (with slightly larger orbits) and hot Neptune-size candidates do exhibit signatures of additional companions with these same tests. These differences between hot Jupiters and other planetary systems denote a distinctly different formation or dynamical history.

Plasmonic Heterodimers with Binding Site-Dependent Hot Spot for Surface-Enhanced Raman Scattering.

PubMed

Tian, Yuanyuan; Shuai, Zhenhua; Shen, Jingjing; Zhang, Lei; Chen, Shufen; Song, Chunyuan; Zhao, Baomin; Fan, Quli; Wang, Lianhui

2018-06-01

A novel plasmonic heterodimer nanostructure with a controllable self-assembled hot spot is fabricated by the conjugation of individual Au@Ag core-shell nanocubes (Au@Ag NCs) and varisized gold nanospheres (GNSs) via the biotin-streptavidin interaction from the ensemble to the single-assembly level. Due to their featured configurations, three types of heterogeneous nanostructures referred to as Vertice, Vicinity, and Middle are proposed and a single hot spot forms between the nanocube and nanosphere, which exhibits distinct diversity in surface plasmon resonance effect. Herein, the calculated surface-enhanced Raman scattering enhancement factors of the three types of heterodimers show a narrow distribution and can be tuned in orders of magnitude by controlling the size of GNSs onto individual Au@Ag NCs. Particularly, the Vertice heterodimer with unique configuration can provide extraordinary enhancement of the electric field for the single hot spot region due to the collaborative interaction of lightning rod effect and interparticle plasmon coupling effect. This established relationship between the architecture and the corresponding optical properties of the heterodimers provides the basis for creating controllable platforms which can be exploited in the applications of plasmonic devices, electronics, and biodetection. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

The Role of Serotonin in Hot Flashes after Breast Cancer

DTIC Science & Technology

2009-03-01

physiological mechanisms involved in hot flashes c.fter breast cancer will enable us to develop more targeted behavioral and/or pharmacological therapi ...s to be used in lieu of, or in addition to, currently available therapies so that we can eradicate hot flashes and improve the quality of life for...flavorings were most palatable - chocolate mint and orange. We rejected a lemon flavoring as being unpalatable. We eliminated the mid-day snack per

Electron Shock Ignition of Inertial Fusion Targets

DOE PAGES

Shang, W. L.; Betti, R.; Hu, S. X.; ...

2017-11-07

Here, it is shown that inertial fusion targets designed with low implosion velocities can be shock ignited using laser–plasma interaction generated hot electrons (hot-e) to obtain high-energy gains. These designs are robust to multimode asymmetries and are predicted to ignite even for significantly distorted implosions. Electron shock ignition requires tens of kilojoules of hot-e, which can only be produced on a large laser facility like the National Ignition Facility, with the laser to hot-e conversion efficiency greater than 10% at laser intensities ~10 16 W/cm 2.

Electron Shock Ignition of Inertial Fusion Targets

NASA Astrophysics Data System (ADS)

Shang, W. L.; Betti, R.; Hu, S. X.; Woo, K.; Hao, L.; Ren, C.; Christopherson, A. R.; Bose, A.; Theobald, W.

2017-11-01

It is shown that inertial confinement fusion targets designed with low implosion velocities can be shock-ignited using laser-plasma interaction generated hot electrons (hot-e 's) to obtain high energy gains. These designs are robust to multimode asymmetries and are predicted to ignite even for significantly distorted implosions. Electron shock ignition requires tens of kilojoules of hot-e 's which can be produced only at a large laser facility like the National Ignition Facility, with the laser-to-hot-e conversion efficiency greater than 10% at laser intensities ˜1016 W /cm2 .

Electron Shock Ignition of Inertial Fusion Targets.

PubMed

Shang, W L; Betti, R; Hu, S X; Woo, K; Hao, L; Ren, C; Christopherson, A R; Bose, A; Theobald, W

2017-11-10

It is shown that inertial confinement fusion targets designed with low implosion velocities can be shock-ignited using laser-plasma interaction generated hot electrons (hot-e's) to obtain high energy gains. These designs are robust to multimode asymmetries and are predicted to ignite even for significantly distorted implosions. Electron shock ignition requires tens of kilojoules of hot-e's which can be produced only at a large laser facility like the National Ignition Facility, with the laser-to-hot-e conversion efficiency greater than 10% at laser intensities ∼10^{16}  W/cm^{2}.

A pilot study of magnetic therapy for hot flashes after breast cancer.

PubMed

Carpenter, Janet S; Wells, Nancy; Lambert, Beth; Watson, Peggy; Slayton, Tami; Chak, Bapsi; Hepworth, Joseph T; Worthington, W Bradley

2002-04-01

The purpose of this randomized placebo-controlled crossover pilot study was to evaluate the effectiveness and acceptability of magnetic therapy for hot flashes among breast cancer survivors. Participants completed a 24-hour baseline hot-flash monitoring session, wore the magnetic devices or placebo for 3 days, completed an after-treatment hot-flash monitoring session, experienced a 10-day washout period, and then crossed over to the opposite study arm. Magnetic devices and placebos were placed on 6 acupressure sites corresponding to hot-flash relief. Complete data were available from 11 survivors of breast cancer. Results indicated magnetic therapy was no more effective than placebo in decreasing hot-flash severity, and contrary to expectations, placebo was significantly more effective than magnets in decreasing hot-flash frequency, bother, interference with daily activities, and overall quality of life. Implications for clinical practice and future research include the need to explore alternative interventions aimed at alleviating hot flashes in this population.

Prototype solar heating and cooling systems, including potable hot water

NASA Technical Reports Server (NTRS)

Bloomquist, D.; Oonk, R. L.

1977-01-01

Progress made in the development, delivery, and support of two prototype solar heating and cooling systems including potable hot water is reported. The system consists of the following subsystems: collector, auxiliary heating, potable hot water, storage, control, transport, and government-furnished site data acquisition. A comparison of the proposed Solaron Heat Pump and Solar Desiccant Heating and Cooling Systems, installation drawings, data on the Akron House at Akron, Ohio, and other program activities are included.

The ATP-binding site of type II topoisomerases as a target for antibacterial drugs.

PubMed

Maxwell, Anthony; Lawson, David M

2003-01-01

DNA topoisomerases are essential enzymes in all cell types and have been found to be valuable drug targets both for antibacterial and anti-cancer chemotherapy. Type II topoisomerases possess a binding site for ATP, which can be exploited as a target for chemo-therapeutic agents. High-resolution structures of protein fragments containing this site complexed with antibiotics or an ATP analogue have provided vital information for the understanding of the action of existing drugs and for the potential development of novel anti-bacterial agents. In this article we have reviewed the structure and function of the ATPase domain of DNA gyrase (bacterial topoisomerase II), particularly highlighting novel information that has been revealed by structural studies. We discuss the efficacy and mode of action of existing drugs and consider the prospects for the development of novel agents.

Nitric oxide synthase inhibition attenuates cutaneous vasodilation during the post-menopausal hot flash

PubMed Central

Hubing, Kimberly A.; Wingo, Jonathan E.; Brothers, R. Matthew; Coso, Juan Del; Low, David A.; Crandall, Craig G.

2010-01-01

Objective The purpose of this study was to test the hypothesis that local inhibition of nitric oxide and prostaglandin synthesis attenuates cutaneous vasodilator responses during post-menopausal hot flashes. Methods Four microdialysis membranes were inserted into forearm skin (dorsal surface) of 8 post-menopausal women (mean ± SD, 51±7 y). Ringers solution (control), 10mM Ketorolac (Keto) to inhibit prostaglandin synthesis, 10mM NG-L-arginine methyl ester (L-NAME) to inhibit nitric oxide synthase, and a combination of 10mM Keto + 10mM L-NAME were each infused at the separate sites. Skin blood flow at each site was indexed using laser-Doppler flowmetry. Cutaneous vascular conductance (CVC) was calculated as laser-Doppler flux/mean arterial blood pressure and was expressed as a percentage of the maximal calculated CVC (CVCmax) obtained following infusion of 50mM sodium nitropruside at all sites at the end of the study. Data from 13 hot flashes were analyzed. Results At the control site, the mean ± SD peak increase in CVC was 15.5±6% CVCmax units. This value was not different relative to the peak increase in CVC at the Keto site (13.0±5 % CVCmax units, P = 0.09). However, the peak increase in CVC during the flash was attenuated at the L-NAME and L-NAME + Keto sites (7.4±4 % CVCmax units and 8.7±7 % CVCmax units, respectively) relative to both the control and the Keto sites (P<0.05 for both comparisons). There were no significant differences in the peak increases in sweat rate between any of the sites (P = 0.24). Conclusions These data demonstrate that cutaneous vasodilation during a hot flash has a nitric oxide component. Increases in CVC despite the inhibition of prostaglandin synthesis suggest prostaglandins do not contribute to cutaneous vasodilation during a hot flash. PMID:20505548

Mohawk Tannery Hazardous Waste Site in New Hampshire included on EPA List of Targeted for Immediate Attention

EPA Pesticide Factsheets

Today, the U.S. Environmental Protection Agency released the list of Superfund sites that Administrator Pruitt has targeted for immediate and intense attention. The former Mohawk Tannery facility (a.k.a. Granite State Leathers) is one of the 21 sites on th

Fusion yield rate recovery by escaping hot-spot fast ions in the neighboring fuel layer

NASA Astrophysics Data System (ADS)

Tang, Xian-Zhu; McDevitt, C. J.; Guo, Zehua; Berk, H. L.

2014-02-01

Free-streaming loss by fast ions can deplete the tail population in the hot spot of an inertial confinement fusion (ICF) target. Escaping fast ions in the neighboring fuel layer of a cryogenic target can produce a surplus of fast ions locally. In contrast to the Knudsen layer effect that reduces hot-spot fusion reactivity due to tail ion depletion, the inverse Knudsen layer effect increases fusion reactivity in the neighboring fuel layer. In the case of a burning ICF target in the presence of significant hydrodynamic mix which aggravates the Knudsen layer effect, the yield recovery largely compensates for the yield reduction. For mix-dominated sub-ignition targets, the yield reduction is the dominant process.

The hot-spot environment of SW Sex in a low state

NASA Astrophysics Data System (ADS)

Groot, Paul J.; Rutten, René G. M.; van Paradijs, Jan

2000-04-01

Based on observations obtained with the 2.5m Isaac Newton Telescope we show that the characteristics of the SW Sex stars can be explained by the dominance of a `hot-spot' like feature in the accretion disk. In SW Sex this `hot-spot' region is located at a distance of 0.5 RL 1 from the white-dwarf and is best visible at phase ϕ=0.95. The location of the hot-spot as deduced from spectral eclipse mapping coincides with the formation site of the main emission lines. We deduce that this hot-spot region is formed by a shock, which we speculate to be the consequence of a high mass-transfer rate and a long spin-period of the non-magnetic white dwarf.

Target and Non-target Site Mechanisms Developed by Glyphosate-Resistant Hairy beggarticks (Bidens pilosa L.) Populations from Mexico

PubMed Central

Alcántara-de la Cruz, Ricardo; Fernández-Moreno, Pablo T.; Ozuna, Carmen V.; Rojano-Delgado, Antonia M.; Cruz-Hipolito, Hugo E.; Domínguez-Valenzuela, José A.; Barro, Francisco; De Prado, Rafael

2016-01-01

In 2014 hairy beggarticks (Bidens pilosa L.) has been identified as being glyphosate-resistant in citrus orchards from Mexico. The target and non-target site mechanisms involved in the response to glyphosate of two resistant populations (R1 and R2) and one susceptible (S) were studied. Experiments of dose-response, shikimic acid accumulation, uptake-translocation, enzyme activity and 5-enolpyruvyl shikimate-3-phosphate synthase (EPSPS) gene sequencing were carried out in each population. The R1 and R2 populations were 20.4 and 2.8-fold less glyphosate sensitive, respectively, than the S population. The resistant populations showed a lesser shikimic acid accumulation than the S population. In the latter one, 24.9% of 14C-glyphosate was translocated to the roots at 96 h after treatment; in the R1 and R2 populations only 12.9 and 15.5%, respectively, was translocated. Qualitative results confirmed the reduced 14C-glyphosate translocation in the resistant populations. The EPSPS enzyme activity of the S population was 128.4 and 8.5-fold higher than the R1 and R2 populations of glyphosate-treated plants, respectively. A single (Pro-106-Ser), and a double (Thr-102-Ile followed by Pro-106-Ser) mutations were identified in the EPSPS2 gene conferred high resistance in R1 population. Target-site mutations associated with a reduced translocation were responsible for the higher glyphosate resistance in the R1 population. The low-intermediate resistance of the R2 population was mediated by reduced translocation. This is the first glyphosate resistance case confirmed in hairy beggarticks in the world. PMID:27752259

The control of hot-electron preheat in shock-ignition implosions

DOE PAGES

Trela, J.; Theobald, W.; Anderson, K. S.; ...

2018-05-22

In the shock-ignition scheme for inertial confinement fusion, hot electrons resulting from laser–plasma instabilities can play a major role during the late stage of the implosion. This article presents the results of an experiment performed on OMEGA in the so-called “40 + 20 configuration.” Using a recent calibration of the time-resolved hard x-ray diagnostic, the hot electrons’ temperature and total energy were measured. One-dimensional radiation–hydrodynamic simulations have been performed that include hot electrons and are in agreement with the measured neutron-rate–averaged areal density. For an early spike launch, both experiment and simulations show the detrimental effect of hot electrons onmore » areal density and neutron yield. Lastly, for a later spike launch, this effect is minimized because of a higher compression of the target.« less

The control of hot-electron preheat in shock-ignition implosions

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

Trela, J.; Theobald, W.; Anderson, K. S.

In the shock-ignition scheme for inertial confinement fusion, hot electrons resulting from laser–plasma instabilities can play a major role during the late stage of the implosion. This article presents the results of an experiment performed on OMEGA in the so-called “40 + 20 configuration.” Using a recent calibration of the time-resolved hard x-ray diagnostic, the hot electrons’ temperature and total energy were measured. One-dimensional radiation–hydrodynamic simulations have been performed that include hot electrons and are in agreement with the measured neutron-rate–averaged areal density. For an early spike launch, both experiment and simulations show the detrimental effect of hot electrons onmore » areal density and neutron yield. For a later spike launch, this effect is minimized because of a higher compression of the target.« less

Opaque-2 is a transcriptional activator that recognizes a specific target site in 22-kD zein genes.

PubMed Central

Schmidt, R J; Ketudat, M; Aukerman, M J; Hoschek, G

1992-01-01

opaque-2 (o2) is a regulatory locus in maize that plays an essential role in controlling the expression of genes encoding the 22-kD zein proteins. Through DNase I footprinting and DNA binding analyses, we have identified the binding site for the O2 protein (O2) in the promoter of 22-kD zein genes. The sequence in the 22-kD zein gene promoter that is recognized by O2 is similar to the target site recognized by other "basic/leucine zipper" (bZIP) proteins in that it contains an ACGT core that is necessary for DNA binding. The site is located in the -300 region relative to the translation start and lies about 20 bp downstream of the highly conserved zein gene sequence motif known as the "prolamin box." Employing gel mobility shift assays, we used O2 antibodies and nuclear extracts from an o2 null mutant to demonstrate that the O2 protein in maize endosperm nuclei recognizes the target site in the zein gene promoter. Mobility shift assays using nuclear proteins from an o2 null mutant indicated that other endosperm proteins in addition to O2 can bind the O2 target site and that O2 may be associated with one of these proteins. We also demonstrated that in yeast cells the O2 protein can activate expression of a lacZ gene containing a multimer of the O2 target sequence as part of its promoter, thus confirming its role as a transcriptional activator. A computer-assisted search indicated that the O2 target site is not present in the promoters of zein genes other than those of the 22-kD class. These data suggest a likely explanation at the molecular level for the differential effect of o2 mutations on expression of certain members of the zein gene family. PMID:1392590

Cre/lox-Recombinase-Mediated Cassette Exchange for Reversible Site-Specific Genomic Targeting of the Disease Vector, Aedes aegypti.

PubMed

Häcker, Irina; Harrell Ii, Robert A; Eichner, Gerrit; Pilitt, Kristina L; O'Brochta, David A; Handler, Alfred M; Schetelig, Marc F

2017-03-07

Site-specific genome modification (SSM) is an important tool for mosquito functional genomics and comparative gene expression studies, which contribute to a better understanding of mosquito biology and are thus a key to finding new strategies to eliminate vector-borne diseases. Moreover, it allows for the creation of advanced transgenic strains for vector control programs. SSM circumvents the drawbacks of transposon-mediated transgenesis, where random transgene integration into the host genome results in insertional mutagenesis and variable position effects. We applied the Cre/lox recombinase-mediated cassette exchange (RMCE) system to Aedes aegypti, the vector of dengue, chikungunya, and Zika viruses. In this context we created four target site lines for RMCE and evaluated their fitness costs. Cre-RMCE is functional in a two-step mechanism and with good efficiency in Ae. aegypti. The advantages of Cre-RMCE over existing site-specific modification systems for Ae. aegypti, phiC31-RMCE and CRISPR, originate in the preservation of the recombination sites, which 1) allows successive modifications and rapid expansion or adaptation of existing systems by repeated targeting of the same site; and 2) provides reversibility, thus allowing the excision of undesired sequences. Thereby, Cre-RMCE complements existing genomic modification tools, adding flexibility and versatility to vector genome targeting.

APPLICATIONS ANALYSIS REPORT: TOXIC TREATMENTS, IN-SITU STEAM/HOT-AIR STRIPPING TECHNOLOGY

EPA Science Inventory

This document is an evaluation of the performance of the Toxic Treatments (USA), Inc., (TTUSA) in situ steam/hot-air stripping technology and its applicability as an on-site treatment technique for hazardous waste site soil cleanup of volatile and semivolatile contaminants. Both ...

Self-Reported Benefits and Adverse Outcomes of Hot Yoga Participation.

PubMed

Mace, Casey; Eggleston, Brandon

2016-01-01

There is little to no scientific data about the health benefits or risks to participating in hot yoga, in particular distinguishing it from the practice of non-hot yoga. This study aims to provide some preliminary evidence about the risks and benefits of participating in hot yoga. Future studies will be able to build off the findings herein. This study utilized online survey software (Qualtrics) and recruited participants through convenience sampling (n = 157) by targeting yoga websites and online forums. As there is currently no known questionnaire that has been developed to assess the risks and benefits of hot yoga participation, an exploratory measure was designed to gain more detailed responses from participants. Descriptive epidemiological analyses we re conducted. Participants of hot yoga had a number of pre-existing health conditions. Both benefits and adverse outcomes were reported. The most frequently reported health benefits of hot yoga in this sample included increased flexibility (63%), improved mood (58%), increased fitness (43%), and improved stamina (42%). Just over half of the participants reported some sort of adverse event during a hot yoga session (n = 82). The most commonly reported adverse events included dizziness (60%), feeling light headed (61%), nausea (35%), and dehydration (34%), amongst others. Further study on the risks and benefits of hot yoga participation is required.

Self-Reported Benefits and Adverse Outcomes of Hot Yoga Participation.

PubMed

Mace, Casey; Eggleston, Brandon

2016-08-15

There is little to no scientific data about the health benefits or risks to participating in hot yoga, in particular distinguishing it from the practice of non-hot yoga. This study aims to provide some preliminary evidence about the risks and benefits of participating in hot yoga. Future studies will be able to build off the findings herein. This study utilized online survey software (Qualtrics) and recruited participants through convenience sampling (n = 157) by targeting yoga websites and online forums. As there is currently no known questionnaire that has been developed to assess the risks and benefits of hot yoga participation, an exploratory measure was designed to gain more detailed responses from participants. Descriptive epidemiological analyses we re conducted. Participants of hot yoga had a number of pre-existing health conditions. Both benefits and adverse outcomes were reported. The most frequently reported health benefits of hot yoga in this sample included increased flexibility (63%), improved mood (58%), increased fitness (43%), and improved stamina (42%). Just over half of the participants reported some sort of adverse event during a hot yoga session (n = 82). The most commonly reported adverse events included dizziness (60%), feeling light headed (61%), nausea (35%), and dehydration (34%), amongst others. Further study on the risks and benefits of hot yoga participation is required.

Hot Mix Asphalt for Intersections in Hot Climates

DOT National Transportation Integrated Search

1998-03-01

Rutting of hot mix asphalt (HMA) pavement at or near intersections is very common both in cold and hot climates. Obviously, the problem is more acute in hot climates compared to cold climates because the stiffness of HMA decreases with increase in pa...

Geothermal Target Areas in Colorado as Identified by Remote Sensing Techniques

DOE Data Explorer

Khalid Hussein

2012-02-01

This layer contains the areas identified as targets of potential geothermal activity. The Criteria used to identify the target areas include: hot/warm surface exposures modeled from ASTER/Landsat satellite imagery and geological characteristics, alteration mineral commonly associated with hot springs (clays, Si, and FeOx) modeled from ASTER and Landsat data, Colorado Geological Survey (CGS) known thermal hot springs/wells and heat-flow data points, Colorado deep-seated fault zones, weakened basement identified from isostatic gravity data, and Colorado sedimentary and topographic characteristics.

Computational study of hot electron generation and energy transport in intense laser produced hot dense matter

NASA Astrophysics Data System (ADS)

Mishra, Rohini

Present ultra high power lasers are capable of producing high energy density (HED) plasmas, in controlled way, with a density greater than solid density and at a high temperature of keV (1 keV ˜ 11,000,000° K). Matter in such extreme states is particularly interesting for (HED) physics such as laboratory studies of planetary and stellar astrophysics, laser fusion research, pulsed neutron source etc. To date however, the physics in HED plasma, especially, the energy transport, which is crucial to realize applications, has not been understood well. Intense laser produced plasmas are complex systems involving two widely distinct temperature distributions and are difficult to model by a single approach. Both kinetic and collisional process are equally important to understand an entire process of laser-solid interaction. By implementing atomic physics models, such as collision, ionization, and radiation damping, self consistently, in state-of-the-art particle-in-cell code (PICLS) has enabled to explore the physics involved in the HED plasmas. Laser absorption, hot electron transport, and isochoric heating physics in laser produced hot dense plasmas are studied with a help of PICLS simulations. In particular, a novel mode of electron acceleration, namely DC-ponderomotive acceleration, is identified in the super intense laser regime which plays an important role in the coupling of laser energy to a dense plasma. Geometric effects on hot electron transport and target heating processes are examined in the reduced mass target experiments. Further, pertinent to fast ignition, laser accelerated fast electron divergence and transport in the experiments using warm dense matter (low temperature plasma) is characterized and explained.

Hot Flashes

MedlinePlus

... report menopausal hot flashes than do women of European descent. Hot flashes are less common in women of Japanese and Chinese descent than in white European women. Complications Nighttime hot flashes (night sweats) can ...

The evolutionary turnover of recombination hot spots contributes to speciation in mice

PubMed Central

Smagulova, Fatima; Brick, Kevin; Pu, Yongmei; Camerini-Otero, R. Daniel; Petukhova, Galina V.

2016-01-01

Meiotic recombination is required for the segregation of homologous chromosomes and is essential for fertility. In most mammals, the DNA double-strand breaks (DSBs) that initiate meiotic recombination are directed to a subset of genomic loci (hot spots) by sequence-specific binding of the PRDM9 protein. Rapid evolution of the DNA-binding specificity of PRDM9 and gradual erosion of PRDM9-binding sites by gene conversion will alter the recombination landscape over time. To better understand the evolutionary turnover of recombination hot spots and its consequences, we mapped DSB hot spots in four major subspecies of Mus musculus with different Prdm9 alleles and in their F1 hybrids. We found that hot spot erosion governs the preferential usage of some Prdm9 alleles over others in hybrid mice and increases sequence diversity specifically at hot spots that become active in the hybrids. As crossovers are disfavored at such hot spots, we propose that sequence divergence generated by hot spot turnover may create an impediment for recombination in hybrids, potentially leading to reduced fertility and, eventually, speciation. PMID:26833728

6. HOT AIR PORTION OF DAMPERS. Hot Springs National ...

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

6. HOT AIR PORTION OF DAMPERS. - Hot Springs National Park, Bathhouse Row, Lamar Bathhouse: Mechanical & Piping Systems, State Highway 7, 1 mile north of U.S. Highway 70, Hot Springs, Garland County, AR

"Hot spots" growth on single nanowire controlled by electric charge.

PubMed

Xi, Shaobo; Liu, Xuehua; He, Ting; Tian, Lei; Wang, Wenhui; Sun, Rui; He, Weina; Zhang, Xuetong; Zhang, Jinping; Ni, Weihai; Zhou, Xiaochun

2016-06-09

"Hot spots" - a kind of highly active site, which are usually composed of some unique units, such as defects, interfaces, catalyst particles or special structures - can determine the performance of nanomaterials. In this paper, we study a model system, i.e. "hot spots" on a single Ag nanowire in the galvanic replacement reaction (GRR), by dark-field microscopy. The research reveals that electric charge can be released by the formation reaction of AgCl, and consequently the electrochemical potential on Ag nanowire drops. The electric charge could induce the reduction of Ag(+) to form the "hot spots" on the nanowire during the GRR. The appearance probability of "hot spots" is almost even along the Ag nanowire, while it is slightly lower near the two ends. The spatial distance between adjacent "hot spots" is also controlled by the charge, and obeys a model based on Boltzmann distribution. In addition, the distance distribution here has an advantage in electron transfer and energy saving. Therefore, it's necessary to consider the functions of electric charge during the synthesis or application of nanomaterials.

The Hot Horizontal-Branch Stars in omega Centauri

NASA Technical Reports Server (NTRS)

Moehler, S.; Dreizler, S.; Lanz, T.; Bono, G.; Sweigart, A. V.; Calamida, A.; Nonino, M.

2010-01-01

Context. UV observations of some massive globular clusters have revealed a significant population of stars hotter and fainter than the hot end of the horizontal branch (HB), the so-called blue hook stars. This feature might be explained either by the late hot flasher scenario where stars experience the helium flash while on the white dwarf cooling curve or by the progeny of the helium-enriched sub-population recently postulated to exist in some clusters. Previous spectroscopic analyses of blue hook stars in co Cen and NGC 2808 support the late hot flasher scenario, but the stars contain much less helium than expected and the predicted C, N enrichment could not be verified. Aims. We compare observed effective temperatures, surface gravities, helium abundances, and carbon line strengths (where detectable) of our targets stars to the predictions of the two scenarios. Methods. Moderately high resolution spectra of hot HB stars in the globular cluster omega-Cen were analysed for radial velocity variations, atmospheric parameters and abundances using LTE and non-LTE model atmospheres. Results. We find no evidence for close binaries among our target stars. All stars below 30 000 K are helium-poor and very similar to HB stars observed in that temperature range in other globular clusters. In the temperature range 30000 K to 50000 K we find that 28% of our stars are helium-poor (log ((sup n)He/(sup n )H)< - 1.6), while 72% have roughly solar or super-solar helium abundance (log ((sup n)He/(sup n )H) >/= -1.5). We also find carbon enrichment strongly correlated with helium enrichment, with a maximum carbon enrichment of 3% by mass. Conclusions. The strong carbon enrichment in tandem with helium enrichment is predicted by the late hot flasher scenario, but not by the helium-enrichment scenario. We conclude that the helium-rich HB stars in omega-Cen cannot be explained solely by the helium-enrichment scenario invoked to explain the blue main sequence.

Aryl-substituted aminobenzimidazoles targeting the hepatitis C virus internal ribosome entry site

PubMed Central

Ding, Kejia; Wang, Annie; Boerneke, Mark A.; Dibrov, Sergey M.; Hermann, Thomas

2014-01-01

We describe the exploration of N1-aryl-substituted benzimidazoles as ligands for the hepatitis C virus (HCV) internal ribosome entry site (IRES) RNA. The design of the compounds was guided by the co-crystal structure of a benzimidazole viral translation inhibitor in complex with the RNA target. Structure-binding activity relationships of aryl-substituted benzimidazole ligands were established that were consistent with the crystal structure of the translation inhibitor complex. PMID:24856063

Visualizing multiple inter-organelle contact sites using the organelle-targeted split-GFP system.

PubMed

Kakimoto, Yuriko; Tashiro, Shinya; Kojima, Rieko; Morozumi, Yuki; Endo, Toshiya; Tamura, Yasushi

2018-04-18

Functional integrity of eukaryotic organelles relies on direct physical contacts between distinct organelles. However, the entity of organelle-tethering factors is not well understood due to lack of means to analyze inter-organelle interactions in living cells. Here we evaluate the split-GFP system for visualizing organelle contact sites in vivo and show its advantages and disadvantages. We observed punctate GFP signals from the split-GFP fragments targeted to any pairs of organelles among the ER, mitochondria, peroxisomes, vacuole and lipid droplets in yeast cells, which suggests that these organelles form contact sites with multiple organelles simultaneously although it is difficult to rule out the possibilities that these organelle contacts sites are artificially formed by the irreversible associations of the split-GFP probes. Importantly, split-GFP signals in the overlapped regions of the ER and mitochondria were mainly co-localized with ERMES, an authentic ER-mitochondria tethering structure, suggesting that split-GFP assembly depends on the preexisting inter-organelle contact sites. We also confirmed that the split-GFP system can be applied to detection of the ER-mitochondria contact sites in HeLa cells. We thus propose that the split-GFP system is a potential tool to observe and analyze inter-organelle contact sites in living yeast and mammalian cells.

Kappa Agonists as a Novel Therapy for Menopausal Hot Flashes

PubMed Central

Oakley, Amy E.; Steiner, Robert A.; Chavkin, Charles; Clifton, Donald K.; Ferrara, Laura K.; Reed, Susan D.

2015-01-01

Objective Postmenopausal hot flash etiology is poorly understood, making it difficult to develop and target ideal therapies. A network of hypothalamic estrogen-sensitive neurons producing Kisspeptin, Neurokinin B, and Dynorphin (KNDy neurons), located adjacent to the thermoregulatory center, regulate pulsatile secretion of GnRH and LH. Dynorphin may inhibit this system by binding kappa opioid receptors within the vicinity of KNDy neurons. We hypothesize that hot flashes are reduced by KNDy neuron manipulation. Methods A double-blind, cross-over, placebo-controlled pilot study evaluated the effect of a kappa agonist (KA).Hot flash frequency was the primary outcome. Twelve healthy postmenopausal women with moderate-severe hot flashes, ages 48-60 years, were randomized. Eight women with sufficient baseline hot flashes for statistical analysis completed all 3 interventions: placebo, standard Pentazocine/Naloxone (50/0.5 mg) or low-dose Pentazocine/Naloxone (25/0.25 mg). In an inpatient research setting, each participant received the 3 interventions, in randomized order, on 3 separate days. On each day, an intravenous catheter was inserted for luteinizing hormone (LH) blood sampling, and skin conductance and Holter monitors were placed. Subjective hot flash frequency and severity were recorded. Results Mean hot flash frequency 2-7 hours following therapy initiation was lower than that for placebo (KA standard-dose: 4.75 ± 0.67; KA low-dose: 4.50 ± 0.57; and placebo: 5.94 ± 0.78 hot flashes/5 hours; p =0.025). Hot flash intensity did not vary between interventions. LH pulsatility mirrored objective hot flashes in some, but not all women. Conclusions This pilot suggests that kappa agonists may affect menopausal vasomotor symptoms. PMID:25988798

Binding site and affinity prediction of general anesthetics to protein targets using docking.

PubMed

Liu, Renyu; Perez-Aguilar, Jose Manuel; Liang, David; Saven, Jeffery G

2012-05-01

The protein targets for general anesthetics remain unclear. A tool to predict anesthetic binding for potential binding targets is needed. In this study, we explored whether a computational method, AutoDock, could serve as such a tool. High-resolution crystal data of water-soluble proteins (cytochrome C, apoferritin, and human serum albumin), and a membrane protein (a pentameric ligand-gated ion channel from Gloeobacter violaceus [GLIC]) were used. Isothermal titration calorimetry (ITC) experiments were performed to determine anesthetic affinity in solution conditions for apoferritin. Docking calculations were performed using DockingServer with the Lamarckian genetic algorithm and the Solis and Wets local search method (http://www.dockingserver.com/web). Twenty general anesthetics were docked into apoferritin. The predicted binding constants were compared with those obtained from ITC experiments for potential correlations. In the case of apoferritin, details of the binding site and their interactions were compared with recent cocrystallization data. Docking calculations for 6 general anesthetics currently used in clinical settings (isoflurane, sevoflurane, desflurane, halothane, propofol, and etomidate) with known 50% effective concentration (EC(50)) values were also performed in all tested proteins. The binding constants derived from docking experiments were compared with known EC(50) values and octanol/water partition coefficients for the 6 general anesthetics. All 20 general anesthetics docked unambiguously into the anesthetic binding site identified in the crystal structure of apoferritin. The binding constants for 20 anesthetics obtained from the docking calculations correlate significantly with those obtained from ITC experiments (P = 0.04). In the case of GLIC, the identified anesthetic binding sites in the crystal structure are among the docking predicted binding sites, but not the top ranked site. Docking calculations suggest a most probable binding site

Binding Site and Affinity Prediction of General Anesthetics to Protein Targets Using Docking

PubMed Central

Liu, Renyu; Perez-Aguilar, Jose Manuel; Liang, David; Saven, Jeffery G.

2012-01-01

Background The protein targets for general anesthetics remain unclear. A tool to predict anesthetic binding for potential binding targets is needed. In this study, we explore whether a computational method, AutoDock, could serve as such a tool. Methods High-resolution crystal data of water soluble proteins (cytochrome C, apoferritin and human serum albumin), and a membrane protein (a pentameric ligand-gated ion channel from Gloeobacter violaceus, GLIC) were used. Isothermal titration calorimetry (ITC) experiments were performed to determine anesthetic affinity in solution conditions for apoferritin. Docking calculations were performed using DockingServer with the Lamarckian genetic algorithm and the Solis and Wets local search method (https://www.dockingserver.com/web). Twenty general anesthetics were docked into apoferritin. The predicted binding constants are compared with those obtained from ITC experiments for potential correlations. In the case of apoferritin, details of the binding site and their interactions were compared with recent co-crystallization data. Docking calculations for six general anesthetics currently used in clinical settings (isoflurane, sevoflurane, desflurane, halothane, propofol, and etomidate) with known EC50 were also performed in all tested proteins. The binding constants derived from docking experiments were compared with known EC50s and octanol/water partition coefficients for the six general anesthetics. Results All 20 general anesthetics docked unambiguously into the anesthetic binding site identified in the crystal structure of apoferritin. The binding constants for 20 anesthetics obtained from the docking calculations correlate significantly with those obtained from ITC experiments (p=0.04). In the case of GLIC, the identified anesthetic binding sites in the crystal structure are among the docking predicted binding sites, but not the top ranked site. Docking calculations suggest a most probable binding site located in the

Drug 'hot-spots', alcohol availability and violence.

PubMed

Gorman, D M; Zhu, Li; Horel, Scott

2005-11-01

Ecological studies have shown a relationship between alcohol outlet densities and violence and between the location of crimes related to illicit drug use (so-called 'hot spots') and violence. To date, no study has compared the effects of alcohol outlets and drug hot spots on rates of violence. The present study examined this relationship in the City of Houston, Texas. An ecological study design was employed, using a sample of 439 census tracts from Houston, Texas. Neighborhood socio-structural, alcohol outlet density, drug crime density and violent crime density data were collected from archival sources and analyzed using multivariate and spatial statistics. Using ordinary least-squares analysis, the neighborhood socio-structural covariates explained about 40% of the variability in violent crime. Adding alcohol outlet density in the target census tracts explained an additional 6%, while the addition of drug crime density explained an additional 32%. In the final model, that controlled for the effects of autocorrelated error, both drug crime density in the target and adjacent census tracts remained significant predictors of violent crime, while only off-sale density in the target census tract remained significant in the model. The findings indicate that drug crime density explained a greater amount of variance in violent crime rates than the alcohol outlet density. The methodological and policy implications of these findings are discussed, along with the shortcomings of the analysis presented.

5. VIEW TO THE SOUTHEAST OF THE HOT BAY AND ...

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

5. VIEW TO THE SOUTHEAST OF THE HOT BAY AND ATTACHED OPERATING GALLERIES ALONG THE WEST SIDE OF THE BAY. - Nevada Test Site, Engine Maintenance Assembly & Disassembly Facility, Area 25, Jackass Flats, Mercury, Nye County, NV

Creep fatigue life prediction for engine hot section materials (isotropic)

NASA Technical Reports Server (NTRS)

Moreno, V.

1983-01-01

The Hot Section Technology (HOST) program, creep fatigue life prediction for engine hot section materials (isotropic), is reviewed. The program is aimed at improving the high temperature crack initiation life prediction technology for gas turbine hot section components. Significant results include: (1) cast B1900 and wrought IN 718 selected as the base and alternative materials respectively; (2) fatigue test specimens indicated that measurable surface cracks appear early in the specimen lives, i.e., 15% of total life at 871 C and 50% of life at 538 c; (3) observed crack initiation sites are all surface initiated and are associated with either grain boundary carbides or local porosity, transgrannular cracking is observed at the initiation site for all conditions tested; and (4) an initial evaluation of two life prediction models, representative of macroscopic (Coffin-Mason) and more microscopic (damage rate) approaches, was conducted using limited data generated at 871 C and 538 C. It is found that the microscopic approach provides a more accurate regression of the data used to determine crack initiation model constants, but overpredicts the effect of strain rate on crack initiation life for the conditions tested.

Lessons from hot spot analysis for fragment-based drug discovery

PubMed Central

Hall, David R.; Vajda, Sandor

2015-01-01

Analysis of binding energy hot spots at protein surfaces can provide crucial insights into the prospects for successful application of fragment-based drug discovery (FBDD), and whether a fragment hit can be advanced into a high affinity, druglike ligand. The key factor is the strength of the top ranking hot spot, and how well a given fragment complements it. We show that published data are sufficient to provide a sophisticated and quantitative understanding of how hot spots derive from protein three-dimensional structure, and how their strength, number and spatial arrangement govern the potential for a surface site to bind to fragment-sized and larger ligands. This improved understanding provides important guidance for the effective application of FBDD in drug discovery. PMID:26538314

LuciPHOr: Algorithm for Phosphorylation Site Localization with False Localization Rate Estimation Using Modified Target-Decoy Approach*

PubMed Central

Fermin, Damian; Walmsley, Scott J.; Gingras, Anne-Claude; Choi, Hyungwon; Nesvizhskii, Alexey I.

2013-01-01

The localization of phosphorylation sites in peptide sequences is a challenging problem in large-scale phosphoproteomics analysis. The intense neutral loss peaks and the coexistence of multiple serine/threonine and/or tyrosine residues are limiting factors for objectively scoring site patterns across thousands of peptides. Various computational approaches for phosphorylation site localization have been proposed, including Ascore, Mascot Delta score, and ProteinProspector, yet few address direct estimation of the false localization rate (FLR) in each experiment. Here we propose LuciPHOr, a modified target-decoy-based approach that uses mass accuracy and peak intensities for site localization scoring and FLR estimation. Accurate estimation of the FLR is a difficult task at the individual-site level because the degree of uncertainty in localization varies significantly across different peptides. LuciPHOr carries out simultaneous localization on all candidate sites in each peptide and estimates the FLR based on the target-decoy framework, where decoy phosphopeptides generated by placing artificial phosphorylation(s) on non-candidate residues compete with the non-decoy phosphopeptides. LuciPHOr also reports approximate site-level confidence scores for all candidate sites as a means to localize additional sites from multiphosphorylated peptides in which localization can be partially achieved. Unlike the existing tools, LuciPHOr is compatible with any search engine output processed through the Trans-Proteomic Pipeline. We evaluated the performance of LuciPHOr in terms of the sensitivity and accuracy of FLR estimates using two synthetic phosphopeptide libraries and a phosphoproteomic dataset generated from complex mouse brain samples. PMID:23918812

Contributions of Hot and Cool Self-Regulation to Preschool Disruptive Behavior and Academic Achievement

PubMed Central

Willoughby, Michael; Kupersmidt, Janis; Voegler-Lee, Mare; Bryant, Donna

2017-01-01

The construct of self-regulation can be meaningfully distinguished into hot and cool components. The current study investigated self-regulation in a sample of 926 children aged 3–5 years old. Children’s performance on self-regulatory tasks was best described by two latent factors representing hot and cool regulation. When considered alone, hot and cool regulation were both significantly correlated with disruptive behavior and academic achievement. When considered together, cool regulation was uniquely associated with academic achievement, while hot regulation was uniquely associated with inattentive-overactive behaviors. Results are discussed with respect to treatment studies that directly target improvement in children’s self-regulation. PMID:21347919

Site-Specific Targeting of Platelet-Rich Plasma via Superparamagnetic Nanoparticles

PubMed Central

Talaie, Tara; Pratt, Stephen J.P.; Vanegas, Camilo; Xu, Su; Henn, R. Frank; Yarowsky, Paul; Lovering, Richard M.

2015-01-01

Background: Muscle strains are one of the most common injuries treated by physicians. Standard conservative therapy for acute muscle strains usually involves short-term rest, ice, and nonsteroidal anti-inflammatory medications, but there is no clear consensus regarding treatments to accelerate recovery. Recently, clinical use of platelet-rich plasma (PRP) has gained momentum as an option for therapy and is appealing for many reasons, most notably because it provides growth factors in physiological proportions and it is autologous, safe, easily accessible, and potentially beneficial. Local delivery of PRP to injured muscles can hasten recovery of function. However, specific targeting of PRP to sites of tissue damage in vivo is a major challenge that can limit its efficacy. Hypothesis: Location of PRP delivery can be monitored and controlled in vivo with noninvasive tools. Study Design: Controlled laboratory study. Methods: Superparamagnetic iron oxide nanoparticles (SPIONs) can be visualized by both magnetic resonance imaging (MRI) (in vivo) and fluorescence microscopy (after tissue harvesting). PRP was labeled with SPIONs and administered by intramuscular injections of SPION-containing platelets. MRI was used to monitor the ability to manipulate and retain the location of PRP in vivo by placement of an external magnet. Platelets were isolated from whole blood and incubated with SPIONs. Following SPION incubation with PRP, a magnetic field was used to manipulate platelet location in culture dishes. In vivo, the tibialis anterior (TA) muscles of anesthetized Sprague-Dawley rats were injected with SPION-containing platelets, and MRI was used to track platelet position with and without a magnet worn over the TA muscles for 4 days. Results: The method used to isolate PRP yielded a high concentration (almost 4-fold increase) of platelets. In vitro experiments showed that the platelets successfully took up SPIONs and then rapidly responded to an applied magnetic field

Five-city economics of a solar hot-water-system

NASA Technical Reports Server (NTRS)

1981-01-01

Report projects energy savings and system costs for five sites using analysis of actual solar energy installation performance in Togus, Maine. Maine system supplies 75 percent of hot water needed for single-family residence; economic payback period is 19 years. Benefits for all sites depend on maintenance or decrease of initial investment required and continuing increase in cost of conventional energy. Report includes analysis weighing potential changes in variables used to evaluate system profitability.

Site-targeted mutagenesis for stabilization of recombinant monoclonal antibody expressed in tobacco (Nicotiana tabacum) plants

PubMed Central

Hehle, Verena K.; Paul, Matthew J.; Roberts, Victoria A.; van Dolleweerd, Craig J.; Ma, Julian K.-C.

2016-01-01

This study examined the degradation pattern of a murine IgG1κ monoclonal antibody expressed in and extracted from transformed Nicotiana tabacum. Gel electrophoresis of leaf extracts revealed a consistent pattern of recombinant immunoglobulin bands, including intact and full-length antibody, as well as smaller antibody fragments. N-terminal sequencing revealed these smaller fragments to be proteolytic cleavage products and identified a limited number of protease-sensitive sites in the antibody light and heavy chain sequences. No strictly conserved target sequence was evident, although the peptide bonds that were susceptible to proteolysis were predominantly and consistently located within or near to the interdomain or solvent-exposed regions in the antibody structure. Amino acids surrounding identified cleavage sites were mutated in an attempt to increase resistance. Different Guy’s 13 antibody heavy and light chain mutant combinations were expressed transiently in N. tabacum and demonstrated intensity shifts in the fragmentation pattern, resulting in alterations to the full-length antibody-to-fragment ratio. The work strengthens the understanding of proteolytic cleavage of antibodies expressed in plants and presents a novel approach to stabilize full-length antibody by site-directed mutagenesis.—Hehle, V. K., Paul, M. J., Roberts, V. A., van Dolleweerd, C. J., Ma, J. K.-C. Site-targeted mutagenesis for stabilization of recombinant monoclonal antibody expressed in tobacco (Nicotiana tabacum) plants. PMID:26712217

Hypnosis for Hot Flashes and Associated Symptomsin Women with Breast Cancer.

PubMed

Roberts, R Lynae; Na, Hyeji; Yek, Ming Hwei; Elkins, Gary

2017-10-01

Women with breast cancer experience a host of physical and psychological symptoms, including hot flashes, sleep difficulties, anxiety, and depression. Therefore, treatment for women with breast cancer should target these symptoms and be individualized to patients' specific presentations. The current article reviews the common symptoms associated with breast cancer in women, then examines clinical hypnosis as a treatment for addressing these symptoms and improving the quality of life of women with breast cancer. Clinical hypnosis is an effective, nonpharmaceutical treatment for hot flashes and addressing many symptoms typically experienced by breast cancer patients. A case example is provided to illustrate the use of clinical hypnosis for the treatment of hot flashes with a patient with breast cancer.

Cooperation between a hierarchical set of recruitment sites targets the X chromosome for dosage compensation

PubMed Central

Albritton, Sarah Elizabeth; Kranz, Anna-Lena; Winterkorn, Lara Heermans; Street, Lena Annika; Ercan, Sevinc

2017-01-01

In many organisms, it remains unclear how X chromosomes are specified for dosage compensation, since DNA sequence motifs shown to be important for dosage compensation complex (DCC) recruitment are themselves not X-specific. Here, we addressed this problem in C. elegans. We found that the DCC recruiter, SDC-2, is required to maintain open chromatin at a small number of primary DCC recruitment sites, whose sequence and genomic context are X-specific. Along the X, primary recruitment sites are interspersed with secondary sites, whose function is X-dependent. A secondary site can ectopically recruit the DCC when additional recruitment sites are inserted either in tandem or at a distance (>30 kb). Deletion of a recruitment site on the X results in reduced DCC binding across several megabases surrounded by topologically associating domain (TAD) boundaries. Our work elucidates that hierarchy and long-distance cooperativity between gene-regulatory elements target a single chromosome for regulation. DOI: http://dx.doi.org/10.7554/eLife.23645.001 PMID:28562241

Comprehensive Experimental and Computational Analysis of Binding Energy Hot Spots at the NF-κB Essential Modulator (NEMO)/IKKβ Protein-Protein Interface

PubMed Central

Golden, Mary S.; Cote, Shaun M.; Sayeg, Marianna; Zerbe, Brandon S.; Villar, Elizabeth A.; Beglov, Dmitri; Sazinsky, Stephen L.; Georgiadis, Rosina M.; Vajda, Sandor; Kozakov, Dima; Whitty, Adrian

2013-01-01

We report a comprehensive analysis of binding energy hot spots at the protein-protein interaction (PPI) interface between NF-κB Essential Modulator (NEMO) and IκB kinase subunit β (IKKβ), an interaction that is critical for NF-κB pathway signaling, using experimental alanine scanning mutagenesis and also the FTMap method for computational fragment screening. The experimental results confirm that the previously identified NBD region of IKKβ contains the highest concentration of hot spot residues, the strongest of which are W739, W741 and L742 (ΔΔG = 4.3, 3.5 and 3.2 kcal/mol, respectively). The region occupied by these residues defines a potentially druggable binding site on NEMO that extends for ~16 Å to additionally include the regions that bind IKKβ L737 and F734. NBD residues D738 and S740 are also important for binding but do not make direct contact with NEMO, instead likely acting to stabilize the active conformation of surrounding residues. We additionally found two previously unknown hot spot regions centered on IKKβ residues L708/V709 and L719/I723. The computational approach successfully identified all three hot spot regions on IKKβ. Moreover, the method was able to accurately quantify the energetic importance of all hot spots residues involving direct contact with NEMO. Our results provide new information to guide the discovery of small molecule inhibitors that target the NEMO/IKKβ interaction. They additionally clarify the structural and energetic complementarity between “pocket-forming” and “pocket occupying” hot spot residues, and further validate computational fragment mapping as a method for identifying hot spots at PPI interfaces. PMID:23506214

Examination of CRISPR/Cas9 design tools and the effect of target site accessibility on Cas9 activity.

PubMed

Lee, Ciaran M; Davis, Timothy H; Bao, Gang

2018-04-01

What is the topic of this review? In this review, we analyse the performance of recently described tools for CRISPR/Cas9 guide RNA design, in particular, design tools that predict CRISPR/Cas9 activity. What advances does it highlight? Recently, many tools designed to predict CRISPR/Cas9 activity have been reported. However, the majority of these tools lack experimental validation. Our analyses indicate that these tools have poor predictive power. Our preliminary results suggest that target site accessibility should be considered in order to develop better guide RNA design tools with improved predictive power. The recent adaptation of the clustered regulatory interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9 (Cas9) system for targeted genome engineering has led to its widespread application in many fields worldwide. In order to gain a better understanding of the design rules of CRISPR/Cas9 systems, several groups have carried out large library-based screens leading to some insight into sequence preferences among highly active target sites. To facilitate CRISPR/Cas9 design, these studies have spawned a plethora of guide RNA (gRNA) design tools with algorithms based solely on direct or indirect sequence features. Here, we demonstrate that the predictive power of these tools is poor, suggesting that sequence features alone cannot accurately inform the cutting efficiency of a particular CRISPR/Cas9 gRNA design. Furthermore, we demonstrate that DNA target site accessibility influences the activity of CRISPR/Cas9. With further optimization, we hypothesize that it will be possible to increase the predictive power of gRNA design tools by including both sequence and target site accessibility metrics. © 2017 The Authors. Experimental Physiology © 2017 The Physiological Society.

SUMOylation target sites at the C terminus protect Axin from ubiquitination and confer protein stability

PubMed Central

Kim, Min Jung; Chia, Ian V.; Costantini, Frank

2008-01-01

Axin is a scaffold protein for the β-catenin destruction complex, and a negative regulator of canonical Wnt signaling. Previous studies implicated the six C-terminal amino acids (C6 motif) in the ability of Axin to activate c-Jun N-terminal kinase, and identified them as a SUMOylation target. Deletion of the C6 motif of mouse Axin in vivo reduced the steady-state protein level, which caused embryonic lethality. Here, we report that this deletion (Axin-ΔC6) causes a reduced half-life in mouse embryonic fibroblasts and an increased susceptibility to ubiquitination in HEK 293T cells. We confirmed the C6 motif as a SUMOylation target in vitro, and found that mutating the C-terminal SUMOylation target residues increased the susceptibility of Axin to polyubiquitination and reduced its steady-state level. Heterologous SUMOylation target sites could replace C6 in providing this protective effect. These findings suggest that SUMOylation of the C6 motif may prevent polyubiquitination, thus increasing the stability of Axin. Although C6 deletion also caused increased association of Axin with Dvl-1, this interaction was not altered by mutating the lysine residues in C6, nor could heterologous SUMOylation motifs replace the C6 motif in this assay. Therefore, some other specific property of the C6 motif seems to reduce the interaction of Axin with Dvl-1.—Kim, M. J., Chia, I. V., Costantini, F. SUMOylation target sites at the C terminus protect Axin from ubiquitination and confer protein stability. PMID:18632848

Site-Specific Integration of Foreign DNA into Minimal Bacterial and Human Target Sequences Mediated by a Conjugative Relaxase

PubMed Central

Agúndez, Leticia; González-Prieto, Coral; Machón, Cristina; Llosa, Matxalen

2012-01-01

Background Bacterial conjugation is a mechanism for horizontal DNA transfer between bacteria which requires cell to cell contact, usually mediated by self-transmissible plasmids. A protein known as relaxase is responsible for the processing of DNA during bacterial conjugation. TrwC, the relaxase of conjugative plasmid R388, is also able to catalyze site-specific integration of the transferred DNA into a copy of its target, the origin of transfer (oriT), present in a recipient plasmid. This reaction confers TrwC a high biotechnological potential as a tool for genomic engineering. Methodology/Principal Findings We have characterized this reaction by conjugal mobilization of a suicide plasmid to a recipient cell with an oriT-containing plasmid, selecting for the cointegrates. Proteins TrwA and IHF enhanced integration frequency. TrwC could also catalyze integration when it is expressed from the recipient cell. Both Y18 and Y26 catalytic tyrosil residues were essential to perform the reaction, while TrwC DNA helicase activity was dispensable. The target DNA could be reduced to 17 bp encompassing TrwC nicking and binding sites. Two human genomic sequences resembling the 17 bp segment were accepted as targets for TrwC-mediated site-specific integration. TrwC could also integrate the incoming DNA molecule into an oriT copy present in the recipient chromosome. Conclusions/Significance The results support a model for TrwC-mediated site-specific integration. This reaction may allow R388 to integrate into the genome of non-permissive hosts upon conjugative transfer. Also, the ability to act on target sequences present in the human genome underscores the biotechnological potential of conjugative relaxase TrwC as a site-specific integrase for genomic modification of human cells. PMID:22292089

Comparative Metagenomics of Eight Geographically Remote Terrestrial Hot Springs.

PubMed

Menzel, Peter; Gudbergsdóttir, Sóley Ruth; Rike, Anne Gunn; Lin, Lianbing; Zhang, Qi; Contursi, Patrizia; Moracci, Marco; Kristjansson, Jakob K; Bolduc, Benjamin; Gavrilov, Sergey; Ravin, Nikolai; Mardanov, Andrey; Bonch-Osmolovskaya, Elizaveta; Young, Mark; Krogh, Anders; Peng, Xu

2015-08-01

Hot springs are natural habitats for thermophilic Archaea and Bacteria. In this paper, we present the metagenomic analysis of eight globally distributed terrestrial hot springs from China, Iceland, Italy, Russia, and the USA with a temperature range between 61 and 92 (∘)C and pH between 1.8 and 7. A comparison of the biodiversity and community composition generally showed a decrease in biodiversity with increasing temperature and decreasing pH. Another important factor shaping microbial diversity of the studied sites was the abundance of organic substrates. Several species of the Crenarchaeal order Thermoprotei were detected, whereas no single bacterial species was found in all samples, suggesting a better adaptation of certain archaeal species to different thermophilic environments. Two hot springs show high abundance of Acidithiobacillus, supporting the idea of a true thermophilic Acidithiobacillus species that can thrive in hyperthermophilic environments. Depending on the sample, up to 58 % of sequencing reads could not be assigned to a known phylum, reinforcing the fact that a large number of microorganisms in nature, including those thriving in hot environments remain to be isolated and characterized.

mRNA-engineered mesenchymal stem cells for targeted delivery of interleukin-10 to sites of inflammation.

PubMed

Levy, Oren; Zhao, Weian; Mortensen, Luke J; Leblanc, Sarah; Tsang, Kyle; Fu, Moyu; Phillips, Joseph A; Sagar, Vinay; Anandakumaran, Priya; Ngai, Jessica; Cui, Cheryl H; Eimon, Peter; Angel, Matthew; Lin, Charles P; Yanik, Mehmet Fatih; Karp, Jeffrey M

2013-10-03

Mesenchymal stem cells (MSCs) are promising candidates for cell-based therapy to treat several diseases and are compelling to consider as vehicles for delivery of biological agents. However, MSCs appear to act through a seemingly limited "hit-and-run" mode to quickly exert their therapeutic impact, mediated by several mechanisms, including a potent immunomodulatory secretome. Furthermore, MSC immunomodulatory properties are highly variable and the secretome composition following infusion is uncertain. To determine whether a transiently controlled antiinflammatory MSC secretome could be achieved at target sites of inflammation, we harnessed mRNA transfection to generate MSCs that simultaneously express functional rolling machinery (P-selectin glycoprotein ligand-1 [PSGL-1] and Sialyl-Lewis(x) [SLeX]) to rapidly target inflamed tissues and that express the potent immunosuppressive cytokine interleukin-10 (IL-10), which is not inherently produced by MSCs. Indeed, triple-transfected PSGL-1/SLeX/IL-10 MSCs transiently increased levels of IL-10 in the inflamed ear and showed a superior antiinflammatory effect in vivo, significantly reducing local inflammation following systemic administration. This was dependent on rapid localization of MSCs to the inflamed site. Overall, this study demonstrates that despite the rapid clearance of MSCs in vivo, engineered MSCs can be harnessed via a "hit-and-run" action for the targeted delivery of potent immunomodulatory factors to treat distant sites of inflammation.

siRNAs targeted to certain polyadenylation sites promote specific, RISC-independent degradation of messenger RNAs.

PubMed

Vickers, Timothy A; Crooke, Stanley T

2012-07-01

While most siRNAs induce sequence-specific target mRNA cleavage and degradation in a process mediated by Ago2/RNA-induced silencing complex (RISC), certain siRNAs have also been demonstrated to direct target RNA reduction through deadenylation and subsequent degradation of target transcripts in a process which involves Ago1/RISC and P-bodies. In the current study, we present data suggesting that a third class of siRNA exist, which are capable of promoting target RNA reduction that is independent of both Ago and RISC. These siRNAs bind the target messenger RNA at the polyA signal and are capable of redirecting a small amount of polyadenylation to downstream polyA sites when present, however, the majority of the activity appears to be due to inhibition of polyadenylation or deadenylation of the transcript, followed by exosomal degradation of the immature mRNA.

Site-to-site interdomain communication may mediate different loss-of-function mechanisms in a cancer-associated NQO1 polymorphism

NASA Astrophysics Data System (ADS)

Medina-Carmona, Encarnación; Neira, Jose L.; Salido, Eduardo; Fuchs, Julian E.; Palomino-Morales, Rogelio; Timson, David J.; Pey, Angel L.

2017-03-01

Disease associated genetic variations often cause intracellular enzyme inactivation, dysregulation and instability. However, allosteric communication of mutational effects to distant functional sites leading to loss-of-function remains poorly understood. We characterize here interdomain site-to-site communication by which a common cancer-associated single nucleotide polymorphism (c.C609T/p.P187S) reduces the activity and stability in vivo of NAD(P)H:quinone oxidoreductase 1 (NQO1). NQO1 is a FAD-dependent, two-domain multifunctional stress protein acting as a Phase II enzyme, activating cancer pro-drugs and stabilizing p53 and p73α oncosuppressors. We show that p.P187S causes structural and dynamic changes communicated to functional sites far from the mutated site, affecting the FAD binding site located at the N-terminal domain (NTD) and accelerating proteasomal degradation through dynamic effects on the C-terminal domain (CTD). Structural protein:protein interaction studies reveal that the cancer-associated polymorphism does not abolish the interaction with p73α, indicating that oncosuppressor destabilization largely mirrors the low intracellular stability of p.P187S. In conclusion, we show how a single disease associated amino acid change may allosterically perturb several functional sites in an oligomeric and multidomain protein. These results have important implications for the understanding of loss-of-function genetic diseases and the identification of novel structural hot spots as targets for pharmacological intervention.

The evolutionary turnover of recombination hot spots contributes to speciation in mice.

PubMed

Smagulova, Fatima; Brick, Kevin; Pu, Yongmei; Camerini-Otero, R Daniel; Petukhova, Galina V

2016-02-01

Meiotic recombination is required for the segregation of homologous chromosomes and is essential for fertility. In most mammals, the DNA double-strand breaks (DSBs) that initiate meiotic recombination are directed to a subset of genomic loci (hot spots) by sequence-specific binding of the PRDM9 protein. Rapid evolution of the DNA-binding specificity of PRDM9 and gradual erosion of PRDM9-binding sites by gene conversion will alter the recombination landscape over time. To better understand the evolutionary turnover of recombination hot spots and its consequences, we mapped DSB hot spots in four major subspecies of Mus musculus with different Prdm9 alleles and in their F1 hybrids. We found that hot spot erosion governs the preferential usage of some Prdm9 alleles over others in hybrid mice and increases sequence diversity specifically at hot spots that become active in the hybrids. As crossovers are disfavored at such hot spots, we propose that sequence divergence generated by hot spot turnover may create an impediment for recombination in hybrids, potentially leading to reduced fertility and, eventually, speciation. Published by Cold Spring Harbor Laboratory Press.

Fitness cost implications of phiC31-mediated site-specific integrations in target-site strains of the Mexican fruit fly, Anastrepha ludens (Diptera: Tephritidae)

USDA-ARS?s Scientific Manuscript database

Site-specific recombination technologies are powerful new tools for the manipulation of genomic DNA in insects that can improve transgenesis strategies such as targeting transgene insertions, allowing transgene cassette exchange and DNA mobilization for transgene stabilization. However, understandin...

Solar domestic hot water system installed at Texas City, Texas

NASA Technical Reports Server (NTRS)

1980-01-01

This is the final technical report of the solar energy system located at LaQuinta Motor Inn, Texas City, Texas. The system was designed to supply 63 percent of the total hot water load for a new 98 unit motor inn. The solar energy system consists of a 2100 square feet Raypack liquid flat plate collector subsystem and a 2500 gallon storage subsystem circulating hot water producing 3.67 x 10 to the 8th power Btu/year. Abstracts from the site files, specification references, drawings, installation, operation, and maintenance instructions are included.

Changes in Extremely Hot Summers over the Global Land Area under Various Warming Targets

PubMed Central

Wang, Lei; Huang, Jianbin; Luo, Yong; Yao, Yao; Zhao, Zongci

2015-01-01

Summer temperature extremes over the global land area were investigated by comparing 26 models of the fifth phase of the Coupled Model Intercomparison Project (CMIP5) with observations from the Goddard Institute for Space Studies (GISS) and the Climate Research Unit (CRU). Monthly data of the observations and models were averaged for each season, and statistics were calculated for individual models before averaging them to obtain ensemble means. The summers with temperature anomalies (relative to 1951–1980) exceeding 3σ (σ is based on the local internal variability) are defined as “extremely hot”. The models well reproduced the statistical characteristics evolution, and partly captured the spatial distributions of historical summer temperature extremes. If the global mean temperature increases 2°C relative to the pre-industrial level, “extremely hot” summers are projected to occur over nearly 40% of the land area (multi-model ensemble mean projection). Summers that exceed 5σ warming are projected to occur over approximately 10% of the global land area, which were rarely observed during the reference period. Scenarios reaching warming levels of 3°C to 5°C were also analyzed. After exceeding the 5°C warming target, “extremely hot” summers are projected to occur throughout the entire global land area, and summers that exceed 5σ warming would become common over 70% of the land area. In addition, the areas affected by “extremely hot” summers are expected to rapidly expand by more than 25%/°C as the global mean temperature increases by up to 3°C before slowing to less than 16%/°C as the temperature continues to increase by more than 3°C. The area that experiences summers with warming of 5σ or more above the warming target of 2°C is likely to maintain rapid expansion of greater than 17%/°C. To reduce the impacts and damage from severely hot summers, the global mean temperature increase should remain low. PMID:26090931

Targeted Delivery of LXR Agonist Using a Site-Specific Antibody-Drug Conjugate.

PubMed

Lim, Reyna K V; Yu, Shan; Cheng, Bo; Li, Sijia; Kim, Nam-Jung; Cao, Yu; Chi, Victor; Kim, Ji Young; Chatterjee, Arnab K; Schultz, Peter G; Tremblay, Matthew S; Kazane, Stephanie A

2015-11-18

Liver X receptor (LXR) agonists have been explored as potential treatments for atherosclerosis and other diseases based on their ability to induce reverse cholesterol transport and suppress inflammation. However, this therapeutic potential has been hindered by on-target adverse effects in the liver mediated by excessive lipogenesis. Herein, we report a novel site-specific antibody-drug conjugate (ADC) that selectively delivers a LXR agonist to monocytes/macrophages while sparing hepatocytes. The unnatural amino acid para-acetylphenylalanine (pAcF) was site-specifically incorporated into anti-CD11a IgG, which binds the α-chain component of the lymphocyte function-associated antigen 1 (LFA-1) expressed on nearly all monocytes and macrophages. An aminooxy-modified LXR agonist was conjugated to anti-CD11a IgG through a stable, cathepsin B cleavable oxime linkage to afford a chemically defined ADC. The anti-CD11a IgG-LXR agonist ADC induced LXR activation specifically in human THP-1 monocyte/macrophage cells in vitro (EC50-27 nM), but had no significant effect in hepatocytes, indicating that payload delivery is CD11a-mediated. Moreover, the ADC exhibited higher-fold activation compared to a conventional synthetic LXR agonist T0901317 (Tularik) (3-fold). This novel ADC represents a fundamentally different strategy that uses tissue targeting to overcome the limitations of LXR agonists for potential use in treating atherosclerosis.

Specular Reflectivity and Hot-Electron Generation in High-Contrast Relativistic Laser-Plasma Interactions

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

Kemp, Gregory Elijah

2013-01-01

Ultra-intense laser (> 1018 W/cm2) interactions with matter are capable of producing relativistic electrons which have a variety of applications in state-of-the-art scientific and medical research conducted at universities and national laboratories across the world. Control of various aspects of these hot-electron distributions is highly desired to optimize a particular outcome. Hot-electron generation in low-contrast interactions, where significant amounts of under-dense pre-plasma are present, can be plagued by highly non-linear relativistic laser-plasma instabilities and quasi-static magnetic field generation, often resulting in less than desirable and predictable electron source characteristics. High-contrast interactions offer more controlled interactions but often at the costmore » of overall lower coupling and increased sensitivity to initial target conditions. An experiment studying the differences in hot-electron generation between high and low-contrast pulse interactions with solid density targets was performed on the Titan laser platform at the Jupiter Laser Facility at Lawrence Livermore National Laboratory in Livermore, CA. To date, these hot-electrons generated in the laboratory are not directly observable at the source of the interaction. Instead, indirect studies are performed using state-of-the-art simulations, constrained by the various experimental measurements. These measurements, more-often-than-not, rely on secondary processes generated by the transport of these electrons through the solid density materials which can susceptible to a variety instabilities and target material/geometry effects. Although often neglected in these types of studies, the specularly reflected light can provide invaluable insight as it is directly influenced by the interaction. In this thesis, I address the use of (personally obtained) experimental specular reflectivity measurements to indirectly study hot-electron generation in the context of high

POTENTIAL AIR TOXICS HOT SPOTS IN TRUCK TERMINALS AND CABS

EPA Science Inventory

All three types of testing sites — upwind and downwind traffic — met the established definition for a hot spot by having periods with concentrations of pollutants that exceeded the EPA’s screening values. Most frequently, the pollutants with concentrations...

Prostate Cancer Clinical Consortium Clinical Research Site: Targeted Therapies

DTIC Science & Technology

2016-10-01

2016 4 . TITLE AND SUBTITLE 5a. CONTRACT NUMBER Prostate Cancer Clinical Consortium Clinical Research Site: Targeted Therapies 5b. GRANT NUMBER 5c...new biomarker driven trials directly to patients W81XWH-14-2-0159 None listed 20 Table of Contents Page 1. Introduction…………………………………………………………. 4 2...Keywords……………………………………………………………. 4 3. Accomplishments ..……..…………………………………………... 4 4 . Impact…………………………...…………………………………… 8 5. Changes/Problems

Lessons from Hot Spot Analysis for Fragment-Based Drug Discovery.

PubMed

Hall, David R; Kozakov, Dima; Whitty, Adrian; Vajda, Sandor

2015-11-01

Analysis of binding energy hot spots at protein surfaces can provide crucial insights into the prospects for successful application of fragment-based drug discovery (FBDD), and whether a fragment hit can be advanced into a high-affinity, drug-like ligand. The key factor is the strength of the top ranking hot spot, and how well a given fragment complements it. We show that published data are sufficient to provide a sophisticated and quantitative understanding of how hot spots derive from a protein 3D structure, and how their strength, number, and spatial arrangement govern the potential for a surface site to bind to fragment-sized and larger ligands. This improved understanding provides important guidance for the effective application of FBDD in drug discovery. Copyright © 2015 Elsevier Ltd. All rights reserved.

Enhanced-Contrast Viewing of White-Hot Objects in Furnaces

NASA Technical Reports Server (NTRS)

Witherow, William K.; Holmes, Richard R.; Kurtz, Robert L.

2006-01-01

An apparatus denoted a laser image contrast enhancement system (LICES) increases the contrast with which one can view a target glowing with blackbody radiation (a white-hot object) against a background of blackbody radiation in a furnace at a temperature as high as approximately 1,500 C. The apparatus utilizes a combination of narrowband illumination, along with band-pass filtering and polarization filtering to pass illumination reflected by the target while suppressing blackbody light from both the object and its background.

Functional annotation of HOT regions in the human genome: implications for human disease and cancer

PubMed Central

Li, Hao; Chen, Hebing; Liu, Feng; Ren, Chao; Wang, Shengqi; Bo, Xiaochen; Shu, Wenjie

2015-01-01

Advances in genome-wide association studies (GWAS) and large-scale sequencing studies have resulted in an impressive and growing list of disease- and trait-associated genetic variants. Most studies have emphasised the discovery of genetic variation in coding sequences, however, the noncoding regulatory effects responsible for human disease and cancer biology have been substantially understudied. To better characterise the cis-regulatory effects of noncoding variation, we performed a comprehensive analysis of the genetic variants in HOT (high-occupancy target) regions, which are considered to be one of the most intriguing findings of recent large-scale sequencing studies. We observed that GWAS variants that map to HOT regions undergo a substantial net decrease and illustrate development-specific localisation during haematopoiesis. Additionally, genetic risk variants are disproportionally enriched in HOT regions compared with LOT (low-occupancy target) regions in both disease-relevant and cancer cells. Importantly, this enrichment is biased toward disease- or cancer-specific cell types. Furthermore, we observed that cancer cells generally acquire cancer-specific HOT regions at oncogenes through diverse mechanisms of cancer pathogenesis. Collectively, our findings demonstrate the key roles of HOT regions in human disease and cancer and represent a critical step toward further understanding disease biology, diagnosis, and therapy. PMID:26113264

Functional annotation of HOT regions in the human genome: implications for human disease and cancer.

PubMed

Li, Hao; Chen, Hebing; Liu, Feng; Ren, Chao; Wang, Shengqi; Bo, Xiaochen; Shu, Wenjie

2015-06-26

Advances in genome-wide association studies (GWAS) and large-scale sequencing studies have resulted in an impressive and growing list of disease- and trait-associated genetic variants. Most studies have emphasised the discovery of genetic variation in coding sequences, however, the noncoding regulatory effects responsible for human disease and cancer biology have been substantially understudied. To better characterise the cis-regulatory effects of noncoding variation, we performed a comprehensive analysis of the genetic variants in HOT (high-occupancy target) regions, which are considered to be one of the most intriguing findings of recent large-scale sequencing studies. We observed that GWAS variants that map to HOT regions undergo a substantial net decrease and illustrate development-specific localisation during haematopoiesis. Additionally, genetic risk variants are disproportionally enriched in HOT regions compared with LOT (low-occupancy target) regions in both disease-relevant and cancer cells. Importantly, this enrichment is biased toward disease- or cancer-specific cell types. Furthermore, we observed that cancer cells generally acquire cancer-specific HOT regions at oncogenes through diverse mechanisms of cancer pathogenesis. Collectively, our findings demonstrate the key roles of HOT regions in human disease and cancer and represent a critical step toward further understanding disease biology, diagnosis, and therapy.

How important is hydrotherapy? Effects of dynamic action of hot spring water as a rehabilitative treatment for burn patients in Switzerland.

PubMed

Moufarrij, S; Deghayli, L; Raffoul, W; Hirt-Burri, N; Michetti, M; de Buys Roessingh, A; Norberg, M; Applegate, L A

2014-12-31

Burn rehabilitation using hydrotherapy can have multiple benefits for the burn patient. The therapy uses specific mineral enriched hot spring water and water jets with varied hydro-pressure to combat hypertrophy, inflammatory reaction signs, abnormal pigmentation, and, more specifically, redness and scarring. Standard operating procedures for burn rehabilitation have been developed and integrated into the Standard of Care at the CHUV hospital using localized hydro-mechanical stimulation of burn sites (20 minutes of alternating anatomical sites) followed by constant pressure large-bore and filiform showers targeting specific scarred areas. These therapeutic regimens are repeated daily for 2 to 3 weeks. Patients showed lasting effects from this regimen (up to 3-6 months), the results becoming permanent with more uniform skin structure, color and visco-elasticity in addition to a decrease in pruritus. The specifications of clinical protocols are described herein along with the virtues of hot spring hydro-pressure therapy for burn rehabilitation. The use of hydrotherapy, which has been a controversial topic among burn units across the world, is also discussed. In North America, hydrotherapy is defined only within the scope of in-patient wound cleansing and is thought to lead to microbial auto-contamination and bacterial resistance. In Switzerland and France the emphasis of hydrotherapy is on rehabilitation after the wound has closed.

Solar heating, cooling and domestic hot water system installed at Columbia Gas System Service Corporation, Columbus, Ohio

NASA Technical Reports Server (NTRS)

1980-01-01

The solar energy system installed in the building has 2,978 sq ft of single axis tracking, concentrating collectors and provides solar energy for space heating, space cooling and domestic hot water. A 1,200,000 Btu/hour water tube gas boiler provides hot water for space heating. Space cooling is provided by a 100 ton hot water fired absorption chiller. Domestic hot water heating is provided by a 50 gallon natural gas domestic storage water heater. Extracts from the site files, specification references, drawings, installation, operation and maintenance instructions are included.

Histological Comparison of Cold versus Hot Snare Resections of the Colorectal Mucosa.

PubMed

Takayanagi, Daisuke; Nemoto, Daiki; Isohata, Noriyuki; Endo, Shungo; Aizawa, Masato; Utano, Kenichi; Kumamoto, Kensuke; Hojo, Hiroshi; Lefor, Alan Kawarai; Togashi, Kazutomo

2018-06-25

Delayed postpolypectomy bleeding occurs more frequently after hot resection than after cold resection. To elucidate the underlying mechanism, we performed a histological comparison of tissue after cold and hot snare resections. This is a prospective study, registered in the University Hospital Medical Information Network (UMIN000020104). This study was conducted at Aizu Medical Center, Fukushima Medical University, Japan. Fifteen patients scheduled to undergo resection of colorectal cancer were enrolled. On the day before surgery, 2 mucosal resections (hot and cold) of normal mucosa were performed on each patient using the same snare without saline injection. The difference was only the application of electrocautery or not. Resection sites were placed close to the cancer to be included in the surgical specimen. The primary outcome measure was the depth of destruction. Secondary outcome measures included the width of destruction, depth of the remaining submucosa, and number of vessels remaining at the resection sites. The number and diameter of vessels in undamaged submucosa were also evaluated. All cold resections were limited to the shallow submucosa, whereas 60% of hot resections advanced to the deep submucosa and 20% to the muscularis propria (p < 0.001). There was no significant difference in the width of destruction. The number of remaining large vessels after hot resections trended toward fewer (p = 0.15) with a decreased depth of remaining submucosa (p = 0.007). In the deep submucosa, the vessel diameter was larger (p < 0.001) and the number of large vessels was greater (p = 0.018). Histological assessment was not blinded to the 2 reviewers. Normal mucosa was used instead of adenomatous tissue. Hot resection caused damage to deeper layers involving more large vessels. This may explain the mechanism for the reduced incidence of hemorrhage after cold snare polypectomy. See Video Abstract at http://links.lww.com/DCR/A631.

Hot-field tectonics

NASA Astrophysics Data System (ADS)

Zonenshain, L. P.; Kuzmin, M. I.; Bocharova, N. Yu.

1991-12-01

Intraplate, hot spot related volcanic occurrences do not have a random distribution on the Earth's surface. They are concentrated in two large regions (up to 10,000 km in diameter), the Pacific and the African, and two smaller areas (2000-3000 km in diameter), the Central Asian and the Tasmanian. These regions are considered as manifestations of hot fields in the mantle, whereas the regions lying in between are expressions of cold fields in the mantle. Large-scale anomalies coincide with the hot fields: topographic swells, geoid highs, uplifts of the "asthenospheric table", inferred heated regions in the lowermost mantle according to seismic tomographic images, geochemical anomalies showing the origin of volcanics from undepleted mantle sources. Hot fields are relatively stable features, having remained in the same position on the Earth's surface during the last 120 Ma, although they have other configurations and other positions in the Late Paleozoic and Early Mesozoic. Available data show that two main hot fields (Pacific and African) are possibly moving one with respect to the other, converging along the Eastern Pacific subduction system and diverging along that of the Western Pacific. If so, well-known differences between these subduction systems can also be connected with related displacement of the hot fields. Hot fields are assumed to correspond to upwelling branches of mantle and rather deep mantle convection, and cold fields to downwelling branches. Thus, hot fields can be regarded as expressions of deeper tectonics, comparative to the plate tectonics, which is operating in the upper layers of the Earth. We call it hot-field tectonics. Plate tectonics is responsible for the opening and closure of oceans and for the formation of orogenic belts, whereas hot-field tectonics accounts for a larger cyclicity of the Earth's evolution and for amalgamation and break up of Pangea-type supercontinents. Hot-field tectonics seems to be the only process to have existed

49 CFR 325.77 - Computation of open site requirements-nonstandard sites.

Code of Federal Regulations, 2010 CFR

2010-10-01

... microphone target point is other than 50 feet (15.2 m), the test site must be an open site within a radius... microphone target point. (b) Plan view diagrams of nonstandard test sites are shown in Figures 3 and 4... (18.3 m) distance between the microphone location point and the microphone target point. (See § 325.79...

49 CFR 325.77 - Computation of open site requirements-nonstandard sites.

Code of Federal Regulations, 2011 CFR

2011-10-01

... microphone target point is other than 50 feet (15.2 m), the test site must be an open site within a radius... microphone target point. (b) Plan view diagrams of nonstandard test sites are shown in Figures 3 and 4... (18.3 m) distance between the microphone location point and the microphone target point. (See § 325.79...

TargetM6A: Identifying N6-Methyladenosine Sites From RNA Sequences via Position-Specific Nucleotide Propensities and a Support Vector Machine.

PubMed

Li, Guang-Qing; Liu, Zi; Shen, Hong-Bin; Yu, Dong-Jun

2016-10-01

As one of the most ubiquitous post-transcriptional modifications of RNA, N 6 -methyladenosine ( [Formula: see text]) plays an essential role in many vital biological processes. The identification of [Formula: see text] sites in RNAs is significantly important for both basic biomedical research and practical drug development. In this study, we designed a computational-based method, called TargetM6A, to rapidly and accurately target [Formula: see text] sites solely from the primary RNA sequences. Two new features, i.e., position-specific nucleotide/dinucleotide propensities (PSNP/PSDP), are introduced and combined with the traditional nucleotide composition (NC) feature to formulate RNA sequences. The extracted features are further optimized to obtain a much more compact and discriminative feature subset by applying an incremental feature selection (IFS) procedure. Based on the optimized feature subset, we trained TargetM6A on the training dataset with a support vector machine (SVM) as the prediction engine. We compared the proposed TargetM6A method with existing methods for predicting [Formula: see text] sites by performing stringent jackknife tests and independent validation tests on benchmark datasets. The experimental results show that the proposed TargetM6A method outperformed the existing methods for predicting [Formula: see text] sites and remarkably improved the prediction performances, with MCC = 0.526 and AUC = 0.818. We also provided a user-friendly web server for TargetM6A, which is publicly accessible for academic use at http://csbio.njust.edu.cn/bioinf/TargetM6A.

Hot atoms in cosmic chemistry.

PubMed

Rossler, K; Jung, H J; Nebeling, B

1984-01-01

High energy chemical reactions and atom molecule interactions might be important for cosmic chemistry with respect to the accelerated species in solar wind, cosmic rays, colliding gas and dust clouds and secondary knock-on particles in solids. "Hot" atoms with energies ranging from a few eV to some MeV can be generated via nuclear reactions and consequent recoil processes. The chemical fate of the radioactive atoms can be followed by radiochemical methods (radio GC or HPLC). Hot atom chemistry may serve for laboratory simulation of the reactions of energetic species with gaseous or solid interstellar matter. Due to the effective measurement of 10(8)-10(10) atoms only it covers a low to medium dose regime and may add to the studies of ion implantation which due to the optical methods applied are necessarily in the high dose regime. Experimental results are given for the systems: C/H2O (gas), C/H2O (solid, 77 K), N/CH4 (solid, 77K) and C/NH3 (solid, 77 K). Nuclear reactions used for the generation of 2 to 3 MeV atoms are: N(p,alpha) 11C, 16O(p,alpha pn) 11C and 12C(d,n) 13N with 8 to 45 MeV protons or deuterons from a cyclotron. Typical reactions products are: CO, CO2, CH4, CH2O, CH3OH, HCOOH, NH3, CH3NH2, cyanamide, formamidine, guanidine etc. Products of hot reactions in solids are more complex than in corresponding gaseous systems, which underlines the importance of solid state reactions for the build-up of precursors for biomolecules in space. As one of the major mechanisms for product formation, the simultaneous or fast consecutive reactions of a hot carbon with two target molecules (reaction complex) is discussed.

Decaleside: a new class of natural insecticide targeting tarsal gustatory sites

NASA Astrophysics Data System (ADS)

Rajashekar, Yallappa; Rao, Lingamallu J. M.; Shivanandappa, Thimmappa

2012-10-01

Natural sources for novel insecticide molecules hold promise in view of their eco-friendly nature, selectivity, and mammalian safety. Recent progress in understanding the biology of insect olfaction and taste offers new strategies for developing selective pest control agents. We have isolated two natural insecticidal molecules from edible roots of Decalepis hamiltonii named Decalesides I and II, which are novel trisaccharides, highly toxic to household insect pests and stored-product insects. We have experimentally shown that insecticidal activity requires contact with tarsi on the legs but is not toxic orally. The insecticidal activity of molecules is lost by hydrolysis, and various sugars modify toxic response, showing that the insecticidal activity is via gustatory sites on the tarsi. Selective toxicity to insects by virtue of their gustatory site of action and the mammalian safety of the new insecticides is inherent in their chemical structure with 1-4 or 1-1 α linkage that is easily hydrolyzed by digestive enzymes of mammals. Decalesides represent a new chemical class of natural insecticides with a unique mode of action targeting tarsal chemosensory/gustatory system of insects.

Are ``Hot Spots'' Hot? - An Overview

NASA Astrophysics Data System (ADS)

Foulger, G. R.

2010-12-01

The term “hot spot” is taken variously to imply a) the presence of excessive volcanism, or b) that the melt formed in an unusually hot source. Case b) is intrinsic to the plume hypothesis. Temperature anomalies of 200-300 degrees Celsius are expected, though there is widespread downward-revision of this where observations do not support it. It is not self-evident that “hot spots” are hot in the sense of case b), despite the fact that this is widely assumed. Furthermore, a hot source is not strongly supported by observations, and is at odds with many data. The temperature of the mantle has been studied using many different methods. Global oceanic heat flow values were recently assessed, but reveal no evidence for elevated temperatures around proposed plume localities. Mapping surface heat flow is only sensitive to anomalies at the level of 100 degrees Celsius, however. Seismological methods include correlating velocity with crustal thickness at LIPs, measuring transition zone thickness, and mapping velocity, e.g., using tomography. The first of these does not find evidence for elevated temperatures. The latter two are both sensitive to the presence of partial melt and variations in rock composition, in addition to temperature, which is the weakest potential effect. They thus cannot be used as thermometers. In particular, it cannot be assumed that red = hot and blue = cold in tomographic cross sections. Petrological and geochemical approaches include the “global systematics”. This has now been shown to not work for estimating temperature and its application should be discontinued. Mineralogical phase relationships are applied by comparing data from laboratory melting experiments to observations. Olivine control-line analysis has been extensively used in attempts to measure the differences in melt-formation temperature between mid-ocean ridges and melting anomalies. Difficulties arise in choosing the correct olivine geothermometer and because picrite glass

Biodiversity hot spot on a hot spot: novel extremophile diversity in Hawaiian fumaroles.

PubMed

Wall, Kate; Cornell, Jennifer; Bizzoco, Richard W; Kelley, Scott T

2015-01-06

Fumaroles (steam vents) are the most common, yet least understood, microbial habitat in terrestrial geothermal settings. Long believed too extreme for life, recent advances in sample collection and DNA extraction methods have found that fumarole deposits and subsurface waters harbor a considerable diversity of viable microbes. In this study, we applied culture-independent molecular methods to explore fumarole deposit microbial assemblages in 15 different fumaroles in four geographic locations on the Big Island of Hawai'i. Just over half of the vents yielded sufficient high-quality DNA for the construction of 16S ribosomal RNA gene sequence clone libraries. The bacterial clone libraries contained sequences belonging to 11 recognized bacterial divisions and seven other division-level phylogenetic groups. Archaeal sequences were less numerous, but similarly diverse. The taxonomic composition among fumarole deposits was highly heterogeneous. Phylogenetic analysis found cloned fumarole sequences were related to microbes identified from a broad array of globally distributed ecotypes, including hot springs, terrestrial soils, and industrial waste sites. Our results suggest that fumarole deposits function as an "extremophile collector" and may be a hot spot of novel extremophile biodiversity. © 2015 The Authors. MicrobiologyOpen published by John Wiley & Sons Ltd.

Biodiversity hot spot on a hot spot: novel extremophile diversity in Hawaiian fumaroles

PubMed Central

Wall, Kate; Cornell, Jennifer; Bizzoco, Richard W; Kelley, Scott T

2015-01-01

Fumaroles (steam vents) are the most common, yet least understood, microbial habitat in terrestrial geothermal settings. Long believed too extreme for life, recent advances in sample collection and DNA extraction methods have found that fumarole deposits and subsurface waters harbor a considerable diversity of viable microbes. In this study, we applied culture-independent molecular methods to explore fumarole deposit microbial assemblages in 15 different fumaroles in four geographic locations on the Big Island of Hawai'i. Just over half of the vents yielded sufficient high-quality DNA for the construction of 16S ribosomal RNA gene sequence clone libraries. The bacterial clone libraries contained sequences belonging to 11 recognized bacterial divisions and seven other division-level phylogenetic groups. Archaeal sequences were less numerous, but similarly diverse. The taxonomic composition among fumarole deposits was highly heterogeneous. Phylogenetic analysis found cloned fumarole sequences were related to microbes identified from a broad array of globally distributed ecotypes, including hot springs, terrestrial soils, and industrial waste sites. Our results suggest that fumarole deposits function as an “extremophile collector” and may be a hot spot of novel extremophile biodiversity. PMID:25565172

Control of target-normal-sheath-accelerated protons from a guiding cone

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

Zou, D. B.; Institut für Theoretische Physik I, Heinrich-Heine-Universität Düsseldorf, Düsseldorf 40225; Zhuo, H. B., E-mail: hongbin.zhuo@gmail.com

2015-06-15

It is demonstrated through particle-in-cell simulations that target-normal-sheath-accelerated protons can be well controlled by using a guiding cone. Compared to a conventional planar target, both the collimation and number density of proton beams are substantially improved, giving a high-quality proton beam which maintained for a longer distance without degradation. The effect is attributed to the radial electric field resulting from the charge due to the hot target electrons propagating along the cone surface. This electric field can effectively suppress the spatial spread of the protons after the expansion of the hot electrons.

Hot-Spot Ignition Mechanisms for Explosives and Propellants

NASA Astrophysics Data System (ADS)

Field, J. E.; Bourne, N. K.; Palmer, S. J. P.; Walley, S. M.

1992-05-01

This paper describes the response of explosives to stress and impact and in particular the mechanisms of `hot-spot' production. Samples in the form of single crystals, powder layers, pressed pellets, gels, polymer bonded explosives (PBXs) and propellants have been studied. Techniques used include a drop-weight facility with transparent anvils which allows photography at microsecond framing intervals, an instrumented drop-weight machine, a miniaturized Hopkinson bar system for high strain rate property measurement, laser speckle for studying the deformation and fracture of PBXs, an automated system for analysing speckle patterns and heat sensitive film for recording the positions and temperatures of hot spots. Polishing and staining methods have been developed to observe the microstructure of PBXs and failure during quasi-static loading. Ignition, when it occurred, took place at local hot-spot sites. Evidence is discussed for a variety of ignition mechanisms including adiabatic shear of the explosive, adiabatic heating of trapped gases during cavity collapse, viscous flow, friction, fracture and shear of added particles and triboluminescent discharge.

Early Market Site Identification Data

DOE Data Explorer

Levi Kilcher

2016-04-01

This data was compiled for the 'Early Market Opportunity Hot Spot Identification' project. The data and scripts included were used in the 'MHK Energy Site Identification and Ranking Methodology' Reports (Part I: Wave, NREL Report #66038; Part II: Tidal, NREL Report #66079). The Python scripts will generate a set of results--based on the Excel data files--some of which were described in the reports. The scripts depend on the 'score_site' package, and the score site package depends on a number of standard Python libraries (see the score_site install instructions).

3. NORTH ELEVATION OF THE HOT BAY, SHOWING RAILROAD TRACKS ...

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

3. NORTH ELEVATION OF THE HOT BAY, SHOWING RAILROAD TRACKS LEADING TO THE MASSIVE STEEL-LINED CONCRETE ENTRANCE DOOR. PART OF THE INTRICATE HVAC SYSTEM IS WEST (RIGHT) OF THE DOOR. - Nevada Test Site, Engine Maintenance Assembly & Disassembly Facility, Area 25, Jackass Flats, Mercury, Nye County, NV

Comparative performance of rubber modified hot mix asphalt under ALF loading.

DOT National Transportation Integrated Search

2003-08-01

Experiment 2 at the Louisiana ALF site involved determining the engineering benefits of using powdered rubber (PRM) in hot mix asphalt mixes. Three full scale test sections were constructed and subjected to increasing loads from the ALF. Lane 2-1 inc...

microRNA-122 target sites in the hepatitis C virus RNA NS5B coding region and 3' untranslated region: function in replication and influence of RNA secondary structure.

PubMed

Gerresheim, Gesche K; Dünnes, Nadia; Nieder-Röhrmann, Anika; Shalamova, Lyudmila A; Fricke, Markus; Hofacker, Ivo; Höner Zu Siederdissen, Christian; Marz, Manja; Niepmann, Michael

2017-02-01

We have analyzed the binding of the liver-specific microRNA-122 (miR-122) to three conserved target sites of hepatitis C virus (HCV) RNA, two in the non-structural protein 5B (NS5B) coding region and one in the 3' untranslated region (3'UTR). miR-122 binding efficiency strongly depends on target site accessibility under conditions when the range of flanking sequences available for the formation of local RNA secondary structures changes. Our results indicate that the particular sequence feature that contributes most to the correlation between target site accessibility and binding strength varies between different target sites. This suggests that the dynamics of miRNA/Ago2 binding not only depends on the target site itself but also on flanking sequence context to a considerable extent, in particular in a small viral genome in which strong selection constraints act on coding sequence and overlapping cis-signals and model the accessibility of cis-signals. In full-length genomes, single and combination mutations in the miR-122 target sites reveal that site 5B.2 is positively involved in regulating overall genome replication efficiency, whereas mutation of site 5B.3 showed a weaker effect. Mutation of the 3'UTR site and double or triple mutants showed no significant overall effect on genome replication, whereas in a translation reporter RNA, the 3'UTR target site inhibits translation directed by the HCV 5'UTR. Thus, the miR-122 target sites in the 3'-region of the HCV genome are involved in a complex interplay in regulating different steps of the HCV replication cycle.

Radioactivity of Nevada hot-spring systems

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

Wollenberg, H.A.

1974-01-01

Field gamma radiometry and laboratory gamma spectrometry of waters and spring deposits were accomplished for some hot-sprin systems in northern Nevada. Gamma dose rates measured on-site range from 2 to 500 mu rphr, and depend msinly on the amounts of the natural radioelements in the spring deposits. At several locations /sup 222/Rn, emanating from the water, casuses recognizable ganna anomalies. High radioactivities, primarily from /sup 226/Ra, are associated with hot-spring systems dominated by CaCO/sub 3/, while silica-dominated systems sre relatively low in radioactivity. Gamma spectrometry disclosed the enrichment of / sup 226/Ra with respect to its parent U in CaCO/submore » 3/-dominated systems. /sup 226/Ra preferentially associates with Ca; therefore, where tufa and siliceous sinter are present in a deposit, the calcareous material is highest in radioacnvity. Spring deposits at fast-flowing CaCO/sub 3/-dominated systems are generally less radioactive than calcareous deposits at slower flowing springs. (auth)« less

The role of hot electrons in the dynamics of a laser-driven strong converging shock

DOE PAGES

Llor Aisa, E.; Ribeyre, X.; Duchateau, G.; ...

2017-11-30

Experiments on strong shock excitation in spherical plastic targets conducted at the Omega Laser Facility are interpreted with the radiation–hydrodynamics code CHIC to account for parametric instabilities excitation and hot-electron generation. The effects of hot electrons on the shock-pressure amplification and upstream preheat are analyzed. In this study, it is demonstrated that both effects contribute to an increase in shock velocity. Comparison of the measured laser reflectivity and shock flash time with numerical simulations make it possible to reconstitute the time history of the ablation and shock pressures. Finally, consequences of this analysis for the shock-ignition target design are discussed.

The role of hot electrons in the dynamics of a laser-driven strong converging shock

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

Llor Aisa, E.; Ribeyre, X.; Duchateau, G.

Experiments on strong shock excitation in spherical plastic targets conducted at the Omega Laser Facility are interpreted with the radiation–hydrodynamics code CHIC to account for parametric instabilities excitation and hot-electron generation. The effects of hot electrons on the shock-pressure amplification and upstream preheat are analyzed. In this study, it is demonstrated that both effects contribute to an increase in shock velocity. Comparison of the measured laser reflectivity and shock flash time with numerical simulations make it possible to reconstitute the time history of the ablation and shock pressures. Finally, consequences of this analysis for the shock-ignition target design are discussed.

Digital-Electronic/Optical Apparatus Would Recognize Targets

NASA Technical Reports Server (NTRS)

Scholl, Marija S.

1994-01-01

Proposed automatic target-recognition apparatus consists mostly of digital-electronic/optical cross-correlator that processes infrared images of targets. Infrared images of unknown targets correlated quickly with images of known targets. Apparatus incorporates some features of correlator described in "Prototype Optical Correlator for Robotic Vision System" (NPO-18451), and some of correlator described in "Compact Optical Correlator" (NPO-18473). Useful in robotic system; to recognize and track infrared-emitting, moving objects as variously shaped hot workpieces on conveyor belt.

The SPOR Domain, a Widely Conserved Peptidoglycan Binding Domain That Targets Proteins to the Site of Cell Division.

PubMed

Yahashiri, Atsushi; Jorgenson, Matthew A; Weiss, David S

2017-07-15

Sporulation-related repeat (SPOR) domains are small peptidoglycan (PG) binding domains found in thousands of bacterial proteins. The name "SPOR domain" stems from the fact that several early examples came from proteins involved in sporulation, but SPOR domain proteins are quite diverse and contribute to a variety of processes that involve remodeling of the PG sacculus, especially with respect to cell division. SPOR domains target proteins to the division site by binding to regions of PG devoid of stem peptides ("denuded" glycans), which in turn are enriched in septal PG by the intense, localized activity of cell wall amidases involved in daughter cell separation. This targeting mechanism sets SPOR domain proteins apart from most other septal ring proteins, which localize via protein-protein interactions. In addition to SPOR domains, bacteria contain several other PG-binding domains that can exploit features of the cell wall to target proteins to specific subcellular sites. Copyright © 2017 American Society for Microbiology.

PIE preparation of the MEGAPIE target

NASA Astrophysics Data System (ADS)

Wohlmuther, Michael; Wagner, Werner

2012-12-01

The MEGAPIE target, after successfully operating for 4 months at a beam power of 0.77 MW, is now being prepared for post irradiation examination PIE. The lead-bismuth eutectic (LBE) target was irradiated from August until December 2006, and in this period received a beam charge of 2.8 A h of 575 MeV protons. After that, the target was stored in the target storage facility of PSI, waiting for its post irradiation examination. In the meantime several campaigns of tests have been conducted by PSI and ZWILAG, the interim storage facility of Swiss nuclear power plants. In these tests the feasibility of the conditioning of the target and the extraction of sample material for the PIE has been proven. After transport to the hot cell facility at ZWILAG in June 2009, the dismantling of the MEGAPIE target started. It finally was cut into 21 pieces. Ten of these pieces will be shipped to the Hot Laboratory of PSI ('PSI hotlab') to extract samples from the structural materials as well as from the LBE. Currently it is foreseen that the sample extraction will start in the first half of 2011. The remaining parts of the MEGAPIE target were conditioned as radioactive waste. The present paper will mainly focus on the dismantling and first visual inspection of the MEGAPIE target. In addition an outlook on the PIE phase of MEGAPIE is given.

Combined facial heating and inhalation of hot air do not alter thermoeffector responses in humans.

PubMed

Wingo, Jonathan E; Low, David A; Keller, David M; Kimura, Kenichi; Crandall, Craig G

2015-09-01

The influence of thermoreceptors in human facial skin on thermoeffector responses is equivocal; furthermore, the presence of thermoreceptors in the respiratory tract and their involvement in thermal homeostasis has not been elucidated. This study tested the hypothesis that hot air directed on the face and inhaled during whole body passive heat stress elicits an earlier onset and greater sensitivity of cutaneous vasodilation and sweating than that directed on an equal skin surface area away from the face. Six men and two women completed two trials separated by ∼1 wk. Participants were passively heated (water-perfused suit; core temperature increase ∼0.9°C) while hot air was directed on either the face or on the lower leg (counterbalanced). Skin blood flux (laser-Doppler flowmetry) and local sweat rate (capacitance hygrometry) were measured at the chest and one forearm. During hot-air heating, local temperatures of the cheek and leg were 38.4 ± 0.8°C and 38.8 ± 0.6°C, respectively (P = 0.18). Breathing hot air combined with facial heating did not affect mean body temperature onsets (P = 0.97 and 0.27 for arm and chest sites, respectively) or slopes of cutaneous vasodilation (P = 0.49 and 0.43 for arm and chest sites, respectively), or the onsets (P = 0.89 and 0.94 for arm and chest sites, respectively), or slopes of sweating (P = 0.48 and 0.65 for arm and chest sites, respectively). Based on these findings, respiratory tract thermoreceptors, if present in humans, and selective facial skin heating do not modulate thermoeffector responses during passive heat stress. Copyright © 2015 the American Physiological Society.

Engineering of a target site-specific recombinase by a combined evolution- and structure-guided approach

PubMed Central

Abi-Ghanem, Josephine; Chusainow, Janet; Karimova, Madina; Spiegel, Christopher; Hofmann-Sieber, Helga; Hauber, Joachim; Buchholz, Frank; Pisabarro, M. Teresa

2013-01-01

Site-specific recombinases (SSRs) can perform DNA rearrangements, including deletions, inversions and translocations when their naive target sequences are placed strategically into the genome of an organism. Hence, in order to employ SSRs in heterologous hosts, their target sites have to be introduced into the genome of an organism before the enzyme can be practically employed. Engineered SSRs hold great promise for biotechnology and advanced biomedical applications, as they promise to extend the usefulness of SSRs to allow efficient and specific recombination of pre-existing, natural genomic sequences. However, the generation of enzymes with desired properties remains challenging. Here, we use substrate-linked directed evolution in combination with molecular modeling to rationally engineer an efficient and specific recombinase (sTre) that readily and specifically recombines a sequence present in the HIV-1 genome. We elucidate the role of key residues implicated in the molecular recognition mechanism and we present a rationale for sTre’s enhanced specificity. Combining evolutionary and rational approaches should help in accelerating the generation of enzymes with desired properties for use in biotechnology and biomedicine. PMID:23275541

Alpha-tocopheryl succinate induces apoptosis by targeting ubiquinone-binding sites in mitochondrial respiratory complex II.

PubMed

Dong, L-F; Low, P; Dyason, J C; Wang, X-F; Prochazka, L; Witting, P K; Freeman, R; Swettenham, E; Valis, K; Liu, J; Zobalova, R; Turanek, J; Spitz, D R; Domann, F E; Scheffler, I E; Ralph, S J; Neuzil, J

2008-07-17

Alpha-tocopheryl succinate (alpha-TOS) is a selective inducer of apoptosis in cancer cells, which involves the accumulation of reactive oxygen species (ROS). The molecular target of alpha-TOS has not been identified. Here, we show that alpha-TOS inhibits succinate dehydrogenase (SDH) activity of complex II (CII) by interacting with the proximal and distal ubiquinone (UbQ)-binding site (Q(P) and Q(D), respectively). This is based on biochemical analyses and molecular modelling, revealing similar or stronger interaction energy of alpha-TOS compared to that of UbQ for the Q(P) and Q(D) sites, respectively. CybL-mutant cells with dysfunctional CII failed to accumulate ROS and underwent apoptosis in the presence of alpha-TOS. Similar resistance was observed when CybL was knocked down with siRNA. Reconstitution of functional CII rendered CybL-mutant cells susceptible to alpha-TOS. We propose that alpha-TOS displaces UbQ in CII causing electrons generated by SDH to recombine with molecular oxygen to yield ROS. Our data highlight CII, a known tumour suppressor, as a novel target for cancer therapy.

α-Tocopheryl succinate induces apoptosis by targeting ubiquinone-binding sites in mitochondrial respiratory complex II

PubMed Central

Dong, Lan-Feng; Low, Pauline; Dyason, Jeffrey C.; Wang, Xiu-Fang; Prochazka, Lubomir; Witting, Paul K.; Freeman, Ruth; Swettenham, Emma; Valis, Karel; Liu, Ji; Zobalova, Renata; Turanek, Jaroslav; Spitz, Doug R.; Domann, Frederick E.; Scheffler, Immo E.; Ralph, Stephen J.; Neuzil, Jiri

2009-01-01

α-Tocopheryl succinate (α-TOS) is a selective inducer of apoptosis in cancer cells, which involves the accumulation of reactive oxygen species (ROS). The molecular target of α-TOS has not been identified. Here we show that α-TOS inhibits succinate dehydrogenase (SDH) activity of complex II (CII) by interacting with the proximal and distal ubiquinone (UbQ) binding site (QP and QD, respectively). This is based on biochemical analyses and molecular modelling, revealing similar or stronger interaction energy of α-TOS compared to that of UbQ for the QP and QD sites, respectively. CybL-mutant cells with dysfunctional CII failed to accumulate ROS and undergo apoptosis in the presence of α-TOS. Similar resistance was observed when CybL was knocked down with siRNA. Reconstitution of functional CII rendered CybL-mutant cells susceptible to α-TOS. We propose that α-TOS displaces UbQ in CII causing electrons generated by SDH to recombine with molecular oxygen to yield ROS. Our data highlight CII, a known tumour suppressor, as a novel target for cancer therapy. PMID:18372923

A method for detecting small targets based on cumulative weighted value of target properties

NASA Astrophysics Data System (ADS)

Jin, Xing; Sun, Gang; Wang, Wei-hua; Liu, Fang; Chen, Zeng-ping

2015-03-01

Laser detection based on the "cat's eye effect" has become the hot research project for its initiative compared to the passivity of sound detection and infrared detection. And the target detection is one of the core technologies in this system. The paper puts forward a method for detecting small targets based on cumulative weighted value of target properties using given data. Firstly, we make a frame difference to the images, then make image processing based on Morphology Principles. Secondly, we segment images, and screen the targets; then find some interesting locations. Finally, comparing to a quantity of frames, we locate the target. We did an exam to 394 true frames, the experimental result shows that the mathod can detect small targets efficiently.

Height growth and site index curves for Douglas-fir on dry sites in the Willamette National Forest.

Treesearch

Joseph E Means; Mary E. Helm

1985-01-01

Equations and curves are presented for estimating height and site index of Douglas-fir (Pseudotsuga menziesii (Mirb.) Franco) on hot, dry sites in the Willamette National Forest in western Oregon. The equations are based on the dissected stems of 27 trees. The curves differ from those previously published for Douglas-fir. Instructions are presented...

MASCARA-1 b. A hot Jupiter transiting a bright mV = 8.3 A-star in a misaligned orbit

NASA Astrophysics Data System (ADS)

Talens, G. J. J.; Albrecht, S.; Spronck, J. F. P.; Lesage, A.-L.; Otten, G. P. P. L.; Stuik, R.; Van Eylen, V.; Van Winckel, H.; Pollacco, D.; McCormac, J.; Grundahl, F.; Fredslund Andersen, M.; Antoci, V.; Snellen, I. A. G.

2017-10-01

We report the discovery of MASCARA-1 b, which is the first exoplanet discovered with the Multi-site All-Sky CAmeRA (MASCARA). This exoplanet is a hot Jupiter orbiting a bright mV = 8.3, rapidly rotating (vsini⋆ > 100 km s-1) A8 star with a period of 2.148780 ± 8 × 10-6 days. The planet has a mass and radius of 3.7 ± 0.9 MJup and 1.5 ± 0.3 RJup, respectively. As with most hot Jupiters transiting early-type stars, we find a misalignment between the planet orbital axis and the stellar spin axis, which may be a signature of the formation and migration histories of this family of planets. MASCARA-1 b has a mean density of 1.5 ± 0.9 g cm-3 and an equilibrium temperature of 2570+50-30K, that is one of the highest temperatures known for a hot Jupiter to date. The system is reminiscent of WASP-33, but the host star lacks apparent delta-scuti variations, making the planet an ideal target for atmospheric characterization. We expect this to be the first of a series of hot Jupiters transiting bright early-type stars that will be discovered by MASCARA. Tables of the photometry and the reduced spectra as FITS files are only available at the CDS via anonymous ftp to cdsarc.u-strasbg.fr (130.79.128.5) or via http://cdsarc.u-strasbg.fr/viz-bin/qcat?J/A+A/606/A73

Transit Photometry of Recently Discovered Hot Jupiters

NASA Astrophysics Data System (ADS)

McCloat, Sean Peter

The University of North Dakota Space Studies Internet Observatory was used to observe the transits of hot Jupiter exoplanets. Targets for this research were selected from the list of currently confirmed exoplanets using the following criteria: radius > 0.5 Rjup, discovered since 2011, orbiting stars with apparent magnitude > 13. Eleven transits were observed distributed across nine targets with the goal of performing differential photometry for parameter refinement and transit timing variation analysis if data quality allowed. Data quality was ultimately insufficient for robust parameter refinement, but tentative calculations of mid-transit times were made of three of the observed transits. Mid-transit times for WASP-103b and WASP-48b were consistent with predictions and the existing database.

Preliminary design package for solar heating and hot water system

NASA Technical Reports Server (NTRS)

1977-01-01

The preliminary design review on the development of a multi-family solar heating and domestic hot water prototype system is presented. The report contains the necessary information to evaluate the system. The system consists of the following subsystems: collector, storage, transport, control and Government-furnished site data acquisition.

Validity, cut-points, and minimally important differences for two hot flash-related daily interference scales.

PubMed

Carpenter, Janet S; Bakoyannis, Giorgos; Otte, Julie L; Chen, Chen X; Rand, Kevin L; Woods, Nancy; Newton, Katherine; Joffe, Hadine; Manson, JoAnn E; Freeman, Ellen W; Guthrie, Katherine A

2017-08-01

To conduct psychometric analyses to condense the Hot Flash-Related Daily Interference Scale (HFRDIS) into a shorter form termed the Hot Flash Interference (HFI) scale; evaluate cut-points for both scales; and establish minimally important differences (MIDs) for both scales. We analyzed baseline and postrandomization patient-reported data pooled across three randomized trials aimed at reducing vasomotor symptoms (VMS) in 899 midlife women. Trials were conducted across five MsFLASH clinical sites between July 2009 and October 2012. We eliminated HFRDIS items based on experts' content validity ratings and confirmatory factor analysis, and evaluated cut-points and established MIDs by mapping HFRDIS and HFI to other measures. The three-item HFI (interference with sleep, mood, and concentration) demonstrated strong internal consistency (alphas of 0.830 and 0.856), showed good fit to the unidimensional "hot flash interference factor," and strong convergent validity with HFRDIS scores, diary VMS, and menopausal quality of life. For both scales, cut-points of mild (0-3.9), moderate (4-6.9), and severe (7-10) interference were associated with increasing diary VMS ratings, sleep, and anxiety. The average MID was 1.66 for the HFRDIS and 2.34 for the HFI. The HFI is a brief assessment of VMS interference and will be useful in busy clinics to standardize VMS assessment or in research studies where response burden may be an issue. The scale cut-points and MIDs should prove useful in targeting those most in need of treatment, monitoring treatment response, and interpreting existing and future research findings.

Measurements of hot electrons in the Extrap T1 reversed-field pinch

NASA Astrophysics Data System (ADS)

Welander, A.; Bergsåker, H.

1998-02-01

The presence of an anisotropic energetic electron population in the edge region is a characteristic feature of reversed-field pinch (RFP) plasmas. In the Extrap T1 RFP, the anisotropic, parallel heat flux in the edge region measured by calorimetry was typically several hundred 0741-3335/40/2/011/img1. To gain more insight into the origin of the hot electron component and to achieve time resolution of the hot electron flow during the discharge, a target probe with a soft x-ray monitor was designed, calibrated and implemented. The x-ray emission from the target was measured with a surface barrier detector covered with a set of different x-ray filters to achieve energy resolution. A calibration in the range 0.5-2 keV electron energy was performed on the same target and detector assembly using a 0741-3335/40/2/011/img2 cathode electron gun. The calibration data are interpolated and extrapolated numerically. A directional asymmetry of more than a factor of 100 for the higher energy electrons is observed. The hot electrons are estimated to constitute 10% of the total electron density at the edge and their energy distribution is approximated by a half-Maxwellian with a temperature slightly higher than the central electron temperature. Scalings with plasma current, as well as correlations with local 0741-3335/40/2/011/img3 measurements and radial dependences, are presented.

Phototrophy in Mildly Acidic Hot Spring Ecosystems

NASA Astrophysics Data System (ADS)

Fecteau, K.; Boyd, E. S.; Shock, E.

2014-12-01

Microbial light-driven reduction of carbon in continental hydrothermal ecosystems is restricted to environments at temperatures less than 73 °C. In circumneutral and alkaline systems bacterial phototrophs (cyanobacteria and anoxygenic phototrophs) are suggested to be principally responsible for this activity whereas algal (i.e., eukaryotic) phototrophs are thought to be responsible for this activity in acidic systems. In Yellowstone National Park numerous examples of phototrophic microbial communities exist at high and low pH, while hot springs with intermediate pH (values 3-5) are rare and commonly dilute. It is thought that the transition from algal photosynthesis to bacterial photosynthesis occurs within this pH range. To test this hypothesis, we sequenced bacterial and eukaryal small subunit ribosomal RNA genes, analyzed pigments, and performed comprehensive geochemical measurements from 12 hot springs within this pH realm. At all sites, the largest phototrophic population was either comprised of Cyanobacteria or affiliated with the algal order Cyanidiales, which are ubiquitous in acidic springs, yet abundant sequences of both lineages were present in 8 of the 12 sites. Nevertheless, some of these samples exceeded the known temperature limit of the algae (56 °C), suggesting that these populations are dead or inactive. Indeed, one site yielded evidence for a large Cyanidiales population as the only phototrophs present, yet an experiment at the time of sampling failed to demonstrate light-driven carbon fixation, and analysis of extracted pigments showed a large amount of the chlorophyll degradation product pheophorbide a and very little intact chlorophyll, indicating photosynthesis occurred at this site when conditions were different. Our observations illustrate the dynamic nature of these systems that may be transiently conducive to photosynthesis, which may open niches for phototrophs of both domains and likely played a role in the evolution of photosynthesis.

Properties of Galvanized and Galvannealed Advanced High Strength Hot Rolled Steels

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

V.Y. Guertsman; E. Essadiqi; S. Dionne

2008-04-01

The objectives of the project were (i) to develop the coating process information to achieve good quality coatings on 3 advanced high strength hot rolled steels while retaining target mechanical properties, (ii) to obtain precise knowledge of the behavior of these steels in the various forming operations and (iii) to establish accurate user property data in the coated conditions. Three steel substrates (HSLA, DP, TRIP) with compositions providing yield strengths in the range of 400-620 MPa were selected. Only HSLA steel was found to be suitable for galnaizing and galvannealing in the hot rolled condition.

Preferential Binding of Hot Spot Mutant p53 Proteins to Supercoiled DNA In Vitro and in Cells

PubMed Central

Brázdová, Marie; Navrátilová, Lucie; Tichý, Vlastimil; Němcová, Kateřina; Lexa, Matej; Hrstka, Roman; Pečinka, Petr; Adámik, Matej; Vojtesek, Borivoj; Paleček, Emil; Deppert, Wolfgang; Fojta, Miroslav

2013-01-01

Hot spot mutant p53 (mutp53) proteins exert oncogenic gain-of-function activities. Binding of mutp53 to DNA is assumed to be involved in mutp53-mediated repression or activation of several mutp53 target genes. To investigate the importance of DNA topology on mutp53-DNA recognition in vitro and in cells, we analyzed the interaction of seven hot spot mutp53 proteins with topologically different DNA substrates (supercoiled, linear and relaxed) containing and/or lacking mutp53 binding sites (mutp53BS) using a variety of electrophoresis and immunoprecipitation based techniques. All seven hot spot mutp53 proteins (R175H, G245S, R248W, R249S, R273C, R273H and R282W) were found to have retained the ability of wild-type p53 to preferentially bind circular DNA at native negative superhelix density, while linear or relaxed circular DNA was a poor substrate. The preference of mutp53 proteins for supercoiled DNA (supercoil-selective binding) was further substantiated by competition experiments with linear DNA or relaxed DNA in vitro and ex vivo. Using chromatin immunoprecipitation, the preferential binding of mutp53 to a sc mutp53BS was detected also in cells. Furthermore, we have shown by luciferase reporter assay that the DNA topology influences p53 regulation of BAX and MSP/MST1 promoters. Possible modes of mutp53 binding to topologically constrained DNA substrates and their biological consequences are discussed. PMID:23555710

Capsicum and capsaicin--a review: case report of the use of hot peppers in child abuse.

PubMed

Tominack, R L; Spyker, D A

1987-01-01

Capsaicin, the active principle of hot peppers of the genus Capsicum, exhibits broad bioactivity. It targets neuronal structures which contain substance P, clinically seen as gastrointestinal and dermatologic irritation, bronchospasm and fibrinolysis. As a research tool, capsaicin profoundly alters neurologic anatomy and function. We review the toxicity of capsaicin and comment briefly on the use of hot peppers in child abuse.

Thermal hydraulic feasibility assessment of the hot conditioning system and process

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

Heard, F.J.

1996-10-10

The Spent Nuclear Fuel Project was established to develop engineered solutions for the expedited removal, stabilization, and storage of spent nuclear fuel from the K Basins at the U.S. Department of Energy`s Hanford Site in Richland, Washington. A series of analyses have been completed investigating the thermal-hydraulic performance and feasibility of the proposed Hot Conditioning System and process for the Spent Nuclear Fuel Project. The analyses were performed using a series of thermal-hydraulic models that could respond to all process and safety-related issues that may arise pertaining to the Hot Conditioning System. The subject efforts focus on independently investigating, quantifying,more » and establishing the governing heat production and removal mechanisms, flow distributions within the multi-canister overpack, and performing process simulations for various purge gases under consideration for the Hot Conditioning System, as well as obtaining preliminary results for comparison with and verification of other analyses, and providing technology- based recommendations for consideration and incorporation into the Hot Conditioning System design bases.« less

A computational tool to predict the evolutionarily conserved protein-protein interaction hot-spot residues from the structure of the unbound protein.

PubMed

Agrawal, Neeraj J; Helk, Bernhard; Trout, Bernhardt L

2014-01-21

Identifying hot-spot residues - residues that are critical to protein-protein binding - can help to elucidate a protein's function and assist in designing therapeutic molecules to target those residues. We present a novel computational tool, termed spatial-interaction-map (SIM), to predict the hot-spot residues of an evolutionarily conserved protein-protein interaction from the structure of an unbound protein alone. SIM can predict the protein hot-spot residues with an accuracy of 36-57%. Thus, the SIM tool can be used to predict the yet unknown hot-spot residues for many proteins for which the structure of the protein-protein complexes are not available, thereby providing a clue to their functions and an opportunity to design therapeutic molecules to target these proteins. Copyright © 2013 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

Saphenous Venous Ablation with Hot Contrast in a Canine Model

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

Prasad, Amit; Qian Zhong; Kirsch, David

2008-01-15

Purpose. To determine the feasibility, efficacy, and safety of thermal ablation of the saphenous vein with hot contrast medium. Methods. Twelve saphenous veins of 6 dogs were percutaneously ablated with hot contrast medium. In all animals, ablation was performed in the vein of one leg, followed by ablation in the contralateral side 1 month later. An occlusion balloon catheter was placed in the infragenicular segment of the saphenous vein via a jugular access to prevent unwanted thermal effects on the non-target segment of the saphenous vein. After inflation of the balloon, 10 ml of hot contrast medium was injected undermore » fluoroscopic control through a sheath placed in the saphenous vein above the ankle. A second 10 ml injection of hot contrast medium was made after 5 min in each vessel. Venographic follow-up of the ablated veins was performed at 1 month (n = 12) and 2 months (n = 6). Results. Follow-up venograms showed that all ablated venous segments were occluded at 1 month. In 6 veins which were followed up to 2 months, 4 (66%) remained occluded, 1 (16%) was partially patent, and the remaining vein (16%) was completely patent. In these latter 2 cases, an inadequate amount of hot contrast was delivered to the lumen due to a closed balloon catheter downstream which did not allow contrast to displace blood within the vessel. Discussion. Hot contrast medium thermal ablation of the saphenous vein appears feasible, safe, and effective in the canine model, provided an adequate amount of embolization agent is used.« less

Minimizing hot spot temperature in asymmetric gradient coil design.

PubMed

While, Peter T; Forbes, Larry K; Crozier, Stuart

2011-08-01

Heating caused by gradient coils is a considerable concern in the operation of magnetic resonance imaging (MRI) scanners. Hot spots can occur in regions where the gradient coil windings are closely spaced. These problem areas are particularly common in the design of gradient coils with asymmetrically located target regions. In this paper, an extension of an existing coil design method is described, to enable the design of asymmetric gradient coils with reduced hot spot temperatures. An improved model is presented for predicting steady-state spatial temperature distributions for gradient coils. A great amount of flexibility is afforded by this model to consider a wide range of geometries and system material properties. A feature of the temperature distribution related to the temperature gradient is used in a relaxed fixed point iteration routine for successively altering coil windings to have a lower hot spot temperature. Results show that significant reductions in peak temperature are possible at little or no cost to coil performance when compared to minimum power coils of equivalent field error.

The fishes of Hot Springs National Park, Arkansas, 2003

USGS Publications Warehouse

Petersen, James C.; Justus, B.G.

2005-01-01

Fish communities were sampled from eight sites within Hot Springs National Park. Fish were collected by seining and electrofishing during base-flow periods in July and October 2003. All individuals were identified to species. More than 1,020 individuals were collected, representing 24 species. The number of species collected at the sites ranged from 5 to 19. Central stoneroller, orangebelly darter, and longear sunfish were among the more abundant fish species at most sites. These species are typical of small streams in this area. An expected species list incorrectly listed 35 species because of incorrect species range or habitat requirements. Upon revising this list, the inventory yielded 24 of the 51 expected species (47 percent). No species collected in 2003 were federally-listed threatened or endangered species. However, two species collected at Hot Springs National Park may be of special interest to National Park Service managers and others. The Ouachita madtom is endemic to the Ouachita Mountains and is listed as a species of special concern by the Arkansas Natural Heritage Commission. The grass carp, which is a native of eastern Asia, is present in Ricks Pond; one individual was collected and no other grass carp were observed. The introduction of grass carp into the United States is a controversial issue because of possible (but undocumented) harmful effects on native species and habitats.

Functional Roles of Acetylated Histone Marks at Mouse Meiotic Recombination Hot Spots

PubMed Central

Wu, Zhen; Fallahi, Mohammad; Ouizem, Souad; Liu, Qin; Li, Weimin; Costi, Roberta; Roush, William R.; Bois, Philippe R. J.

2016-01-01

ABSTRACT Meiotic recombination initiates following the formation of DNA double-strand breaks (DSBs) by the Spo11 endonuclease early in prophase I, at discrete regions in the genome coined “hot spots.” In mammals, meiotic DSB site selection is directed in part by sequence-specific binding of PRDM9, a polymorphic histone H3 (H3K4Me3) methyltransferase. However, other chromatin features needed for meiotic hot spot specification are largely unknown. Here we show that the recombinogenic cores of active hot spots in mice harbor several histone H3 and H4 acetylation and methylation marks that are typical of open, active chromatin. Further, deposition of these open chromatin-associated histone marks is dynamic and is manifest at spermatogonia and/or pre-leptotene-stage cells, which facilitates PRDM9 binding and access for Spo11 to direct the formation of DSBs, which are initiated at the leptotene stage. Importantly, manipulating histone acetylase and deacetylase activities established that histone acetylation marks are necessary for both hot spot activity and crossover resolution. We conclude that there are functional roles for histone acetylation marks at mammalian meiotic recombination hot spots. PMID:27821479

How important is hydrotherapy? Effects of dynamic action of hot spring water as a rehabilitative treatment for burn patients in Switzerland

PubMed Central

Moufarrij, S.; Deghayli, L.; Raffoul, W.; Hirt-Burri, N.; Michetti, M.; de Buys Roessingh, A.; Norberg, M.; Applegate, L.A.

2014-01-01

Summary Burn rehabilitation using hydrotherapy can have multiple benefits for the burn patient. The therapy uses specific mineral enriched hot spring water and water jets with varied hydro-pressure to combat hypertrophy, inflammatory reaction signs, abnormal pigmentation, and, more specifically, redness and scarring. Standard operating procedures for burn rehabilitation have been developed and integrated into the Standard of Care at the CHUV hospital using localized hydro-mechanical stimulation of burn sites (20 minutes of alternating anatomical sites) followed by constant pressure large-bore and filiform showers targeting specific scarred areas. These therapeutic regimens are repeated daily for 2 to 3 weeks. Patients showed lasting effects from this regimen (up to 3-6 months), the results becoming permanent with more uniform skin structure, color and visco-elasticity in addition to a decrease in pruritus. The specifications of clinical protocols are described herein along with the virtues of hot spring hydro-pressure therapy for burn rehabilitation. The use of hydrotherapy, which has been a controversial topic among burn units across the world, is also discussed. In North America, hydrotherapy is defined only within the scope of in-patient wound cleansing and is thought to lead to microbial auto-contamination and bacterial resistance. In Switzerland and France the emphasis of hydrotherapy is on rehabilitation after the wound has closed. PMID:26336365

Exterior Companions to Hot Jupiters Orbiting Cool Stars Are Coplanar

NASA Astrophysics Data System (ADS)

Becker, Juliette C.; Vanderburg, Andrew; Adams, Fred C.; Khain, Tali; Bryan, Marta

2017-12-01

The existence of hot Jupiters has challenged theories of planetary formation since the first extrasolar planets were detected. Giant planets are generally believed to form far from their host stars, where volatile materials like water exist in their solid phase, making it easier for giant planet cores to accumulate. Several mechanisms have been proposed to explain how giant planets can migrate inward from their birth sites to short-period orbits. One such mechanism, called Kozai-Lidov migration, requires the presence of distant companions in orbits inclined by more than ˜40° with respect to the plane of the hot Jupiter’s orbit. The high occurrence rate of wide companions in hot-Jupiter systems lends support to this theory for migration. However, the exact orbital inclinations of these detected planetary and stellar companions is not known, so it is not clear whether the mutual inclination of these companions is large enough for the Kozai-Lidov process to operate. This paper shows that in systems orbiting cool stars with convective outer layers, the orbits of most wide planetary companions to hot Jupiters must be well aligned with the orbits of the hot Jupiters and the spins of the host stars. For a variety of possible distributions for the inclination of the companion, the width of the distribution must be less than ˜20° to recreate the observations with good fidelity. As a result, the companion orbits are likely well aligned with those of the hot Jupiters, and the Kozai-Lidov mechanism does not enforce migration in these systems.

Scalding in Turkish children: comparison of burns caused by hot water and hot milk.

PubMed

Tarim, Akin; Nursal, Tarik Zafer; Basaran, Ozgür; Yildirim, Sedat; Türk, Emin; Moray, Gökhan; Haberal, Mehmet

2006-06-01

Our aim in this study was to compare the clinical differences and etiologic risk factors for hot water and hot milk scald burns in Turkish children. The retrospective study examined the cases of 140 children aged 0.1-7 years who had scald burns treated in three burn units of a Turkish hospital network between March 2000 and December 2004. The patients were categorized in two groups: hot water burns or hot milk burns. Ninety-five (67.9%) patients had hot water burns and 45 (47.1%) had hot milk burns. The proportion of patients with hot milk burns who lived in rural areas was significantly higher than the corresponding proportion for the hot water cases (75.6% versus 52.6%, respectively; p<0.01). In 20 (44%) of the hot milk cases, the burn was caused by milk being boiled in large pots outdoors for cheese production. The other 25 hot milk cases were caused by milk being boiled in the kitchen. The mean (+/-S.D.) percentage total body surface area burned in the hot milk cases was higher than that in the hot water cases (33.6+/-2.24% versus 21.42+/-1.43%, respectively; p<0.001), and the corresponding mean percentages of TBSA with full-thickness burns were 9.2+/-2.52% versus 3.13+/-0.83%, respectively; (p=0.083). The mean percentages of TBSA with second-degree burns showed the same trend (29.0+/-12.39% versus 18.8+/-1.47%, respectively; p<0.001) higher percentage of the children with hot milk burns required antibiotics (78% versus 52.8%, respectively; p<0.006). Seven (7.4%) of the hot water burn patients and 15 (33.3%) of the hot milk burn patients died during the study period (p=0.025; overall mortality rate 15.7%). Children scalded with hot milk tend to have more extensive burns, and thus have higher mortality, than those scalded with hot water. To create effective programs for preventing scald injuries in Turkey and elsewhere, it is essential to consider ethnic and cultural issues based on these characteristics. Simple precautions should be explained and methods of

Targeting the Allosteric Site of Oncoprotein BCR-ABL as an Alternative Strategy for Effective Target Protein Degradation.

PubMed

Shimokawa, Kenichiro; Shibata, Norihito; Sameshima, Tomoya; Miyamoto, Naoki; Ujikawa, Osamu; Nara, Hiroshi; Ohoka, Nobumichi; Hattori, Takayuki; Cho, Nobuo; Naito, Mikihiko

2017-10-12

Protein degradation technology based on hybrid small molecules is an emerging drug modality that has significant potential in drug discovery and as a unique method of post-translational protein knockdown in the field of chemical biology. Here, we report the first example of a novel and potent protein degradation inducer that binds to an allosteric site of the oncogenic BCR-ABL protein. BCR-ABL allosteric ligands were incorporated into the SNIPER (Specific and Nongenetic inhibitor of apoptosis protein [IAP]-dependent Protein Erasers) platform, and a series of in vitro biological assays of binding affinity, target protein modulation, signal transduction, and growth inhibition were carried out. One of the designed compounds, 6 (SNIPER(ABL)-062), showed desirable binding affinities against ABL1, cIAP1/2, and XIAP and consequently caused potent BCR-ABL degradation.

Delineation of Spatial Variability in the Temperature-Mortality Relationship on Extremely Hot Days in Greater Vancouver, Canada.

PubMed

Ho, Hung Chak; Knudby, Anders; Walker, Blake Byron; Henderson, Sarah B

2017-01-01

Climate change has increased the frequency and intensity of extremely hot weather. The health risks associated with extemely hot weather are not uniform across affected areas owing to variability in heat exposure and social vulnerability, but these differences are challenging to map with precision. We developed a spatially and temporally stratified case-crossover approach for delineation of areas with higher and lower risks of mortality on extremely hot days and applied this approach in greater Vancouver, Canada. Records of all deaths with an extremely hot day as a case day or a control day were extracted from an administrative vital statistics database spanning the years of 1998-2014. Three heat exposure and 11 social vulnerability variables were assigned at the residential location of each decedent. Conditional logistic regression was used to estimate the odds ratio for a 1°C increase in daily mean temperature at a fixed site with an interaction term for decedents living above and below different values of the spatial variables. The heat exposure and social vulnerability variables with the strongest spatially stratified results were the apparent temperature and the labor nonparticipation rate, respectively. Areas at higher risk had values ≥ 34.4°C for the maximum apparent temperature and ≥ 60% of the population neither employed nor looking for work. These variables were combined in a composite index to quantify their interaction and to enhance visualization of high-risk areas. Our methods provide a data-driven framework for spatial delineation of the temperature--mortality relationship by heat exposure and social vulnerability. The results can be used to map and target the most vulnerable areas for public health intervention. Citation: Ho HC, Knudby A, Walker BB, Henderson SB. 2017. Delineation of spatial variability in the temperature-mortality relationship on extremely hot days in greater Vancouver, Canada. Environ Health Perspect 125:66-75;�

Delineation of Spatial Variability in the Temperature–Mortality Relationship on Extremely Hot Days in Greater Vancouver, Canada

PubMed Central

Ho, Hung Chak; Knudby, Anders; Walker, Blake Byron; Henderson, Sarah B.

2016-01-01

Background: Climate change has increased the frequency and intensity of extremely hot weather. The health risks associated with extemely hot weather are not uniform across affected areas owing to variability in heat exposure and social vulnerability, but these differences are challenging to map with precision. Objectives: We developed a spatially and temporally stratified case-crossover approach for delineation of areas with higher and lower risks of mortality on extremely hot days and applied this approach in greater Vancouver, Canada. Methods: Records of all deaths with an extremely hot day as a case day or a control day were extracted from an administrative vital statistics database spanning the years of 1998–2014. Three heat exposure and 11 social vulnerability variables were assigned at the residential location of each decedent. Conditional logistic regression was used to estimate the odds ratio for a 1°C increase in daily mean temperature at a fixed site with an interaction term for decedents living above and below different values of the spatial variables. Results: The heat exposure and social vulnerability variables with the strongest spatially stratified results were the apparent temperature and the labor nonparticipation rate, respectively. Areas at higher risk had values ≥ 34.4°C for the maximum apparent temperature and ≥ 60% of the population neither employed nor looking for work. These variables were combined in a composite index to quantify their interaction and to enhance visualization of high-risk areas. Conclusions: Our methods provide a data-driven framework for spatial delineation of the temperature-–mortality relationship by heat exposure and social vulnerability. The results can be used to map and target the most vulnerable areas for public health intervention. Citation: Ho HC, Knudby A, Walker BB, Henderson SB. 2017. Delineation of spatial variability in the temperature–mortality relationship on extremely hot days in greater

Identification of the hot spot residues for pyridine derivative inhibitor CCT251455 and ATP substrate binding on monopolar spindle 1 (MPS1) kinase by molecular dynamic simulation.

PubMed

Chen, Kai; Duan, Wenxiu; Han, Qianqian; Sun, Xuan; Li, Wenqian; Hu, Shuangyun; Wan, Jiajia; Wu, Jiang; Ge, Yushu; Liu, Dan

2018-03-08

Protein kinase monopolar spindle 1 plays an important role in spindle assembly checkpoint at the onset of mitosis. Over expression of MPS1 correlated with a wide range of human tumors makes it an attractive target for finding an effective and specific inhibitor. In this work, we performed molecular dynamics simulations of protein MPS1 itself as well as protein bound systems with the inhibitor and natural substrate based on crystal structures. The reported orally bioavailable 1 h-pyrrolo [3,2-c] pyridine inhibitors of MPS1 maintained stable binding in the catalytic site, while natural substrate ATP could not stay. Comparative study of stability and flexibility of three systems reveals position shifting of β-sheet region within the catalytic site, which indicates inhibition mechanism was through stabilizing the β-sheet region. Binding free energies calculated with MM-GB/PBSA method shows different binding affinity for inhibitor and ATP. Finally, interactions between protein and inhibitor during molecular dynamic simulations were measured and counted. Residue Gly605 and Leu654 were suggested as important hot spots for stable binding of inhibitor by molecular dynamic simulation. Our results reveal an important position shifting within catalytic site for non-inhibited proteins. Together with hot spots found by molecular dynamic simulation, the results provide important information of inhibition mechanism and will be referenced for designing novel inhibitors.

The distribution of hot spots

NASA Technical Reports Server (NTRS)

Stefanick, M.; Jurdy, D. M.

1984-01-01

Statistical analyses are compared for two published hot spot data sets, one minimal set of 42 and another larger set of 117, using three different approaches. First, the earths surface is divided into 16 equal-area fractions and the observed distribution of hot spots among them is analyzed using chi-square tests. Second, cumulative distributions about the principal axes of the hot spot inertia tensor are used to describe hot spot distribution. Finally, a hot spot density function is constructed for each of the two hot spot data sets. The methods all indicate that hot spots have a nonuniform distribution, even when statistical fluctuations are considered. To the first order, hot spots are concentrated on one half of of the earth's surface area; within that portion, the distribution is consistent with a uniform distribution. The observed hot spot densities for neither data set are explained solely by plate speed.

TISSUE ASSAYS AND POPULATION CHARACTERISTICS OF ROOSEVELT HOT SPRINGS' ANIMALS (1977-1978)

EPA Science Inventory

Geothermal energy exploration is being conducted at several locations in the United States including a site at Roosevelt Hot Springs in southwest Utah. To assess any possible impact and to help design a monitoring strategy for geothermal development, element concentrations in ani...

Enhanced target normal sheath acceleration based on the laser relativistic self-focusing

NASA Astrophysics Data System (ADS)

Zou, D. B.; Zhuo, H. B.; Yang, X. H.; Shao, F. Q.; Ma, Y. Y.; Yu, T. P.; Wu, H. C.; Yin, Y.; Ge, Z. Y.; Li, X. H.

2014-06-01

The enhanced target normal sheath acceleration of ions in laser target interaction via the laser relativistic self-focusing effect is investigated by theoretical analysis and particle-in-cell simulations. The temperature of the hot electrons in the underdense plasma is greatly increased due to the occurrence of resonant absorption, while the electron-betatron-oscillation frequency is close to its witnessed laser frequency [Pukhov et al., Phys. Plasma 6, 2847 (1999)]. While these hot electrons penetrate through the backside solid target, a stronger sheath electric field at the rear surface of the target is induced, which can accelerate the protons to a higher energy. It is also shown that the optimum length of the underdense plasma is approximately equal to the self-focusing distance.

Hot flash report and measurement among Bangladeshi migrants, their London neighbors, and their community of origin.

PubMed

Sievert, L L; Begum, K; Sharmeen, T; Murphy, L; Whitcomb, B W; Chowdhury, O; Muttukrishna, S; Bentley, G R

2016-12-01

To examine hot flashes in relation to climate and activity patterns, and to compare subjective and objective hot flashes among Bangladeshi immigrants to London, their white London neighbors, and women still living in their community of origin, Sylhet, Bangladesh ("sedentees"). Ninety-five women, aged 40-55, wore the Biolog ambulatory hot flash monitor. Objective measurements and subjective hot flash reports were examined in relation to demographic, reproductive, anthropometric, and lifestyle variables; temperature and humidity at 12:00 and 18:00; and time spent on housework and cooking. Concordance of objective and subjective hot flashes was assessed by Kappa statistics and by sensitivity of hot flash classification. During the study period, Bangladeshi sedentees reported more subjective hot flashes (p < .05), but there was no difference in number of objective hot flashes. White Londoners were more likely to describe hot flashes on their face and neck compared to Bangladeshis (p < .05). Sedentees were more likely to describe hot flashes on their feet (p < .05). Postmenopausal status, increasing parity, and high levels of housework were significant determinants of subjective hot flashes, while ambient temperature and humidity were not. Measures of subjective/objective concordance were low but similar across groups (10-20%). The proportion of objective hot flashes that were also self-reported was lowest among immigrants. Hot flashes were not associated with warmer temperatures, but were associated with housework and with site-specific patterns of cooking. The number of objective hot flash measures did not differ, but differences in subjective experience suggest the influence of culture. © 2016 Wiley Periodicals, Inc.

Simultaneous quantification of protein phosphorylation sites using liquid chromatography-tandem mass spectrometry-based targeted proteomics: a linear algebra approach for isobaric phosphopeptides.

PubMed

Xu, Feifei; Yang, Ting; Sheng, Yuan; Zhong, Ting; Yang, Mi; Chen, Yun

2014-12-05

As one of the most studied post-translational modifications (PTM), protein phosphorylation plays an essential role in almost all cellular processes. Current methods are able to predict and determine thousands of phosphorylation sites, whereas stoichiometric quantification of these sites is still challenging. Liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS)-based targeted proteomics is emerging as a promising technique for site-specific quantification of protein phosphorylation using proteolytic peptides as surrogates of proteins. However, several issues may limit its application, one of which relates to the phosphopeptides with different phosphorylation sites and the same mass (i.e., isobaric phosphopeptides). While employment of site-specific product ions allows for these isobaric phosphopeptides to be distinguished and quantified, site-specific product ions are often absent or weak in tandem mass spectra. In this study, linear algebra algorithms were employed as an add-on to targeted proteomics to retrieve information on individual phosphopeptides from their common spectra. To achieve this simultaneous quantification, a LC-MS/MS-based targeted proteomics assay was first developed and validated for each phosphopeptide. Given the slope and intercept of calibration curves of phosphopeptides in each transition, linear algebraic equations were developed. Using a series of mock mixtures prepared with varying concentrations of each phosphopeptide, the reliability of the approach to quantify isobaric phosphopeptides containing multiple phosphorylation sites (≥ 2) was discussed. Finally, we applied this approach to determine the phosphorylation stoichiometry of heat shock protein 27 (HSP27) at Ser78 and Ser82 in breast cancer cells and tissue samples.

The Root Transition Zone: A Hot Spot for Signal Crosstalk.

PubMed

Kong, Xiangpei; Liu, Guangchao; Liu, Jiajia; Ding, Zhaojun

2018-05-01

The root transition zone (TZ), located between the apical meristem and basal elongation region, has a unique role in root growth and development. The root TZ is not only the active site for hormone crosstalk, but also the perception site for various environmental cues, such as aluminum (Al) stress and low phosphate (Pi) stress. We propose that the root TZ is a hot spot for the integration of diverse inputs from endogenous (hormonal) and exogenous (sensorial) stimuli to control root growth. Copyright © 2018 Elsevier Ltd. All rights reserved.

Physiological responses during continuous work in hot dry and hot humid environments in Indians

NASA Astrophysics Data System (ADS)

Sen Gupta, J.; Swamy, Y. V.; Pichan, G.; Dimri, G. P.

1984-06-01

Studies have been conducted on six young healthy heat acclimatised Indians to determine the physiological changes in prolonged continuous work in thermally neutral and in hot dry and hot humid environments. Physiological responses in maximal efforts i.e. Vo2 max, VE max and Cf max were noted. In addition, duration in continuous work at three sub-maximal rate of work in three simulated environments were also noted. Physiological responses like Vo2, VE and Cf were noted every 15 minutes of work. Besides these responses, rectal temperature (Tre), mean skin temperature (Ts) and mean sweat rate were also recorded during continuous work. Results indicated a significant decrease in maximum oxygen uptake capacity (Vo2 max) in heat with no change in maximum exercise ventilation (VE max) and maximum cardiac frequency. However, the fall in Vo2 max was more severe in the hot humid environment than in the hot dry climate. Cardiac frequency at fixed oxygen consumption of 1.0, 1.5 and 2.0 l/min was distinctly higher in the hot humid environment than in the hot dry and comfortable temperature. The duration in continuous physical effort in various grades of activities decreased in hot dry environment from that in the-comfortable climate and further decreased significantly in hot humid environment. The highest rate of sweating was observed during work in humid heat. The mean skin temperature (Ts) showed a fall in all the three rates of work in comfortable and hot dry conditions whereas in hot humid environment it showed a linear rise during the progress of work. The rectal temperature on the other hand maintained a near steady state while working at 65 and 82 watts in comfortable and hot dry environments but kept on rising during work in hot humid environment. At the highest work rate of 98 watts, the rectal temperature showed a steady increase even in the hot dry condition. It was thus concluded from the study that a hot humid climate imposes more constraints on the

The Median Isn't the Message: Elucidating Nutrient Hot spots and Hot Moments in a Sierra Nevada Forest Soil

NASA Astrophysics Data System (ADS)

Barnes, M. E.; Hart, S. C.; Johnson, D. W.; Meadows, M. W.

2015-12-01

Most biogeochemical studies in forests have concentrated on nutrient pools and transformations occurring at relatively large spatial scales (i.e., stand or small catchment), over monthly or annual time scales. Many of these studies have also focused on the average or medial values observed across the spatial or temporal scale studied, discounting outliers. However, extremely high values found consistently (hot spot) or infrequently (hot moment) at a given soil microsite may be critical for nutrient acquisition by organisms and nutrient retention by terrestrial ecosystems. We have been evaluating soil nutrient hot-spot and hot-moment phenomena vertically (to a 60-cm depth) and horizontally (2-m sampling interval within a 6 m x 6 m grid) in two areas within a mixed-conifer, Sierran forest experiencing a Mediterranean-type climate. Nutrient fluxes in space and time were measured using ion exchange resin capsules placed at various depths and collected at two times (first significant precipitation in fall and post-snowmelt in spring) per year. Our previous work over a single year showed that fluxes of Ca2+ and Mg2+ in mineral soil were substantially greater in the spring than in the fall, suggesting that soil water was a major factor in controlling these nutrient fluxes. The opposite pattern was found for NH4+ and Na+, where greater fluxes occurred following the first precipitation event in fall. Here, we report new data over two additional years at these same sites. Over the entire 3-year study, nutrient fluxes were greater in the fall for all mineral soil nutrients except Ca2+ and Mg2+. Calcium fluxes were consistent with previous results; however, Mg2+ demonstrated no statistical significance between fall and spring sampling dates. Generally, the number of high statistical outliers persisted through time for Ca2+ and Mg2+, suggesting hot spots for these nutrients. In contrast, large seasonal and annual changes in the number of high statistical outliers occurred for

Rational modification of protein stability by targeting surface sites leads to complicated results

PubMed Central

Xiao, Shifeng; Patsalo, Vadim; Shan, Bing; Bi, Yuan; Green, David F.; Raleigh, Daniel P.

2013-01-01

The rational modification of protein stability is an important goal of protein design. Protein surface electrostatic interactions are not evolutionarily optimized for stability and are an attractive target for the rational redesign of proteins. We show that surface charge mutants can exert stabilizing effects in distinct and unanticipated ways, including ones that are not predicted by existing methods, even when only solvent-exposed sites are targeted. Individual mutation of three solvent-exposed lysines in the villin headpiece subdomain significantly stabilizes the protein, but the mechanism of stabilization is very different in each case. One mutation destabilizes native-state electrostatic interactions but has a larger destabilizing effect on the denatured state, a second removes the desolvation penalty paid by the charged residue, whereas the third introduces unanticipated native-state interactions but does not alter electrostatics. Our results show that even seemingly intuitive mutations can exert their effects through unforeseen and complex interactions. PMID:23798426

Analytical modeling of the temporal evolution of hot spot temperatures in silicon solar cells

NASA Astrophysics Data System (ADS)

Wasmer, Sven; Rajsrima, Narong; Geisemeyer, Ino; Fertig, Fabian; Greulich, Johannes Michael; Rein, Stefan

2018-03-01

We present an approach to predict the equilibrium temperature of hot spots in crystalline silicon solar cells based on the analysis of their temporal evolution right after turning on a reverse bias. For this end, we derive an analytical expression for the time-dependent heat diffusion of a breakdown channel that is assumed to be cylindrical. We validate this by means of thermography imaging of hot spots right after turning on a reverse bias. The expression allows to be used to extract hot spot powers and radii from short-term measurements, targeting application in inline solar cell characterization. The extracted hot spot powers are validated at the hands of long-term dark lock-in thermography imaging. Using a look-up table of expected equilibrium temperatures determined by numerical and analytical simulations, we utilize the determined hot spot properties to predict the equilibrium temperatures of about 100 industrial aluminum back-surface field solar cells and achieve a high correlation coefficient of 0.86 and a mean absolute error of only 3.3 K.

Clean subglacial access: prospects for future deep hot-water drilling

PubMed Central

Pearce, David; Hodgson, Dominic A.; Smith, Andrew M.; Rose, Mike; Ross, Neil; Mowlem, Matt; Parnell, John

2016-01-01

Accessing and sampling subglacial environments deep beneath the Antarctic Ice Sheet presents several challenges to existing drilling technologies. With over half of the ice sheet believed to be resting on a wet bed, drilling down to this environment must conform to international agreements on environmental stewardship and protection, making clean hot-water drilling the most viable option. Such a drill, and its water recovery system, must be capable of accessing significantly greater ice depths than previous hot-water drills, and remain fully operational after connecting with the basal hydrological system. The Subglacial Lake Ellsworth (SLE) project developed a comprehensive plan for deep (greater than 3000 m) subglacial lake research, involving the design and development of a clean deep-ice hot-water drill. However, during fieldwork in December 2012 drilling was halted after a succession of equipment issues culminated in a failure to link with a subsurface cavity and abandonment of the access holes. The lessons learned from this experience are presented here. Combining knowledge gained from these lessons with experience from other hot-water drilling programmes, and recent field testing, we describe the most viable technical options and operational procedures for future clean entry into SLE and other deep subglacial access targets. PMID:26667913

Hot and cold executive functions in youth with psychotic symptoms.

PubMed

MacKenzie, L E; Patterson, V C; Zwicker, A; Drobinin, V; Fisher, H L; Abidi, S; Greve, A N; Bagnell, A; Propper, L; Alda, M; Pavlova, B; Uher, R

2017-12-01

Psychotic symptoms are common in children and adolescents and may be early manifestations of liability to severe mental illness (SMI), including schizophrenia. SMI and psychotic symptoms are associated with impairment in executive functions. However, previous studies have not differentiated between 'cold' and 'hot' executive functions. We hypothesized that the propensity for psychotic symptoms is specifically associated with impairment in 'hot' executive functions, such as decision-making in the context of uncertain rewards and losses. In a cohort of 156 youth (mean age 12.5, range 7-24 years) enriched for familial risk of SMI, we measured cold and hot executive functions with the spatial working memory (SWM) task (total errors) and the Cambridge Gambling Task (decision-making), respectively. We assessed psychotic symptoms using the semi-structured Kiddie Schedule for Affective Disorders and Schizophrenia interview, Structured Interview for Prodromal Syndromes, Funny Feelings, and Schizophrenia Proneness Instrument - Child and Youth version. In total 69 (44.23%) youth reported psychotic symptoms on one or more assessments. Cold executive functioning, indexed with SWM errors, was not significantly related to psychotic symptoms [odds ratio (OR) 1.36, 95% confidence interval (CI) 0.85-2.17, p = 0.204). Poor hot executive functioning, indexed as decision-making score, was associated with psychotic symptoms after adjustment for age, sex and familial clustering (OR 2.37, 95% CI 1.25-4.50, p = 0.008). The association between worse hot executive functions and psychotic symptoms remained significant in sensitivity analyses controlling for general cognitive ability and cold executive functions. Impaired hot executive functions may be an indicator of risk and a target for pre-emptive early interventions in youth.

Economic evaluation of a solar hot-water system--Palm Beach County, Florida

NASA Technical Reports Server (NTRS)

1981-01-01

Report projects solar-energy costs and savings for residential hot-water system over 20 year period. Evaluation uses technical and economic models with inputs based on working characteristics of installed system. Primary analysis permits calculation of economic viability for four other U.S. sites.

Epitope-based peptide vaccine design and target site depiction against Ebola viruses: an immunoinformatics study.

PubMed

Khan, M A; Hossain, M U; Rakib-Uz-Zaman, S M; Morshed, M N

2015-07-01

Ebola viruses (EBOVs) have been identified as an emerging threat in recent year as it causes severe haemorrhagic fever in human. Epitope-based vaccine design for EBOVs remains a top priority because a mere progress has been made in this regard. Another reason is the lack of antiviral drug and licensed vaccine although there is a severe outbreak in Central Africa. In this study, we aimed to design an epitope-based vaccine that can trigger a significant immune response as well as to prognosticate inhibitor that can bind with potential drug target sites using various immunoinformatics and docking simulation tools. The capacity to induce both humoral and cell-mediated immunity by T cell and B cell was checked for the selected protein. The peptide region spanning 9 amino acids from 42 to 50 and the sequence TLASIGTAF were found as the most potential B and T cell epitopes, respectively. This peptide could interact with 12 HLAs and showed high population coverage up to 80.99%. Using molecular docking, the epitope was further appraised for binding against HLA molecules to verify the binding cleft interaction. In addition with this, the allergenicity of the epitopes was also evaluated. In the post-therapeutic strategy, docking study of predicted 3D structure identified suitable therapeutic inhibitor against targeted protein. However, this computational epitope-based peptide vaccine designing and target site prediction against EBOVs open up a new horizon which may be the prospective way in Ebola viruses research; the results require validation by in vitro and in vivo experiments. © 2015 John Wiley & Sons Ltd.

Roosevelt Hot Springs, Utah FORGE X-Ray Diffraction Data

DOE Data Explorer

Nash, Greg; Jones, Clay

2018-02-07

This dataset contains X-ray diffraction (XRD) data taken from wells and outcrops as part of the DOE GTO supported Utah FORGE project located near Roosevelt Hot Springs. It contains an Excel spreadsheet with the XRD data, a text file with sample site names, types, and locations in UTM, Zone 12, NAD83 coordinates, and a GIS shapefile of the sample locations with attributes.

Geothermal energy in Washington: site data base and development status

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

Bloomquist, R.G.

1979-04-01

This is an attempt to identify the factors which have affected and will continue to affect geothermal assessment and development in the state. The eight potential sites chosen for detailed analysis include: Indian Heaven KGRA, Mount St. Helens KGRA, Kennedy Hot Springs KGRA, Mount Adams PGRA (Potential Geothermal Resource Area), Mount Rainier PGRA, Mount Baker PGRA, Olympic-Sol Duc Hot Springs, and Yakima. The following information is included for each site: site data, site location and physical description, geological/geophysical description, reservoir characteristics, land ownership and leasing, geothermal development status, institutional characteristics, environmental factors, transportation and utilities, and population. A number ofmore » serious impediments to geothermal development were identified which can be solved only by legislative action at the state or federal level and/or changes in attitudes by regulatory agencies. (MHR)« less

TargetSpy: a supervised machine learning approach for microRNA target prediction.

PubMed

Sturm, Martin; Hackenberg, Michael; Langenberger, David; Frishman, Dmitrij

2010-05-28

Virtually all currently available microRNA target site prediction algorithms require the presence of a (conserved) seed match to the 5' end of the microRNA. Recently however, it has been shown that this requirement might be too stringent, leading to a substantial number of missed target sites. We developed TargetSpy, a novel computational approach for predicting target sites regardless of the presence of a seed match. It is based on machine learning and automatic feature selection using a wide spectrum of compositional, structural, and base pairing features covering current biological knowledge. Our model does not rely on evolutionary conservation, which allows the detection of species-specific interactions and makes TargetSpy suitable for analyzing unconserved genomic sequences.In order to allow for an unbiased comparison of TargetSpy to other methods, we classified all algorithms into three groups: I) no seed match requirement, II) seed match requirement, and III) conserved seed match requirement. TargetSpy predictions for classes II and III are generated by appropriate postfiltering. On a human dataset revealing fold-change in protein production for five selected microRNAs our method shows superior performance in all classes. In Drosophila melanogaster not only our class II and III predictions are on par with other algorithms, but notably the class I (no-seed) predictions are just marginally less accurate. We estimate that TargetSpy predicts between 26 and 112 functional target sites without a seed match per microRNA that are missed by all other currently available algorithms. Only a few algorithms can predict target sites without demanding a seed match and TargetSpy demonstrates a substantial improvement in prediction accuracy in that class. Furthermore, when conservation and the presence of a seed match are required, the performance is comparable with state-of-the-art algorithms. TargetSpy was trained on mouse and performs well in human and drosophila

TargetSpy: a supervised machine learning approach for microRNA target prediction

PubMed Central

2010-01-01

Background Virtually all currently available microRNA target site prediction algorithms require the presence of a (conserved) seed match to the 5' end of the microRNA. Recently however, it has been shown that this requirement might be too stringent, leading to a substantial number of missed target sites. Results We developed TargetSpy, a novel computational approach for predicting target sites regardless of the presence of a seed match. It is based on machine learning and automatic feature selection using a wide spectrum of compositional, structural, and base pairing features covering current biological knowledge. Our model does not rely on evolutionary conservation, which allows the detection of species-specific interactions and makes TargetSpy suitable for analyzing unconserved genomic sequences. In order to allow for an unbiased comparison of TargetSpy to other methods, we classified all algorithms into three groups: I) no seed match requirement, II) seed match requirement, and III) conserved seed match requirement. TargetSpy predictions for classes II and III are generated by appropriate postfiltering. On a human dataset revealing fold-change in protein production for five selected microRNAs our method shows superior performance in all classes. In Drosophila melanogaster not only our class II and III predictions are on par with other algorithms, but notably the class I (no-seed) predictions are just marginally less accurate. We estimate that TargetSpy predicts between 26 and 112 functional target sites without a seed match per microRNA that are missed by all other currently available algorithms. Conclusion Only a few algorithms can predict target sites without demanding a seed match and TargetSpy demonstrates a substantial improvement in prediction accuracy in that class. Furthermore, when conservation and the presence of a seed match are required, the performance is comparable with state-of-the-art algorithms. TargetSpy was trained on mouse and performs well

Disaggregating Hot Water Use and Predicting Hot Water Waste in Five Test Homes

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

Henderson, H.; Wade, J.

2014-04-01

While it is important to make the equipment (or 'plant') in a residential hot water system more efficient, the hot water distribution system also affects overall system performance and energy use. Energy wasted in heating water that is not used is estimated to be on the order of 10 to 30 percent of total domestic hot water (DHW) energy use. This field monitoring project installed temperature sensors on the distribution piping (on trunks and near fixtures) and programmed a data logger to collect data at 5 second intervals whenever there was a hot water draw. This data was used tomore » assign hot water draws to specific end uses in the home as well as to determine the portion of each hot water that was deemed useful (i.e., above a temperature threshold at the fixture). Five houses near Syracuse NY were monitored. Overall, the procedures to assign water draws to each end use were able to successfully assign about 50% of the water draws, but these assigned draws accounted for about 95% of the total hot water use in each home. The amount of hot water deemed as useful ranged from low of 75% at one house to a high of 91% in another. At three of the houses, new water heaters and distribution improvements were implemented during the monitoring period and the impact of these improvements on hot water use and delivery efficiency were evaluated.« less

Disaggregating Hot Water Use and Predicting Hot Water Waste in Five Test Homes

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

Henderson, Hugh; Wade, Jeremy

2014-04-01

While it is important to make the equipment (or "plant") in a residential hot water system more efficient, the hot water distribution system also affects overall system performance and energy use. Energy wasted in heating water that is not used is estimated to be on the order of 10%-30% of total domestic hot water (DHW) energy use. This field monitoring project installed temperature sensors on the distribution piping (on trunks and near fixtures) in five houses near Syracuse, NY, and programmed a data logger to collect data at 5 second intervals whenever there was a hot water draw. This datamore » was used to assign hot water draws to specific end uses in the home as well as to determine the portion of each hot water that was deemed useful (i.e., above a temperature threshold at the fixture). Overall, the procedures to assign water draws to each end use were able to successfully assign about 50% of the water draws, but these assigned draws accounted for about 95% of the total hot water use in each home. The amount of hot water deemed as useful ranged from low of 75% at one house to a high of 91% in another. At three of the houses, new water heaters and distribution improvements were implemented during the monitoring period and the impact of these improvements on hot water use and delivery efficiency were evaluated.« less

Exploratory study of hot-in-place recycling of asphalt pavements, volume II : appendices.

DOT National Transportation Integrated Search

1994-11-01

Hot-in-place recycling (HIR) is a method for rehabilitation of asphalt pavements. Potential for cost savings and resource preservation are high because existing pavement materials are processed on-site, with only the addition of small amounts of recy...

Hot cracking susceptibility of Alloy 52M weld overlays onto CF8 stainless steel

NASA Astrophysics Data System (ADS)

Chu, H. A.; Young, M. C.; Chu, H. C.; Tsay, L. W.; Chen, C.

2013-02-01

In this study, weld overlays of Alloy 52M (a nickel-based filler metal) onto CF8 stainless steel (SS) were performed using the gas tungsten arc welding process. Hot cracking in the weld overlays was observed particularly near the interfacial region of the Alloy 52M/CF8 weld overlay. In general, the hot cracks were most likely to occur at the sites with high dilution rates, e.g., at the weld start/end locations of a single pass or in the first and second passes in multi-pass overlays. The region near the weld interface between Alloy 52M and the CF8 SS had a higher hot cracking tendency than the other regions. It was found that the dilution rate and the formation of eutectic-type constituents (i.e., γ/NbC) both played significant roles in the determination of the hot cracking susceptibility of these weld overlays. Nevertheless, hot cracks were entirely eliminated by proper deposition of a SS buffer layer prior to overlaying with Alloy 52M.

RNA interference as a method for target-site screening in the Western Corn Rootworm, Diabrotica virgifera virgifera

USDA-ARS?s Scientific Manuscript database

RNA interference (RNAi) is one of the most powerful and extraordinarily-specific means by which to silence genes. The ability of RNAi to silence genes makes it possible to ascertain function from genomic data, thereby making it an excellent choice for target-site screening. To test the efficacy of...

Glioma Dual-Targeting Nanohybrid Protein Toxin Constructed by Intein-Mediated Site-Specific Ligation for Multistage Booster Delivery

PubMed Central

Chen, Yingzhi; Zhang, Meng; Jin, Hongyue; Li, Dongdong; Xu, Fan; Wu, Aihua; Wang, Jinyu; Huang, Yongzhuo

2017-01-01

Malignant glioma is one of the most untreatable cancers because of the formidable blood-brain barrier (BBB), through which few therapeutics can penetrate and reach the tumors. Biologics have been booming in cancer therapy in the past two decades, but their application in brain tumor has long been ignored due to the impermeable nature of BBB against effective delivery of biologics. Indeed, it is a long unsolved problem for brain delivery of macromolecular drugs, which becomes the Holy Grail in medical and pharmaceutical sciences. Even assisting by targeting ligands, protein brain delivery still remains challenging because of the synthesis difficulties of ligand-modified proteins. Herein, we propose a rocket-like, multistage booster delivery system of a protein toxin, trichosanthin (TCS), for antiglioma treatment. TCS is a ribosome-inactivating protein with the potent activity against various solid tumors but lack of specific action and cell penetration ability. To overcome the challenge of its poor druggability and site-specific modification, intein-mediated ligation was applied, by which a gelatinase-cleavable peptide and cell-penetrating peptide (CPP)-fused recombinant TCS toxin can be site-specifically conjugated to lactoferrin (LF), thus constructing a BBB-penetrating, gelatinase-activatable cell-penetrating nanohybrid TCS toxin. This nanohybrid TCS system is featured by the multistage booster strategy for glioma dual-targeting delivery. First, LF can target to the BBB-overexpressing low-density lipoprotein receptor-related protein-1 (LRP-1), and assist with BBB penetration. Second, once reaching the tumor site, the gelatinase-cleavable peptide acts as a separator responsive to the glioma-associated matrix metalloproteinases (MMPs), thus releasing to the CPP-fused toxin. Third, CPP mediates intratumoral and intracellular penetration of TCS toxin, thereby enhancing its antitumor activity. The BBB penetration and MMP-2-activability of this delivery system were

Modelling Hot Air Balloons.

ERIC Educational Resources Information Center

Brimicombe, M. W.

1991-01-01

A macroscopic way of modeling hot air balloons using a Newtonian approach is presented. Misleading examples using a car tire and the concept of hot air rising are discussed. Pressure gradient changes in the atmosphere are used to explain how hot air balloons work. (KR)

Hot Groups.

ERIC Educational Resources Information Center

Vail, Kathleen

1996-01-01

Collaborators sparked by creative ideas and obsessed by a common task may not realize they're part of a "hot group"--a term coined by business professors Harold J. Leavitt and Jean Lipman-Blumen. Spawned by group decision making and employee empowerment, hot groups can flourish in education settings. They're typically small, short lived,…

Site Targeted Press Coated Delivery of Methylprednisolone Using Eudragit RS 100 and Chitosan for Treatment of Colitis.

PubMed

Jagdale, Swati; Chandekar, Apoorva

2016-01-01

Inflammatory bowel disease (IBD) is one of the five most prevalent gastrointestinal disease burdens which commonly require lifetime care. Worldwide incidence rate of ulcerative colitis and Crohn's disease is about 16.8% and 13.4% respectively. Colitis is an inflammation of the colon. Colon targeted drug delivery will direct the drug to the colon. The drug will reach at the site of action and hence its side effects as well as dose can be reduced. Recent patent describes treatment of ulcerative colitis using anti CD3 antibodies, with nicotine and anti-depressant drugs, budesonide foam etc. Present study deals with optimization of site targeted methylprednisolone delivery for treatment of colitis. Chitosan and Eudragit RS 100 were used as coating polymers. Tablets were prepared by press coated technology. The core tablets contain drug, avicel as binder, croscarmellose sodium as super disintegrant and dicalcium phosphate as diluent. Drug excipient compatibility was carried out using FTIR, UV and DSC. Design of experiment was used to optimize the formulation. Tablets were evaluated for thickness, weight variation, hardness, swelling index, in-vitro drug release and release of drug in simulated media. Optimized batch (B2) contained chitosan 40% and eudragit RS 100 17.5%. B2 showed in-vitro drug release 85.65 ± 7.6% in 6.8 pH phosphate buffer and 96.7 ±9.1% in simulated media after 7.5 hours. In-vivo x-ray placebo study for formulation B2 had shown that the tablet reached to the ascending colon after 5 hours. This indicated a potential site targeted delivery of optimized batch B2.

Building America Case Study: Performance of a Hot-Dry Climate Whole House Retrofit, Stockton, California (Fact Sheet)

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

ARBI

2014-09-01

The Stockton house retrofit is a two-story tudor style single family deep retrofit in the hot-dry climate of Stockton, CA. The home is representative of a deep retrofit option of the scaled home energy upgrade packages offered to targeted neighborhoods under the pilot Large-Scale Retrofit Program (LSRP) administered by the Alliance for Residential Building Innovation (ARBI). Deep retrofit packages expand on the standard package by adding HVAC, water heater and window upgrades to the ducting, attic and floor insulation, domestic hot water insulation, envelope sealing, lighting and ventilation upgrades. Site energy savings with the deep retrofit were 23% compared tomore » the pre-retrofit case, and 15% higher than the savings estimated for the standard retrofit package. Energy savings were largely a result of the water heater upgrade, and a combination of the envelope sealing, insulation and HVAC upgrade. The HVAC system was of higher efficiency than the building code standard. Overall the financed retrofit would have been more cost effective had a less expensive HVAC system been selected and barriers to wall insulation remedied. The homeowner experienced improved comfort throughout the monitored period and was satisfied with the resulting utility bill savings.« less

Resolving hot spot microstructure using x-ray penumbral imaging (invited)

NASA Astrophysics Data System (ADS)

Bachmann, B.; Hilsabeck, T.; Field, J.; Masters, N.; Reed, C.; Pardini, T.; Rygg, J. R.; Alexander, N.; Benedetti, L. R.; Döppner, T.; Forsman, A.; Izumi, N.; LePape, S.; Ma, T.; MacPhee, A. G.; Nagel, S.; Patel, P.; Spears, B.; Landen, O. L.

2016-11-01

We have developed and fielded x-ray penumbral imaging on the National Ignition Facility in order to enable sub-10 μm resolution imaging of stagnated plasma cores (hot spots) of spherically shock compressed spheres and shell implosion targets. By utilizing circular tungsten and tantalum apertures with diameters ranging from 20 μm to 2 mm, in combination with image plate and gated x-ray detectors as well as imaging magnifications ranging from 4 to 64, we have demonstrated high-resolution imaging of hot spot plasmas at x-ray energies above 5 keV. Here we give an overview of the experimental design criteria involved and demonstrate the most relevant influences on the reconstruction of x-ray penumbral images, as well as mitigation strategies of image degrading effects like over-exposed pixels, artifacts, and photon limited source emission. We describe experimental results showing the advantages of x-ray penumbral imaging over conventional Fraunhofer and photon limited pinhole imaging and showcase how internal hot spot microstructures can be resolved.

Resolving hot spot microstructure using x-ray penumbral imaging (invited).

PubMed

Bachmann, B; Hilsabeck, T; Field, J; Masters, N; Reed, C; Pardini, T; Rygg, J R; Alexander, N; Benedetti, L R; Döppner, T; Forsman, A; Izumi, N; LePape, S; Ma, T; MacPhee, A G; Nagel, S; Patel, P; Spears, B; Landen, O L

2016-11-01

We have developed and fielded x-ray penumbral imaging on the National Ignition Facility in order to enable sub-10 μm resolution imaging of stagnated plasma cores (hot spots) of spherically shock compressed spheres and shell implosion targets. By utilizing circular tungsten and tantalum apertures with diameters ranging from 20 μm to 2 mm, in combination with image plate and gated x-ray detectors as well as imaging magnifications ranging from 4 to 64, we have demonstrated high-resolution imaging of hot spot plasmas at x-ray energies above 5 keV. Here we give an overview of the experimental design criteria involved and demonstrate the most relevant influences on the reconstruction of x-ray penumbral images, as well as mitigation strategies of image degrading effects like over-exposed pixels, artifacts, and photon limited source emission. We describe experimental results showing the advantages of x-ray penumbral imaging over conventional Fraunhofer and photon limited pinhole imaging and showcase how internal hot spot microstructures can be resolved.

MAPK Target Sites of Eyes Absent Are Not Required for Eye Development or Survival in Drosophila

PubMed Central

Jusiak, Barbara; Abulimiti, Abuduaini; Haelterman, Nele; Chen, Rui; Mardon, Graeme

2012-01-01

Eyes absent (Eya) is a highly conserved transcription cofactor and protein phosphatase that plays an essential role in eye development and survival in Drosophila. Ectopic eye induction assays using cDNA transgenes have suggested that mitogen activated protein kinase (MAPK) activates Eya by phosphorylating it on two consensus target sites, S402 and S407, and that this activation potentiates the ability of Eya to drive eye formation. However, this mechanism has never been tested in normal eye development. In the current study, we generated a series of genomic rescue transgenes to investigate how loss- and gain-of-function mutations at these two MAPK target sites within Eya affect Drosophila survival and normal eye formation: eya+GR, the wild-type control; eyaSAGR, which lacks phosphorylation at the two target residues; and eyaSDEGR, which contains phosphomimetic amino acids at the same two residues. Contrary to the previous studies in ectopic eye development, all eya genomic transgenes tested rescue both eye formation and survival equally effectively. We conclude that, in contrast to ectopic eye formation, MAPK-mediated phosphorylation of Eya on S402 and S407 does not play a role in normal development. This is the first study in Drosophila to evaluate the difference in outcomes between genomic rescue and ectopic cDNA-based overexpression of the same gene. These findings indicate similar genomic rescue strategies may prove useful for re-evaluating other long-standing Drosophila developmental models. PMID:23251383

Understanding the effects of laser imprint on plastic-target implosions on OMEGA

NASA Astrophysics Data System (ADS)

Hu, S. X.; Michel, D. T.; Davis, A. K.; Betti, R.; Radha, P. B.; Campbell, E. M.; Froula, D. H.; Stoeckl, C.

2016-10-01

Understanding the effects of laser imprint on target performance is critical to the success of direct-drive inertial confinement fusion. Directly measuring the disruption caused by laser imprints to the imploding shell and hot-spot formation, in comparison with multidimensional radiation-hydrodynamic simulations, can provide a clear picture of how laser nonuniformities cause target performance to degrade. With the recently developed x-ray self-emission imaging technique and the state-of-the-art physics models recently implemented in the two-dimensional hydrocode DRACO, a systematic study of laser-imprint effects on warm target implosions on OMEGA has been performed using both experimental results and simulations. By varying the laser-picket intensity, the imploding shells were set at different adiabats (from α = 2 to α = 6). As the shell adiabats decreased, it was observed that (1) the measured shell thickness at the time the hot spot lit up became larger than the uniform one-dimensional (1-D) predictions; (2) the hot-spot core emitted earlier than the corresponding 1-D predictions; (3) the measured neutron yield first increased then decreased as the shell adiabat α was reduced; and (4) the hot-spot size reduced as α decreased for cases where SSD (smoothing by spectral dispersion) was on but became larger for low-α shots in cases where SSD was off. Most of these experimental observations are well reproduced by DRACO simulations with laser imprints including modes up to λmax = 200. These studies identify the importance of laser imprint as the major source of degrading target performance for OMEGA implosions of adiabat α ≤ 3. Mitigating laser imprints is required to improve low-α target performance.

Prototype solar heating and hot water systems

NASA Technical Reports Server (NTRS)

1977-01-01

Alternative approaches to solar heating and hot water system configurations were studied, parametrizing the number and location of the dampers, the number and location of the fans, the interface locations with the furnace, the size and type of subsystems, and operating modes. A two-pass air-heating collector was selected based on efficiency and ease of installation. Also, an energy transport module was designed to compactly contain all the mechanical and electrical control components. System performance calculations were carried out over a heating season for the tentative site location at Tunkhnana, Pa. Results illustrate the effect of collector size, storage capacity, and use of a reflector. Factors which affected system performance include site location, insulative quality of the house, and of the system components. A preliminary system performance specification is given.

Menopausal hot flashes: Randomness or rhythmicity

NASA Astrophysics Data System (ADS)

Kronenberg, Fredi

1991-10-01

Menopausal hot flashes are episodes of flushing, increased heart rate, skin blood flow and skin temperature, and a sensation of heat. The thermoregulatory and cardiovascular concomitants of hot flashes are associated with peaks in the levels of various hormones and neurotransmitters in the peripheral circulation. Although hot flashes affect about 75% of women, and are the primary reason that women at menopause seek medical attention, the mechanism of hot flashes is still not understood. Hot flashes vary in frequency and intensity both within and between individuals, and have been thought of as occurring randomly. Yet, some women report that their hot flashes are worse at a particular time of day or year. Initial examination of subjects' recordings of their hot flashes showed diurnal patterns of hot flash occurrence. There also seems to be a diurnal rhythm of hot flash intensity. Continuous physiological monitoring of hot flashes is facilitating the analysis of these patterns, which is revealing circadian and ultradian periodicities. The occurrence of hot flashes can be modulated by external and internal factors, including ambient temperature and fever. Rhythms of thermoregulatory and endocrine functions also may influence hot flash patterns. Examination of the interrelationships between the various systems of the body involved in hot flashes, and a multidisciplinary approach to the analysis of hot flash patterns, will aid our understanding of this complex phenomenon.

Action Memorandum for Decommissioning of TAN-607 Hot Shop Area

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

M. A. Pinzel

The Department of Energy is documenting the selection of an alternative for the TAN-607 Hot Shop Area using a Comprehensive Environmental Response, Compensation, and Liability Act non-time-critical removal action (NTCRA). The scope of the removal action is limited to TAN-607 Hot Shop Area. An engineering evaluation/cost analysis (EE/CA) has assisted the Department of Energy Idaho Operations Office in identifuomg the most effective method for performing the decommissioning of this structure whose mission has ended. TAN-607 Hot Shop Area is located at Test Area North Technical Support Facility within the Idaho National Laboratory Site. The selected alternative consists of demolishing themore » TAN-607 aboveground structures and components, removing belowground noninert components (e.g. wood products), and removing the radiologically contaminated debris that does not meet remedial action objectives (RAOs), as defined in the Record of Decision Amendment for the V-Tanks and Explanation of Significant Differences for the PM-2A Tanks at Test Area North, Operable Unit 1-10.« less

Hot Accretion Spots and Nitrogen Enhancement in Algol-Type Interacting Binary Systems

NASA Astrophysics Data System (ADS)

Peters, Geraldine J.

2013-07-01

The shock from the impact of a gas stream onto the photosphere of a mass gainer in an Algol system is expected to produce a hot spot and also heat circumstellar material that is splashed from the impact site. Furthermore in some cases we expect the stripped-down mass loser (a late-type subgiant) to be nitrogen rich and carbon poor if CNO-processed material is currently being transferred. I will present observational evidence from the Kepler and FUSE spacecrafts for the presence of hot spots and discuss their behavior. FUSE observations of Algols that convincingly show that the gas stream material from some Algol secondaries is N-enhanced and virtually devoid of carbon is also presented. From Kepler data we have identified a long-term phenomenon in which the relative brightness of the quadrature light varies by a few percent and numerically reverses over a time scale of about a 100-400 days. We call the systems T/L (trailing hemisphere/leading hemisphere) variables. Such behavior has never been identified from ground-based photometry. WX Draconis (A8 + K0 IV, P = 1.80 d), a system whose primary displays delta Scuti-like pulsations, is the prototype. The Kepler light curves are being modeled with the latest version of the Wilson-Devinney program that includes the capability of treating migrating hot/cool spots. I will discuss whether the T/L behavior is likely due to a migrating hot accretion spot on the primary or variability in a large cool-spotted area on the secondary. From archival FUSE data we have confirmed the presence of a hot accretion spot in the Algol system U Cephei and present information on the spot parameters/behavior and conditions in a splash plasma from the impact site. Kepler and archival FUSE observations continue to provide important information on the nature of the component stars in Algol systems and the detailed physics of mass transfer, especially the role of accretion hot spots. We are grateful for support from NASA grants NNX11AC78G and

Proton beam shaped by “particle lens” formed by laser-driven hot electrons

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

Zhai, S. H.; Shen, B. F., E-mail: bfshen@mail.shcnc.ac.cn, E-mail: wwpvin@hotmail.com, E-mail: yqgu@caep.cn; Wang, W. P., E-mail: bfshen@mail.shcnc.ac.cn, E-mail: wwpvin@hotmail.com, E-mail: yqgu@caep.cn

2016-05-23

Two-dimensional tailoring of a proton beam is realized by a “particle lens” in our experiment. A large quantity of electrons, generated by an intense femtosecond laser irradiating a polymer target, produces an electric field strong enough to change the trajectory and distribution of energetic protons flying through the electron area. The experiment shows that a strip pattern of the proton beam appears when hot electrons initially converge inside the plastic plate. Then the shape of the proton beam changes to a “fountain-like” pattern when these hot electrons diffuse after propagating a distance.

Novel therapeutic approaches for pulmonary arterial hypertension: Unique molecular targets to site-specific drug delivery.

PubMed

Vaidya, Bhuvaneshwar; Gupta, Vivek

2015-08-10

Pulmonary arterial hypertension (PAH) is a cardiopulmonary disorder characterized by increased blood pressure in the small arterioles supplying blood to lungs for oxygenation. Advances in understanding of molecular and cellular biology techniques have led to the findings that PAH is indeed a cascade of diseases exploiting multi-faceted complex pathophysiology, with cellular proliferation and vascular remodeling being the key pathogenic events along with several cellular pathways involved. While current therapies for PAH do provide for amelioration of disease symptoms and acute survival benefits, their full therapeutic potential is hindered by patient incompliance and off-target side effects. To overcome the issues related with current therapy and to devise a more selective therapy, various novel pathways are being investigated for PAH treatment. In addition, inability to deliver anti-PAH drugs to the disease site i.e., distal pulmonary arterioles has been one of the major challenges in achieving improved patient outcomes and improved therapeutic efficacy. Several novel carriers have been explored to increase the selectivity of currently approved anti-PAH drugs and to act as suitable carriers for the delivery of investigational drugs. In the present review, we have discussed potential of various novel molecular pathways/targets including RhoA/Rho kinase, tyrosine kinase, endothelial progenitor cells, vasoactive intestinal peptide, and miRNA in PAH therapeutics. We have also discussed various techniques for site-specific drug delivery of anti-PAH therapeutics so as to improve the efficacy of approved and investigational drugs. This review will provide gainful insights into current advances in PAH therapeutics with an emphasis on site-specific drug payload delivery. Copyright © 2015 Elsevier B.V. All rights reserved.

Improved design of hammerhead ribozyme for selective digestion of target RNA through recognition of site-specific adenosine-to-inosine RNA editing

PubMed Central

Fukuda, Masatora; Kurihara, Kei; Yamaguchi, Shota; Oyama, Yui; Deshimaru, Masanobu

2014-01-01

Adenosine-to-inosine (A-to-I) RNA editing is an endogenous regulatory mechanism involved in various biological processes. Site-specific, editing-state–dependent degradation of target RNA may be a powerful tool both for analyzing the mechanism of RNA editing and for regulating biological processes. Previously, we designed an artificial hammerhead ribozyme (HHR) for selective, site-specific RNA cleavage dependent on the A-to-I RNA editing state. In the present work, we developed an improved strategy for constructing a trans-acting HHR that specifically cleaves target editing sites in the adenosine but not the inosine state. Specificity for unedited sites was achieved by utilizing a sequence encoding the intrinsic cleavage specificity of a natural HHR. We used in vitro selection methods in an HHR library to select for an extended HHR containing a tertiary stabilization motif that facilitates HHR folding into an active conformation. By using this method, we successfully constructed highly active HHRs with unedited-specific cleavage. Moreover, using HHR cleavage followed by direct sequencing, we demonstrated that this ribozyme could cleave serotonin 2C receptor (HTR2C) mRNA extracted from mouse brain, depending on the site-specific editing state. This unedited-specific cleavage also enabled us to analyze the effect of editing state at the E and C sites on editing at other sites by using direct sequencing for the simultaneous quantification of the editing ratio at multiple sites. Our approach has the potential to elucidate the mechanism underlying the interdependencies of different editing states in substrate RNA with multiple editing sites. PMID:24448449

Anomalous ultrafast dynamics of hot plasmonic electrons in nanostructures with hot spots

DOE PAGES

Harutyunyan, Hayk; Martinson, Alex B. F.; Rosenmann, Daniel; ...

2015-08-03

The interaction of light and matter in metallic nanosystems is mediated by the collective oscillation of surface electrons, called plasmons. After excitation, plasmons are absorbed by the metal electrons through inter- and intraband transitions, creating a highly non-thermal distribution of electrons. The electron population then decays through electron-electron interactions, creating a hot electron distribution within a few hundred femtoseconds, followed by a further relaxation via electron-phonon scattering on the timescale of a few pico-seconds. In the spectral domain, hot plasmonic electrons induce changes to the plasmonic resonance of the nanostructure by modifying the dielectric constant of the metal. Here, wemore » report on the observation of anomalously strong changes to the ultrafast temporal and spectral responses of these excited hot plasmonic electrons in hybrid metal/oxide nanostructures as a result of varying the geometry and composition of the nanostructure and the excitation wavelength. In particular, we show a large ultrafast, pulsewidth-limited contribution to the excited electron decay signal in hybrid nanostructures containing hot spots. The intensity of this contribution correlates with the efficiency of the generation of highly excited surface electrons. Using theoretical models, we attribute this effect to the generation of hot plasmonic electrons from hot spots. Finally, we then develop general principles to enhance the generation of energetic electrons through specifically designed plasmonic nanostructures that could be used in applications where hot electron generation is beneficial, such as in solar photocatalysis, photodetectors and nonlinear devices.« less

Anomalous ultrafast dynamics of hot plasmonic electrons in nanostructures with hot spots.

PubMed

Harutyunyan, Hayk; Martinson, Alex B F; Rosenmann, Daniel; Khorashad, Larousse Khosravi; Besteiro, Lucas V; Govorov, Alexander O; Wiederrecht, Gary P

2015-09-01

The interaction of light and matter in metallic nanosystems is mediated by the collective oscillation of surface electrons, called plasmons. After excitation, plasmons are absorbed by the metal electrons through inter- and intraband transitions, creating a highly non-thermal distribution of electrons. The electron population then decays through electron-electron interactions, creating a hot electron distribution within a few hundred femtoseconds, followed by a further relaxation via electron-phonon scattering on the timescale of a few picoseconds. In the spectral domain, hot plasmonic electrons induce changes to the plasmonic resonance of the nanostructure by modifying the dielectric constant of the metal. Here, we report on the observation of anomalously strong changes to the ultrafast temporal and spectral responses of these excited hot plasmonic electrons in hybrid metal/oxide nanostructures as a result of varying the geometry and composition of the nanostructure and the excitation wavelength. In particular, we show a large ultrafast, pulsewidth-limited contribution to the excited electron decay signal in hybrid nanostructures containing hot spots. The intensity of this contribution correlates with the efficiency of the generation of highly excited surface electrons. Using theoretical models, we attribute this effect to the generation of hot plasmonic electrons from hot spots. We then develop general principles to enhance the generation of energetic electrons through specifically designed plasmonic nanostructures that could be used in applications where hot electron generation is beneficial, such as in solar photocatalysis, photodetectors and nonlinear devices.

Horizontal-to-Vertical Spectral Ratio for Estimating Thickness of Sedimentary Deposits across the PoroTomo site in Brady Hot Springs, Nevada (USA)

NASA Astrophysics Data System (ADS)

Parker, L.; Fratta, D.; Zeng, X.; Lord, N. E.; Wang, H. F.; Thurber, C. H.; Lin, F. C.; Feigl, K. L.; Team, P.

2016-12-01

During March 2016, the PoroTomo research team deployed more than 8700 m of DAS and DTS cable in horizontal and vertical sensing arrays, 244 three-component surface geophones, inSAR images, pressure transducers, and a vibroseis truck to actively and passively image the response of a geothermal field in Brady Hot Springs, Nevada. During the imaging period the geothermal field was manipulated to change the pore pressure in the formation. The objective of the study is to invert for poroelastic parameters within a 1500 m by 500 m by 400 m volume using tomographic techniques. Among the different imaging techniques, the research team is using passive horizontal-to-vertical spectral ratio data captured with the three-component geophones to estimate the thickness of the sedimentary deposits across the PoroTomo site. The interpretation of the inverted data is complicated due the heterogeneity in the near surface deposits at the site. These deposits include diatomaceous earth, sandy/silty layers, and hardened silica associated with the presence of fumaroles. In spite of the challenges associated with deposits of very different stiffness, the mapping of sediment thickness across the Natural Laboratory helps constrain the inversion of Multiple Channel Analysis of Surface Waves to improve the quality of the solution images.

Specular reflectivity and hot-electron generation in high-contrast relativistic laser-plasma interactions

NASA Astrophysics Data System (ADS)

Kemp, Gregory Elijah

Ultra-intense laser (> 1018 W/cm2) interactions with matter are capable of producing relativistic electrons which have a variety of applications in state-of-the-art scientific and medical research conducted at universities and national laboratories across the world. Control of various aspects of these hot-electron distributions is highly desired to optimize a particular outcome. Hot-electron generation in low-contrast interactions, where significant amounts of under-dense pre-plasma are present, can be plagued by highly non-linear relativistic laser-plasma instabilities and quasi-static magnetic field generation, often resulting in less than desirable and predictable electron source characteristics. High-contrast interactions offer more controlled interactions but often at the cost of overall lower coupling and increased sensitivity to initial target conditions. An experiment studying the differences in hot-electron generation between high and low-contrast pulse interactions with solid density targets was performed on the Titan laser platform at the Jupiter Laser Facility at Lawrence Livermore National Laboratory in Livermore, CA. To date, these hot-electrons generated in the laboratory are not directly observable at the source of the interaction. Instead, indirect studies are performed using state-of-the-art simulations, constrained by the various experimental measurements. These measurements, more-often-than-not, rely on secondary processes generated by the transport of these electrons through the solid density materials which can susceptible to a variety instabilities and target material/geometry effects. Although often neglected in these types of studies, the specularly reflected light can provide invaluable insight as it is directly influenced by the interaction. In this thesis, I address the use of (personally obtained) experimental specular reflectivity measurements to indirectly study hot-electron generation in the context of high-contrast, relativistic

Mitigation of Hot Electrons from Laser-Plasma Instabilities in Laser-Generated X-Ray Sources

NASA Astrophysics Data System (ADS)

Fein, Jeffrey R.

This thesis describes experiments to understand and mitigate energetic or "hot" electrons from laser-plasma instabilities (LPIs) in an effort to improve radiographic techniques using laser-generated x-ray sources. Initial experiments on the OMEGA-60 laser show evidence of an underlying background generated by x-rays with energies over 10 keV on radiographs using backlit pinhole radiography, whose source is consistent with hard x-rays from LPI-generated hot electrons. Mitigating this background can dramatically reduce uncertainties in measured object densities from radiographs and may be achieved by eliminating the target components in which LPIs are most likely to grow. Experiments were performed on the OMEGA-EP laser to study hot electron production from laser-plasma instabilities in high-Z plasmas relevant to laser-generated x-ray sources. Measurements of hard x-rays show a dramatic reduction in hot-electron energy going from low-Z CH to high-Z Au targets, in a manner that is consistent with steepening electron density profiles that were also measured. The profile-steepening, we infer, increased thresholds of LPIs and contributed to the reduced hot-electron production at higher Z. Possible mechanisms for generating hot electrons include the two-plasmon decay and stimulated Raman scattering instabilities driven by multiple laser beams. Radiation hydrodynamic simulations using the CRASH code predict that both of these instabilities were above threshold with linear threshold parameters that decreased with increasing Z due to steepening length-scales, as well as enhanced laser absorption and increased collisional and Landau damping of electron plasma waves. Another set of experiments were performed on the OMEGA-60 laser to test whether hard x-ray background could be mitigated in backlit pinhole imagers by controlling laser-plasma instabilities. Based on the results above, we hypothesized that LPIs and hot electrons that lead to hard x-ray background would be reduced

Submolecular Gates Self-Assemble for Hot-Electron Transfer in Proteins.

PubMed

Filip-Granit, Neta; Goldberg, Eran; Samish, Ilan; Ashur, Idan; van der Boom, Milko E; Cohen, Hagai; Scherz, Avigdor

2017-07-27

Redox reactions play key roles in fundamental biological processes. The related spatial organization of donors and acceptors is assumed to undergo evolutionary optimization facilitating charge mobilization within the relevant biological context. Experimental information from submolecular functional sites is needed to understand the organization strategies and driving forces involved in the self-development of structure-function relationships. Here we exploit chemically resolved electrical measurements (CREM) to probe the atom-specific electrostatic potentials (ESPs) in artificial arrays of bacteriochlorophyll (BChl) derivatives that provide model systems for photoexcited (hot) electron donation and withdrawal. On the basis of computations we show that native BChl's in the photosynthetic reaction center (RC) self-assemble at their ground-state as aligned gates for functional charge transfer. The combined computational and experimental results further reveal how site-specific polarizability perpendicular to the molecular plane enhances the hot-electron transport. Maximal transport efficiency is predicted for a specific, ∼5 Å, distance above the center of the metalized BChl, which is in remarkably close agreement with the distance and mutual orientation of corresponding native cofactors. These findings provide new metrics and guidelines for analysis of biological redox centers and for designing charge mobilizing machines such as artificial photosynthesis.

Protein binding hot spots prediction from sequence only by a new ensemble learning method.

PubMed

Hu, Shan-Shan; Chen, Peng; Wang, Bing; Li, Jinyan

2017-10-01

Hot spots are interfacial core areas of binding proteins, which have been applied as targets in drug design. Experimental methods are costly in both time and expense to locate hot spot areas. Recently, in-silicon computational methods have been widely used for hot spot prediction through sequence or structure characterization. As the structural information of proteins is not always solved, and thus hot spot identification from amino acid sequences only is more useful for real-life applications. This work proposes a new sequence-based model that combines physicochemical features with the relative accessible surface area of amino acid sequences for hot spot prediction. The model consists of 83 classifiers involving the IBk (Instance-based k means) algorithm, where instances are encoded by important properties extracted from a total of 544 properties in the AAindex1 (Amino Acid Index) database. Then top-performance classifiers are selected to form an ensemble by a majority voting technique. The ensemble classifier outperforms the state-of-the-art computational methods, yielding an F1 score of 0.80 on the benchmark binding interface database (BID) test set. http://www2.ahu.edu.cn/pchen/web/HotspotEC.htm .

Demonstration of Fuel Hot-Spot Pressure in Excess of 50 Gbar for Direct-Drive, Layered Deuterium-Tritium Implosions on OMEGA

NASA Astrophysics Data System (ADS)

Regan, S. P.; Goncharov, V. N.; Igumenshchev, I. V.; Sangster, T. C.; Betti, R.; Bose, A.; Boehly, T. R.; Bonino, M. J.; Campbell, E. M.; Cao, D.; Collins, T. J. B.; Craxton, R. S.; Davis, A. K.; Delettrez, J. A.; Edgell, D. H.; Epstein, R.; Forrest, C. J.; Frenje, J. A.; Froula, D. H.; Gatu Johnson, M.; Glebov, V. Yu.; Harding, D. R.; Hohenberger, M.; Hu, S. X.; Jacobs-Perkins, D.; Janezic, R.; Karasik, M.; Keck, R. L.; Kelly, J. H.; Kessler, T. J.; Knauer, J. P.; Kosc, T. Z.; Loucks, S. J.; Marozas, J. A.; Marshall, F. J.; McCrory, R. L.; McKenty, P. W.; Meyerhofer, D. D.; Michel, D. T.; Myatt, J. F.; Obenschain, S. P.; Petrasso, R. D.; Radha, P. B.; Rice, B.; Rosenberg, M. J.; Schmitt, A. J.; Schmitt, M. J.; Seka, W.; Shmayda, W. T.; Shoup, M. J.; Shvydky, A.; Skupsky, S.; Solodov, A. A.; Stoeckl, C.; Theobald, W.; Ulreich, J.; Wittman, M. D.; Woo, K. M.; Yaakobi, B.; Zuegel, J. D.

2016-07-01

A record fuel hot-spot pressure Phs=56 ±7 Gbar was inferred from x-ray and nuclear diagnostics for direct-drive inertial confinement fusion cryogenic, layered deuterium-tritium implosions on the 60-beam, 30-kJ, 351-nm OMEGA Laser System. When hydrodynamically scaled to the energy of the National Ignition Facility, these implosions achieved a Lawson parameter ˜60 % of the value required for ignition [A. Bose et al., Phys. Rev. E 93, LM15119ER (2016)], similar to indirect-drive implosions [R. Betti et al., Phys. Rev. Lett. 114, 255003 (2015)], and nearly half of the direct-drive ignition-threshold pressure. Relative to symmetric, one-dimensional simulations, the inferred hot-spot pressure is approximately 40% lower. Three-dimensional simulations suggest that low-mode distortion of the hot spot seeded by laser-drive nonuniformity and target-positioning error reduces target performance.

Cost analysis of new and retrofit hot-air type solar assisted heating systems

NASA Technical Reports Server (NTRS)

Stewart, R. D.; Hawkins, B. J.

1978-01-01

A detailed cost analysis/cost improvement study was performed on two Department of Energy/National Aeronautics and Space Administration operational test sites to determine actual costs and potential cost improvements of new and retrofit hot air type, solar assisted heating and hot water systems for single family sized structures. This analysis concentrated on the first cost of a system which included procurement, installation, and integration of a solar assisted heating and hot water system on a new or retrofit basis; it also provided several cost projections which can be used as inputs to payback analyses, depending upon the degree of optimism or future improvements assumed. Cost definitions were developed for five categories of cost, and preliminary estimates were developed for each. The costing methodology, approach, and results together with several candidate low cost designs are described.

Onco-Regulon: an integrated database and software suite for site specific targeting of transcription factors of cancer genes

PubMed Central

Tomar, Navneet; Mishra, Akhilesh; Mrinal, Nirotpal; Jayaram, B.

2016-01-01

Transcription factors (TFs) bind at multiple sites in the genome and regulate expression of many genes. Regulating TF binding in a gene specific manner remains a formidable challenge in drug discovery because the same binding motif may be present at multiple locations in the genome. Here, we present Onco-Regulon (http://www.scfbio-iitd.res.in/software/onco/NavSite/index.htm), an integrated database of regulatory motifs of cancer genes clubbed with Unique Sequence-Predictor (USP) a software suite that identifies unique sequences for each of these regulatory DNA motifs at the specified position in the genome. USP works by extending a given DNA motif, in 5′→3′, 3′ →5′ or both directions by adding one nucleotide at each step, and calculates the frequency of each extended motif in the genome by Frequency Counter programme. This step is iterated till the frequency of the extended motif becomes unity in the genome. Thus, for each given motif, we get three possible unique sequences. Closest Sequence Finder program predicts off-target drug binding in the genome. Inclusion of DNA-Protein structural information further makes Onco-Regulon a highly informative repository for gene specific drug development. We believe that Onco-Regulon will help researchers to design drugs which will bind to an exclusive site in the genome with no off-target effects, theoretically. Database URL: http://www.scfbio-iitd.res.in/software/onco/NavSite/index.htm PMID:27515825

A mutation creating a potential illegitimate microRNA target site in the myostatin gene affects muscularity in sheep.

PubMed

Clop, Alex; Marcq, Fabienne; Takeda, Haruko; Pirottin, Dimitri; Tordoir, Xavier; Bibé, Bernard; Bouix, Jacques; Caiment, Florian; Elsen, Jean-Michel; Eychenne, Francis; Larzul, Catherine; Laville, Elisabeth; Meish, Françoise; Milenkovic, Dragan; Tobin, James; Charlier, Carole; Georges, Michel

2006-07-01

Texel sheep are renowned for their exceptional meatiness. To identify the genes underlying this economically important feature, we performed a whole-genome scan in a Romanov x Texel F2 population. We mapped a quantitative trait locus with a major effect on muscle mass to chromosome 2 and subsequently fine-mapped it to a chromosome interval encompassing the myostatin (GDF8) gene. We herein demonstrate that the GDF8 allele of Texel sheep is characterized by a G to A transition in the 3' UTR that creates a target site for mir1 and mir206, microRNAs (miRNAs) that are highly expressed in skeletal muscle. This causes translational inhibition of the myostatin gene and hence contributes to the muscular hypertrophy of Texel sheep. Analysis of SNP databases for humans and mice demonstrates that mutations creating or destroying putative miRNA target sites are abundant and might be important effectors of phenotypic variation.

A Search for Rapidly Pulsating Hot Subdwarf Stars in the GALEX Survey

NASA Astrophysics Data System (ADS)

Boudreaux, Thomas M.; Barlow, Brad N.; Fleming, Scott W.; Vasquez Soto, Alan; Million, Chase; Reichart, Dan E.; Haislip, Josh B.; Linder, Tyler R.; Moore, Justin P.

2017-08-01

NASA’s Galaxy Evolution Explorer (GALEX) provided near- and far-UV observations for approximately 77% of the sky over a 10-year period; however, the data reduction pipeline initially only released single NUV and FUV images to the community. The recently released Python module gPhoton changes this, allowing calibrated time-series aperture photometry to be extracted easily from the raw GALEX data set. Here we use gPhoton to generate light curves for all hot subdwarf B (sdB) stars that were observed by GALEX, with the intention of identifying short-period, p-mode pulsations. We find that the spacecraft’s short visit durations, uneven gaps between visits, and dither pattern make the detection of hot subdwarf pulsations difficult. Nonetheless, we detect UV variations in four previously known pulsating targets and report their UV pulsation amplitudes and frequencies. Additionally, we find that several other sdB targets not previously known to vary show promising signals in their periodograms. Using optical follow-up photometry with the Skynet Robotic Telescope Network, we confirm p-mode pulsations in one of these targets, LAMOST J082517.99+113106.3, and report it as the most recent addition to the sdBV r class of variable stars.

A Search for Rapidly Pulsating Hot Subdwarf Stars in the GALEX Survey

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

Boudreaux, Thomas M.; Barlow, Brad N.; Soto, Alan Vasquez

NASA’s Galaxy Evolution Explorer ( GALEX ) provided near- and far-UV observations for approximately 77% of the sky over a 10-year period; however, the data reduction pipeline initially only released single NUV and FUV images to the community. The recently released Python module gPhoton changes this, allowing calibrated time-series aperture photometry to be extracted easily from the raw GALEX data set. Here we use gPhoton to generate light curves for all hot subdwarf B (sdB) stars that were observed by GALEX , with the intention of identifying short-period, p-mode pulsations. We find that the spacecraft’s short visit durations, uneven gapsmore » between visits, and dither pattern make the detection of hot subdwarf pulsations difficult. Nonetheless, we detect UV variations in four previously known pulsating targets and report their UV pulsation amplitudes and frequencies. Additionally, we find that several other sdB targets not previously known to vary show promising signals in their periodograms. Using optical follow-up photometry with the Skynet Robotic Telescope Network, we confirm p-mode pulsations in one of these targets, LAMOST J082517.99+113106.3, and report it as the most recent addition to the sdBV{sub r} class of variable stars.« less

Abundant off-target edits from site-directed RNA editing can be reduced by nuclear localization of the editing enzyme.

PubMed

Vallecillo-Viejo, Isabel C; Liscovitch-Brauer, Noa; Montiel-Gonzalez, Maria Fernanda; Eisenberg, Eli; Rosenthal, Joshua J C

2018-01-02

Site-directed RNA editing (SDRE) is a general strategy for making targeted base changes in RNA molecules. Although the approach is relatively new, several groups, including our own, have been working on its development. The basic strategy has been to couple the catalytic domain of an adenosine (A) to inosine (I) RNA editing enzyme to a guide RNA that is used for targeting. Although highly efficient on-target editing has been reported, off-target events have not been rigorously quantified. In this report we target premature termination codons (PTCs) in messages encoding both a fluorescent reporter protein and the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) protein transiently transfected into human epithelial cells. We demonstrate that while on-target editing is efficient, off-target editing is extensive, both within the targeted message and across the entire transcriptome of the transfected cells. By redirecting the editing enzymes from the cytoplasm to the nucleus, off-target editing is reduced without compromising the on-target editing efficiency. The addition of the E488Q mutation to the editing enzymes, a common strategy for increasing on-target editing efficiency, causes a tremendous increase in off-target editing. These results underscore the need to reduce promiscuity in current approaches to SDRE.

Max-E47, a Designed Minimalist Protein that Targets the E-Box DNA Site In Vivo and In Vitro

PubMed Central

Xu, Jing; Chen, Gang; De Jong, Antonia T.; Shahravan, S. Hesam; Shin, Jumi A.

2009-01-01

Max-E47 is a designed hybrid protein comprising the Max DNA-binding basic region and E47 HLH dimerization subdomain. In the yeast one-hybrid system (Y1H), Max-E47 shows strong transcriptional activation from the E-box site, 5'-CACGTG, targeted by the Myc/Max/Mad network of transcription factors; two mutants, Max-E47Y and Max-E47YF, activate more weakly from the E-box in the Y1H. Quantitative fluorescence anisotropy titrations to gain free energies of protein:DNA binding gave low nM Kd values for the native MaxbHLHZ, Max-E47, and the Y and YF mutants binding to the E-box site (14 nM, 15 nM, 9 nM, and 6 nM, respectively), with no detectable binding to a nonspecific control duplex. Because these minimalist, E-box-binding hybrids have no activation domain and no interactions with the c-MycbHLHZ, as shown by the yeast two-hybrid assay, they can potentially serve as dominant-negative inhibitors that suppress activation of E-box-responsive genes targeted by transcription factors including the c-Myc/Max complex. As proof-of-principle, we used our modified Y1H, which allows direct competition between two proteins vying for a DNA target, to show that Max-E47 effectively outcompetes the native MaxbHLHZ for the E-box; weaker competition is observed from the two mutants, consistent with Y1H results. These hybrids provide a minimalist scaffold for further exploration of the relationship between protein structure and DNA-binding function and may have applications as protein therapeutics or biochemical probes capable of targeting the E-box site. PMID:19449889

Targeting of Magnetic Nanoparticle-coated Microbubbles to the Vascular Wall Empowers Site-specific Lentiviral Gene Delivery in vivo.

PubMed

Heun, Yvonn; Hildebrand, Staffan; Heidsieck, Alexandra; Gleich, Bernhard; Anton, Martina; Pircher, Joachim; Ribeiro, Andrea; Mykhaylyk, Olga; Eberbeck, Dietmar; Wenzel, Daniela; Pfeifer, Alexander; Woernle, Markus; Krötz, Florian; Pohl, Ulrich; Mannell, Hanna

2017-01-01

In the field of vascular gene therapy, targeting systems are promising advancements to improve site-specificity of gene delivery. Here, we studied whether incorporation of magnetic nanoparticles (MNP) with different magnetic properties into ultrasound sensitive microbubbles may represent an efficient way to enable gene targeting in the vascular system after systemic application. Thus, we associated novel silicon oxide-coated magnetic nanoparticle containing microbubbles (SO-Mag MMB) with lentiviral particles carrying therapeutic genes and determined their physico-chemical as well as biological properties compared to MMB coated with polyethylenimine-coated magnetic nanoparticles (PEI-Mag MMB). While there were no differences between both MMB types concerning size and lentivirus binding, SO-Mag MMB exhibited superior characteristics regarding magnetic moment, magnetizability as well as transduction efficiency under static and flow conditions in vitro . Focal disruption of lentiviral SO-Mag MMB by ultrasound within isolated vessels exposed to an external magnetic field decisively improved localized VEGF expression in aortic endothelium ex vivo and enhanced the angiogenic response. Using the same system in vivo , we achieved a highly effective, site-specific lentiviral transgene expression in microvessels of the mouse dorsal skin after arterial injection. Thus, we established a novel lentiviral MMB technique, which has great potential towards site-directed vascular gene therapy.

Understanding the effects of laser imprint on plastic-target implosions on OMEGA

DOE PAGES

Hu, S. X.; Michel, D. T.; Davis, A. K.; ...

2016-10-03

Understanding the effects of laser imprint on target performance is critical to the success of direct-drive inertial confinement fusion. Directly measuring the disruption caused by laser imprints to the imploding shell and hot-spot formation, in comparison with multidimensional radiation–hydrodynamic simulations, can provide a clear picture of how laser nonuniformities cause target performance to degrade. With the recently developed x-ray self-emission imaging technique and the state-of-the-art physics models recently implemented in the two-dimensional hydrocode DRACO, a systematic study of laser-imprint effects on warm target implosions on OMEGA has been performed using both experimental results and simulations. By varying the laser-picket intensity,more » the imploding shells were set at different adiabats (from α = 2 to α = 6). As the shell adiabats decreased, it was observed that (1) the measured shell thickness at the time the hot spot lit up became larger than the uniform one-dimensional (1-D) predictions; (2) the hot-spot core emitted earlier than the corresponding 1-D predictions; (3) the measured neutron yield first increased then decreased as the shell adiabat α was reduced; and (4) the hot-spot size reduced as α decreased for cases where SSD (smoothing by spectral dispersion) was on but became larger for low-α shots in cases where SSD was off. Most of these experimental observations are well reproduced by DRACO simulations with laser imprints including modes up to λ max = 200. In addition, these studies identify the importance of laser imprint as the major source of degrading target performance for OMEGA implosions of adiabat α ≤ 3. Mitigating laser imprints is required to improve low-α target performance.« less

Understanding the effects of laser imprint on plastic-target implosions on OMEGA

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

Hu, S. X.; Michel, D. T.; Davis, A. K.

Understanding the effects of laser imprint on target performance is critical to the success of direct-drive inertial confinement fusion. Directly measuring the disruption caused by laser imprints to the imploding shell and hot-spot formation, in comparison with multidimensional radiation–hydrodynamic simulations, can provide a clear picture of how laser nonuniformities cause target performance to degrade. With the recently developed x-ray self-emission imaging technique and the state-of-the-art physics models recently implemented in the two-dimensional hydrocode DRACO, a systematic study of laser-imprint effects on warm target implosions on OMEGA has been performed using both experimental results and simulations. By varying the laser-picket intensity,more » the imploding shells were set at different adiabats (from α = 2 to α = 6). As the shell adiabats decreased, it was observed that (1) the measured shell thickness at the time the hot spot lit up became larger than the uniform one-dimensional (1-D) predictions; (2) the hot-spot core emitted earlier than the corresponding 1-D predictions; (3) the measured neutron yield first increased then decreased as the shell adiabat α was reduced; and (4) the hot-spot size reduced as α decreased for cases where SSD (smoothing by spectral dispersion) was on but became larger for low-α shots in cases where SSD was off. Most of these experimental observations are well reproduced by DRACO simulations with laser imprints including modes up to λ max = 200. In addition, these studies identify the importance of laser imprint as the major source of degrading target performance for OMEGA implosions of adiabat α ≤ 3. Mitigating laser imprints is required to improve low-α target performance.« less

Hot ash burns in the children of Western Australia: how and why they happen.

PubMed

Martin, L; Rea, S; McWilliams, T; Wood, F

2014-08-01

Burns from hot ash are common in the paediatric population in Western Australia. Fifty children were admitted to the paediatric burn centre with hot ash contact burns to the feet in 2011 and 2012. It is important to examine the extent of the problem, seasonal variations, and identify those at risk to determine strategies for prevention campaigns. Retrospective review of medical notes for all admissions to the paediatric burns unit was undertaken for 2011 and 2012. Data were collected for patient demographics, time, circumstance of injury, burn severity and treatment. Hot ash burns accounted for 8.6% of admissions but 16.1% of burns sustained in non-metro areas. Median age was just under 3 years, male or female. Median burn TBSA was 2%, and 44% of children required surgery. The burns were less common in summer, more common on non-school days and in children who were on camping trips away from home. Previous work has shown the value of targeted campaigns. The group for targeted prevention campaigns are the carers of very young children who go camping. Information distributed at camping shows and stores about the principles of campfire safety would reach the people at risk. Copyright © 2013 Elsevier Ltd and ISBI. All rights reserved.

Broadly neutralizing antibodies from human survivors target a conserved site in the Ebola virus glycoprotein HR2-MPER region.

PubMed

Flyak, Andrew I; Kuzmina, Natalia; Murin, Charles D; Bryan, Christopher; Davidson, Edgar; Gilchuk, Pavlo; Gulka, Christopher P; Ilinykh, Philipp A; Shen, Xiaoli; Huang, Kai; Ramanathan, Palaniappan; Turner, Hannah; Fusco, Marnie L; Lampley, Rebecca; Kose, Nurgun; King, Hannah; Sapparapu, Gopal; Doranz, Benjamin J; Ksiazek, Thomas G; Wright, David W; Saphire, Erica Ollmann; Ward, Andrew B; Bukreyev, Alexander; Crowe, James E

2018-05-07

Ebola virus (EBOV) in humans causes a severe illness with high mortality rates. Several strategies have been developed in the past to treat EBOV infection, including the antibody cocktail ZMapp, which has been shown to be effective in nonhuman primate models of infection 1 and has been used under compassionate-treatment protocols in humans 2 . ZMapp is a mixture of three chimerized murine monoclonal antibodies (mAbs) 3-6 that target EBOV-specific epitopes on the surface glycoprotein 7,8 . However, ZMapp mAbs do not neutralize other species from the genus Ebolavirus, such as Bundibugyo virus (BDBV), Reston virus (RESTV) or Sudan virus (SUDV). Here, we describe three naturally occurring human cross-neutralizing mAbs, from BDBV survivors, that target an antigenic site in the canonical heptad repeat 2 (HR2) region near the membrane-proximal external region (MPER) of the glycoprotein. The identification of a conserved neutralizing antigenic site in the glycoprotein suggests that these mAbs could be used to design universal antibody therapeutics against diverse ebolavirus species. Furthermore, we found that immunization with a peptide comprising the HR2-MPER antigenic site elicits neutralizing antibodies in rabbits. Structural features determined by conserved residues in the antigenic site described here could inform an epitope-based vaccine design against infection caused by diverse ebolavirus species.

p62 Targeting to the autophagosome formation site requires self-oligomerization but not LC3 binding.

PubMed

Itakura, Eisuke; Mizushima, Noboru

2011-01-10

Autophagy is an intracellular degradation process by which cytoplasmic contents are degraded in the lysosome. In addition to nonselective engulfment of cytoplasmic materials, the autophagosomal membrane can selectively recognize specific proteins and organelles. It is generally believed that the major selective substrate (or cargo receptor) p62 is recruited to the autophagosomal membrane through interaction with LC3. In this study, we analyzed loading of p62 and its related protein NBR1 and found that they localize to the endoplasmic reticulum (ER)-associated autophagosome formation site independently of LC3 localization to membranes. p62 colocalizes with upstream autophagy factors such as ULK1 and VMP1 even when autophagosome formation is blocked by wortmannin or FIP200 knockout. Self-oligomerization of p62 is essential for its localization to the autophagosome formation site. These results suggest that p62 localizes to the autophagosome formation site on the ER, where autophagosomes are nucleated. This process is similar to the yeast cytoplasm to vacuole targeting pathway.

Finding the target sites of RNA-binding proteins

PubMed Central

Li, Xiao; Kazan, Hilal; Lipshitz, Howard D; Morris, Quaid D

2014-01-01

RNA–protein interactions differ from DNA–protein interactions because of the central role of RNA secondary structure. Some RNA-binding domains (RBDs) recognize their target sites mainly by their shape and geometry and others are sequence-specific but are sensitive to secondary structure context. A number of small- and large-scale experimental approaches have been developed to measure RNAs associated in vitro and in vivo with RNA-binding proteins (RBPs). Generalizing outside of the experimental conditions tested by these assays requires computational motif finding. Often RBP motif finding is done by adapting DNA motif finding methods; but modeling secondary structure context leads to better recovery of RBP-binding preferences. Genome-wide assessment of mRNA secondary structure has recently become possible, but these data must be combined with computational predictions of secondary structure before they add value in predicting in vivo binding. There are two main approaches to incorporating structural information into motif models: supplementing primary sequence motif models with preferred secondary structure contexts (e.g., MEMERIS and RNAcontext) and directly modeling secondary structure recognized by the RBP using stochastic context-free grammars (e.g., CMfinder and RNApromo). The former better reconstruct known binding preferences for sequence-specific RBPs but are not suitable for modeling RBPs that recognize shape and geometry of RNAs. Future work in RBP motif finding should incorporate interactions between multiple RBDs and multiple RBPs in binding to RNA. WIREs RNA 2014, 5:111–130. doi: 10.1002/wrna.1201 PMID:24217996

Recent Progress in the Design and Discovery of RXR Modulators Targeting Alternate Binding Sites of the Receptor.

PubMed

Su, Ying; Zeng, Zhiping; Chen, Ziwen; Xu, Dan; Zhang, Weidong; Zhang, Xiao-Kun

2017-01-01

Retinoid X receptors (RXRs) occupy a central position within the nuclear receptor superfamily. They not only function as important transcriptional factors but also exhibit diverse nongenomic biological activities. The pleiotropic actions of RXRs under both physiological and pathophysiological conditions confer RXRs important drug targets for the treatment of cancer, and metabolic and neurodegenerative diseases. RXR modulators have been studied for the purpose of developing both drug molecules and chemical tools for biological investigation of RXR. Development of RXR modulators has focused on small molecules targeting the canonical ligand-binding pocket. However, accumulating results have demonstrated that there are other binding mechanisms by which small molecules interact with RXR to act as RXR modulators. This review discusses the recent development in the design and discovery of RXR modulators with a focus on those targeting novel binding sites on RXR.

Design and Synthesis of Irreversible Analogues of Bardoxolone Methyl for the Identification of Pharmacologically Relevant Targets and Interaction Sites.

PubMed

Wong, Michael H L; Bryan, Holly K; Copple, Ian M; Jenkins, Rosalind E; Chiu, Pak Him; Bibby, Jaclyn; Berry, Neil G; Kitteringham, Neil R; Goldring, Christopher E; O'Neill, Paul M; Park, B Kevin

2016-03-24

Semisynthetic triterpenoids such as bardoxolone methyl (methyl-2-cyano 3,12-dioxooleano-1,9-dien-28-oate; CDDO-Me) (4) are potent inducers of antioxidant and anti-inflammatory signaling pathways, including those regulated by the transcription factor Nrf2. However, the reversible nature of the interaction between triterpenoids and thiols has hindered attempts to identify pharmacologically relevant targets and characterize the sites of interaction. Here, we report a shortened synthesis and SAR profiling of 4, enabling the design of analogues that react irreversibly with model thiols, as well as the model protein glutathione S-transferase P1, in vitro. We show that one of these analogues, CDDO-epoxide (13), is comparable to 4 in terms of cytotoxicity and potency toward Nrf2 in rat hepatoma cells and stably modifies specific cysteine residues (namely, Cys-257, -273, -288, -434, -489, and -613) within Keap1, the major repressor of Nrf2, both in vitro and in living cells. Supported by molecular modeling, these data demonstrate the value of 13 for identifying site(s) of interaction with pharmacologically relevant targets and informing the continuing development of triterpenoids as novel drug candidates.

Prevention of crack in stretch flanging process using hot stamping technique

NASA Astrophysics Data System (ADS)

Syafiq, Y. Mohd; Hamedon, Z.; Azila Aziz, Wan; Razlan Yusoff, Ahmad

2017-10-01

Demand for enhancing of passenger safety as well as weight reduction of automobiles has increased the use of high strength steel sheets. As a sheet metal is a lightweight having high strength is suitable for producing automotive parts such as white body panel. The stretch flanging of the high strength steel sheet is a problem due to high springback and easy to crack. This study uses three methods to stretch flange the sheets; using lubricants, shear-edge polishing and hot stamping. The effectiveness of these methods will be measured by comparing the flange length of each methods can achieved. For stretch flange with lubricant and polished sheared edge, the flange length failed to achieve the target 15 mm while hot stamping improved the formability of the sheet and preventing the occurrence of the springback and crack. Hot stamping not only improved formability of the sheet but also transformed the microstructure into martensite thus improve the hardness and the strength of the sheet after been quenched with the dies.

The relative contribution of target-site mutations in complex acaricide resistant phenotypes as assessed by marker assisted backcrossing in Tetranychus urticae.

PubMed

Riga, Maria; Bajda, Sabina; Themistokleous, Christos; Papadaki, Stavrini; Palzewicz, Maria; Dermauw, Wannes; Vontas, John; Leeuwen, Thomas Van

2017-08-23

The mechanisms underlying insecticide and acaricide resistance in insects and mites are often complex, including additive effects of target-site insensitivity, increased metabolism and transport. The extent to which target-site resistance mutations contribute to the resistance phenotype is, however, not well studied. Here, we used marker-assisted backcrossing to create 30 congenic lines carrying nine mutations (alone, or in combination in a few cases) associated with resistance to avermectins, pyrethroids, mite growth inhibitors and mitochondrial complex III inhibitors (QoI) in a polyphagous arthropod pest, the spider mite Tetranychus urticae. Toxicity tests revealed that mutations in the voltage-gated sodium channel, chitin synthase 1 and cytochrome b confer high levels of resistance and, when fixed in a population, these mutations alone can result in field failure of acaricide treatment. In contrast, although we confirmed the implication of mutations in glutamate-gated chloride channels in abamectin and milbemectin insensitivity, these mutations do not lead to the high resistance levels that are often reported in abamectin resistant strains of T. urticae. Overall, this study functionally validates reported target-site resistance mutations in T. urticae, by uncoupling them from additional mechanisms, allowing to finally investigate the strength of the conferred phenotype in vivo.

Techniques for hot structures testing

NASA Technical Reports Server (NTRS)

Deangelis, V. Michael; Fields, Roger A.

1990-01-01

Hot structures testing have been going on since the early 1960's beginning with the Mach 6, X-15 airplane. Early hot structures test programs at NASA-Ames-Dryden focused on operational testing required to support the X-15 flight test program, and early hot structures research projects focused on developing lab test techniques to simulate flight thermal profiles. More recent efforts involved numerous large and small hot structures test programs that served to develop test methods and measurement techniques to provide data that promoted the correlation of test data with results from analytical codes. In Nov. 1988 a workshop was sponsored that focused on the correlation of hot structures test data with analysis. Limited material is drawn from the workshop and a more formal documentation is provided of topics that focus on hot structures test techniques used at NASA-Ames-Dryden. Topics covered include the data acquisition and control of testing, the quartz lamp heater systems, current strain and temperature sensors, and hot structures test techniques used to simulate the flight thermal environment in the lab.

Identification of thyroid hormone receptor binding sites and target genes using ChIP-on-chip in developing mouse cerebellum.

PubMed

Dong, Hongyan; Yauk, Carole L; Rowan-Carroll, Andrea; You, Seo-Hee; Zoeller, R Thomas; Lambert, Iain; Wade, Michael G

2009-01-01

Thyroid hormone (TH) is critical to normal brain development, but the mechanisms operating in this process are poorly understood. We used chromatin immunoprecipitation to enrich regions of DNA bound to thyroid receptor beta (TRbeta) of mouse cerebellum sampled on post natal day 15. Enriched target was hybridized to promoter microarrays (ChIP-on-chip) spanning -8 kb to +2 kb of the transcription start site (TSS) of 5000 genes. We identified 91 genes with TR binding sites. Roughly half of the sites were located in introns, while 30% were located within 1 kb upstream (5') of the TSS. Of these genes, 83 with known function included genes involved in apoptosis, neurodevelopment, metabolism and signal transduction. Two genes, MBP and CD44, are known to contain TREs, providing validation of the system. This is the first report of TR binding for 81 of these genes. ChIP-on-chip results were confirmed for 10 of the 13 binding fragments using ChIP-PCR. The expression of 4 novel TH target genes was found to be correlated with TH levels in hyper/hypothyroid animals providing further support for TR binding. A TRbeta binding site upstream of the coding region of myelin associated glycoprotein was demonstrated to be TH-responsive using a luciferase expression system. Motif searches did not identify any classic binding elements, indicating that not all TR binding sites conform to variations of the classic form. These findings provide mechanistic insight into impaired neurodevelopment resulting from TH deficiency and a rich bioinformatics resource for developing a better understanding of TR binding.

Metals from deep atmosphere to exosphere in hot-Jupiters

NASA Astrophysics Data System (ADS)

Lecavelier des Etangs, Alain

2017-08-01

With STIS/UV observations we detected magnesium atoms at high altitude in the atmosphere of the hot-Jupiter HD209458b, probing lower regions in the atmosphere than previously done with Lyman-alpha observations (Vidal-Madjar et al. 2013). With the present program, we will search for magnesium and other heavy species in escaping atmospheres of 2 giant planets orbiting hot A and F-type stars: WASP-94Ab and WASP-33b.The observations will provide unprecedented information on the physical conditions (velocity, temperature, and density) in the upper atmosphere of these two hot-Jupiters. Targets have been selected for the expected high significance level of the atmospheric detections (>10 sigma). These exoplanets present favorable configuration for upper atmosphere observations because of the combination of high escape rates and large spatial extensions of the magnesium clouds surrounding them. The atmospheric signatures of the magnesium and other metals are therefore expected to be easily detectable. Moreover, the two selected exoplanets have highly different equilibrium temperatures, below and above the MgSiO3 condensation temperature. Consequently, because the metals observed in the escaping flow originate from deeper in the atmosphere where haze can condensate, the observations will constrain the physical processes taking place in the clouds that cannot be observed directly.

PREFACE: Hot Quarks 2004

NASA Astrophysics Data System (ADS)

Antinori, Federico; Bass, Steffen A.; Bellwied, Rene; Ullrich, Thomas; Velkovska, Julia; Wiedemann, Urs

2005-04-01

his research and we spent an entire week talking physics and having fun from breakfast in the morning until late at night. A symbolic award was instituted for the best presentation at the workshop, dedicated to the memory of Klaus Kinder-Geiger, a sharp and brilliant young theorist who perished in the crash of Swissair Flight 111 on 2 September 1998 off the coast of Nova Scotia. It went to Denesh Molnar from Ohio State University for his outstanding talk on parton coalescence. The organizers wish to extend their gratitude to all participants for the high quality presentations making Hot Quarks 2004 a notable event. We are also very grateful for the superb hospitality of the staff of the Snakedance Inn, in particular Mitch Daniels who worked sheer miracles. Given the success of the first Hot Quarks workshop we decided to organize a second one, possibly even turning Hot Quarks into a series. The next meeting will be held in the late spring of 2006, probably in Italy. We hope it will be as memorable as the first one! Last but not least, we wish to thank all the generous sponsors of the conference: Brookhaven National Laboratory, European Organization for Nuclear Research (CERN), Gesellschaft fA~ 1/4 r Schwerionenforschung (GSI), Institute of Physics Publishing, Los Alamos National Laboratory, National Science Foundation, and Vanderbilt University. We are grateful for their support and are particularly happy that this support came from institutions both in the US and in Europe and from all the main experimental facilities that pursue a prominent heavy-ion program. Their support was essential for the success of a workshop targeting young scientists.

Demonstration of fuel hot-spot pressure in excess of 50 Gbar for direct-drive, layered deuterium-tritium implosions on OMEGA

DOE PAGES

Regan, S. P.; Goncharov, V. N.; Igumenshchev, I. V.; ...

2016-07-07

A record fuel hot-spot pressure P hs = 56±7 Gbar was inferred from x-ray and nuclear diagnostics for direct-drive inertial confinement fusion cryogenic, layered deuterium–tritium implosions on the 60-beam, 30-kJ, 351-nm OMEGA Laser System. When hydrodynamically scaled to the energy of the National Ignition Facility (NIF), these implosions achieved a Lawson parameter ~60% of the value required for ignition [A. Bose et al., Phys. Rev. E (in press)], similar to indirect-drive implosions [R. Betti et al., Phys. Rev. Lett. 114, 255003 (2015)], and nearly half of the direct-drive ignition-threshold pressure. Relative to symmetric, one-dimensional simulations, the inferred hot-spot pressure ismore » ~40% lower. Furthermore, three-dimensional simulations suggest that low-mode distortion of the hot spot seeded by laser-drive nonuniformity and target-positioning error reduces target performance.« less

Demonstration of fuel hot-spot pressure in excess of 50 Gbar for direct-drive, layered deuterium-tritium implosions on OMEGA

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

Regan, S. P.; Goncharov, V. N.; Igumenshchev, I. V.

A record fuel hot-spot pressure P hs = 56±7 Gbar was inferred from x-ray and nuclear diagnostics for direct-drive inertial confinement fusion cryogenic, layered deuterium–tritium implosions on the 60-beam, 30-kJ, 351-nm OMEGA Laser System. When hydrodynamically scaled to the energy of the National Ignition Facility (NIF), these implosions achieved a Lawson parameter ~60% of the value required for ignition [A. Bose et al., Phys. Rev. E (in press)], similar to indirect-drive implosions [R. Betti et al., Phys. Rev. Lett. 114, 255003 (2015)], and nearly half of the direct-drive ignition-threshold pressure. Relative to symmetric, one-dimensional simulations, the inferred hot-spot pressure ismore » ~40% lower. Furthermore, three-dimensional simulations suggest that low-mode distortion of the hot spot seeded by laser-drive nonuniformity and target-positioning error reduces target performance.« less

Metabolic and Target-Site Mechanisms Combine to Confer Strong DDT Resistance in Anopheles gambiae

PubMed Central

Mitchell, Sara N.; Rigden, Daniel J.; Dowd, Andrew J.; Lu, Fang; Wilding, Craig S.; Weetman, David; Dadzie, Samuel; Jenkins, Adam M.; Regna, Kimberly; Boko, Pelagie; Djogbenou, Luc; Muskavitch, Marc A. T.; Ranson, Hilary; Paine, Mark J. I.; Mayans, Olga; Donnelly, Martin J.

2014-01-01

The development of resistance to insecticides has become a classic exemplar of evolution occurring within human time scales. In this study we demonstrate how resistance to DDT in the major African malaria vector Anopheles gambiae is a result of both target-site resistance mechanisms that have introgressed between incipient species (the M- and S-molecular forms) and allelic variants in a DDT-detoxifying enzyme. Sequencing of the detoxification enzyme, Gste2, from DDT resistant and susceptible strains of An. gambiae, revealed a non-synonymous polymorphism (I114T), proximal to the DDT binding domain, which segregated with strain phenotype. Recombinant protein expression and DDT metabolism analysis revealed that the proteins from the susceptible strain lost activity at higher DDT concentrations, characteristic of substrate inhibition. The effect of I114T on GSTE2 protein structure was explored through X-ray crystallography. The amino acid exchange in the DDT-resistant strain introduced a hydroxyl group nearby the hydrophobic DDT-binding region. The exchange does not result in structural alterations but is predicted to facilitate local dynamics and enzyme activity. Expression of both wild-type and 114T alleles the allele in Drosophila conferred an increase in DDT tolerance. The 114T mutation was significantly associated with DDT resistance in wild caught M-form populations and acts in concert with target-site mutations in the voltage gated sodium channel (Vgsc-1575Y and Vgsc-1014F) to confer extreme levels of DDT resistance in wild caught An. gambiae. PMID:24675797

Hot spots of Io

NASA Technical Reports Server (NTRS)

Pearl, J. C.; Sinton, W. M.

1982-01-01

The size and temperature, morphology and distribution, variability, possible absorption features, and processes of hot spots on Io are discussed, and an estimate of the global heat flux is made. Size and temperature information is deconvolved to obtain equivalent radius and temperature of hot spots, and simultaneously obtained Voyager thermal and imaging data is used to match hot sources with specific geologic features. In addition to their thermal output, it is possible that hot spots are also characterized by production of various gases and particulate materials; the spectral signature of SO2 has been seen. Origins for relatively stable, low temperature sources, transient high temperature sources, and relatively stable, high-tmperature sources are discussed.

The analysis of the hot water consumption and energy performance before and after renovation in multi-apartment buildings

NASA Astrophysics Data System (ADS)

Tumanova, K.; Borodinecs, A.; Geikins, A.

2017-10-01

The article presents the results of hot water supply system analysis. Taking into account that the current consumption of hot water differs from normative values, real measured data of hot water consumption in multi-apartment buildings from year 2013 until year 2015 have been analyzed. Also, the thermal energy consumption for hot water preparation has been analyzed. Based on aggregated data and taking into account the fact that renovated systems of hot water supply in existing multi-apartment buildings have same pipelines’ diameters, it was analyzed how these systems are economically and energy efficient. For the study, residential buildings in Riga, which have different architectural and engineering solutions for hot water supply systems, were selected. The study was based on thermal energy consumption measurements, which were taken at the individual heating system’s manifolds. This study was done in order to develop database on hot water consumption in civil buildings and define difference in key performance criteria in unclassified buildings. Obtained results allows to reach European Regional Development Fund project “NEARLY ZERO ENERGY SOLUTIONS FOR UNCLASSIFIED BUILDINGS” Nr. 1.1.1.116A048 main targets.

Hot Gas Halos in Galaxies

NASA Astrophysics Data System (ADS)

Mulchaey, John

Most galaxy formation models predict that massive low-redshift disk galaxies are embedded in extended hot halos of externally accreted gas. Such gas appears necessary to maintain ongoing star formation in isolated spirals like the Milky Way. To explain the large population of red galaxies in rich groups and clusters, most galaxy evolution models assume that these hot gas halos are stripped completely when a galaxy enters a denser environment. This simple model has been remarkably successful at reproducing many observed properties of galaxies. Although theoretical arguments suggest hot gas halos are an important component in galaxies, we know very little about this gas from an observational standpoint. In fact, previous observations have failed to detect soft X-ray emission from such halos in disk galaxies. Furthermore, the assumption that hot gas halos are stripped completely when a galaxy enters a group or cluster has not been verified. We propose to combine proprietary and archival XMM-Newton observations of galaxies in the field, groups and clusters to study how hot gas halos are impacted by environment. Our proposed program has three components: 1) The deepest search to date for a hot gas halo in a quiescent spiral galaxy. A detection will confirm a basic tenet of disk galaxy formation models, whereas a non-detection will seriously challenge these models and impose new constraints on the growth mode and feedback history of disk galaxies. 2) A detailed study of the hot gas halos properties of field early-type galaxies. As environmental processes such as stripping are not expected to be important in the field, a study of hot gas halos in this environment will allow us to better understand how feedback and other internal processes impact hot gas halos. 3) A study of hot gas halos in the outskirts of groups and clusters. By comparing observations with our suite of simulations we can begin to understand what role the stripping of hot gas halos plays in galaxy

Prostate-Specific Membrane Antigen-Targeted Site-Directed Antibody-Conjugated Apoferritin Nanovehicle Favorably Influences In Vivo Side Effects of Doxorubicin.

PubMed

Dostalova, Simona; Polanska, Hana; Svobodova, Marketa; Balvan, Jan; Krystofova, Olga; Haddad, Yazan; Krizkova, Sona; Masarik, Michal; Eckschlager, Tomas; Stiborova, Marie; Heger, Zbynek; Adam, Vojtech

2018-06-11

Herein, we describe the in vivo effects of doxorubicin (DOX) encapsulated in ubiquitous protein apoferritin (APO) and its efficiency and safety in anti-tumor treatment. APODOX is both passively (through Enhanced Permeability and Retention effect) and actively targeted to tumors through prostate-specific membrane antigen (PSMA) via mouse antibodies conjugated to the surface of horse spleen APO. To achieve site-directed conjugation of the antibodies, a HWRGWVC heptapeptide linker was used. The prostate cancer-targeted and non-targeted nanocarriers were tested using subcutaneously implanted LNCaP cells in athymic mice models, and compared to free DOX. Prostate cancer-targeted APODOX retained the high potency of DOX in attenuation of tumors (with 55% decrease in tumor volume after 3 weeks of treatment). DOX and non-targeted APODOX treatment caused damage to liver, kidney and heart tissues. In contrast, no elevation in liver or kidney enzymes and negligible changes were revealed by histological assessment in prostate cancer-targeted APODOX-treated mice. Overall, we show that the APO nanocarrier provides an easy encapsulation protocol, reliable targeting, high therapeutic efficiency and very low off-target toxicity, and is thus a promising delivery system for translation into clinical use.

Diversity of dsDNA Viruses in a South African Hot Spring Assessed by Metagenomics and Microscopy.

PubMed

Zablocki, Olivier; van Zyl, Leonardo Joaquim; Kirby, Bronwyn; Trindade, Marla

2017-11-18

The current view of virus diversity in terrestrial hot springs is limited to a few sampling sites. To expand our current understanding of hot spring viral community diversity, this study aimed to investigate the first African hot spring (Brandvlei hot spring; 60 °C, pH 5.7) by means of electron microscopy and sequencing of the virus fraction. Microscopy analysis revealed a mixture of regular- and 'jumbo'-sized tailed morphotypes ( Caudovirales ), lemon-shaped virions ( Fuselloviridae- like; salterprovirus-like) and pleiomorphic virus-like particles. Metavirome analysis corroborated the presence of His1-like viruses and has expanded the current clade of salterproviruses using a polymerase B gene phylogeny. The most represented viral contig was to a cyanophage genome fragment, which may underline basic ecosystem functioning provided by these viruses. Furthermore, a putative Gemmata -related phage was assembled with high coverage, a previously undocumented phage-host association. This study demonstrated that a moderately thermophilic spring environment contained a highly novel pool of viruses and should encourage future characterization of a wider temperature range of hot springs throughout the world.

Amorphous-silicon module hot-spot testing

NASA Technical Reports Server (NTRS)

Gonzalez, C. C.

1985-01-01

Hot spot heating occurs when cell short-circuit current is lower than string operating current. Amorphous cell hot spot are tested to develop the techniques required for performing reverse bias testing of amorphous cells. Also, to quantify the response of amorphous cells to reverse biasing. Guidelines are developed from testing for reducing hot spot susceptibility of amorphous modules and to develop a qualification test for hot spot testing of amorphous modules. It is concluded that amorphous cells undergo hot spot heating similarly to crystalline cells. Comparison of results obtained with submodules versus actual modules indicate heating levels lower in actual modules. Module design must address hot spot testing and hot spot qualification test conducted on modules showed no instabilities and minor cell erosion.

Intein-mediated site-specific synthesis of tumor-targeting protein delivery system: Turning PEG dilemma into prodrug-like feature

PubMed Central

Chen, Yingzhi; Zhang, Meng; Jin, Hongyue; Tang, Yisi; Wang, Huiyuan; Xu, Qin; Li, Yaping; Li, Feng; Huang, Yongzhuo

2017-01-01

Poor tumor-targeted and cytoplasmic delivery is a bottleneck for protein toxin-based cancer therapy. Ideally, a protein toxin drug should remain stealthy in circulation for prolonged half-life and reduced side toxicity, but turn activated at tumor. PEGylation is a solution to achieve the first goal, but creates a hurdle for the second because PEG rejects interaction between the drugs and tumor cells therein. Such PEG dilemma is an unsolved problem in protein delivery. Herein proposed is a concept of turning PEG dilemma into prodrug-like feature. A site-selectively PEGylated, gelatinase-triggered cell-penetrating trichosanthin protein delivery system is developed with three specific aims. The first is to develop an intein-based ligation method for achieving site-specific modification of protein toxins. The second is to develop a prodrug feature that renders protein toxins remaining stealthy in blood for reduced side toxicity and improved EPR effect. The third is to develop a gelatinase activatable cell-penetration strategy for enhanced tumor targeting and cytoplasmic delivery. Of note, site-specific modification is a big challenge in protein drug research, especially for such a complicated, multifunctional protein delivery system. We successfully develop a protocol for constructing a macromolecular prodrug system with intein-mediated ligation synthesis. With an on-column process of purification and intein-mediated cleavage, the site-specific PEGylation then can be readily achieved by conjugation with the activated C-terminus, thus constructing a PEG-capped, cell-penetrating trichosanthin system with a gelatinase-cleavable linker that enables tumor-specific activation of cytoplasmic delivery. It provides a promising method to address the PEG dilemma for enhanced protein drug delivery, and importantly, a facile protocol for site-specific modification of such a class of protein drugs for improving their druggability and industrial translation. PMID:27914267

Electron transport estimated from electron spectra using electron spectrometer in LFEX laser target experiments

NASA Astrophysics Data System (ADS)

Ozaki, T.; Hata, M.; Matsuo, K.; Kojima, S.; Arikawa, Y.; Fujioka, S.; Sakagami, H.; Sunahara, A.; Nagatomo, H.; Johzaki, T.; Yogo, A.; Morace, A.; Zhang, Z.; Shiraga, H.; Sakata, S.; Nagai, T.; Abe, Y.; Lee, S.; Nakai, M.; Nishimura, H.; Azechi, H.; FIREX Group; GXII-LFEX Group

2016-05-01

Hot electrons which are generated from targets irradiated by a high-intense laser are measured by two electron spectrometers (ESMs). However, total electron energy observed by the ESM is only less than 1%. Hot electrons are confined by self-fields due to the huge current. When an external magnetic field of several hundred Tesla is applied during the laser irradiation on targets, the ESM signals always increase. In the simulation, the same result can be obtained. The reason is that the Alfvén limit can be mitigated due to the external longitudinal magnetic field.

Homing in on Hot Dogs

NASA Image and Video Library

2012-08-29

This image is a portion of the all-sky survey from NASA WISE. It highlights the first of about 1,000 hot DOGs found by the mission magenta circle. Hot DOGs are hot dust-obscured galaxies and are among the most powerful galaxies known.

KELT-12b: A P ˜ 5 day, Highly Inflated Hot Jupiter Transiting a Mildly Evolved Hot Star

NASA Astrophysics Data System (ADS)

Stevens, Daniel J.; Collins, Karen A.; Gaudi, B. Scott; Beatty, Thomas G.; Siverd, Robert J.; Bieryla, Allyson; Fulton, Benjamin J.; Crepp, Justin R.; Gonzales, Erica J.; Coker, Carl T.; Penev, Kaloyan; Stassun, Keivan G.; Jensen, Eric L. N.; Howard, Andrew W.; Latham, David W.; Rodriguez, Joseph E.; Zambelli, Roberto; Bozza, Valerio; Reed, Phillip A.; Gregorio, Joao; Buchhave, Lars A.; Penny, Matthew T.; Pepper, Joshua; Berlind, Perry; Calchi Novati, Sebastiano; Calkins, Michael L.; D'Ago, Giuseppe; Eastman, Jason D.; Bayliss, D.; Colón, Knicole D.; Curtis, Ivan A.; DePoy, D. L.; Esquerdo, Gilbert A.; Gould, Andrew; Joner, Michael D.; Kielkopf, John F.; Labadie-Bartz, Jonathan; Lund, Michael B.; Manner, Mark; Marshall, Jennifer L.; McLeod, Kim K.; Oberst, Thomas E.; Pogge, Richard W.; Scarpetta, Gaetano; Stephens, Denise C.; Stockdale, Christopher; Tan, T. G.; Trueblood, Mark; Trueblood, Patricia

2017-04-01

We announce the discovery of KELT-12b, a highly inflated Jupiter-mass planet transiting the mildly evolved, V = 10.64 host star TYC 2619-1057-1. We followed up the initial transit signal in the KELT-North survey data with precise ground-based photometry, high-resolution spectroscopy, precise radial velocity measurements, and high-resolution adaptive optics imaging. Our preferred best-fit model indicates that the host star has {T}{eff} = 6279 ± 51 K, {log}{g}\\star = 3.89 ± 0.05, [Fe/H] = {0.19}-0.09+0.08, {M}* = {1.59}-0.09+0.07 {M}⊙ , and {R}* = 2.37 ± 0.17 {R}⊙ . The planetary companion has {M}{{P}} = 0.95 ± 0.14 {M}{{J}}, {R}{{P}} = {1.78}-0.16+0.17 {R}{{J}}, {log}{g}{{P}} = {2.87}-0.10+0.09, and density {ρ }{{P}} = {0.21}-0.05+0.07 g cm-3, making it one of the most inflated giant planets known. Furthermore, for future follow-up, we report a high-precision time of inferior conjunction in {{BJD}}{TDB} of 2,457,083.660459 ± 0.000894 and period of P=5.0316216+/- 0.000032 days. Despite the relatively large separation of ˜0.07 au implied by its ˜5.03-day orbital period, KELT-12b receives significant flux of {2.38}-0.29+0.32× {10}9 erg s-1 cm-2 from its host. We compare the radii and insolations of transiting gas giant planets around hot ({T}{eff}≥slant 6250 K) and cool stars, noting that the observed paucity of known transiting giants around hot stars with low insolation is likely due to selection effects. We underscore the significance of long-term ground-based monitoring of hot stars and space-based targeting of hot stars with the Transiting Exoplanet Survey Satellite to search for inflated gas giants in longer-period orbits.

Update on the KELT Transit Survey: Hot Planets around Hot Stars

NASA Astrophysics Data System (ADS)

Gaudi, B. Scott; Stassun, Keivan G.; Pepper, Joshua; KELT Collaboration

2018-01-01

The KELT Transit Survey consists of a pair of small-aperture, wide-angle automated telescopes located at Winer Observatory in Sonoita, Arizona and the South African Astronomical Observatory (SAAO) in Sutherland, South Africa. Together, they are surveying roughly 70% of the sky for transiting planets. By virtue of their small apertures (42 mm) and large fields-of-view (26 degrees x 26 degrees), KELT is most sensitive to hot Jupiters transiting relatively bright (V~8-11), and thus relatively hot stars. I will provide an update on the planets discovered by KELT, focusing in detail on our recent discoveries of very hot planets transiting several bright A and early F stars.

Barriers to Liposomal Gene Delivery: from Application Site to the Target.

PubMed

Saffari, Mostafa; Moghimi, Hamid Reza; Dass, Crispin R

2016-01-01

Gene therapy is a therapeutic approach to deliver genetic material into cells to alter their function in entire organism. One promising form of gene delivery system (DDS) is liposomes. The success of liposome-mediated gene delivery is a multifactorial issue and well-designed liposomal systems might lead to optimized gene transfection particularly in vivo. Liposomal gene delivery systems face different barriers from their site of application to their target, which is inside the cells. These barriers include presystemic obstacles (epithelial barriers), systemic barriers in blood circulation and cellular barriers. Epithelial barriers differ depending on the route of administration. Systemic barriers include enzymatic degradation, binding and opsonisation. Both of these barriers can act as limiting hurdles that genetic material and their vector should overcome before reaching the cells. Finally liposomes should overcome cellular barriers that include cell entrance, endosomal escape and nuclear uptake. These barriers and their impact on liposomal gene delivery will be discussed in this review.

The chromodomain of Tf1 integrase promotes binding to cDNA and mediates target site selection.

PubMed

Chatterjee, Atreyi Ghatak; Leem, Young Eun; Kelly, Felice D; Levin, Henry L

2009-03-01

The long terminal repeat (LTR) retrotransposon Tf1 of Schizosaccharomyces pombe integrates specifically into the promoters of pol II-transcribed genes. Its integrase (IN) contains a C-terminal chromodomain related to the chromodomains that bind to the N-terminal tail of histone H3. Although we have been unable to detect an interaction between histone tails and the chromodomain of Tf1 IN, it is possible that the chromodomain plays a role in directing IN to its target sites. To test this idea, we generated transposons with single amino acid substitutions in highly conserved residues of the chromodomain and created a chromodomain-deleted mutant. The mutations, V1290A, Y1292A, W1305A, and CHDDelta, substantially reduced transposition activity in vivo. Blotting assays showed that there was little or no reduction in the levels of IN or cDNA. By measuring the homologous recombination between cDNA and the plasmid copy of Tf1, we found that two of the mutations did not reduce the import of cDNA into the nucleus, while another caused a 33% reduction. Chromatin immunoprecipitation assays revealed that CHDDelta caused an approximately threefold reduction in the binding of IN to the downstream LTR of the cDNA. These data indicate that the chromodomain contributed directly to integration. We therefore tested whether the chromodomain contributed to selecting insertion sites. Results of a target plasmid assay showed that the deletion of the chromodomain resulted in a drastic reduction in the preference for pol II promoters. Collectively, these data indicate that the chromodomain promotes binding of cDNA and plays a key role in efficient targeting.

Quenching and Partitioning Process Development to Replace Hot Stamping of High Strength Automotive Steel

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

De Moor, Emmanuel

the target properties. Twelve alloys were designed and laboratory produced involving melting, alloying, casting, hot rolling, and cold rolling to obtain sheet steels of approximately 1 mm thickness. Q&P processing of the samples was then conducted. Target properties were achieved and substantially exceeded demonstrating success in the developed and employed alloy design approaches. The best combinations of tensile properties were found at approximately 1550 MPa with a total elongation in excess of 20 pct clearly showing the potential for replacement of hot stamping to produce advanced high strength steels.« less

The interaction between hot and cold gas in early-type galaxies

NASA Technical Reports Server (NTRS)

Bregman, Joel N.; Hogg, David E.; Roberts, Morton S.

1995-01-01

SO and Sa galaxies have approximately equal masses of H I and X-ray emitting gas and are ideal sites for studying the interaction between hot and cold gas. An X-ray observation of the Sa galaxy NGC 1291 with the ROSAT position sensitive proportional counter (PSPC) shows a striking spatial anticorrelation between hot and cold gas where X-ray emitting material fills the large central black hole in the H I disk. This supports a previous suggestion that hot gas is a bulge phenomenon and neutral hydrogen is a disk phenomenon. The X-ray luminosity (1.5 x 10(exp 40) ergs/s) and radial surface brightness distribution (beta = 0.51) is the same as for elliptical galaxies with optical luminosities and velocity dispersions like that of the bulge of NGC 1291. Modeling of the X-ray spectrum requires a component with a temperature of 0.15 keV, similar to that expected from the velocity dispersion of the stars, and with a hotter component where kT = 1.07 keV. This hotter component is not due to emission from stars and its origin remains unclear. PSPC observations are reported for the SO NGC 4203, where a nuclear point source dominates the emission, preventing a study of the radial distribution of the hot gas relative to the H I.

Seismic evidence for a possible deep crustal hot zone beneath Southwest Washington.

PubMed

Flinders, Ashton F; Shen, Yang

2017-08-07

Crustal pathways connecting deep sources of melt and the active volcanoes they supply are poorly understood. Beneath Mounts St. Helens, Adams, and Rainier these pathways connect subduction-induced ascending melts to shallow magma reservoirs. Petrogenetic modeling predicts that when these melts are emplaced as a succession of sills into the lower crust they generate deep crustal hot zones. While these zones are increasingly recognized as a primary site for silicic differentiation at a range of volcanic settings globally, imaging them remains challenging. Near Mount Rainier, ascending melt has previously been imaged ~28 km northwest of the volcano, while to the south, the volcano lies on the margin of a broad conductive region in the deep crust. Using 3D full-waveform tomography, we reveal an expansive low-velocity zone, which we interpret as a possible hot zone, linking ascending melts and shallow reservoirs. This hot zone may supply evolved magmas to Mounts St. Helens and Adams, and possibly Rainier, and could contain approximately twice the melt volume as the total eruptive products of all three volcanoes combined. Hot zones like this may be the primary reservoirs for arc volcanism, influencing compositional variations and spatial-segmentation along the entire 1100 km-long Cascades Arc.

Seismic evidence for a possible deep crustal hot zone beneath Southwest Washington

USGS Publications Warehouse

Flinders, Ashton; Shen, Yang

2017-01-01

Crustal pathways connecting deep sources of melt and the active volcanoes they supply are poorly understood. Beneath Mounts St. Helens, Adams, and Rainier these pathways connect subduction-induced ascending melts to shallow magma reservoirs. Petrogenetic modeling predicts that when these melts are emplaced as a succession of sills into the lower crust they generate deep crustal hot zones. While these zones are increasingly recognized as a primary site for silicic differentiation at a range of volcanic settings globally, imaging them remains challenging. Near Mount Rainier, ascending melt has previously been imaged ~28 km northwest of the volcano, while to the south, the volcano lies on the margin of a broad conductive region in the deep crust. Using 3D full-waveform tomography, we reveal an expansive low-velocity zone, which we interpret as a possible hot zone, linking ascending melts and shallow reservoirs. This hot zone may supply evolved magmas to Mounts St. Helens and Adams, and possibly Rainier, and could contain approximately twice the melt volume as the total eruptive products of all three volcanoes combined. Hot zones like this may be the primary reservoirs for arc volcanism, influencing compositional variations and spatial-segmentation along the entire 1100 km-long Cascades Arc.

Shock ignition targets: gain and robustness vs ignition threshold factor

NASA Astrophysics Data System (ADS)

Atzeni, Stefano; Antonelli, Luca; Schiavi, Angelo; Picone, Silvia; Volponi, Gian Marco; Marocchino, Alberto

2017-10-01

Shock ignition is a laser direct-drive inertial confinement fusion scheme, in which the stages of compression and hot spot formation are partly separated. The hot spot is created at the end of the implosion by a converging shock driven by a final ``spike'' of the laser pulse. Several shock-ignition target concepts have been proposed and relevant gain curves computed (see, e.g.). Here, we consider both pure-DT targets and more facility-relevant targets with plastic ablator. The investigation is conducted with 1D and 2D hydrodynamic simulations. We determine ignition threshold factors ITF's (and their dependence on laser pulse parameters) by means of 1D simulations. 2D simulations indicate that robustness to long-scale perturbations increases with ITF. Gain curves (gain vs laser energy), for different ITF's, are generated using 1D simulations. Work partially supported by Sapienza Project C26A15YTMA, Sapienza 2016 (n. 257584), Eurofusion Project AWP17-ENR-IFE-CEA-01.

Oxidation and hot corrosion of hot-pressed Si3N4 at 1000 deg C

NASA Technical Reports Server (NTRS)

Fielder, W. L.

1985-01-01

The oxidation and hot corrosion of a commercial, hot-pressed Si3N4 were investigated at 1000 C under an atmosphere of flowing O2. For the hot corrosion studies, thin films of Na2SO4 were airbrushed on the Si3N4 surface. The hot corrosion attack was monitored by the following techniques: continuous weight measurements, SO2 evolution, film morphology, and chemical analyses. Even though the hot corrosion weight changes after 25 hr were relatively small, the formation of SiO2 from oxidation of Si3N4 was an order of magnitude greater in the presence of molten Na2SO4. The formation of a protective SiO2 phase at the Si3N4 surface is minimized by the fluxing action of the molten Na2SO4 thereby allowing the oxidation of the Si3N4 to proceed more rapidly. A simple process is proposed to account for the hot corrosion process.

Demonstration of Fuel Hot-Spot Pressure in Excess of 50 Gbar for Direct-Drive, Layered Deuterium-Tritium Implosions on OMEGA.

PubMed

Regan, S P; Goncharov, V N; Igumenshchev, I V; Sangster, T C; Betti, R; Bose, A; Boehly, T R; Bonino, M J; Campbell, E M; Cao, D; Collins, T J B; Craxton, R S; Davis, A K; Delettrez, J A; Edgell, D H; Epstein, R; Forrest, C J; Frenje, J A; Froula, D H; Gatu Johnson, M; Glebov, V Yu; Harding, D R; Hohenberger, M; Hu, S X; Jacobs-Perkins, D; Janezic, R; Karasik, M; Keck, R L; Kelly, J H; Kessler, T J; Knauer, J P; Kosc, T Z; Loucks, S J; Marozas, J A; Marshall, F J; McCrory, R L; McKenty, P W; Meyerhofer, D D; Michel, D T; Myatt, J F; Obenschain, S P; Petrasso, R D; Radha, P B; Rice, B; Rosenberg, M J; Schmitt, A J; Schmitt, M J; Seka, W; Shmayda, W T; Shoup, M J; Shvydky, A; Skupsky, S; Solodov, A A; Stoeckl, C; Theobald, W; Ulreich, J; Wittman, M D; Woo, K M; Yaakobi, B; Zuegel, J D

2016-07-08

A record fuel hot-spot pressure P_{hs}=56±7  Gbar was inferred from x-ray and nuclear diagnostics for direct-drive inertial confinement fusion cryogenic, layered deuterium-tritium implosions on the 60-beam, 30-kJ, 351-nm OMEGA Laser System. When hydrodynamically scaled to the energy of the National Ignition Facility, these implosions achieved a Lawson parameter ∼60% of the value required for ignition [A. Bose et al., Phys. Rev. E 93, 011201(R) (2016)], similar to indirect-drive implosions [R. Betti et al., Phys. Rev. Lett. 114, 255003 (2015)], and nearly half of the direct-drive ignition-threshold pressure. Relative to symmetric, one-dimensional simulations, the inferred hot-spot pressure is approximately 40% lower. Three-dimensional simulations suggest that low-mode distortion of the hot spot seeded by laser-drive nonuniformity and target-positioning error reduces target performance.

Complementarity of stability patches at the interfaces of protein complexes: Implication for the structural organization of energetic hot spots.

PubMed

Kuttner, Yosef Y; Engel, Stanislav

2018-02-01

A rational design of protein complexes with defined functionalities and of drugs aimed at disrupting protein-protein interactions requires fundamental understanding of the mechanisms underlying the formation of specific protein complexes. Efforts to develop efficient small-molecule or protein-based binders often exploit energetic hot spots on protein surfaces, namely, the interfacial residues that provide most of the binding free energy in the complex. The molecular basis underlying the unusually high energy contribution of the hot spots remains obscure, and its elucidation would facilitate the design of interface-targeted drugs. To study the nature of the energetic hot spots, we analyzed the backbone dynamic properties of contact surfaces in several protein complexes. We demonstrate that, in most complexes, the backbone dynamic landscapes of interacting surfaces form complementary "stability patches," in which static areas from the opposing surfaces superimpose, and that these areas are predominantly located near the geometric center of the interface. We propose that a diminished enthalpy-entropy compensation effect augments the degree to which residues positioned within the complementary stability patches contribute to complex affinity, thereby giving rise to the energetic hot spots. These findings offer new insights into the nature of energetic hot spots and the role that backbone dynamics play in facilitating intermolecular recognition. Mapping the interfacial stability patches may provide guidance for protein engineering approaches aimed at improving the stability of protein complexes and could facilitate the design of ligands that target complex interfaces. © 2017 Wiley Periodicals, Inc.

Hot tub folliculitis or hot hand-foot syndrome caused by Pseudomonas aeruginosa.

PubMed

Yu, Yue; Cheng, Amy S; Wang, Lawrence; Dunne, W Michael; Bayliss, Susan J

2007-10-01

Pseudomonas aeruginosa is a ubiquitous gram-negative rod that can cause a well-recognized, acquired skin infection from bacterial colonization of contaminated water called "hot tub folliculitis." We report an outbreak of pseudomonas skin infection associated with the use of a hot tub at a pool party in 33 children. In particular, 2 of the children were admitted to our hospital; both presented with high leukocyte counts, intermittent low grade fevers, and painful, erythematous nodules and papules on their palms and soles. One of the 2 children also presented with small erythematous pustular lesions on the face and trunk, which led to the diagnosis. Cultures from these pustules grew P aeruginosa. Thirty two other children at this pool/hot tub party developed similar lesions of varying severity 6 to 48 hours after the party. These findings were most consistent with the diagnosis of pseudomonas folliculitis/hot hand.

HOT CELL BUILDING, TRA632, INTERIOR. HOT CELL NO. 1 (THE ...

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

HOT CELL BUILDING, TRA-632, INTERIOR. HOT CELL NO. 1 (THE FIRST BUILT) IN LABORATORY 101. CAMERA FACES SOUTHEAST. SHIELDED OPERATING WINDOWS ARE ON LEFT (NORTH) SIDE. OBSERVATION WINDOW IS AT LEFT OF VIEW (ON WEST SIDE). PLASTIC COVERS SHROUD MASTER/SLAVE MANIPULATORS AT WINDOWS IN LEFT OF VIEW. NOTE MINERAL OIL RESERVOIR ABOVE "CELL 1" SIGN, INDICATING LEVEL OF THE FLUID INSIDE THE THICK WINDOWS. HOT CELL HAS BEVELED CORNER BECAUSE A SQUARED CORNER WOULD HAVE SUPPLIED UNNECESSARY SHIELDING. NOTE PUMICE BLOCK WALL AT LEFT OF VIEW. INL NEGATIVE NO. HD46-28-1. Mike Crane, Photographer, 2/2005 - Idaho National Engineering Laboratory, Test Reactor Area, Materials & Engineering Test Reactors, Scoville, Butte County, ID

Surveillance of Vittaforma corneae in hot springs by a small-volume procedure.

PubMed

Chen, Jung-Sheng; Hsu, Tsui-Kang; Hsu, Bing-Mu; Huang, Tung-Yi; Huang, Yu-Li; Shaio, Men-Fang; Ji, Dar-Der

2017-07-01

Vittaforma corneae is an obligate intracellular fungus and can cause human ocular microsporidiosis. Although accumulating reports of V. corneae causing keratoconjunctivitis in both healthy and immunocompromised persons have been published, little is known about the organism's occurrence in aquatic environments. Limitations in detection sensitivity have meant a large sampling volume is required to detect the pathogen up to now, which is problematic. A recent study in Taiwan has shown that some individuals suffering from microsporidial keratitis (MK) were infected after exposure to the pathogen at a hot spring. As a consequence of this, a survey and analysis of environmental V. corneae present in hot springs became an urgent need. In this study, sixty water samples from six hot spring recreation areas around Taiwan were analyzed. One liter of water from each sample site was filtered to harvest the fungi. The positive samples were detected using a modified nested PCR approach followed by sequencing using specific SSU rRNA gene primer pairs for V. corneae. In total fifteen V. corneae-like isolates were identified (25.0% of sites). Among them, six isolates, which were collected from recreational areas B, C and D, were highly similar to known V. corneae keratitis strains from Taiwan and other countries. Furthermore, five isolates, which were collected from recreation areas A, C, E and F, were very similar to Vittaforma-like diarrhea strains isolated in Portugal. Cold spring water tubs and public foot bath pools had the highest detection rate (50%), suggesting that hot springs might be contaminated via untreated water sources. Comparing the detection rate across different regions of Taiwan, Taitung, which is in the east of the island, gave the highest positive rate (37.5%). Statistical analysis showed that outdoor/soil exposure and a high heterotrophic plate count (HPC) were risk factors for the occurrence of V. corneae. Our findings provide empirical evidence

p62 targeting to the autophagosome formation site requires self-oligomerization but not LC3 binding

PubMed Central

Itakura, Eisuke

2011-01-01

Autophagy is an intracellular degradation process by which cytoplasmic contents are degraded in the lysosome. In addition to nonselective engulfment of cytoplasmic materials, the autophagosomal membrane can selectively recognize specific proteins and organelles. It is generally believed that the major selective substrate (or cargo receptor) p62 is recruited to the autophagosomal membrane through interaction with LC3. In this study, we analyzed loading of p62 and its related protein NBR1 and found that they localize to the endoplasmic reticulum (ER)–associated autophagosome formation site independently of LC3 localization to membranes. p62 colocalizes with upstream autophagy factors such as ULK1 and VMP1 even when autophagosome formation is blocked by wortmannin or FIP200 knockout. Self-oligomerization of p62 is essential for its localization to the autophagosome formation site. These results suggest that p62 localizes to the autophagosome formation site on the ER, where autophagosomes are nucleated. This process is similar to the yeast cytoplasm to vacuole targeting pathway. PMID:21220506

The novel cyst nematode effector protein 30D08 targets host nuclear functions to alter gene expression in feeding sites.

PubMed

Verma, Anju; Lee, Chris; Morriss, Stephanie; Odu, Fiona; Kenning, Charlotte; Rizzo, Nancy; Spollen, William G; Lin, Marriam; McRae, Amanda G; Givan, Scott A; Hewezi, Tarek; Hussey, Richard; Davis, Eric L; Baum, Thomas J; Mitchum, Melissa G

2018-05-04

Cyst nematodes deliver effector proteins into host cells to manipulate cellular processes and establish a metabolically hyperactive feeding site. The novel 30D08 effector protein is produced in the dorsal gland of parasitic juveniles, but its function has remained unknown. We demonstrate that expression of 30D08 contributes to nematode parasitism, the protein is packaged into secretory granules and it is targeted to the plant nucleus where it interacts with SMU2 (homolog of suppressor of mec-8 and unc-52 2), an auxiliary spliceosomal protein. We show that SMU2 is expressed in feeding sites and an smu2 mutant is less susceptible to nematode infection. In Arabidopsis expressing 30D08 under the SMU2 promoter, several genes were found to be alternatively spliced and the most abundant functional classes represented among differentially expressed genes were involved in RNA processing, transcription and binding, as well as in development, and hormone and secondary metabolism, representing key cellular processes known to be important for feeding site formation. In conclusion, we demonstrated that the 30D08 effector is secreted from the nematode and targeted to the plant nucleus where its interaction with a host auxiliary spliceosomal protein may alter the pre-mRNA splicing and expression of a subset of genes important for feeding site formation. © 2018 The Authors. New Phytologist © 2018 New Phytologist Trust.

Actin filaments target the oligomeric maturation of the dynamin GTPase Drp1 to mitochondrial fission sites

PubMed Central

Ji, Wei-ke; Hatch, Anna L; Merrill, Ronald A; Strack, Stefan; Higgs, Henry N

2015-01-01

While the dynamin GTPase Drp1 plays a critical role during mitochondrial fission, mechanisms controlling its recruitment to fission sites are unclear. A current assumption is that cytosolic Drp1 is recruited directly to fission sites immediately prior to fission. Using live-cell microscopy, we find evidence for a different model, progressive maturation of Drp1 oligomers on mitochondria through incorporation of smaller mitochondrially-bound Drp1 units. Maturation of a stable Drp1 oligomer does not forcibly lead to fission. Drp1 oligomers also translocate directionally along mitochondria. Ionomycin, a calcium ionophore, causes rapid mitochondrial accumulation of actin filaments followed by Drp1 accumulation at the fission site, and increases fission rate. Inhibiting actin polymerization, myosin IIA, or the formin INF2 reduces both un-stimulated and ionomycin-induced Drp1 accumulation and mitochondrial fission. Actin filaments bind purified Drp1 and increase GTPase activity in a manner that is synergistic with the mitochondrial protein Mff, suggesting a role for direct Drp1/actin interaction. We propose that Drp1 is in dynamic equilibrium on mitochondria in a fission-independent manner, and that fission factors such as actin filaments target productive oligomerization to fission sites. DOI: http://dx.doi.org/10.7554/eLife.11553.001 PMID:26609810

Detection of canonical A-to-G editing events at 3' UTRs and microRNA target sites in human lungs using next-generation sequencing.

PubMed

Soundararajan, Ramani; Stearns, Timothy M; Griswold, Anthony L; Mehta, Arpit; Czachor, Alexander; Fukumoto, Jutaro; Lockey, Richard F; King, Benjamin L; Kolliputi, Narasaiah

2015-11-03

RNA editing is a post-transcriptional modification of RNA. The majority of these changes result from adenosine deaminase acting on RNA (ADARs) catalyzing the conversion of adenosine residues to inosine in double-stranded RNAs (dsRNAs). Massively parallel sequencing has enabled the identification of RNA editing sites in human transcriptomes. In this study, we sequenced DNA and RNA from human lungs and identified RNA editing sites with high confidence via a computational pipeline utilizing stringent analysis thresholds. We identified a total of 3,447 editing sites that overlapped in three human lung samples, and with 50% of these sites having canonical A-to-G base changes. Approximately 27% of the edited sites overlapped with Alu repeats, and showed A-to-G clustering (>3 clusters in 100 bp). The majority of edited sites mapped to either 3' untranslated regions (UTRs) or introns close to splice sites; whereas, only few sites were in exons resulting in non-synonymous amino acid changes. Interestingly, we identified 652 A-to-G editing events in the 3' UTR of 205 target genes that mapped to 932 potential miRNA target binding sites. Several of these miRNA edited sites were validated in silico. Additionally, we validated several A-to-G edited sites by Sanger sequencing. Altogether, our study suggests a role for RNA editing in miRNA-mediated gene regulation and splicing in human lungs. In this study, we have generated a RNA editome of human lung tissue that can be compared with other RNA editomes across different lung tissues to delineate a role for RNA editing in normal and diseased states.

Hot-isostatically pressed wasteforms for Magnox sludge immobilisation

NASA Astrophysics Data System (ADS)

Heath, Paul G.; Stewart, Martin W. A.; Moricca, Sam; Hyatt, Neil C.

2018-02-01

Thermal treatment technologies offer many potential benefits for the treatment of radioactive wastes including the passivation of reactive species and significant waste volume reductions. This paper presents a study investigating the production of wasteforms using Hot-isostatic pressing technology for the immobilisation of Magnox sludges from the UK's Sellafield Site. Simulants considered physically representative of these sludges were used to determine possible processing parameters and to determine the phase assemblages and morphologies produced during processing. The study showed hot-isostatic pressing is capable of processing Magnox sludges at up to 60 wt% (oxide basis) into dense, mixed ceramic wasteforms. The wasteforms produced are a glass-bonded ceramic of mixed magnesium titanates, encapsulating localised grains of periclase. The ability to co-process Magnox sludges with SIXEP sand/clinoptilolite slurries has also been demonstrated. The importance of these results is presented through a comparison of volume reduction data, which shows HIPing may provide a 20-fold volume reduction over the current cementitious baseline and double the volume reduction attainable for vitrification technologies.

Hot Dry Rock; Geothermal Energy

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

None

1990-01-01

The commercial utilization of geothermal energy forms the basis of the largest renewable energy industry in the world. More than 5000 Mw of electrical power are currently in production from approximately 210 plants and 10 000 Mw thermal are used in direct use processes. The majority of these systems are located in the well defined geothermal generally associated with crustal plate boundaries or hot spots. The essential requirements of high subsurface temperature with huge volumes of exploitable fluids, coupled to environmental and market factors, limit the choice of suitable sites significantly. The Hot Dry Rock (HDR) concept at any depthmore » originally offered a dream of unlimited expansion for the geothermal industry by relaxing the location constraints by drilling deep enough to reach adequate temperatures. Now, after 20 years intensive work by international teams and expenditures of more than $250 million, it is vital to review the position of HDR in relation to the established geothermal industry. The HDR resource is merely a body of rock at elevated temperatures with insufficient fluids in place to enable the heat to be extracted without the need for injection wells. All of the major field experiments in HDR have shown that the natural fracture systems form the heat transfer surfaces and that it is these fractures that must be for geothermal systems producing from naturally fractured formations provide a basis for directing the forthcoming but, equally, they require accepting significant location constraints on HDR for the time being. This paper presents a model HDR system designed for commercial operations in the UK and uses production data from hydrothermal systems in Japan and the USA to demonstrate the reservoir performance requirements for viable operations. It is shown that these characteristics are not likely to be achieved in host rocks without stimulation processes. However, the long term goal of artificial geothermal systems developed by

Investigating inertial confinement fusion target fuel conditions through x-ray spectroscopya)

NASA Astrophysics Data System (ADS)

Hansen, Stephanie B.

2012-05-01

Inertial confinement fusion (ICF) targets are designed to produce hot, dense fuel in a neutron-producing core that is surrounded by a shell of compressing material. The x-rays emitted from ICF plasmas can be analyzed to reveal details of the temperatures, densities, gradients, velocities, and mix characteristics of ICF targets. Such diagnostics are critical to understand the target performance and to improve the predictive power of simulation codes.

Preliminary results on the composition of Jupiter's troposphere in hot spot regions from the JIRAM/Juno instrument

NASA Astrophysics Data System (ADS)

Grassi, D.; Adriani, A.; Mura, A.; Dinelli, B. M.; Sindoni, G.; Turrini, D.; Filacchione, G.; Migliorini, A.; Moriconi, M. L.; Tosi, F.; Noschese, R.; Cicchetti, A.; Altieri, F.; Fabiano, F.; Piccioni, G.; Stefani, S.; Atreya, S.; Lunine, J.; Orton, G.; Ingersoll, A.; Bolton, S.; Levin, S.; Connerney, J.; Olivieri, A.; Amoroso, M.

2017-05-01

The Jupiter InfraRed Auroral Mapper (JIRAM) instrument on board the Juno spacecraft performed observations of two bright Jupiter hot spots around the time of the first Juno pericenter passage on 27 August 2016. The spectra acquired in the 4-5 µm spectral range were analyzed to infer the residual opacities of the uppermost cloud deck as well as the mean mixing ratios of water, ammonia, and phosphine at the approximate level of few bars. Our results support the current view of hot spots as regions of prevailing descending vertical motions in the atmosphere but extend this view suggesting that upwelling may occur at the southern boundaries of these structures. Comparison with the global ammonia abundance measured by Juno Microwave Radiometer suggests also that hot spots may represent sites of local enrichment of this gas. JIRAM also identifies similar spatial patterns in water and phosphine contents in the two hot spots.

Target-site resistance to neonicotinoids.

PubMed

Crossthwaite, Andrew J; Rendine, Stefano; Stenta, Marco; Slater, Russell

2014-10-01

Neonicotinoid insecticides selectively target the invertebrate nicotinic acetylcholine receptor and disrupt excitatory cholinergic neurotransmission. First launched over 20 years ago, their broad pest spectrum, variety of application methods and relatively low risk to nontarget organisms have resulted in this class dominating the insecticide market with global annual sales in excess of $3.5 bn. This remarkable commercial success brings with it conditions in the field that favour selection of resistant phenotypes. A number of important pest species have been identified with mutations at the nicotinic acetylcholine receptor associated with insensitivity to neonicotinoids. The detailed characterization of these mutations has facilitated a greater understanding of the invertebrate nicotinic acetylcholine receptor.

Hot Spots and Hot Moments of Nitrogen in a Riparian Corridor

NASA Astrophysics Data System (ADS)

Dwivedi, Dipankar; Arora, Bhavna; Steefel, Carl I.; Dafflon, Baptiste; Versteeg, Roelof

2018-01-01

We use 3-D high-resolution reactive transport modeling to investigate whether the spatial distribution of organic-carbon-rich and chemically reduced sediments located in the riparian zone and temporal variability in groundwater flow direction impact the formation and distribution of nitrogen hot spots (regions that exhibit higher reaction rates when compared to other locations nearby) and hot moments (times that exhibit high reaction rates as compared to longer intervening time periods) within the Rifle floodplain in Colorado. Groundwater flows primarily toward the Colorado River from the floodplain but changes direction at times of high river stage. The result is that oxic river water infiltrates the Rifle floodplain during these relatively short-term events. Simulation results indicate that episodic rainfall in the summer season leads to the formation of nitrogen hot moments associated with Colorado River rise and resulting river infiltration into the floodplain. The results further demonstrate that the naturally reduced zones (NRZs) present in sediments of the Rifle floodplain have a higher potential for nitrate removal, approximately 70% greater than non-NRZs for typical hydrological conditions. During river water infiltration, nitrate reduction capacity remains the same within the NRZs, however, these conditions impact non-NRZs to a greater extent (approximately 95% less nitrate removal). Model simulations indicate chemolithoautotrophs are primarily responsible for the removal of nitrate in the Rifle floodplain. These nitrogen hot spots and hot moments are sustained by microbial respiration and the chemolithoautotrophic oxidation of reduced minerals in the riparian zone.

Linking Oviposition Site Choice to Offspring Fitness in Aedes aegypti: Consequences for Targeted Larval Control of Dengue Vectors

PubMed Central

Wong, Jacklyn; Morrison, Amy C.; Stoddard, Steven T.; Astete, Helvio; Chu, Yui Yin; Baseer, Imaan; Scott, Thomas W.

2012-01-01

Background Current Aedes aegypti larval control methods are often insufficient for preventing dengue epidemics. To improve control efficiency and cost-effectiveness, some advocate eliminating or treating only highly productive containers. The population-level outcome of this strategy, however, will depend on details of Ae. aegypti oviposition behavior. Methodology/Principal Findings We simultaneously monitored female oviposition and juvenile development in 80 experimental containers located across 20 houses in Iquitos, Peru, to test the hypothesis that Ae. aegypti oviposit preferentially in sites with the greatest potential for maximizing offspring fitness. Females consistently laid more eggs in large vs. small containers (β = 9.18, p<0.001), and in unmanaged vs. manually filled containers (β = 5.33, p<0.001). Using microsatellites to track the development of immature Ae. aegypti, we found a negative correlation between oviposition preference and pupation probability (β = −3.37, p<0.001). Body size of emerging adults was also negatively associated with the preferred oviposition site characteristics of large size (females: β = −0.19, p<0.001; males: β = −0.11, p = 0.002) and non-management (females: β = −0.17, p<0.001; males: β = −0.11, p<0.001). Inside a semi-field enclosure, we simulated a container elimination campaign targeting the most productive oviposition sites. Compared to the two post-intervention trials, egg batches were more clumped during the first pre-intervention trial (β = −0.17, P<0.001), but not the second (β = 0.01, p = 0.900). Overall, when preferred containers were unavailable, the probability that any given container received eggs increased (β = 1.36, p<0.001). Conclusions/Significance Ae. aegypti oviposition site choice can contribute to population regulation by limiting the production and size of adults. Targeted larval control strategies may unintentionally lead to

Targeted Nanotechnology for Cancer Imaging

PubMed Central

Toy, Randall; Bauer, Lisa; Hoimes, Christopher; Ghaghada, Ketan B.; Karathanasis, Efstathios

2014-01-01

Targeted nanoparticle imaging agents provide many benefits and new opportunities to facilitate accurate diagnosis of cancer and significantly impact patient outcome. Due to the highly engineerable nature of nanotechnology, targeted nanoparticles exhibit significant advantages including increased contrast sensitivity, binding avidity and targeting specificity. Considering the various nanoparticle designs and their adjustable ability to target a specific site and generate detectable signals, nanoparticles can be optimally designed in terms of biophysical interactions (i.e., intravascular and interstitial transport) and biochemical interactions (i.e., targeting avidity towards cancer-related biomarkers) for site-specific detection of very distinct microenvironments. This review seeks to illustrate that the design of a nanoparticle dictates its in vivo journey and targeting of hard-to-reach cancer sites, facilitating early and accurate diagnosis and interrogation of the most aggressive forms of cancer. We will report various targeted nanoparticles for cancer imaging using X-ray computed tomography, ultrasound, magnetic resonance imaging, nuclear imaging and optical imaging. Finally, to realize the full potential of targeted nanotechnology for cancer imaging, we will describe the challenges and opportunities for the clinical translation and widespread adaptation of targeted nanoparticles imaging agents. PMID:25116445

Hot dry rock geothermal energy: status of exploration and assessment. Report No. 1 of the hot dry rock assessment panel

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

Not Available

1977-06-01

The status of knowledge of attempts to utilize hot dry rock (HDR) geothermal energy is summarized. It contains (1) descriptions or case histories of the ERDA-funded projects at Marysville, MT, Fenton Hill, NM, and Coso Hot Springs, CA; (2) a review of the status of existing techniques available for exploration and delineation of HDR; (3) descriptions of other potential HDR sites; (4) definitions of the probable types of HDR resource localities; and (5) an estimate of the magnitude of the HDR resource base in the conterminous United States. The scope is limited to that part of HDR resource assessment relatedmore » to the determination of the extent and character of HDR, with emphasis on the igneous-related type. It is estimated that approximately 74 Q (1 Q = 1,000 Quads) of heat is stored in these sites within the conterminous U.S. at depths less than 10 km and temperatures above 150/sup 0/C, the minimum for power generation. (Q = 10/sup 18/ BTU = 10/sup 21/J; the total U.S. consumption for 1972 was approximately 0.07 Q). Approximately 6300 Q are stored in the conduction-dominated parts of the crust in the western U.S. (23% of the total surface area), again at depths less than 10 km and temperatures above 150/sup 0/C. Nearly 10,000 Q are believed to be contained in crustal rocks underlying the entire conterminous U.S., at temperatures above 150/sup 0/C. The resource base is significantly larger for lower grade heat. (JGB)« less

Tidd hot gas clean up program. Final report

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

NONE

This Final Report on the Tidd Hot Gas Clean Up Program covers the period from initial Proof-of-Concept testing in August, 1990, through final equipment inspections in May, 1995. The Tidd Hot Gas Clean Up (HGCU) system was installed in the Tidd Pressurized Fluidized Bed Combustion (PFBC) Demonstration Plant, which is the first utility-scale PFBC plant in the United States. Detailed design work on the project began in July, 1990, and site construction began in December, 1991. Initial operation of the system occurred in May, 1992, and the hot gas filter was commissioned in October, 1992. The test program ended inmore » March, 1995, when the Tidd Plant was shut down following its four-year test program. Section 1.0 of this report is an executive summary of the project covering the project background, system description, test results and conclusions. Section 2.0 is an introduction covering the program objectives and schedule. Section 3.0 provides detailed descriptions of the system and its major components. Section 4.0 provides detailed results of all testing including observations and posttest inspection results. Sections 5.0 and 6.0 list the program conclusions and recommendations, respectively. Appendix I is a report prepared by Southern Research Institute on the properties of Tidd PFBC ash sampled during the test program. Appendix II is a report prepared by Westinghouse STC on the performance of candle filter fail-safe regenerator devices.« less

Hot Jupiters and Hot Spots: The Short- and Long-Term Chromospheric Activity on Stars with Giant Planets

NASA Astrophysics Data System (ADS)

Shkolnik, E.; Walker, G. A. H.; Bohlender, D. A.; Gu, P.-G.; Kürster, M.

2005-04-01

We monitored the chromospheric activity in the Ca II H and K lines of 13 solar-type stars (including the Sun): 8 of them over 3 years at the Canada-France-Hawaii Telescope (CFHT) and 5 in a single run at the Very Large Telescope (VLT). A total of 10 of the 13 targets have close planetary companions. All of the stars observed at the CFHT show long-term (months to years) changes in H and K intensity levels. Four stars display short-term (days) cyclical activity. For two, HD 73256 and κ1 Cet, the activity is likely associated with an active region rotating with the star; however, the flaring in excess of the rotational modulation may be associated with a hot Jupiter. A planetary companion remains a possibility for κ1 Cet. For the other two, HD 179949 and υ And, the cyclic variation is synchronized to the hot Jupiter's orbit. For both stars this synchronicity with the orbit is clearly seen in two out of three epochs. The effect is only marginal in the third epoch at which the seasonal level of chromospheric activity had changed for both stars. Short-term chromospheric activity appears weakly dependent on the mean K line reversal intensities for the sample of 13 stars. In addition, a suggestive correlation exists between this activity and the Mpsini of the star's hot Jupiter. Because of their small separation (<=0.1 AU), many of the hot Jupiters lie within the Alfvén radius of their host stars, which allows a direct magnetic interaction with the stellar surface. We discuss the conditions under which a planet's magnetic field might induce activity on the stellar surface and why no such effect was seen for the prime candidate, τ Boo. This work opens up the possibility of characterizing planet-star interactions, with implications for extrasolar planet magnetic fields and the energy contribution to stellar atmospheres. Based on observations collected at the Canada-France-Hawaii Telescope operated by the National Research Council of Canada, the Centre National de la

Universal surface-enhanced Raman scattering amplification detector for ultrasensitive detection of multiple target analytes.

PubMed

Zheng, Jing; Hu, Yaping; Bai, Junhui; Ma, Cheng; Li, Jishan; Li, Yinhui; Shi, Muling; Tan, Weihong; Yang, Ronghua

2014-02-18

Up to now, the successful fabrication of efficient hot-spot substrates for surface-enhanced Raman scattering (SERS) remains an unsolved problem. To address this issue, we describe herein a universal aptamer-based SERS biodetection approach that uses a single-stranded DNA as a universal trigger (UT) to induce SERS-active hot-spot formation, allowing, in turn, detection of a broad range of targets. More specifically, interaction between the aptamer probe and its target perturbs a triple-helix aptamer/UT structure in a manner that activates a hybridization chain reaction (HCR) among three short DNA building blocks that self-assemble into a long DNA polymer. The SERS-active hot-spots are formed by conjugating 4-aminobenzenethiol (4-ABT)-encoded gold nanoparticles with the DNA polymer through a specific Au-S bond. As proof-of-principle, we used this approach to quantify multiple target analytes, including thrombin, adenosine, and CEM cancer cells, achieving lowest limit of detection values of 18 pM, 1.5 nM, and 10 cells/mL, respectively. As a universal SERS detector, this prototype can be applied to many other target analytes through the use of suitable DNA-functional partners, thus inspiring new designs and applications of SERS for bioanalysis.

Thiamethoxam acts as a target-site synergist of spinosad in resistant strains of Frankliniella occidentalis.

PubMed

Guillén, Juan; Bielza, Pablo

2013-02-01

Previous studies have suggested that the resistance mechanism towards spinosad in Frankliniella occidentalis (Pergande) is an altered target site. Like the neonicotinoids, the spinosyns act on nicotinic acetylcholine receptors (nAChRs) in insects, but at a distinct site. The changes in nAChRs related to spinosad resistance in thrips might involve interaction with neonicotinoids. In this study, the efficacy of spinosad and neonicotinoids, alone and in combination, was evaluated in susceptible and spinosad-resistant thrips strains. The neonicotinoids tested were imidacloprid, thiacloprid, acetamiprid, thiamethoxam and clothianidin. No cross-resistance was shown between spinosad and any of the neonicotinoids. However, an increased toxicity was observed when a mixture of spinosad with thiamethoxam or clothianidin was tested. No synergism was found in the susceptible strains. The more spinosad-resistant the thrips strain, the stronger was the synergism. Data suggest that spinosad and thiamethoxam may interact at the nAChRs in spinosad-resistant thrips, facilitating enhanced insecticidal action. Copyright © 2012 Society of Chemical Industry.

The Distinction of Hot Herbal Compress, Hot Compress, and Topical Diclofenac as Myofascial Pain Syndrome Treatment.

PubMed

Boonruab, Jurairat; Nimpitakpong, Netraya; Damjuti, Watchara

2018-01-01

This randomized controlled trial aimed to investigate the distinctness after treatment among hot herbal compress, hot compress, and topical diclofenac. The registrants were equally divided into groups and received the different treatments including hot herbal compress, hot compress, and topical diclofenac group, which served as the control group. After treatment courses, Visual Analog Scale and 36-Item Short Form Health survey were, respectively, used to establish the level of pain intensity and quality of life. In addition, cervical range of motion and pressure pain threshold were also examined to identify the motional effects. All treatments showed significantly decreased level of pain intensity and increased cervical range of motion, while the intervention groups exhibited extraordinary capability compared with the topical diclofenac group in pressure pain threshold and quality of life. In summary, hot herbal compress holds promise to be an efficacious treatment parallel to hot compress and topical diclofenac.

Hot-Film and Hot-Wire Anemometry for a Boundary Layer Active Flow Control Test

NASA Technical Reports Server (NTRS)

Lenahan, Keven C.; Schatzman, David M.; Wilson, Jacob Samuel

2013-01-01

Unsteady active flow control (AFC) has been used experimentally for many years to minimize bluff-body drag. This technology could significantly improve performance of rotorcraft by cleaning up flow separation. It is important, then, that new actuator technologies be studied for application to future vehicles. A boundary layer wind tunnel was constructed with a 1ft-x-3ft test section and unsteady measurement instrumentation to study how AFC manipulates the boundary layer to overcome adverse pressure gradients and flow separation. This unsteady flow control research requires unsteady measurement methods. In order to measure the boundary layer characteristics, both hot-wire and hot-film Constant Temperature Anemometry is used. A hot-wire probe is mounted in the flow to measure velocity while a hot-film array lays on the test surface to measure skin friction. Hot-film sensors are connected to an anemometer, a Wheatstone bridge circuit with an output that corresponds to the dynamic flow response. From this output, the time varying flow field, turbulence, and flow reversal can be characterized. Tuning the anemometers requires a fan test on the hot-film sensors to adjust each output. This is a delicate process as several variables drastically affect the data, including control resistance, signal input, trim, and gain settings.

Formation of target-specific binding sites in enzymes: solid-phase molecular imprinting of HRP

NASA Astrophysics Data System (ADS)

Czulak, J.; Guerreiro, A.; Metran, K.; Canfarotta, F.; Goddard, A.; Cowan, R. H.; Trochimczuk, A. W.; Piletsky, S.

2016-05-01

Here we introduce a new concept for synthesising molecularly imprinted nanoparticles by using proteins as macro-functional monomers. For a proof-of-concept, a model enzyme (HRP) was cross-linked using glutaraldehyde in the presence of glass beads (solid-phase) bearing immobilized templates such as vancomycin and ampicillin. The cross-linking process links together proteins and protein chains, which in the presence of templates leads to the formation of permanent target-specific recognition sites without adverse effects on the enzymatic activity. Unlike complex protein engineering approaches commonly employed to generate affinity proteins, the method proposed can be used to produce protein-based ligands in a short time period using native protein molecules. These affinity materials are potentially useful tools especially for assays since they combine the catalytic properties of enzymes (for signaling) and molecular recognition properties of antibodies. We demonstrate this concept in an ELISA-format assay where HRP imprinted with vancomycin and ampicillin replaced traditional enzyme-antibody conjugates for selective detection of templates at micromolar concentrations. This approach can potentially provide a fast alternative to raising antibodies for targets that do not require high assay sensitivities; it can also find uses as a biochemical research tool, as a possible replacement for immunoperoxidase-conjugates.Here we introduce a new concept for synthesising molecularly imprinted nanoparticles by using proteins as macro-functional monomers. For a proof-of-concept, a model enzyme (HRP) was cross-linked using glutaraldehyde in the presence of glass beads (solid-phase) bearing immobilized templates such as vancomycin and ampicillin. The cross-linking process links together proteins and protein chains, which in the presence of templates leads to the formation of permanent target-specific recognition sites without adverse effects on the enzymatic activity. Unlike

Rhodium(II) proximity-labeling identifies a novel target site on STAT3 for inhibitors with potent anti-leukemia activity

PubMed Central

Minus, Matthew B.; Liu, Wei; Vohidov, Farrukh; Kasembeli, Moses M.; Long, Xin; Krueger, Michael; Stevens, Alexandra; Kolosov, Mikhail I.; Sison, Edward Allen R.; Ball, Zachary T.

2015-01-01

Nearly 40% of children with acute myeloid leukemia (AML) suffer relapse due to chemoresistance, often involving upregulation of the oncoprotein STAT3 (signal transducer and activator of transcription 3). In this paper, rhodium(II)-catalyzed, proximity-driven modification identifies the STAT3 coiled-coil domain (CCD) as a novel ligand-binding site, and we describe a new naphthalene sulfonamide inhibitor that targets the CCD, blocks STAT3 function, and halts its disease-promoting effects in vitro, in tumor growth models, and in a leukemia mouse model, validating this new therapeutic target for resistant AML. PMID:26480340

Preliminary design package for solar heating and hot water system

NASA Technical Reports Server (NTRS)

1977-01-01

The preliminary design review on the development of two prototype solar heating and hot water systems is presented. The information contained in this report includes system certification, system functional description, system configuration, system specification, system performance and other documents pertaining to the progress and the design of the system. This system, which is intended for use in the normal single-family residence, consists of the following subsystems: collector, storage, control, transport, and Government-furnished Site Data Acquisition.

Dengue vector management using insecticide treated materials and targeted interventions on productive breeding-sites in Guatemala.

PubMed

Rizzo, Nidia; Gramajo, Rodrigo; Escobar, Maria Cabrera; Arana, Byron; Kroeger, Axel; Manrique-Saide, Pablo; Petzold, Max

2012-10-30

In view of the epidemiological expansion of dengue worldwide and the availability of new tools and strategies particularly for controlling the primary dengue vector Aedes aegypti, an intervention study was set up to test the efficacy, cost and feasibility of a combined approach of insecticide treated materials (ITMs) alone and in combination with appropriate targeted interventions of the most productive vector breeding-sites. The study was conducted as a cluster randomized community trial using "reduction of the vector population" as the main outcome variable. The trial had two arms: 10 intervention clusters (neighborhoods) and 10 control clusters in the town of Poptun Guatemala. Activities included entomological assessments (characteristics of breeding-sites, pupal productivity, Stegomyia indices) at baseline, 6 weeks after the first intervention (coverage of window and exterior doorways made of PermaNet 2.0 netting, factory treated with deltamethrin at 55 mg/m2, and of 200 L drums with similar treated material) and 6 weeks after the second intervention (combination of treated materials and other suitable interventions targeting productive breeding-sites i.e larviciding with Temephos, elimination etc.). The second intervention took place 17 months after the first intervention. The insecticide residual activity and the insecticidal content were also studied at different intervals. Additionally, information about demographic characteristics, cost of the intervention, coverage of houses protected and satisfaction in the population with the interventions was collected. At baseline (during the dry season) a variety of productive container types for Aedes pupae were identified: various container types holding >20 L, 200 L drums, washbasins and buckets (producing 83.7% of all pupae). After covering 100% of windows and exterior doorways and a small number of drums (where the commercial cover could be fixed) in 970 study households, tropical rains occurred in the area and

Dengue vector management using insecticide treated materials and targeted interventions on productive breeding-sites in Guatemala

PubMed Central

2012-01-01

Background In view of the epidemiological expansion of dengue worldwide and the availability of new tools and strategies particularly for controlling the primary dengue vector Aedes aegypti, an intervention study was set up to test the efficacy, cost and feasibility of a combined approach of insecticide treated materials (ITMs) alone and in combination with appropriate targeted interventions of the most productive vector breeding-sites. Methods The study was conducted as a cluster randomized community trial using “reduction of the vector population” as the main outcome variable. The trial had two arms: 10 intervention clusters (neighborhoods) and 10 control clusters in the town of Poptun Guatemala. Activities included entomological assessments (characteristics of breeding-sites, pupal productivity, Stegomyia indices) at baseline, 6 weeks after the first intervention (coverage of window and exterior doorways made of PermaNet 2.0 netting, factory treated with deltamethrin at 55 mg/m2, and of 200 L drums with similar treated material) and 6 weeks after the second intervention (combination of treated materials and other suitable interventions targeting productive breeding-sites i.e larviciding with Temephos, elimination etc.). The second intervention took place 17 months after the first intervention. The insecticide residual activity and the insecticidal content were also studied at different intervals. Additionally, information about demographic characteristics, cost of the intervention, coverage of houses protected and satisfaction in the population with the interventions was collected. Results At baseline (during the dry season) a variety of productive container types for Aedes pupae were identified: various container types holding >20 L, 200 L drums, washbasins and buckets (producing 83.7% of all pupae). After covering 100% of windows and exterior doorways and a small number of drums (where the commercial cover could be fixed) in 970 study households, tropical

Microscopic physical biomarkers in carbonate hot springs: implications in the search for life on Mars

NASA Technical Reports Server (NTRS)

Allen, C. C.; Albert, F. G.; Chafetz, H. S.; Combie, J.; Graham, C. R.; Kieft, T. L.; Kivett, S. J.; McKay, D. S.; Steele, A.; Taunton, A. E.;

Spectral bidirectional and hemispherical reflectance characteristics of selected sites in the Streletskaya steppe

NASA Technical Reports Server (NTRS)

Eck, Thomas F.; Deering, Donald W.

1992-01-01

Measurements of plant canopy bidirectional reflectance made by the PARABOLA (portable apparatus for rapid acquisition of bidirectional observations of the land and atmosphere) instrument in three spectral bands are analyzed for steppe grassland sites of differing productivity levels. The variation of spectral reflectance and the normalized difference vegetation index in the solar principal plane is presented. Comparisons are made with PARABOLA measurements from selected first ISLSCP field experiment (FIFE) grassland sites in the Konza prairie, Kansas. The Streletskaya steppe sites showed no strong hot spot reflectance, while this effect was present in some FIFE sites but absent in others. The hot spot effect seems to be dependent on canopy geometry and background reflectance characteristics of these sites. Spectral hemispherical reflectance was computed from the angular integration of the bidirectional measurements for the steppe sites. Total shortwave albedo was estimated from these hemispherical reflectance measurements and compared to albedo measured by pyranometers. The albedo estimates from PARABOLA were found to be approximately 12-17 percent higher than the pyranometer measurements.

Glyphosate resistance in Ambrosia trifida: Part 2. Rapid response physiology and non-target-site resistance.

PubMed

Moretti, Marcelo L; Van Horn, Christopher R; Robertson, Renae; Segobye, Kabelo; Weller, Stephen C; Young, Bryan G; Johnson, William G; Douglas Sammons, R; Wang, Dafu; Ge, Xia; d' Avignon, André; Gaines, Todd A; Westra, Philip; Green, Amanda C; Jeffery, Taylor; Lespérance, Mackenzie A; Tardif, François J; Sikkema, Peter H; Christopher Hall, J; McLean, Michael D; Lawton, Mark B; Schulz, Burkhard

2018-05-01

The glyphosate-resistant rapid response (GR RR) resistance mechanism in Ambrosia trifida is not due to target-site resistance (TSR) mechanisms. This study explores the physiology of the rapid response and the possibility of reduced translocation and vacuolar sequestration as non-target-site resistance (NTSR) mechanisms. GR RR leaf discs accumulated hydrogen peroxide within minutes of glyphosate exposure, but only in mature leaf tissue. The rapid response required energy either as light or exogenous sucrose. The combination of phenylalanine and tyrosine inhibited the rapid response in a dose-dependent manner. Reduced glyphosate translocation was observed in GR RR, but only when associated with tissue death caused by the rapid response. Nuclear magnetic resonance studies indicated that glyphosate enters the cytoplasm and reaches chloroplasts, and it is not moved into the vacuole of GR RR, GR non-rapid response or glyphosate-susceptible A. trifida. The GR RR mechanism of resistance is not associated with vacuole sequestration of glyphosate, and the observed reduced translocation is likely a consequence of rapid tissue death. Rapid cell death was inhibited by exogenous application of aromatic amino acids phenylalanine and tyrosine. The mechanism by which these amino acids inhibit rapid cell death in the GR RR phenotype remains unknown, and it could involve glyphosate phytotoxicity or other agents generating reactive oxygen species. Implications of these findings are discussed. The GR RR mechanism is distinct from the currently described glyphosate TSR or NTSR mechanisms in other species. © 2017 Society of Chemical Industry. © 2017 Society of Chemical Industry.

Focal hot spot induced by a central subclavian line on bone scan.

PubMed

Moslehi, Masood; Cheki, Mohsen; Dehghani, Tohid; Eftekhari, Mansoureh

2014-01-01

The diagnostic accuracy of nuclear medicine reporting can be improved by awareness of these instrument-related artifacts. Both awareness and experience are also important when it comes to detecting and identifying normal (and abnormal) variants. We present a case of hot spot on the upper right chest in the region of right subclavicular region resulting from injection of radiotracer from central subclavian line. A 52-year-old woman with a history of left breast cancer and recent bone pain was referred to our nuclear medicine department for skeletal survey. Anterior views of chest show a focus of increased radiotracer uptake corresponding to anterior arch of one of the right second rib. The nuclear physician reported it as a focal rib bony lesion and recommended radiological evaluation. As technician later explained, physicians realized that injection site was a central subclavian line on the right side and hot spot on that region is due to injection site. The appearance of both skeletal and soft-tissue uptake depends heavily on imaging technique (such as the route of radiotracer administration) and the interpreting physicians should be aware of the impact of technical factors on image quality.

CRISPR/Cas9-Mediated Insertion of loxP Sites in the Mouse Dock7 Gene Provides an Effective Alternative to Use of Targeted Embryonic Stem Cells.

PubMed

Bishop, Kathleen A; Harrington, Anne; Kouranova, Evguenia; Weinstein, Edward J; Rosen, Clifford J; Cui, Xiaoxia; Liaw, Lucy

2016-07-07

Targeted gene mutation in the mouse is a primary strategy to understand gene function and relation to phenotype. The Knockout Mouse Project (KOMP) had an initial goal to develop a public resource of mouse embryonic stem (ES) cell clones that carry null mutations in all genes. Indeed, many useful novel mouse models have been generated from publically accessible targeted mouse ES cell lines. However, there are limitations, including incorrect targeting or cassette structure, and difficulties with germline transmission of the allele from chimeric mice. In our experience, using a small sample of targeted ES cell clones, we were successful ∼50% of the time in generating germline transmission of a correctly targeted allele. With the advent of CRISPR/Cas9 as a mouse genome modification tool, we assessed the efficiency of creating a conditional targeted allele in one gene, dedicator of cytokinesis 7 (Dock7), for which we were unsuccessful in generating a null allele using a KOMP targeted ES cell clone. The strategy was to insert loxP sites to flank either exons 3 and 4, or exons 3 through 7. By coinjecting Cas9 mRNA, validated sgRNAs, and oligonucleotide donors into fertilized eggs from C57BL/6J mice, we obtained a variety of alleles, including mice homozygous for the null alleles mediated by nonhomologous end joining, alleles with one of the two desired loxP sites, and correctly targeted alleles with both loxP sites. We also found frequent mutations in the inserted loxP sequence, which is partly attributable to the heterogeneity in the original oligonucleotide preparation. Copyright © 2016 Bishop et al.

Structural basis for microRNA targeting

DOE PAGES

Schirle, Nicole T.; Sheu-Gruttadauria, Jessica; MacRae, Ian J.

2014-10-31

MicroRNAs (miRNAs) control expression of thousands of genes in plants and animals. miRNAs function by guiding Argonaute proteins to complementary sites in messenger RNAs (mRNAs) targeted for repression. In this paper, we determined crystal structures of human Argonaute-2 (Ago2) bound to a defined guide RNA with and without target RNAs representing miRNA recognition sites. These structures suggest a stepwise mechanism, in which Ago2 primarily exposes guide nucleotides (nt) 2 to 5 for initial target pairing. Pairing to nt 2 to 5 promotes conformational changes that expose nt 2 to 8 and 13 to 16 for further target recognition. Interactions withmore » the guide-target minor groove allow Ago2 to interrogate target RNAs in a sequence-independent manner, whereas an adenosine binding-pocket opposite guide nt 1 further facilitates target recognition. Spurious slicing of miRNA targets is avoided through an inhibitory coordination of one catalytic magnesium ion. Finally, these results explain the conserved nucleotide-pairing patterns in animal miRNA target sites first observed over two decades ago.« less

Hot Corrosion of Inconel 625 Overlay Weld Cladding in Smelting Off-Gas Environment

NASA Astrophysics Data System (ADS)

Mohammadi Zahrani, E.; Alfantazi, A. M.

2013-10-01

Degradation mechanisms and hot corrosion behavior of weld overlay alloy 625 were studied. Phase structure, morphology, thermal behavior, and chemical composition of deposited salt mixture on the weld overlay were characterized utilizing XRD, SEM/EDX, DTA, and ICP/OES, respectively. Dilution level of Fe in the weldment, dendritic structure, and degradation mechanisms of the weld were investigated. A molten phase formed on the weld layer at the operating temperature range of the boiler, which led to the hot corrosion attack in the water wall and the ultimate failure. Open circuit potential and weight-loss measurements and potentiodynamic polarization were carried out to study the hot corrosion behavior of the weld in the simulated molten salt medium at 873 K, 973 K, and 1073 K (600 °C, 700 °C, and 800 °C). Internal oxidation and sulfidation plus pitting corrosion were identified as the main hot corrosion mechanisms in the weld and boiler tubes. The presence of a significant amount of Fe made the dendritic structure of the weld susceptible to preferential corrosion. Preferentially corroded (Mo, Nb)-depleted dendrite cores acted as potential sites for crack initiation from the surface layer. The penetration of the molten phase into the cracks accelerated the cracks' propagation mainly through the dendrite cores and further crack branching/widening.

Gene duplication in the major insecticide target site, Rdl, in Drosophila melanogaster

PubMed Central

Remnant, Emily J.; Good, Robert T.; Schmidt, Joshua M.; Lumb, Christopher; Robin, Charles; Daborn, Phillip J.; Batterham, Philip

2013-01-01

The Resistance to Dieldrin gene, Rdl, encodes a GABA-gated chloride channel subunit that is targeted by cyclodiene and phenylpyrazole insecticides. The gene was first characterized in Drosophila melanogaster by genetic mapping of resistance to the cyclodiene dieldrin. The 4,000-fold resistance observed was due to a single amino acid replacement, Ala301 to Ser. The equivalent change was subsequently identified in Rdl orthologs of a large range of resistant insect species. Here, we report identification of a duplication at the Rdl locus in D. melanogaster. The 113-kb duplication contains one WT copy of Rdl and a second copy with two point mutations: an Ala301 to Ser resistance mutation and Met360 to Ile replacement. Individuals with this duplication exhibit intermediate dieldrin resistance compared with single copy Ser301 homozygotes, reduced temperature sensitivity, and altered RNA editing associated with the resistant allele. Ectopic recombination between Roo transposable elements is involved in generating this genomic rearrangement. The duplication phenotypes were confirmed by construction of a transgenic, artificial duplication integrating the 55.7-kb Rdl locus with a Ser301 change into an Ala301 background. Gene duplications can contribute significantly to the evolution of insecticide resistance, most commonly by increasing the amount of gene product produced. Here however, duplication of the Rdl target site creates permanent heterozygosity, providing unique potential for adaptive mutations to accrue in one copy, without abolishing the endogenous role of an essential gene. PMID:23959864

Uranium Bioreduction Rates across Scales: Biogeochemical Hot Moments and Hot Spots during a Biostimulation Experiment at Rifle, Colorado

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

Bao, Chen; Wu, Hongfei; Li, Li

2014-09-02

We aim to understand the scale-dependent evolution of uranium bioreduction during a field experiment at a former uranium mill site near Rifle, Colorado. Acetate was injected to stimulate Fe-reducing bacteria (FeRB) and to immobilize aqueous U(VI) to insoluble U(IV). Bicarbonate was coinjected in half of the domain to mobilize sorbed U(VI). We used reactive transport modeling to integrate hydraulic and geochemical data and to quantify rates at the grid block (0.25 m) and experimental field scale (tens of meters). Although local rates varied by orders of magnitude in conjunction with biostimulation fronts propagating downstream, field-scale rates were dominated by thosemore » orders of magnitude higher rates at a few selected hot spots where Fe(III), U(VI), and FeRB were at their maxima in the vicinity of the injection wells. At particular locations, the hot moments with maximum rates negatively corresponded to their distance from the injection wells. Although bicarbonate injection enhanced local rates near the injection wells by a maximum of 39.4%, its effect at the field scale was limited to a maximum of 10.0%. We propose a rate-versus-measurement-length relationship (log R' = -0.63« less

Menopausal Hot Flashes and White Matter Hyperintensities

PubMed Central

Thurston, Rebecca C.; Aizenstein, Howard J.; Derby, Carol A.; Sejdić, Ervin; Maki, Pauline M.

2015-01-01

Objective Hot flashes are the classic menopausal symptom. Emerging data links hot flashes to cardiovascular disease (CVD) risk, yet how hot flashes are related to brain health is poorly understood. We examined the relationship between hot flashes - measured via physiologic monitor and self-report - and white matter hyperintensities (WMH) among midlife women. Methods Twenty midlife women ages 40-60 without clinical CVD, with their uterus and both ovaries, and not taking hormone therapy were recruited. Women underwent 24 hours of ambulatory physiologic and diary hot flash monitoring to quantify hot flashes; magnetic resonance imaging to assess WMH burden; 72 hours of actigraphy and questionnaires to quantify sleep; and a blood draw, questionnaires, and physical measures to quantify demographics and CVD risk factors. Test of a priori hypotheses regarding relations between physiologically-monitored and self-reported wake and sleep hot flashes and WMH were conducted in linear regression models. Results More physiologically-monitored hot flashes during sleep were associated with greater WMH, controlling for age, race, and body mass index [beta(standard error)=.0002 (.0001), p=.03]. Findings persisted controlling for sleep characteristics and additional CVD risk factors. No relations were observed for self-reported hot flashes. Conclusions More physiologically-monitored hot flashes during sleep were associated with greater WMH burden among midlife women free of clinical CVD. Results suggest that relations between hot flashes and CVD risk observed in the periphery may extend to the brain. Future work should consider the unique role of sleep hot flashes in brain health. PMID:26057822