Analysis of Genotoxic and Cytotoxic Responses Induced by Simulated Space Radiation Qualities by Use of Recombinant Bacteria Carrying a Dual-Function Dual-Reporter Construct

NASA Astrophysics Data System (ADS)

Baumstark-Khan, Christa; Hellweg, Christine; Zahoor, Ahmed; Testard, Isabelle; Reitz, Guenther

Along with the long-term space exploration come various potential health risks due to unique physical factors of the space environment. Space radiation is one of the primary environmental hazards associated with space flight. In order to deal with space-related risk radiation exposure must be properly characterised and quantified, and biological effects of charged particles have to be analysed in ground based research, especially as astronauts are subjected to a differing radiation quality in space than they receive on Earth. For risk assessment, the mutagenic potential of the heavy ion component of the galactic cosmic radiation is of major concern for tumour induction as radiation late effects. The recombinant SWITCH test is based on TA1535 Salmonella typhimurium cells transformed with a dual-function dual-reporter vector harbouring (a) the genes for bioluminescence production from Photobacterium leiognathi under the control of a DNA-damage inducible promoter and (b) the gene for green fluorescent protein from the jellyfish Aequorea victoria under the control of a constitutive promoter. Suchlike genetically modified organism report on the presence of genotoxic conditions by dose dependent increase of bioluminescence induction and on the presence of cytotoxic conditions by dose dependent decrease in GFP fluorescence. By this, it is possible to analyse bacterial inactivation and mutation induction by ionizing radiation in parallel in the same cell within short time. Experiments with heavy ions have been performed with the SWITCH test at GANIL with the following accelerated heavy ions: 35 MeV/u (72 keV/µm) and 75 MeV/u (37 keV/µm) carbon, 95 MeV/u argon (377 keV/µm), 95 MeV/u neon (98 keV/µm), 75 MeV/u nickel (967 keV/µm) and 29 MeV/u lead (10238 keV/µm). The results obtained clearly show that the numbers of hits (particles per cm2 ) necessary to inactivate the bacteria (cytotoxicity) depend on LET. The higher the ionisation capacity of the accelerated ion, the less hits resulted in the same test effect, e.g. 37 % survival. For genotoxicity induction it can be seen, that for very high LET radiation the number of hits required is much less then for lower LET radiation (e.g. 1.4x106 /cm2 hits for lead versus 1.3x107 /cm2 hits for carbon). The power of the genotoxic response seems to be inversely related to LET. While 200 kV X-rays induced a 99.6x induction, carbon radiation results in a maximal induction of 72.6x (37 keV/m) and of 76.5x (72 keV/m), argon radiation (377 keV/m) leads to a 29.4x value, neon radiation (98 keV/m) leads to a 16.1x value, nickel radiation (967 keV/m) leads to a 15.4x value and lead radiation (10238 keV/m) results in only a factor of 4.8. Inactivation cross sections (σRCP) peak at a LET between 100 and 300 keV/m. The same is true for genotoxicity cross sections (σRGP for 2x), while maximal luminescence emission (for peak response) decreases with increasing LET. The response of the SWITCH test to space radiation qualities can be seen as indicative for an increased astronauts' risk from high LET radiation.

Fragment Linking and Optimization of Inhibitors of the Aspartic Protease Endothiapepsin: Fragment-Based Drug Design Facilitated by Dynamic Combinatorial Chemistry.

PubMed

Mondal, Milon; Radeva, Nedyalka; Fanlo-Virgós, Hugo; Otto, Sijbren; Klebe, Gerhard; Hirsch, Anna K H

2016-08-01

Fragment-based drug design (FBDD) affords active compounds for biological targets. While there are numerous reports on FBDD by fragment growing/optimization, fragment linking has rarely been reported. Dynamic combinatorial chemistry (DCC) has become a powerful hit-identification strategy for biological targets. We report the synergistic combination of fragment linking and DCC to identify inhibitors of the aspartic protease endothiapepsin. Based on X-ray crystal structures of endothiapepsin in complex with fragments, we designed a library of bis-acylhydrazones and used DCC to identify potent inhibitors. The most potent inhibitor exhibits an IC50 value of 54 nm, which represents a 240-fold improvement in potency compared to the parent hits. Subsequent X-ray crystallography validated the predicted binding mode, thus demonstrating the efficiency of the combination of fragment linking and DCC as a hit-identification strategy. This approach could be applied to a range of biological targets, and holds the potential to facilitate hit-to-lead optimization. © 2016 The Authors. Published by Wiley-VCH Verlag GmbH & Co. KGaA.

Observation of high-energy gamma-rays with the AMS-02 electromagnetic calorimeter

NASA Astrophysics Data System (ADS)

Morescalchi, L.

2017-05-01

The Alpha Magnetic Spectrometer (AMS-02) is a multipurpose astroparticle physics detector installed on the International Space Station (ISS). Since more than 5 years it is measuring with an unprecedented accuracy flux and composition of primary cosmic rays, searching for primordial anti-matter and probing the nature of dark matter. Despite the fact that AMS-02 has been primarily designed as a charged-particle spectrometer, it can also perform precision observations of γ -rays from a few GeV to beyond one TeV. The key sub-detector used for the photon identification is a lead-scintillating fibers sampling calorimeter (ECAL). Its high granularity allows to reconstruct the direction of the incoming photon with a resolution better than 1 degree. The 3D shower image reconstructed by the calorimeter together with the absence of hits along the reconstructed photon direction allow to reach a very good signal over background ratio. This experimental technique offers the unusual possibility to reconstruct a sky map of the very high-energy photon sources.

Identification of potential inhibitors based on compound proposal contest: Tyrosine-protein kinase Yes as a target.

PubMed

Chiba, Shuntaro; Ikeda, Kazuyoshi; Ishida, Takashi; Gromiha, M Michael; Taguchi, Y-H; Iwadate, Mitsuo; Umeyama, Hideaki; Hsin, Kun-Yi; Kitano, Hiroaki; Yamamoto, Kazuki; Sugaya, Nobuyoshi; Kato, Koya; Okuno, Tatsuya; Chikenji, George; Mochizuki, Masahiro; Yasuo, Nobuaki; Yoshino, Ryunosuke; Yanagisawa, Keisuke; Ban, Tomohiro; Teramoto, Reiji; Ramakrishnan, Chandrasekaran; Thangakani, A Mary; Velmurugan, D; Prathipati, Philip; Ito, Junichi; Tsuchiya, Yuko; Mizuguchi, Kenji; Honma, Teruki; Hirokawa, Takatsugu; Akiyama, Yutaka; Sekijima, Masakazu

2015-11-26

A search of broader range of chemical space is important for drug discovery. Different methods of computer-aided drug discovery (CADD) are known to propose compounds in different chemical spaces as hit molecules for the same target protein. This study aimed at using multiple CADD methods through open innovation to achieve a level of hit molecule diversity that is not achievable with any particular single method. We held a compound proposal contest, in which multiple research groups participated and predicted inhibitors of tyrosine-protein kinase Yes. This showed whether collective knowledge based on individual approaches helped to obtain hit compounds from a broad range of chemical space and whether the contest-based approach was effective.

Identification of potential inhibitors based on compound proposal contest: Tyrosine-protein kinase Yes as a target

PubMed Central

Chiba, Shuntaro; Ikeda, Kazuyoshi; Ishida, Takashi; Gromiha, M. Michael; Taguchi, Y-h.; Iwadate, Mitsuo; Umeyama, Hideaki; Hsin, Kun-Yi; Kitano, Hiroaki; Yamamoto, Kazuki; Sugaya, Nobuyoshi; Kato, Koya; Okuno, Tatsuya; Chikenji, George; Mochizuki, Masahiro; Yasuo, Nobuaki; Yoshino, Ryunosuke; Yanagisawa, Keisuke; Ban, Tomohiro; Teramoto, Reiji; Ramakrishnan, Chandrasekaran; Thangakani, A. Mary; Velmurugan, D.; Prathipati, Philip; Ito, Junichi; Tsuchiya, Yuko; Mizuguchi, Kenji; Honma, Teruki; Hirokawa, Takatsugu; Akiyama, Yutaka; Sekijima, Masakazu

2015-01-01

A search of broader range of chemical space is important for drug discovery. Different methods of computer-aided drug discovery (CADD) are known to propose compounds in different chemical spaces as hit molecules for the same target protein. This study aimed at using multiple CADD methods through open innovation to achieve a level of hit molecule diversity that is not achievable with any particular single method. We held a compound proposal contest, in which multiple research groups participated and predicted inhibitors of tyrosine-protein kinase Yes. This showed whether collective knowledge based on individual approaches helped to obtain hit compounds from a broad range of chemical space and whether the contest-based approach was effective. PMID:26607293

Flaws in the LNT single-hit model for cancer risk: An historical assessment.

PubMed

Calabrese, Edward J

2017-10-01

The LNT single-hit model was derived from the Nobel Prize-winning research of Herman J. Muller who showed that x-rays could induce gene mutations in Drosophila and that the dose response for these so-called mutational events was linear. Lewis J. Stadler, another well-known and respected geneticist at the time, strongly disagreed with and challenged Muller's claims. Detailed evaluations by Stadler over a prolonged series of investigations revealed that Muller's experiments had induced gross heritable chromosomal damage instead of specific gene mutations as had been claimed by Muller at his Nobel Lecture. These X-ray-induced alterations became progressively more frequent and were of larger magnitude (more destructive) with increasing doses. Thus, Muller's claim of having induced discrete gene mutations represented a substantial speculative overreach and was, in fact, without proof. The post hoc arguments of Muller to support his gene mutation hypothesis were significantly challenged and weakened by a series of new findings in the areas of cytogenetics, reverse mutation, adaptive and repair processes, and modern molecular methods for estimating induced genetic damage. These findings represented critical and substantial limitations to Muller's hypothesis of X-ray-induced gene mutations. Furthermore, they challenged the scientific foundations used in support of the LNT single-hit model by severing the logical nexus between Muller's data on radiation-induced inheritable alterations and the LNT single-hit model. These findings exposed fundamental scientific flaws that undermined not only the seminal recommendation of the 1956 BEAR I Genetics Panel to adopt the LNT single-hit Model for risk assessment but also any rationale for its continued use in the present day. Copyright © 2017 Elsevier Inc. All rights reserved.

Visible and Ultraviolet Detectors for High Earth Orbit and Lunar Observatories

NASA Technical Reports Server (NTRS)

Woodgate, Bruce E.

1989-01-01

The current status of detectors for the visible and UV for future large observatories in earth orbit and the moon is briefly reviewed. For the visible, CCDs have the highest quantum efficiency, but are subject to contamination of the data by cosmic ray hits. For the moon, the level of hits can be brought down to that at the earth's surface by shielding below about 20 meters of rock. For high earth orbits above the geomagnetic shield, CCDs might be able to be used by combining many short exposures and vetoing the cosmic ray hits, otherwise photoemissive detectors will be necessary. For the UV, photoemissive detectors will be necessary to reject the visible; to use CCDs would require the development of UV-efficient filters which reject the visible by many orders of magnitude. Development of higher count rate capability would be desirable for photoemissive detectors.

Results of the joint utilization of laser integrated experiments flown on payload GAS-449 aboard Columbia mission 61-C

NASA Technical Reports Server (NTRS)

Muckerheide, M. C.

1987-01-01

The high peak power neodymium YAG laser and the HeNe laser aboard GAS-449 have demonstrated the survivability of the devices in the micro-gravity, cosmic radiation, thermal, and shock environment of space. Some pharmaceuticals and other materials flown in both the active and passive status have demonstrated reduction in volume and unusual spectroscopic changes. X-ray detectors have shown cosmic particle hits with accompanying destruction at their interaction points. Some scattering in the plates is in evidence. Some results of both active and passive experiments on board the GAS-449 payload are evaluated.

Optimization of a pyrazole hit from FBDD into a novel series of indazoles as ketohexokinase inhibitors.

PubMed

Zhang, Xuqing; Song, Fengbing; Kuo, Gee-Hong; Xiang, Amy; Gibbs, Alan C; Abad, Marta C; Sun, Weimei; Kuo, Lawrence C; Sui, Zhihua

2011-08-15

A series of indazoles have been discovered as KHK inhibitors from a pyrazole hit identified through fragment-based drug discovery (FBDD). The optimization process guided by both X-ray crystallography and solution activity resulted in lead-like compounds with good pharmaceutical properties. Copyright © 2011 Elsevier Ltd. All rights reserved.

Multiple-hit parameter estimation in monolithic detectors.

PubMed

Hunter, William C J; Barrett, Harrison H; Lewellen, Tom K; Miyaoka, Robert S

2013-02-01

We examine a maximum-a-posteriori method for estimating the primary interaction position of gamma rays with multiple interaction sites (hits) in a monolithic detector. In assessing the performance of a multiple-hit estimator over that of a conventional one-hit estimator, we consider a few different detector and readout configurations of a 50-mm-wide square cerium-doped lutetium oxyorthosilicate block. For this study, we use simulated data from SCOUT, a Monte-Carlo tool for photon tracking and modeling scintillation- camera output. With this tool, we determine estimate bias and variance for a multiple-hit estimator and compare these with similar metrics for a one-hit maximum-likelihood estimator, which assumes full energy deposition in one hit. We also examine the effect of event filtering on these metrics; for this purpose, we use a likelihood threshold to reject signals that are not likely to have been produced under the assumed likelihood model. Depending on detector design, we observe a 1%-12% improvement of intrinsic resolution for a 1-or-2-hit estimator as compared with a 1-hit estimator. We also observe improved differentiation of photopeak events using a 1-or-2-hit estimator as compared with the 1-hit estimator; more than 6% of photopeak events that were rejected by likelihood filtering for the 1-hit estimator were accurately identified as photopeak events and positioned without loss of resolution by a 1-or-2-hit estimator; for PET, this equates to at least a 12% improvement in coincidence-detection efficiency with likelihood filtering applied.

Video-Puff of Air Hits Ball of Water in Space Onboard the International Space Station (ISS)

NASA Technical Reports Server (NTRS)

2003-01-01

Saturday Morning Science, the science of opportunity series of applied experiments and demonstrations, performed aboard the International Space Station (ISS) by Expedition 6 astronaut Dr. Don Pettit, revealed some remarkable findings. In this video clip, Dr. Pettit demonstrates the phenomenon of a puff of air hitting a ball of water that is free floating in space. Watch the video to see why Dr. Pettit remarks 'I'd hate think that our planet would go through these kinds of gyrations if it got whacked by a big asteroid'.

Experimental simulation of radiation damage of polymers in space applications by cosmic-ray-type high energy heavy ions and the resulting changes in optical properties

NASA Astrophysics Data System (ADS)

Hossain, U. H.; Ensinger, W.

2015-12-01

Devices operating in space, e.g. in satellites, are being hit by cosmic rays. These include so-called HZE-ions, with High mass (Z) and energy (E). These highly energetic heavy ions penetrate deeply into the materials and deposit a large amount of energy, typically several keV per nm range. Serious damage is created. In space vehicles, polymers are used which are degraded under ion bombardment. HZE ion irradiation can experimentally be simulated in large scale accelerators. In the present study, the radiation damage of aliphatic vinyl- and fluoro-polymers by heavy ions with energies in the GeV range is described. The ions cause bond scission and create volatile small molecular species, leading to considerable mass loss of the polymers. Since hydrogen, oxygen and fluorine-containing molecules are created and these elements are depleted, the remaining material is carbon-richer than the original polymers and contains conjugated CC double bonds. This process is investigated by measuring the optical band gap with UV-Vis absorption spectrometry as a function of ion fluence. The results show how the optical band gaps shift from the UV into the Vis region upon ion irradiation for the different polymers.

Interpretation of mutation induction by accelerated heavy ions in bacteria

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

Kozubek, S.; Ryznar, L.; Horneck, G.

In this report, a quantitative interpretation of mutation induction cross sections by heavy charged particles in bacterial cells is presented. The approach is based on the calculation of the fraction of energy deposited by indirect hits in the sensitive structure. In these events the particle does not pass through the sensitive volume, but this region is hit by {delta} rays. Four track structure models, developed by Katz, Chatterjee et al, Kiefer and Straaten and Kudryashov et al., respectively, were used for the calculations. With the latter two models, very good agreement of the calculations with experimental results on mutagenesis inmore » bacteria was obtained. Depending on the linear energy transfer (LET{infinity}) of the particles, two different modes of mutagenic action of heavy ions are distinguished: {open_quotes}{delta}-ray mutagenesis,{close_quotes} which is related to those radiation qualities that preferentially kill the cells in direct hits (LET{infinity} {ge} 100 keV/{mu}m), and {open_quotes}track core mutagenesis,{close_quotes} which arises from direct hits and is observed for lighter ions or ions with high energy (LET{infinity} {le} 100 keV/{mu}m). 37 refs., 6 figs., 1 tab.« less

Multiple-Hit Parameter Estimation in Monolithic Detectors

PubMed Central

Barrett, Harrison H.; Lewellen, Tom K.; Miyaoka, Robert S.

2014-01-01

We examine a maximum-a-posteriori method for estimating the primary interaction position of gamma rays with multiple interaction sites (hits) in a monolithic detector. In assessing the performance of a multiple-hit estimator over that of a conventional one-hit estimator, we consider a few different detector and readout configurations of a 50-mm-wide square cerium-doped lutetium oxyorthosilicate block. For this study, we use simulated data from SCOUT, a Monte-Carlo tool for photon tracking and modeling scintillation- camera output. With this tool, we determine estimate bias and variance for a multiple-hit estimator and compare these with similar metrics for a one-hit maximum-likelihood estimator, which assumes full energy deposition in one hit. We also examine the effect of event filtering on these metrics; for this purpose, we use a likelihood threshold to reject signals that are not likely to have been produced under the assumed likelihood model. Depending on detector design, we observe a 1%–12% improvement of intrinsic resolution for a 1-or-2-hit estimator as compared with a 1-hit estimator. We also observe improved differentiation of photopeak events using a 1-or-2-hit estimator as compared with the 1-hit estimator; more than 6% of photopeak events that were rejected by likelihood filtering for the 1-hit estimator were accurately identified as photopeak events and positioned without loss of resolution by a 1-or-2-hit estimator; for PET, this equates to at least a 12% improvement in coincidence-detection efficiency with likelihood filtering applied. PMID:23193231

Chemical Space Expansion of Bromodomain Ligands Guided by in Silico Virtual Couplings (AutoCouple).

PubMed

Batiste, Laurent; Unzue, Andrea; Dolbois, Aymeric; Hassler, Fabrice; Wang, Xuan; Deerain, Nicholas; Zhu, Jian; Spiliotopoulos, Dimitrios; Nevado, Cristina; Caflisch, Amedeo

2018-02-28

Expanding the chemical space and simultaneously ensuring synthetic accessibility is of upmost importance, not only for the discovery of effective binders for novel protein classes but, more importantly, for the development of compounds against hard-to-drug proteins. Here, we present AutoCouple, a de novo approach to computational ligand design focused on the diversity-oriented generation of chemical entities via virtual couplings. In a benchmark application, chemically diverse compounds with low-nanomolar potency for the CBP bromodomain and high selectivity against the BRD4(1) bromodomain were achieved by the synthesis of about 50 derivatives of the original fragment. The binding mode was confirmed by X-ray crystallography, target engagement in cells was demonstrated, and antiproliferative activity was showcased in three cancer cell lines. These results reveal AutoCouple as a useful in silico coupling method to expand the chemical space in hit optimization campaigns resulting in potent, selective, and cell permeable bromodomain ligands.

X-ray emissions from centimeter-long streamer corona discharges

NASA Astrophysics Data System (ADS)

da Silva, C. L.; Millan, R. M.; McGaw, D. G.; Yu, C. T.; Putter, A. S.; Labelle, J. W.; Dwyer, J. R.

2017-12-01

In this work we provide extensive evidence that runaway electron acceleration and subsequent bremsstrahlung X-ray emission are a common feature in electrical discharges of negative polarity. They can be easily detected at voltages as low as 100 kV, indicating that all negative lightning could potentially produce runaway electrons. We show that centimeter-long streamer corona discharges produce bursts of X-ray radiation that are emitted by a source that is highly compact in space and time. Therefore, the emitted X-ray photons arrive together at the detector and pile up. Median burst energies vary between 33-96% of the total 100 keV available electrostatic energy that an electron can acquire in the gap. We present detailed statistical analysis of 5000+ discharges, showing that X-rays are observed in as many as 60% of the triggers, depending on the configuration. X-ray detection is more frequent when: the streamer corona discharge is not followed by a spark, the detector is oriented perpendicular to the gap, and a thicker anode is used. We show that for an 8-cm-long gap, X-rays are produced when runaway electrons hit the anode, and that the runaway electron acceleration is not correlated with streamer collisions, as inferred in meter-long discharges. The described experiment is a promising way for measuring the runaway electron distribution very close to the source and its dependence on the applied voltage.

My 35 Years in X-ray Astronomy (Not)

NASA Astrophysics Data System (ADS)

Urry, C. M.

2013-01-01

My contact with X-ray astronomy started with HEAO-1, just before launch, when I was a summer student at the Harvard/Smithsonian Center for Astrophysics. Another summer position followed at NASA’s Goddard Space Flight Center, where I later did my PhD thesis on HEAO1 and HEAO2 (and IUE) data. Next I was a postdoc at MIT working with Einstein and Ginga observations, and I then continued observing blazars and other AGN with ASCA, Exosat, RXTE, Chandra, XMM, Swift, Suzaku, and Fermi. I have also witnessed or participated in many proposals for future X-ray missions. Fortunately for the audience, I will not recall all these times... So many photons, so little time! But this long history does mean I met most of the great figures in X-ray astronomy when they were young and I probably have embarrassing stories to tell about many of them. For my 2-minute vignette in a panel discussion, I will entertain you with one of the more interesting (and pertinent) memories. Acknowledgement: Thank you to all my high-energy astrophysics colleagues, who taught me a great deal, and to NASA for the hit parade of high-energy missions.

Lead generation and examples opinion regarding how to follow up hits.

PubMed

Orita, Masaya; Ohno, Kazuki; Warizaya, Masaichi; Amano, Yasushi; Niimi, Tatsuya

2011-01-01

In fragment-based drug discovery (FBDD), not only identifying the starting fragment hit to be developed but also generating a drug lead from that starting fragment hit is important. Converting fragment hits to leads is generally similar to a high-throughput screening (HTS) hits-to-leads approach in that properties associated with activity for a target protein, such as selectivity against other targets and absorption, distribution, metabolism, excretion, and toxicity (ADME/Tox), and physicochemical properties should be taken into account. However, enhancing the potency of the fragment hit is a key requirement in FBDD, unlike HTS, because initial fragment hits are generally weak. This enhancement is presently achieved by adding additional chemical groups which bind to additional parts of the target protein or by joining or combining two or more hit fragments; however, strategies for effecting greater improvements in effective activity are needed. X-ray analysis is a key technology attractive for converting fragments to drug leads. This method makes it clear whether a fragment hit can act as an anchor and provides insight regarding introduction of functional groups to improve fragment activity. Data on follow-up chemical synthesis of fragment hits has allowed for the differentiation of four different strategies: fragment optimization, fragment linking, fragment self-assembly, and fragment evolution. Here, we discuss our opinion regarding how to follow up on fragment hits, with a focus on the importance of fragment hits as an anchor moiety to so-called hot spots in the target protein using crystallographic data. Copyright © 2011 Elsevier Inc. All rights reserved.

Evaluation of a combined electrostatic and magnetostatic configuration for active space-radiation shielding

NASA Astrophysics Data System (ADS)

Joshi, Ravindra P.; Qiu, Hao; Tripathi, Ram K.

2013-05-01

Developing successful and optimal solutions to mitigating the hazards of severe space radiation in deep space long duration missions is critical for the success of deep-space explorations. A recent report (Tripathi et al., 2008) had explored the feasibility of using electrostatic shielding. Here, we continue to extend the electrostatic shielding strategy and examine a hybrid configuration that utilizes both electrostatic and magnetostatic fields. The main advantages of this system are shown to be: (i) a much better shielding and repulsion of incident ions from both solar particle events (SPE) and galactic cosmic rays (GCR), (ii) reductions in the power requirement for re-charging the electrostatic sub-system, and (iii) low requirements of the magnetic fields that are well below the thresholds set for health and safety for long-term exposures. Furthermore, our results show transmission levels reduced to levels as low as 30% for energies around 1000 MeV, and near total elimination of SPE radiation by these hybrid configurations. It is also shown that the power needed to replenish the electrostatic charges due to particle hits from the GCR and SPE radiation is minimal.

Big Data Hits Beamline

Science.gov Websites

all want the same thing: amazing, scientifically illuminating, micron-scale X-ray views of matter , generating a cascade of bright X-ray photons. These photons are tuned and focused to feed 60 simultaneously experiments, but a big jump for an X-ray source. Second, light sources have gotten brighter at a rate even

Model predictions and visualization of the particle flux on the surface of Mars.

PubMed

Cucinotta, Francis A; Saganti, Premkumar B; Wilson, John W; Simonsen, Lisa C

2002-12-01

Model calculations of the particle flux on the surface of Mars due to the Galactic Cosmic Rays (GCR) can provide guidance on radiobiological research and shielding design studies in support of Mars exploration science objectives. Particle flux calculations for protons, helium ions, and heavy ions are reported for solar minimum and solar maximum conditions. These flux calculations include a description of the altitude variations on the Martian surface using the data obtained by the Mars Global Surveyor (MGS) mission with its Mars Orbiter Laser Altimeter (MOLA) instrument. These particle flux calculations are then used to estimate the average particle hits per cell at various organ depths of a human body in a conceptual shelter vehicle. The estimated particle hits by protons for an average location at skin depth on the Martian surface are about 10 to 100 particle-hits/cell/year and the particle hits by heavy ions are estimated to be 0.001 to 0.01 particle-hits/cell/year.

Increasing the Coverage of Medicinal Chemistry-Relevant Space in Commercial Fragments Screening

PubMed Central

2014-01-01

Analyzing the chemical space coverage in commercial fragment screening collections revealed the overlap between bioactive medicinal chemistry substructures and rule-of-three compliant fragments is only ∼25%. We recommend including these fragments in fragment screening libraries to maximize confidence in discovering hit matter within known bioactive chemical space, while incorporation of nonoverlapping substructures could offer novel hits in screening libraries. Using principal component analysis, polar and three-dimensional substructures display a higher-than-average enrichment of bioactive compounds, indicating increasing representation of these substructures may be beneficial in fragment screening. PMID:24405118

Macrocyclic BACE inhibitors: Optimization of a micromolar hit to nanomolar leads.

PubMed

Huang, Yifang; Strobel, Eric D; Ho, Chih Y; Reynolds, Charles H; Conway, Kelly A; Piesvaux, Jennifer A; Brenneman, Douglas E; Yohrling, George J; Moore Arnold, H; Rosenthal, Daniel; Alexander, Richard S; Tounge, Brett A; Mercken, Marc; Vandermeeren, Marc; Parker, Michael H; Reitz, Allen B; Baxter, Ellen W

2010-05-15

We have identified macrocyclic inhibitors of the aspartic protease BACE, implicated in the etiology of Alzheimer's disease. An X-ray structure of screening hit 1 in the BACE active site revealed a hairpin conformation suggesting that constrained macrocyclic derivatives may also bind there. Several of the analogs we prepared were >100x more potent than 1, such as 7 (5 nM K(i)). Copyright 2010 Elsevier Ltd. All rights reserved.

Progress and Plans for the HIT--SI Experiment

NASA Astrophysics Data System (ADS)

Sieck, P. E.; Gu, P.; Hamp, W. T.; Izzo, V. A.; Jarboe, T. R.; Nelson, B. A.; O'Neill, R. G.; Redd, A. J.; Rogers, J. A.; Smith, R. J.

2002-11-01

The next step in the Helicity Injected Torus (HIT) program is HIT--SI, a ``bow tie'' spheromak to be formed and sustained by Steady Inductive Helicity Injection (SIHI). SIHI injects helicity at a nearly constant rate with no open field lines intersecting the boundary.(T. R. Jarboe, Fusion Technology 36) (1), p. 85, 1999 HIT--SI has been designed with a bow tie geometry to achieve stable high-β (>10%) spheromak equilibria.(U. Shumlak and T. R. Jarboe, Phys. Plasmas 7) (7), p. 2959, 2000 Injector dynamics depend greatly on reconnection rates in two locations: deep in the injector, and at the edge of the spheromak equilibrium. The first stage of HIT--SI operation concentrates on formation of a spheromak and sustainment for 1 ms, where the injector dynamics can be studied and the formation parameter space can be explored. Once these goals are met, the experiment will move into the second stage of operation, where the discharge duration will be extended and the device will inherit a suite of diagnostics from the existing HIT--II device.

Fragment-based drug design.

PubMed

Feyfant, Eric; Cross, Jason B; Paris, Kevin; Tsao, Désirée H H

2011-01-01

Fragment-based drug design (FBDD), which is comprised of both fragment screening and the use of fragment hits to design leads, began more than 15 years ago and has been steadily gaining in popularity and utility. Its origin lies on the fact that the coverage of chemical space and the binding efficiency of hits are directly related to the size of the compounds screened. Nevertheless, FBDD still faces challenges, among them developing fragment screening libraries that ensure optimal coverage of chemical space, physical properties and chemical tractability. Fragment screening also requires sensitive assays, often biophysical in nature, to detect weak binders. In this chapter we will introduce the technologies used to address these challenges and outline the experimental advantages that make FBDD one of the most popular new hit-to-lead process.

Cosmic Ray Hits in the Central Nervous System at Solar Maximum

NASA Technical Reports Server (NTRS)

Curtis, S. B.; Vazquez, M. E.; Wilson, J. W.; Kim, M.-H. Y.

1997-01-01

It has been suggested that a manned mission to Mars be launched at solar maximum rather than at solar minimum to minimize the radiation exposure to galactic cosmic rays. It is true that the number of hits from highly ionizing particles to critical regions in the brain will be less at solar maximum, and it is of some interest to estimate how much less. We present here calculations for several sites within the brain from iron ions (z = 26) and from particles with charge, z, greater than or equal to 15. The same shielding configurations and sites in the brain used in an earlier paper for solar minimum are employed so that direct comparison of results between the two solar activity conditions can be made. A simple pressure-vessel wall and an equipment room onboard a spacecraft are chosen as shielding examples. In the equipment room, typical results for the thalamus (100 mm2 area) are that the probability of any given cell nucleus being hit decreases from 10 percent at solar minimum to 6 percent at solar maximum for particles with z greater than or equal to 15 and from 2.3 percent to 1.3 percent for iron ions. We conclude that this modest decrease in hit frequency (less than a factor of two) is not a compelling reason to avoid solar minimum for a manned mission to Mars.

[Three cases of acute interhemispheric subdural hematoma].

PubMed

Takeda, N; Kurihara, E; Matsuoka, H; Kose, S; Tamaki, N; Matsumoto, S

1988-01-01

Traumatic acute subdural hematomas over the convexity of the cerebral hemispheres are often encountered, but acute interhemispheric subdural hematomas are rare. Fourty-eight cases of acute subdural hematomas was admitted to our hospital between 1977 and 1986, and three cases of them (6%) were located in the interhemispheric subdural space. In this paper, these three cases are reported with 20 documented cases. Case 1: an 81-year-old female was admitted to our hospital because of headache, nausea and vomiting. She hit her occiput a week ago. CT scan demonstrated contusion in the right frontal lobe and a high density in the interhemispheric space of the right frontal region. Her complaints disappeared gradually by conservative therapy and she returned to her social life. Case 2: a 50-year-old male fell downstairs and hit his vertex. As he lost consciousness, he was admitted to our hospital. He was stuporous and had left-hemiparesis. Skull X-ray film showed fracture line extending from the right temporal bone to the left parietal bone across the midline. CT scan revealed intracerebral hematoma in both frontal lobe and right parietal lobe and subarachnoid hemorrhage in the basal cistern and Sylvian fissure of the right side. And interhemispheric subdural hematoma in the right parietal region was visualized. Angiography demonstrated a lateral displacement of the right callosomarginal artery and an avascular area between the falx and the callosomarginal artery. After admission his consciousness recovered and convulsion was controlled by drug. Left-hemiparesis was improved by conservative therapy and he was discharged on foot.(ABSTRACT TRUNCATED AT 250 WORDS)

Cosmic Ray Hits in the Central Nervous System at Solar Maximum

NASA Technical Reports Server (NTRS)

Curtis, S. B.; Vazquez, M. E.; Wilson, J. W.; Atwell, W.; Kin, M.-H. Y.

2000-01-01

It has been suggested that a manned mission to Mars be launched at solar maximum rather than at solar minimum to minimize the radiation exposure to galactic cosmic rays. It is true that the number of hits from highly ionizing particles to critical regions in the brain will be less at solar maximum, and it is of interest to estimate how much less. We present here calculations for several sites within the brain from iron ions (z = 26) and from particles with charge, z, greater than or equal to 15. The same shielding configurations and sites in the brain used in an earlier paper for solar minimum are employed so that direct comparison of results between the two solar activity conditions can be made. A simple pressure-vessel wall and an equipment room onboard a spacecraft are chosen as shielding examples. In the equipment room, typical results for the thalamus are that the probability of any particles with z greater than or equal to 15 and from 2.3 percent to 1.3 percent for iron ions. The extra shielding provided in the equipment room makes little difference in these numbers. We conclude that this decrease in hit frequency (less than a factor of two) does not provide a compelling reason to avoid solar minimum for a manned mission to Mars. This conclusion could be revised, however, if a very small number of hits is found to cause critical malfunction within the brain.

A Probable Taurid Impact on the Moon

NASA Technical Reports Server (NTRS)

Cooke, William J.; Suggs, R. M.; Swift, Wesley R.

2006-01-01

On November 7, 2005, at 23:41:52 UT, observers located at the Marshall Space Flight Center captured the flash produced by a kilogram-size meteoroid striking the lunar surface. Photometric analysis of the event video, combined with the plausible assumptions of a luminous efficiency of 2x10" and that the meteoroid was a member of the Taurid meteoroid stream, yield a striking power of approximately 640 lbs of TNT and a mass of approximately 3.8 kg. Even though no confirming independent observations are known to exist, there is high confidence in the impact origin of the flash; reasonable attempts have been made to eliminate other possibilities, such as cosmic ray hits on the CCD and glints from satellites that may have crossed the lunar disk near the impact time.

Structural insights into binding of inhibitors to soluble epoxide hydrolase gained by fragment screening and X-ray crystallography.

PubMed

Amano, Yasushi; Yamaguchi, Tomohiko; Tanabe, Eiki

2014-04-15

Soluble epoxide hydrolase (sEH) is a component of the arachidonic acid cascade and is a candidate target for therapies for hypertension or inflammation. Although many sEH inhibitors are available, their scaffolds are not structurally diverse, and knowledge of their specific interactions with sEH is limited. To obtain detailed structural information about protein-ligand interactions, we conducted fragment screening of sEH, analyzed the fragments using high-throughput X-ray crystallography, and determined 126 fragment-bound structures at high resolution. Aminothiazole and benzimidazole derivatives were identified as novel scaffolds that bind to the catalytic triad of sEH with good ligand efficiency. We further identified fragment hits that bound to subpockets of sEH called the short and long branches. The water molecule conserved in the structure plays an important role in binding to the long branch, whereas Asp496 and the main chain of Phe497 form hydrogen bonds with fragment hits in the short branch. Fragment hits and their crystal structures provide structural insights into ligand binding to sEH that will facilitate the discovery of novel and potent inhibitors of sEH. Copyright © 2014 Elsevier Ltd. All rights reserved.

X-ray transparent microfluidic chips for high-throughput screening and optimization of in meso membrane protein crystallization

PubMed Central

Schieferstein, Jeremy M.; Pawate, Ashtamurthy S.; Wan, Frank; Sheraden, Paige N.; Broecker, Jana; Ernst, Oliver P.; Gennis, Robert B.

2017-01-01

Elucidating and clarifying the function of membrane proteins ultimately requires atomic resolution structures as determined most commonly by X-ray crystallography. Many high impact membrane protein structures have resulted from advanced techniques such as in meso crystallization that present technical difficulties for the set-up and scale-out of high-throughput crystallization experiments. In prior work, we designed a novel, low-throughput X-ray transparent microfluidic device that automated the mixing of protein and lipid by diffusion for in meso crystallization trials. Here, we report X-ray transparent microfluidic devices for high-throughput crystallization screening and optimization that overcome the limitations of scale and demonstrate their application to the crystallization of several membrane proteins. Two complementary chips are presented: (1) a high-throughput screening chip to test 192 crystallization conditions in parallel using as little as 8 nl of membrane protein per well and (2) a crystallization optimization chip to rapidly optimize preliminary crystallization hits through fine-gradient re-screening. We screened three membrane proteins for new in meso crystallization conditions, identifying several preliminary hits that we tested for X-ray diffraction quality. Further, we identified and optimized the crystallization condition for a photosynthetic reaction center mutant and solved its structure to a resolution of 3.5 Å. PMID:28469762

Software Technology Readiness Assessment. Defense Acquisition Guidance with Space Examples

DTIC Science & Technology

2010-04-01

are never Software CTE candidates 19 Algorithm Example: Filters • Definitions – Filters in Signal Processing • A filter is a mathematical algorithm...Segment Segment • SOA as a CTE? – Google produced 40 million (!) hits in 0.2 sec for “SOA”. Even if we discount hits on the Society of Actuaries and

Fast-forwarding hit to lead: aurora and epidermal growth factor receptor kinase inhibitor lead identification.

PubMed

Coumar, Mohane Selvaraj; Chu, Chang-Ying; Lin, Cheng-Wei; Shiao, Hui-Yi; Ho, Yun-Lung; Reddy, Randheer; Lin, Wen-Hsing; Chen, Chun-Hwa; Peng, Yi-Hui; Leou, Jiun-Shyang; Lien, Tzu-Wen; Huang, Chin-Ting; Fang, Ming-Yu; Wu, Szu-Huei; Wu, Jian-Sung; Chittimalla, Santhosh Kumar; Song, Jen-Shin; Hsu, John T-A; Wu, Su-Ying; Liao, Chun-Chen; Chao, Yu-Sheng; Hsieh, Hsing-Pang

2010-07-08

A focused library of furanopyrimidine (350 compounds) was rapidly synthesized in parallel reactors and in situ screened for Aurora and epidermal growth factor receptor (EGFR) kinase activity, leading to the identification of some interesting hits. On the basis of structural biology observations, the hit 1a was modified to better fit the back pocket, producing the potent Aurora inhibitor 3 with submicromolar antiproliferative activity in HCT-116 colon cancer cell line. On the basis of docking studies with EGFR hit 1s, introduction of acrylamide Michael acceptor group led to 8, which inhibited both the wild and mutant EGFR kinase and also showed antiproliferative activity in HCC827 lung cancer cell line. Furthermore, the X-ray cocrystal study of 3 and 8 in complex with Aurora and EGFR, respectively, confirmed their hypothesized binding modes. Library construction, in situ screening, and structure-based drug design (SBDD) strategy described here could be applied for the lead identification of other kinases.

Discovery of a new chemical series of BRD4(1) inhibitors using protein-ligand docking and structure-guided design.

PubMed

Duffy, Bryan C; Liu, Shuang; Martin, Gregory S; Wang, Ruifang; Hsia, Ming Min; Zhao, He; Guo, Cheng; Ellis, Michael; Quinn, John F; Kharenko, Olesya A; Norek, Karen; Gesner, Emily M; Young, Peter R; McLure, Kevin G; Wagner, Gregory S; Lakshminarasimhan, Damodharan; White, Andre; Suto, Robert K; Hansen, Henrik C; Kitchen, Douglas B

2015-07-15

Bromodomains are key transcriptional regulators that are thought to be druggable epigenetic targets for cancer, inflammation, diabetes and cardiovascular therapeutics. Of particular importance is the first of two bromodomains in bromodomain containing 4 protein (BRD4(1)). Protein-ligand docking in BRD4(1) was used to purchase a small, focused screening set of compounds possessing a large variety of core structures. Within this set, a small number of weak hits each contained a dihydroquinoxalinone ring system. We purchased other analogs with this ring system and further validated the new hit series and obtained improvement in binding inhibition. Limited exploration by new analog synthesis showed that the binding inhibition in a FRET assay could be improved to the low μM level making this new core a potential hit-to-lead series. Additionally, the predicted geometries of the initial hit and an improved analog were confirmed by X-ray co-crystallography with BRD4(1). Copyright © 2015 Elsevier Ltd. All rights reserved.

Hit-to-lead evaluation of a novel class of sphingosine 1-phosphate lyase inhibitors.

PubMed

Dinges, Jurgen; Harris, Christopher M; Wallace, Grier A; Argiriadi, Maria A; Queeney, Kara L; Perron, Denise C; Dominguez, Eric; Kebede, Tegest; Desino, Kelly E; Patel, Hetal; Vasudevan, Anil

2016-05-01

Inhibition of sphingosine-1-phosphate lyase has recently been proposed as a potential treatment option for inflammatory disorders such as multiple sclerosis, rheumatoid arthritis, and inflammatory bowel disease. In this report we describe our hit-to-lead evaluation of the isoxazolecarboxamide 6, a high-throughput screening hit (in vitro IC50=1.0 μM, cell IC50=1.8 μM), as a novel S1P lyase inhibitor. We were able to establish basic structure-activity relationships around 6 and succeeded in obtaining X-ray structural information which enabled structure-based design. With the discovery of 28, enzyme activity was quickly improved to IC50=120 nM and cell potency to IC50=230 nM. The main liability in the established isoxazolecarboxamide hit series was determined to be metabolic stability. In particular we identified that future lead-optimization efforts to overcome this problem should focus on blocking the N-dealkylation on the secondary amine. Copyright © 2016 Elsevier Ltd. All rights reserved.

Track structure model of microscopic energy deposition by protons and heavy ions in segments of neuronal cell dendrites represented by cylinders or spheres

PubMed Central

Alp, Murat; Cucinotta, Francis A.

2017-01-01

Changes to cognition, including memory, following radiation exposure are a concern for cosmic ray exposures to astronauts and in Hadron therapy with proton and heavy ion beams. The purpose of the present work is to develop computational methods to evaluate microscopic energy deposition (ED) in volumes representative of neuron cell structures, including segments of dendrites and spines, using a stochastic track structure model. A challenge for biophysical models of neuronal damage is the large sizes (>100 μm) and variability in volumes of possible dendritic segments and pre-synaptic elements (spines and filopodia). We consider cylindrical and spherical microscopic volumes of varying geometric parameters and aspect ratios from 0.5 to 5 irradiated by protons, and 3He and 12C particles at energies corresponding to a distance of 1 cm to the Bragg peak, which represent particles of interest in Hadron therapy as well as space radiation exposure. We investigate the optimal axis length of dendritic segments to evaluate microscopic ED and hit probabilities along the dendritic branches at a given macroscopic dose. Because of large computation times to analyze ED in volumes of varying sizes, we developed an analytical method to find the mean primary dose in spheres that can guide numerical methods to find the primary dose distribution for cylinders. Considering cylindrical segments of varying aspect ratio at constant volume, we assess the chord length distribution, mean number of hits and ED profiles by primary particles and secondary electrons (δ-rays). For biophysical modeling applications, segments on dendritic branches are proposed to have equal diameters and axes lengths along the varying diameter of a dendritic branch. PMID:28554507

Track structure model of microscopic energy deposition by protons and heavy ions in segments of neuronal cell dendrites represented by cylinders or spheres

NASA Astrophysics Data System (ADS)

Alp, Murat; Cucinotta, Francis A.

2017-05-01

Changes to cognition, including memory, following radiation exposure are a concern for cosmic ray exposures to astronauts and in Hadron therapy with proton and heavy ion beams. The purpose of the present work is to develop computational methods to evaluate microscopic energy deposition (ED) in volumes representative of neuron cell structures, including segments of dendrites and spines, using a stochastic track structure model. A challenge for biophysical models of neuronal damage is the large sizes (> 100 μm) and variability in volumes of possible dendritic segments and pre-synaptic elements (spines and filopodia). We consider cylindrical and spherical microscopic volumes of varying geometric parameters and aspect ratios from 0.5 to 5 irradiated by protons, and 3He and 12C particles at energies corresponding to a distance of 1 cm to the Bragg peak, which represent particles of interest in Hadron therapy as well as space radiation exposure. We investigate the optimal axis length of dendritic segments to evaluate microscopic ED and hit probabilities along the dendritic branches at a given macroscopic dose. Because of large computation times to analyze ED in volumes of varying sizes, we developed an analytical method to find the mean primary dose in spheres that can guide numerical methods to find the primary dose distribution for cylinders. Considering cylindrical segments of varying aspect ratio at constant volume, we assess the chord length distribution, mean number of hits and ED profiles by primary particles and secondary electrons (δ-rays). For biophysical modeling applications, segments on dendritic branches are proposed to have equal diameters and axes lengths along the varying diameter of a dendritic branch.

Track structure model of microscopic energy deposition by protons and heavy ions in segments of neuronal cell dendrites represented by cylinders or spheres.

PubMed

Alp, Murat; Cucinotta, Francis A

2017-05-01

Changes to cognition, including memory, following radiation exposure are a concern for cosmic ray exposures to astronauts and in Hadron therapy with proton and heavy ion beams. The purpose of the present work is to develop computational methods to evaluate microscopic energy deposition (ED) in volumes representative of neuron cell structures, including segments of dendrites and spines, using a stochastic track structure model. A challenge for biophysical models of neuronal damage is the large sizes (> 100µm) and variability in volumes of possible dendritic segments and pre-synaptic elements (spines and filopodia). We consider cylindrical and spherical microscopic volumes of varying geometric parameters and aspect ratios from 0.5 to 5 irradiated by protons, and 3 He and 12 C particles at energies corresponding to a distance of 1cm to the Bragg peak, which represent particles of interest in Hadron therapy as well as space radiation exposure. We investigate the optimal axis length of dendritic segments to evaluate microscopic ED and hit probabilities along the dendritic branches at a given macroscopic dose. Because of large computation times to analyze ED in volumes of varying sizes, we developed an analytical method to find the mean primary dose in spheres that can guide numerical methods to find the primary dose distribution for cylinders. Considering cylindrical segments of varying aspect ratio at constant volume, we assess the chord length distribution, mean number of hits and ED profiles by primary particles and secondary electrons (δ-rays). For biophysical modeling applications, segments on dendritic branches are proposed to have equal diameters and axes lengths along the varying diameter of a dendritic branch. Copyright © 2017. Published by Elsevier Ltd.

Efficient hit-finding approaches for histone methyltransferases: the key parameters.

PubMed

Ahrens, Thomas; Bergner, Andreas; Sheppard, David; Hafenbradl, Doris

2012-01-01

For many novel epigenetics targets the chemical ligand space and structural information were limited until recently and are still largely unknown for some targets. Hit-finding campaigns are therefore dependent on large and chemically diverse libraries. In the specific case of the histone methyltransferase G9a, the authors have been able to apply an efficient process of intelligent selection of compounds for primary screening, rather than screening the full diverse deck of 900 000 compounds to identify hit compounds. A number of different virtual screening methods have been applied for the compound selection, and the results have been analyzed in the context of their individual success rates. For the primary screening of 2112 compounds, a FlashPlate assay format and full-length histone H3.1 substrate were employed. Validation of hit compounds was performed using the orthogonal fluorescence lifetime technology. Rated by purity and IC(50) value, 18 compounds (0.9% of compound screening deck) were finally considered validated primary G9a hits. The hit-finding approach has led to novel chemotypes being identified, which can facilitate hit-to-lead projects. This study demonstrates the power of virtual screening technologies for novel, therapeutically relevant epigenetics protein targets.

Revisiting adoption of high transmission PSM: pros, cons and path forward

NASA Astrophysics Data System (ADS)

Ma, Z. Mark; McDonald, Steve; Progler, Chris

2009-12-01

High transmission attenuated phase shift masks (Hi-T PSM) have been successfully applied in volume manufacturing for certain memory devices. Moreover, numerous studies have shown the potential benefits of Hi-T PSM for specific lithography applications. In this paper, the potential for extending Hi-T PSM to logic devices, is revisited with an emphasis on understanding layout, transmission, and manufacturing of Hi-T PSM versus traditional 6% embedded attenuated phase shift mask (EAPSM). Simulations on various layouts show Hi-T PSM has advantage over EAPSM in low duty cycle line patterns and high duty cycle space patterns. The overall process window can be enhanced when Hi- T PSM is combined with optimized optical proximity correction (OPC), sub-resolution assist features (SRAF), and source illumination. Therefore, Hi-T PSM may be a viable and lower cost alternative to other complex resolution enhancement technology (RET) approaches. Aerial image measurement system (AIMS) results on test masks, based on an inverse lithography technology (ILT) generated layout, confirm the simulation results. New advancement in high transmission blanks also make low topography Hi-T PSM a reality, which can minimize scattering effects in high NA lithography.

Biostack: A study of the biological effects on HZE galactic cosmic radiation

NASA Technical Reports Server (NTRS)

Buecker, H.

1975-01-01

The Biostack experiment designed to study the effect of individual heavy nucleii of the cosmic radiation environment upon biological systems during actual space flight is described. In each Biostack, several thousand biological objects were hit by an HZE particle. The response of the biological objects was studied. Results are discussed in terms of sensitivity to the hit.

Cosmic Radiation | RadTown USA | US EPA

EPA Pesticide Factsheets

2017-08-07

Radiation from space is constantly hitting the Earth. Radiation from space is called cosmic radiation. Cosmic radiation makes up about five percent of annual radiation exposure of an average person in the United States.

Well There’s Your Problem: Isolating the Crash-Inducing Bits in a Fuzzed File

DTIC Science & Technology

2012-10-01

CurrHD end for for all CDChance[i] do Calculate Phit [i] [see (7)] BitReduction[i] ← CurrHD × CDChance[i] ExpectedReduction[i] ← Phit [i...at least one hit left to be found in the search space. Here we use the identity that phit = 1 — pmiss (14) and observe that the chance of getting...at least one hit in x tries is P (≥ 1_hit_in_ x_ tries) = 1 – pxmiss =1 − (1 − phit )x (15) Another way to interpret equation (15) is that if we try x

High-throughput imaging of heterogeneous cell organelles with an X-ray laser (CXIDB ID 25)

DOE Data Explorer

Hantke, Max, F.

2014-11-17

Preprocessed detector images that were used for the paper "High-throughput imaging of heterogeneous cell organelles with an X-ray laser". The CXI file contains the entire recorded data - including both hits and blanks. It also includes down-sampled images and LCLS machine parameters. Additionally, the Cheetah configuration file is attached that was used to create the pre-processed data.

Composing compound libraries for hit discovery--rationality-driven preselection or random choice by structural diversity?

PubMed

Weidel, Elisabeth; Negri, Matthias; Empting, Martin; Hinsberger, Stefan; Hartmann, Rolf W

2014-01-01

In order to identify new scaffolds for drug discovery, surface plasmon resonance is frequently used to screen structurally diverse libraries. Usually, hit rates are low and identification processes are time consuming. Hence, approaches which improve hit rates and, thus, reduce the library size are required. In this work, we studied three often used strategies for their applicability to identify inhibitors of PqsD. In two of them, target-specific aspects like inhibition of a homologous protein or predicted binding determined by virtual screening were used for compound preselection. Finally, a fragment library, covering a large chemical space, was screened and served as comparison. Indeed, higher hit rates were observed for methods employing preselected libraries indicating that target-oriented compound selection provides a time-effective alternative.

Trigger design for a gamma ray detector of HIRFL-ETF

NASA Astrophysics Data System (ADS)

Du, Zhong-Wei; Su, Hong; Qian, Yi; Kong, Jie

2013-10-01

The Gamma Ray Array Detector (GRAD) is one subsystem of HIRFL-ETF (the External Target Facility (ETF) of the Heavy Ion Research Facility in Lanzhou (HIRFL)). It is capable of measuring the energy of gamma-rays with 1024 CsI scintillators in in-beam nuclear experiments. The GRAD trigger should select the valid events and reject the data from the scintillators which are not hit by the gamma-ray. The GRAD trigger has been developed based on the Field Programmable Gate Array (FPGAs) and PXI interface. It makes prompt trigger decisions to select valid events by processing the hit signals from the 1024 CsI scintillators. According to the physical requirements, the GRAD trigger module supplies 12-bit trigger information for the global trigger system of ETF and supplies a trigger signal for data acquisition (DAQ) system of GRAD. In addition, the GRAD trigger generates trigger data that are packed and transmitted to the host computer via PXI bus to be saved for off-line analysis. The trigger processing is implemented in the front-end electronics of GRAD and one FPGA of the GRAD trigger module. The logic of PXI transmission and reconfiguration is implemented in another FPGA of the GRAD trigger module. During the gamma-ray experiments, the GRAD trigger performs reliably and efficiently. The function of GRAD trigger is capable of satisfying the physical requirements.

An Algorithm of an X-ray Hit Allocation to a Single Pixel in a Cluster and Its Test-Circuit Implementation

DOE PAGES

Deptuch, Grzegorz W.; Fahim, Farah; Grybos, Pawel; ...

2017-06-28

An on-chip implementable algorithm for allocation of an X-ray photon imprint, called a hit, to a single pixel in the presence of charge sharing in a highly segmented pixel detector is described. Its proof-of-principle implementation is also given supported by the results of tests using a highly collimated X-ray photon beam from a synchrotron source. The algorithm handles asynchronous arrivals of X-ray photons. Activation of groups of pixels, comparisons of peak amplitudes of pulses within an active neighborhood and finally latching of the results of these comparisons constitute the three procedural steps of the algorithm. A grouping of pixels tomore » one virtual pixel, that recovers composite signals and event driven strobes, to control comparisons of fractional signals between neighboring pixels are the actuators of the algorithm. The circuitry necessary to implement the algorithm requires an extensive inter-pixel connection grid of analog and digital signals, that are exchanged between pixels. A test-circuit implementation of the algorithm was achieved with a small array of 32 × 32 pixels and the device was exposed to an 8 keV highly collimated to a diameter of 3-μm X-ray beam. Furthermore, the results of these tests are given in this paper assessing physical implementation of the algorithm.« less

Helicopter In-Flight Tracking System (HITS) for the Gulf of Mexico

NASA Technical Reports Server (NTRS)

Martone, Patrick; Tucker, George; Aiken, Edwin W. (Technical Monitor)

2001-01-01

The National Aeronautics and Space Administration (NASA) Ames Research Center (ARC) is sponsoring deployment and testing of the Helicopter In-flight Tracking System (HITS) in a portion of the Gulf of Mexico offshore area. Using multilateration principles, HITS determines the location and altitude of all transponder-equipped aircraft without requiring changes to current Mode A, C or S avionics. HITS tracks both rotary and fixed-wing aircraft operating in the 8,500 sq. mi. coverage region. The minimum coverage altitude of 100 ft. is beneficial for petroleum industry, allowing helicopters to be tracked onto the pad of most derricks. In addition to multilateration, HITS provides surveillance reports for aircraft equipped for Automatic Dependent Surveillance - Broadcast (ADS-B), a new surveillance system under development by the Federal Aviation Administration (FAA). The U.S. Department of Transportation (DOT) Volpe National Transportation Systems Center (Volpe Center) is supporting NASA in managing HITS installation and operation, and in evaluating the system's effectiveness. Senses Corporation is supplying, installing and maintaining the HITS ground system. Project activities are being coordinated with the FAA and local helicopter operators. Flight-testing in the Gulf will begin in early 2002. This paper describes the HITS project - specifically, the system equipment (architecture, remote sensors, central processing system at Intracoastal City, LA, and communications) and its performance (accuracy, coverage, and reliability). The paper also presents preliminary results of flight tests.

The Mysterious Origins of Solar Flares: New observations are beginning to reveal what triggers these hughes explosions of the sun's atmosphere

NASA Technical Reports Server (NTRS)

Holman, Gordon D.

2006-01-01

Solar flares can release the energy equivalent of billions of atomic bombs in the span of just a few minutes. These explosions give off a burst of x-rays and charged particles, some of which may later hit Earth, endangering satellites and causing power outages. The sun's tumultuous magnetic fields provide the fuel of flares. The sudden release of energy in a flare results from a process called reconnection, whereby oppositely directed magnetic field lines come together and partially annihilate each other. Although theoretical studies of magnetic reconnection on the sun have been carried out for decades, only recently have space probes uncovered observational evidence for this phenomenon. The telltale signs include pointed magnetic loops located below the spot where magnetic reconnection is taking place.

NMR-based platform for fragment-based lead discovery used in screening BRD4-targeted compounds

PubMed Central

Yu, Jun-lan; Chen, Tian-tian; Zhou, Chen; Lian, Fu-lin; Tang, Xu-long; Wen, Yi; Shen, Jing-kang; Xu, Ye-chun; Xiong, Bing; Zhang, Nai-xia

2016-01-01

Aim: Fragment-based lead discovery (FBLD) is a complementary approach in drug research and development. In this study, we established an NMR-based FBLD platform that was used to screen novel scaffolds targeting human bromodomain of BRD4, and investigated the binding interactions between hit compounds and the target protein. Methods: 1D NMR techniques were primarily used to generate the fragment library and to screen compounds. The inhibitory activity of hits on the first bromodomain of BRD4 [BRD4(I)] was examined using fluorescence anisotropy binding assay. 2D NMR and X-ray crystallography were applied to characterize the binding interactions between hit compounds and the target protein. Results: An NMR-based fragment library containing 539 compounds was established, which were clustered into 56 groups (8–10 compounds in each group). Eight hits with new scaffolds were found to inhibit BRD4(I). Four out of the 8 hits (compounds 1, 2, 8 and 9) had IC50 values of 100–260 μmol/L, demonstrating their potential for further BRD4-targeted hit-to-lead optimization. Analysis of the binding interactions revealed that compounds 1 and 2 shared a common quinazolin core structure and bound to BRD4(I) in a non-acetylated lysine mimetic mode. Conclusion: An NMR-based platform for FBLD was established and used in discovery of BRD4-targeted compounds. Four potential hit-to-lead optimization candidates have been found, two of them bound to BRD4(I) in a non-acetylated lysine mimetic mode, being selective BRD4(I) inhibitors. PMID:27238211

Near-optimal alternative generation using modified hit-and-run sampling for non-linear, non-convex problems

NASA Astrophysics Data System (ADS)

Rosenberg, D. E.; Alafifi, A.

2016-12-01

Water resources systems analysis often focuses on finding optimal solutions. Yet an optimal solution is optimal only for the modelled issues and managers often seek near-optimal alternatives that address un-modelled objectives, preferences, limits, uncertainties, and other issues. Early on, Modelling to Generate Alternatives (MGA) formalized near-optimal as the region comprising the original problem constraints plus a new constraint that allowed performance within a specified tolerance of the optimal objective function value. MGA identified a few maximally-different alternatives from the near-optimal region. Subsequent work applied Markov Chain Monte Carlo (MCMC) sampling to generate a larger number of alternatives that span the near-optimal region of linear problems or select portions for non-linear problems. We extend the MCMC Hit-And-Run method to generate alternatives that span the full extent of the near-optimal region for non-linear, non-convex problems. First, start at a feasible hit point within the near-optimal region, then run a random distance in a random direction to a new hit point. Next, repeat until generating the desired number of alternatives. The key step at each iterate is to run a random distance along the line in the specified direction to a new hit point. If linear equity constraints exist, we construct an orthogonal basis and use a null space transformation to confine hits and runs to a lower-dimensional space. Linear inequity constraints define the convex bounds on the line that runs through the current hit point in the specified direction. We then use slice sampling to identify a new hit point along the line within bounds defined by the non-linear inequity constraints. This technique is computationally efficient compared to prior near-optimal alternative generation techniques such MGA, MCMC Metropolis-Hastings, evolutionary, or firefly algorithms because search at each iteration is confined to the hit line, the algorithm can move in one step to any point in the near-optimal region, and each iterate generates a new, feasible alternative. We use the method to generate alternatives that span the near-optimal regions of simple and more complicated water management problems and may be preferred to optimal solutions. We also discuss extensions to handle non-linear equity constraints.

The importance of interaction in the implementation of information technology in health care: a symbolic interactionism study on the meaning of accessibility.

PubMed

Nilsson, Lina; Hofflander, Malin; Eriksén, Sara; Borg, Christel

2012-12-01

A challenge when groups from different disciplines work together in implementing health information technology (HIT) in a health-care context is that words often have different meanings depending upon work practices, and definition of situations. Accessibility is a word commonly associated with HIT implementation. This study aimed to investigate different meanings of accessibility when implementing HIT in everyday work practice in a health-care context. It focused on the perspective of nurses to highlight another view of the complex relationship between HIT and information in a health-care context. This is a qualitative study influenced by institutional ethnographic. District nurses and student nurses were interviewed. The results indicate that when implementing HIT accessibility depends on working routines, social structures and patient relationship. The findings of the study suggest that interaction needs to take on a more important role when implementing HIT because people act upon words from the interpreted meaning of them. Symbolic interactionism is proposed as a way to set a mutual stage to facilitate an overall understanding of the importance of the meaning of words. There is a need for making place and space for negotiation of the meaning of words when implementing HIT in everyday work practice.

Hit discovery of 4-amino-N-(4-(3-(trifluoromethyl)phenoxy)pyrimidin-5-yl)benzamide: A novel EGFR inhibitor from a designed small library.

PubMed

Elkamhawy, Ahmed; Paik, Sora; Hassan, Ahmed H E; Lee, Yong Sup; Roh, Eun Joo

2017-12-01

Searching for hit compounds within the huge chemical space resembles the attempt to find a needle in a haystack. Cheminformatics-guided selection of few representative molecules of a rationally designed virtual combinatorial library is a powerful tool to confront this challenge, speed up hit identification and cut off costs. Herein, this approach has been applied to identify hit compounds with novel scaffolds able to inhibit EGFR kinase. From a generated virtual library, six 4-aryloxy-5-aminopyrimidine scaffold-derived compounds were selected, synthesized and evaluated as hit EGFR inhibitors. 4-Aryloxy-5-benzamidopyrimidines inhibited EGFR with IC 50 1.05-5.37 μM. Cell-based assay of the most potent EGFR inhibitor hit (10ac) confirmed its cytotoxicity against different cancerous cells. In spite of no EGFR, HER2 or VEGFR1 inhibition was elicited by 4-aryloxy-5-(thio)ureidopyrimidine derivatives, cell-based evaluation suggested them as antiproliferative hits acting by other mechanism(s). Molecular docking study provided a plausible explanation of incapability of 4-aryloxy-5-(thio)ureidopyrimidines to inhibit EGFR and suggested a reasonable binding mode of 4-aryloxy-5-benzamidopyrimidines which provides a basis to develop more optimized ligands. Copyright © 2017 Elsevier Inc. All rights reserved.

Radiation Measured for Chinese Satellite SJ-10 Space Mission

NASA Astrophysics Data System (ADS)

Zhou, Dazhuang; Sun, Yeqing; Zhang, Binquan; Zhang, Shenyi; Sun, Yueqiang; Liang, Jinbao; Zhu, Guangwu; Jing, Tao; Yuan, Bin; Zhang, Huanxin; Zhang, Meng; Wang, Wei; Zhao, Lei

2018-02-01

Space biological effects are mainly a result of space radiation particles with high linear energy transfer (LET); therefore, accurate measurement of high LET space radiation is vital. The radiation in low Earth orbits is composed mainly of high-energy galactic cosmic rays (GCRs), solar energetic particles, particles of radiation belts, the South Atlantic Anomaly, and the albedo neutrons and protons scattered from the Earth's atmosphere. CR-39 plastic nuclear track detectors sensitive to high LET are the best passive detectors to measure space radiation. The LET method that employs CR-39 can measure all the radiation LET spectra and quantities. CR-39 detectors can also record the incident directions and coordinates of GCR heavy ions that pass through both CR-39 and biosamples, and the impact parameter, the distance between the particle's incident point and the seed's spore, can then be determined. The radiation characteristics and impact parameter of GCR heavy ions are especially beneficial for in-depth research regarding space radiation biological effects. The payload returnable satellite SJ-10 provided an excellent opportunity to investigate space radiation biological effects with CR-39 detectors. The space bio-effects experiment was successfully conducted on board the SJ-10 satellite. This paper introduces space radiation in low Earth orbits and the LET method in radiation-related research and presents the results of nuclear tracks and biosamples hitting distributions of GCR heavy ions, the radiation LET spectra, and the quantities measured for the SJ-10 space mission. The SJ-10 bio-experiment indicated that radiation may produce significant bio-effects.

Assessment of Dengue virus helicase and methyltransferase as targets for fragment-based drug discovery.

PubMed

Coutard, Bruno; Decroly, Etienne; Li, Changqing; Sharff, Andrew; Lescar, Julien; Bricogne, Gérard; Barral, Karine

2014-06-01

Seasonal and pandemic flaviviruses continue to be leading global health concerns. With the view to help drug discovery against Dengue virus (DENV), a fragment-based experimental approach was applied to identify small molecule ligands targeting two main components of the flavivirus replication complex: the NS3 helicase (Hel) and the NS5 mRNA methyltransferase (MTase) domains. A library of 500 drug-like fragments was first screened by thermal-shift assay (TSA) leading to the identification of 36 and 32 fragment hits binding Hel and MTase from DENV, respectively. In a second stage, we set up a fragment-based X-ray crystallographic screening (FBS-X) in order to provide both validated fragment hits and structural binding information. No fragment hit was confirmed for DENV Hel. In contrast, a total of seven fragments were identified as DENV MTase binders and structures of MTase-fragment hit complexes were solved at resolution at least 2.0Å or better. All fragment hits identified contain either a five- or six-membered aromatic ring or both, and three novel binding sites were located on the MTase. To further characterize the fragment hits identified by TSA and FBS-X, we performed enzymatic assays to assess their inhibition effect on the N7- and 2'-O-MTase enzymatic activities: five of these fragment hits inhibit at least one of the two activities with IC50 ranging from 180μM to 9mM. This work validates the FBS-X strategy for identifying new anti-flaviviral hits targeting MTase, while Hel might not be an amenable target for fragment-based drug discovery (FBDD). This approach proved to be a fast and efficient screening method for FBDD target validation and discovery of starting hits for the development of higher affinity molecules that bind to novel allosteric sites. Copyright © 2014 Elsevier B.V. All rights reserved.

An Analytic Model for the Success Rate of a Robotic Actuator System in Hitting Random Targets.

PubMed

Bradley, Stuart

2015-11-20

Autonomous robotic systems are increasingly being used in a wide range of applications such as precision agriculture, medicine, and the military. These systems have common features which often includes an action by an "actuator" interacting with a target. While simulations and measurements exist for the success rate of hitting targets by some systems, there is a dearth of analytic models which can give insight into, and guidance on optimization, of new robotic systems. The present paper develops a simple model for estimation of the success rate for hitting random targets from a moving platform. The model has two main dimensionless parameters: the ratio of actuator spacing to target diameter; and the ratio of platform distance moved (between actuator "firings") to the target diameter. It is found that regions of parameter space having specified high success are described by simple equations, providing guidance on design. The role of a "cost function" is introduced which, when minimized, provides optimization of design, operating, and risk mitigation costs.

Identification of N-ethylmethylamine as a novel scaffold for inhibitors of soluble epoxide hydrolase by crystallographic fragment screening.

PubMed

Amano, Yasushi; Tanabe, Eiki; Yamaguchi, Tomohiko

2015-05-15

Soluble epoxide hydrolase (sEH) is a potential target for the treatment of inflammation and hypertension. X-ray crystallographic fragment screening was used to identify fragment hits and their binding modes. Eight fragment hits were identified via soaking of sEH crystals with fragment cocktails, and the co-crystal structures of these hits were determined via individual soaking. Based on the binding mode, N-ethylmethylamine was identified as a promising scaffold that forms hydrogen bonds with the catalytic residues of sEH, Asp335, Tyr383, and Tyr466. Compounds containing this scaffold were selected from an in-house chemical library and assayed. Although the starting fragment had a weak inhibitory activity (IC50: 800μM), we identified potent inhibitors including 2-({[2-(adamantan-1-yl)ethyl]amino}methyl)phenol exhibiting the highest inhibitory activity (IC50: 0.51μM). This corresponded to a more than 1500-fold increase in inhibitory activity compared to the starting fragment. Co-crystal structures of the hit compounds demonstrate that the binding of N-ethylmethylamine to catalytic residues is similar to that of the starting fragment. We therefore consider crystallographic fragment screening to be appropriate for the identification of weak but promising fragment hits. Copyright © 2015 Elsevier Ltd. All rights reserved.

Concluding Remarks II

NASA Astrophysics Data System (ADS)

Ziółkowski, Janusz

2003-12-01

The program of the conference was prepared so well (thanks to the organizers) that we got complete and competent reviews in all important fields of high energy cosmic sources. It is not easy to select just a few topics and any choice will be, necessarily, arbitrary. I decided to make brief comments on cosmology, on gamma ray bursts and on X-ray flashes. My personal nomination for the hit of the conference goes this year to the ``Rosetta stone" of gamma ray bursts (term used by Elena Pian): GRB030329 = SN 2003dh.

Readout Electronics for BGO Calorimeter of DAMPE: Status during the First Half-year after Launching

NASA Astrophysics Data System (ADS)

Ma, Siyuan; Feng, Changqing; Zhang, Deliang; Wang, Qi

2016-07-01

The DAMPE (DArk Matter Particle Explorer) is a scientic satellite which was successfully launched into a 500 Km sun-synchronous orbit, on December 17th, 2015, from the Jiuquan Satellite Launch Center of China. The major scientific objective of DAMPE mission is indirect searching for dark matter by observing high energy primary cosmic rays, especially positrons/electrons and gamma rays with an energy range from 5 GeV to 10 TeV. The BGO (Bismuth Germanate Oxide) calorimeter, which is a critical sub-detector of DAMPE payload, was developed for measuring the energy of cosmic particles, distinguishing positrons/electrons and gamma rays from hadron background, and providing trigger information. It is composed of 308 BGO crystal logs, with the size of 2.5cm*2.5cm*60cm for each log to form a total absorption electromagnetic calorimeter. All the BGO logs are stacked in 14 layers, with each layer consisting of 22 BGO crystal logs and each log is viewed by two Hamamatsu R5610A PMTs (photomultiplier tubes), from both sides respectively. Each PMT incorporates a three dynode pick off to achieve a large dynamic range, which results in 616 PMTs and 1848 signal channels. The main function of readout electronics system, which consists of 16 FEE(Front End Electronics) modules, is to precisely measure the charge of PMT signals and providing "hit" signals. The hit signals are sent to the trigger module of PDPU (Payload Data Process Unit) to generate triggers for the payload. The calibration of the BGO calorimeter is composed of pedestal testing and electronic linear scale, which are executed frequently in the space after launching. The data of the testing is transmitted to ground station in the form of scientific data. The monitor status consists of temperature, current and status words of the FEE, which are measured and recorded every 16 seconds and packed in the engineering data, then transmitted to ground station. The status of the BGO calorimeter can be evaluated by the calibration and monitor status. The preliminary results of the status in the first six month after launching are introduced in this paper.

Novel approach of fragment-based lead discovery applied to renin inhibitors.

PubMed

Tawada, Michiko; Suzuki, Shinkichi; Imaeda, Yasuhiro; Oki, Hideyuki; Snell, Gyorgy; Behnke, Craig A; Kondo, Mitsuyo; Tarui, Naoki; Tanaka, Toshimasa; Kuroita, Takanobu; Tomimoto, Masaki

2016-11-15

A novel approach was conducted for fragment-based lead discovery and applied to renin inhibitors. The biochemical screening of a fragment library against renin provided the hit fragment which showed a characteristic interaction pattern with the target protein. The hit fragment bound only to the S1, S3, and S3 SP (S3 subpocket) sites without any interactions with the catalytic aspartate residues (Asp32 and Asp215 (pepsin numbering)). Prior to making chemical modifications to the hit fragment, we first identified its essential binding sites by utilizing the hit fragment's substructures. Second, we created a new and smaller scaffold, which better occupied the identified essential S3 and S3 SP sites, by utilizing library synthesis with high-throughput chemistry. We then revisited the S1 site and efficiently explored a good building block attaching to the scaffold with library synthesis. In the library syntheses, the binding modes of each pivotal compound were determined and confirmed by X-ray crystallography and the library was strategically designed by structure-based computational approach not only to obtain a more active compound but also to obtain informative Structure Activity Relationship (SAR). As a result, we obtained a lead compound offering synthetic accessibility as well as the improved in vitro ADMET profiles. The fragments and compounds possessing a characteristic interaction pattern provided new structural insights into renin's active site and the potential to create a new generation of renin inhibitors. In addition, we demonstrated our FBDD strategy integrating highly sensitive biochemical assay, X-ray crystallography, and high-throughput synthesis and in silico library design aimed at fragment morphing at the initial stage was effective to elucidate a pocket profile and a promising lead compound. Copyright © 2016 Elsevier Ltd. All rights reserved.

Ray tracing a three-dimensional scene using a hierarchical data structure

DOEpatents

Wald, Ingo; Boulos, Solomon; Shirley, Peter

2012-09-04

Ray tracing a three-dimensional scene made up of geometric primitives that are spatially partitioned into a hierarchical data structure. One example embodiment is a method for ray tracing a three-dimensional scene made up of geometric primitives that are spatially partitioned into a hierarchical data structure. In this example embodiment, the hierarchical data structure includes at least a parent node and a corresponding plurality of child nodes. The method includes a first act of determining that a first active ray in the packet hits the parent node and a second act of descending to each of the plurality of child nodes.

Effects of Cutoffs on Galactic Cosmic-Ray Interactions in Solar-System Matter

NASA Technical Reports Server (NTRS)

Kim, K. J.; Reedy, R. C.; Masarik, J.

2005-01-01

The energetic particles in the galactic cosmic rays (GCR) induce many interactions in a variety of solar-system matter. Cosmogenic nuclides are used to study the histories of meteorites and lunar samples. Gamma rays and neutrons are used to map the compositions of planetary surfaces, such as Mars, the Moon, and asteroids. In almost all of these cases, the spectra of incident GCR particles are fairly similar, with only some modulation by the Sun over an 11-year cycle. Strong magnetic fields can seriously affect the energy spectrum of GCR particles hitting the surface of objects inside the magnetic fields. The Earth s geomagnetic field is strong enough that only GCR particles with magnetic rigidities above approx. 17 GV (a proton energy of approx. 17 GeV) reach the atmosphere over certain regions near the equator. This effect of removing lower-energy GCR particles is called a cutoff. The jovian magnetic fields are so strong that the fluxes of GCR particles hitting the 4 large Galilean satellites are similarly affected. The cutoff at Europa is estimated to be similar to or a little higher than at the Earth s equator.

The 11 years solar cycle as the manifestation of the dark Universe

DOE PAGES

Zioutas, K.; Semertzidis, Y.; Tsagri, M.; ...

2014-11-26

Sun’s luminosity in the visible changes at the 10 -3 level, following an 11 years period. In X-rays, which should not be there, the amplitude varies even ~10 5 times stronger, making their mysterious origin since the discovery in 1938 even more puzzling, and inspiring. We suggest that the multifaceted mysterious solar cycle is due to some kind of dark matter streams hitting the Sun. Planetary gravitational lensing enhances (occasionally) slow moving flows of dark constituents towards the Sun, giving rise to the periodic behaviour. Jupiter provides the driving oscillatory force, though its 11.8 years orbital period appears slightly decreased,more » just as 11 years, if the lensing impact of other planets is included. Then, the 11 years solar clock may help to decipher (overlooked) signatures from the dark sector in laboratory experiments or observations in space.« less

INFLUENCE OF DEATH CRITERIA ON THE X-RAY SURVIVAL CURVES OF THE FUNGUS, NEUROSPORA

PubMed Central

Uber, Fred M.; Goddard, David R.

1934-01-01

1. When ascospores of Neurospora tetrasperma were irradiated with 11 kv. X-rays, the single spore cultures obtained displayed a wide variety of mutated forms. 2. Control germinations of ascospores showed uniform behavior, ranging from 92–95 per cent germination. 3. The shape of the survival curves was found to be a function of the criterion of death. The following criteria were used: germination, growth, production of mature ascospores, and the production of normal perithecia. 4. The germination survival curve exhibited a rhythmic variation with dosage. Germination is not a significant criterion of death. 5. Half-survival dosages for growth and ascospore production were approximately 30,000 and 20,000 roentgens, respectively. 6. Multiple hit-to-kill relations were found on the basis of the quantum hit theory; no accurate analysis was possible. 7. The studies indicate that ascospore death does not result from a single well defined reaction, but rather from the integrated effects of several deleterious processes initiated by the radiation. PMID:19872801

Energy dependent features of X-ray signals in a GridPix detector

NASA Astrophysics Data System (ADS)

Krieger, C.; Kaminski, J.; Vafeiadis, T.; Desch, K.

2018-06-01

We report on the calibration of an argon/isobutane (97.7%/2.3%)-filled GridPix detector with soft X-rays (277 eV to 8 keV) using the variable energy X-ray source of the CAST Detector Lab at CERN. We study the linearity and energy resolution of the detector using both the number of pixels hit and the total measured charge as energy measures. For the latter, the energy resolution σE / E is better than 10% (20%) for energies above 2 keV (0.5 keV). Several characteristics of the recorded events are studied.

On determination of charge transfer efficiency of thick, fully depleted CCDs with 55 Fe x-rays

DOE PAGES

Yates, D.; Kotov, I.; Nomerotski, A.

2017-07-01

Charge transfer efficiency (CTE) is one of the most important CCD characteristics. Our paper examines ways to optimize the algorithms used to analyze 55Fe x-ray data on the CCDs, as well as explores new types of observables for CTE determination that can be used for testing LSST CCDs. Furthermore, the observables are modeled employing simple Monte Carlo simulations to determine how the charge diffusion in thick, fully depleted silicon affects the measurement. The data is compared to the simulations for one of the observables, integral flux of the x-ray hit.

Apollo-Soyuz pamphlet no. 6: Cosmic ray dosage. [experimental designiradiation hazards and dosage

NASA Technical Reports Server (NTRS)

Page, L. W.; From, T. P.

1977-01-01

The radiation hazard inside spacecraft is discussed with emphasis on its effects on the crew, biological specimens, and spacecraft instruments. The problem of light flash sensations in the eyes of astronauts is addressed and experiment MA-106 is described. In this experiment, light flashes seen by blindfolded astronauts were counted and high energy cosmic ray intensity in the command module cabin were measured. The damage caused by cosmic ray hits on small living organisms was investigated in the Biostack 3 experiment (MA-107). Individual cosmic rays were tracked through layers of bacterial spores, small seeds, and eggs interleaved with layers of AgCl-crystal wafers, special plastic, and special photographic film that registered each cosmic ray particle passed.

Using task dynamics to quantify the affordances of throwing for long distance and accuracy.

PubMed

Wilson, Andrew D; Weightman, Andrew; Bingham, Geoffrey P; Zhu, Qin

2016-07-01

In 2 experiments, the current study explored how affordances structure throwing for long distance and accuracy. In Experiment 1, 10 expert throwers (from baseball, softball, and cricket) threw regulation tennis balls to hit a vertically oriented 4 ft × 4 ft target placed at each of 9 locations (3 distances × 3 heights). We measured their release parameters (angle, speed, and height) and showed that they scaled their throws in response to changes in the target's location. We then simulated the projectile motion of the ball and identified a continuous subspace of release parameters that produce hits to each target location. Each subspace describes the affordance of our target to be hit by a tennis ball moving in a projectile motion to the relevant location. The simulated affordance spaces showed how the release parameter combinations required for hits changed with changes in the target location. The experts tracked these changes in their performance and were successful in hitting the targets. We next tested unusual (horizontal) targets that generated correspondingly different affordance subspaces to determine whether the experts would track the affordance to generate successful hits. Do the experts perceive the affordance? They do. In Experiment 2, 5 cricketers threw to hit either vertically or horizontally oriented targets and successfully hit both, exhibiting release parameters located within the requisite affordance subspaces. We advocate a task dynamical approach to the study of affordances as properties of objects and events in the context of tasks as the future of research in this area. (PsycINFO Database Record (c) 2016 APA, all rights reserved).

Lessons learnt from the Wenchuan earthquake: performance evaluation of treatment of critical injuries in hardest-hit areas.

PubMed

Jiang, Jie; Li, Youping; Huang, Xiaolin; Li, Bing; Su, Lin; Zhong, Dake; Shi, Chenghu; Li, Mingxu; Shan, Juan; Chen, Yin

2012-08-01

Critical injury treatment in the hardest-hit areas after a great earthquake was retrospectively analyzed to determine how best to reduce mortality and disability and increase the rehabilitation rate through postquake medical relief. Retrospective analysis, primary sources, and secondary sources were comprehensively retrieved and analyzed. According to incomplete data, 30,620 injured were rescued by themselves among the hardest-hit areas in the 72 hours immediately following the earthquake. Critically injured patients accounted for 22% of total inpatients. Mortality rates declined with greater distance from the epicenter: rates were 12.21% for municipal healthcare centers in the hardest-hit areas, 4.50% for municipal medical units in peripheral quake-hit areas, 2.50% for provincial medical units in peripheral quake-hit areas, and 2.17% for Ministry of Health-affiliated hospitals in peripheral quake-hit areas. The number of injured with fractures on body, limbs or unknown-parts, severe conditions as well as other kinds of non-traumatic diseases received in second-line hospitals was much more than those treated in first-line hospitals with more severe injuries. Among 10,373 injured in stable condition transferred to third-line hospitals, 99.07% were discharged from hospitals within four months, while the mortality rate was 0.017%. The medical relief model of "supervising body helping subordinate unit, severely stricken areas assisting hardest-hit areas, least-hit areas supporting both hardest-hit and severely stricken areas, and self help and mutual assistance applied between hardest-hit areas" was roughly established for injured from severely stricken areas after the Wenchuan Earthquake. The "four-centralization" treatment principle, which referred to concentrating patients, experts, resources and treatment for those injured in critical condition effectively reduced the mortality from 15.06% to 2.9%. Timely, scientific, and standard on-site triage and postmedical transfer guided by accurate injury information determine rescue effect for the injured, while there is large space to fulfill as for treatment for critical diseases among the hardest-hit areas under extreme conditions after the Wenchuan earthquake. © 2012 Wiley Publishing Asia Pty Ltd and Chinese Cochrane Center, West China Hospital of Sichuan University.

Dual hit lipopolysaccharide & oleic acid combination induced rat model of acute lung injury/acute respiratory distress syndrome.

PubMed

Hagawane, T N; Gaikwad, R V; Kshirsagar, N A

2016-05-01

Despite advances in therapy and overall medical care, acute lung injury (ALI)/acute respiratory distress syndrome (ARDS) management remains a problem. Hence the objective of this study was to develop a rat model that mimics human ALI/ARDS. Four groups of Wistar rats, 48 per group were treated with (i) intratracheal (IT) lipopolysaccharide (LPS) (5 mg/kg) dissolved in normal saline (NS), (ii) intravenous (iv) oleic acid (OA) (250 μl/kg) suspension in bovine serum albumin (BSA), (iii) dual hit: IT LPS (2 mg/kg) dissolved in NS and iv OA (100 μl/kg) and (iv) control group: IT NS and iv BSA. From each group at set periods of time various investigations like chest x-rays, respiratory rate (RR), tidal volume (TV), total cell count, differential cell count, total protein count and cytokine levels in bronchoalveolar lavage fluid (BALF), lung wet/dry weight ratio and histopathological examination were done. It was noted that the respiratory rate, and tumour necrosis factor-α (TNF-α) levels were significantly higher at 4 h in the dual hit group as compared to LPS, OA and control groups. Interleukin-6 (IL-6) levels were significantly higher in the dual hit group as compared to LPS at 8 and 24 h, OA at 8 h and control (at all time intervals) group. IL-1β levels were significantly higher in LPS and dual hit groups at all time intervals, but not in OA and control groups. The injury induced in dual hit group was earlier and more sustained as compared to LPS and OA alone. The lung pathology and changes in respiration functions produced by the dual hit model were closer to the diagnostic criteria of ALI/ARDS in terms of clinical manifestations and pulmonary injury and the injury persisted longer as compared to LPS and OA single hit model. Therefore, the ARDS model produced by the dual hit method was closer to the diagnostic criteria of ARDS in terms of clinical manifestations and pulmonary injury.

Chemical Space of DNA-Encoded Libraries.

PubMed

Franzini, Raphael M; Randolph, Cassie

2016-07-28

In recent years, DNA-encoded chemical libraries (DECLs) have attracted considerable attention as a potential discovery tool in drug development. Screening encoded libraries may offer advantages over conventional hit discovery approaches and has the potential to complement such methods in pharmaceutical research. As a result of the increased application of encoded libraries in drug discovery, a growing number of hit compounds are emerging in scientific literature. In this review we evaluate reported encoded library-derived structures and identify general trends of these compounds in relation to library design parameters. We in particular emphasize the combinatorial nature of these libraries. Generally, the reported molecules demonstrate the ability of this technology to afford hits suitable for further lead development, and on the basis of them, we derive guidelines for DECL design.

Enhanced HTS hit selection via a local hit rate analysis.

PubMed

Posner, Bruce A; Xi, Hualin; Mills, James E J

2009-10-01

The postprocessing of high-throughput screening (HTS) results is complicated by the occurrence of false positives (inactive compounds misidentified as active by the primary screen) and false negatives (active compounds misidentified as inactive by the primary screen). An activity cutoff is frequently used to select "active" compounds from HTS data; however, this approach is insensitive to both false positives and false negatives. An alternative method that can minimize the occurrence of these artifacts will increase the efficiency of hit selection and therefore lead discovery. In this work, rather than merely using the activity of a given compound, we look at the presence and absence of activity among all compounds in its "chemical space neighborhood" to give a degree of confidence in its activity. We demonstrate that this local hit rate (LHR) analysis method outperforms hit selection based on ranking by primary screen activity values across ten diverse high throughput screens, spanning both cell-based and biochemical assay formats of varying biology and robustness. On average, the local hit rate analysis method was approximately 2.3-fold and approximately 1.3-fold more effective in identifying active compounds and active chemical series, respectively, than selection based on primary activity alone. Moreover, when applied to finding false negatives, this method was 2.3-fold better than ranking by primary activity alone. In most cases, novel hit series were identified that would have otherwise been missed. Additional uses of and observations regarding this HTS analysis approach are also discussed.

Predictive properties of the video head impulse test: measures of caloric symmetry and self-report dizziness handicap.

PubMed

McCaslin, Devin L; Jacobson, Gary P; Bennett, Marc L; Gruenwald, Jill M; Green, Andrea P

2014-01-01

The purpose of this investigation was to determine whether a predictable relationship existed between self-reported dizziness handicap and video Head Impulse Test (vHIT) results in a large sample of patients reporting to a dizziness clinic. Secondary objectives included describing the characteristics of the vHIT ipsilesional and contralesional vestibulo-ocular reflex slow-phase velocity in patients with varying levels of canal paresis. Finally, the authors calculated the sensitivity and specificity of the vHIT for detecting horizontal semicircular canal impairment using the caloric test as the "gold standard." Participants were 115 adults presenting to a tertiary medical care center with symptoms of dizziness. Participants were administered a measure of self-report dizziness handicap (i.e., Dizziness Handicap Inventory) and underwent caloric testing and vHIT at the same appointment. Results showed that (1) there were no significant group differences (i.e., vHIT normal versus vHIT abnormal) in the Dizziness Handicap Inventory total score, (2) both ipsilesional and contralateral velocity gain decreased with increases in caloric paresis, and (3) a caloric asymmetry of 39.5% was determined to be the cutoff that maximized discrimination of vHIT outcome. The level of self-reported dizziness handicap is not predicted by the outcome of the vHIT, which is consistent with the majority of published reports describing the poor relationship between quantitative tests of vestibular function and dizziness handicap. Further, the study findings have demonstrated that vHIT and caloric data are not redundant, and each test provides unique information regarding the functional integrity of the horizontal semicircular canal at different points on the frequency spectrum. The vHIT does offer some advantages over caloric testing, but at the expense of sensitivity. The vHIT can be completed in less time, is not noxious to the patient, and requires very little laboratory space. However, the study data show that a caloric asymmetry of 39.5% is required to optimize discrimination between an abnormal and normal vHIT. It is the authors' contention that the vHIT is a complementary test to the balance function examination and should viewed as such rather than as a replacement for caloric testing.

Final Prep on SSME

NASA Image and Video Library

2005-10-25

Alvin Pittman Sr., lead electronics technician with Pratt & Whitney Rocketdyne, and Janine Cuevas, a mechanical technician with PWR, perform final preparations on the space shuttle main engine tested Oct. 25, 2005, at NASA's Stennis Space Center. It was the first main engine test since Hurricane Katrina hit the Gulf Coast on Aug. 29.

Final Prep on SSME

NASA Technical Reports Server (NTRS)

2005-01-01

Alvin Pittman Sr., lead electronics technician with Pratt & Whitney Rocketdyne, and Janine Cuevas, a mechanical technician with PWR, perform final preparations on the space shuttle main engine tested Oct. 25, 2005, at NASA's Stennis Space Center. It was the first main engine test since Hurricane Katrina hit the Gulf Coast on Aug. 29.

Fast Movements, Slow Processes

ERIC Educational Resources Information Center

Jordan, Jay

2016-01-01

This semester, for the second time in the last couple of years, the author is leading a graduate seminar on histories of rhetoric. Little scholarship traces the development of multilingual composition in antiquity (with Brian Ray's article as a clear and excellent exception), so the author typically feels like students hit a rich but untapped…

Universal Hitting Time Statistics for Integrable Flows

NASA Astrophysics Data System (ADS)

Dettmann, Carl P.; Marklof, Jens; Strömbergsson, Andreas

2017-02-01

The perceived randomness in the time evolution of "chaotic" dynamical systems can be characterized by universal probabilistic limit laws, which do not depend on the fine features of the individual system. One important example is the Poisson law for the times at which a particle with random initial data hits a small set. This was proved in various settings for dynamical systems with strong mixing properties. The key result of the present study is that, despite the absence of mixing, the hitting times of integrable flows also satisfy universal limit laws which are, however, not Poisson. We describe the limit distributions for "generic" integrable flows and a natural class of target sets, and illustrate our findings with two examples: the dynamics in central force fields and ellipse billiards. The convergence of the hitting time process follows from a new equidistribution theorem in the space of lattices, which is of independent interest. Its proof exploits Ratner's measure classification theorem for unipotent flows, and extends earlier work of Elkies and McMullen.

A pulse shape discriminator and an online system for the balloon-borne hard X-ray/gamma-ray detector

NASA Astrophysics Data System (ADS)

Takahashi, T.; Kamae, T.; Tanaka, M.; Gunji, S.; Miyazuki, S.; Tamura, T.; Sekimoto, Y.; Yamaoka, N.; Nishimura, J.; Yajima, N.

Attention is given to a new kind of phoswich counters (the well-type phoswich counter) that will be capable of detecting very low flux hard X-rays/gamma-rays (40-1000 keV) from astronomical objects. A specially designed pulse-shape discriminator (PSD) selects hard X-rays/gamma-rays that has deposited energy only in the detection part. Sixty-four such counters are assembled into an array where each phoswich element acts as an active shield to the neighboring elements too. The ADCs, the TDCs, the hit-pattern latches, and the precision clock are read out by a VME-based online system, stored on an 8-mm video tape, and transmitted to the ground station. The design and performance of the pulse shape discriminator and the online system are described.

The importance of hydration thermodynamics in fragment-to-lead optimization.

PubMed

Ichihara, Osamu; Shimada, Yuzo; Yoshidome, Daisuke

2014-12-01

Using a computational approach to assess changes in solvation thermodynamics upon ligand binding, we investigated the effects of water molecules on the binding energetics of over 20 fragment hits and their corresponding optimized lead compounds. Binding activity and X-ray crystallographic data of published fragment-to-lead optimization studies from various therapeutically relevant targets were studied. The analysis reveals a distinct difference between the thermodynamic profile of water molecules displaced by fragment hits and those displaced by the corresponding optimized lead compounds. Specifically, fragment hits tend to displace water molecules with notably unfavorable excess entropies-configurationally constrained water molecules-relative to those displaced by the newly added moieties of the lead compound during the course of fragment-to-lead optimization. Herein we describe the details of this analysis with the goal of providing practical guidelines for exploiting thermodynamic signatures of binding site water molecules in the context of fragment-to-lead optimization. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Fragment-based hit discovery and structure-based optimization of aminotriazoloquinazolines as novel Hsp90 inhibitors.

PubMed

Casale, Elena; Amboldi, Nadia; Brasca, Maria Gabriella; Caronni, Dannica; Colombo, Nicoletta; Dalvit, Claudio; Felder, Eduard R; Fogliatto, Gianpaolo; Galvani, Arturo; Isacchi, Antonella; Polucci, Paolo; Riceputi, Laura; Sola, Francesco; Visco, Carlo; Zuccotto, Fabio; Casuscelli, Francesco

2014-08-01

In the last decade the heat shock protein 90 (Hsp90) has emerged as a major therapeutic target and many efforts have been dedicated to the discovery of Hsp90 inhibitors as new potent anticancer agents. Here we report the identification of a novel class of Hsp90 inhibitors by means of a biophysical FAXS-NMR based screening of a library of fragments. The use of X-ray structure information combined with modeling studies enabled the fragment evolution of the initial triazoloquinazoline hit to a class of compounds with nanomolar potency and drug-like properties suited for further lead optimization. Copyright © 2014 Elsevier Ltd. All rights reserved.

Inhibitors of acetyltransferase domain of N-acetylglucosamine-1-phosphate-uridyltransferase/glucosamine-1-phosphate-acetyltransferase (GlmU). Part 1: Hit to lead evaluation of a novel arylsulfonamide series.

PubMed

Green, Oluyinka M; McKenzie, Andrew R; Shapiro, Adam B; Otterbein, Ludovic; Ni, Haihong; Patten, Arthur; Stokes, Suzanne; Albert, Robert; Kawatkar, Sameer; Breed, Jason

2012-02-15

A novel arylsulfonamide-containing series of compounds represented by 1, discovered by highthroughput screening, inhibit the acetyltransferase domain of N-acetylglucosamine-1-phosphate-uridyltransferase/glucosamine-1-phosphate-acetyltransferase (GlmU). X-ray structure determination confirmed that inhibitor binds at the site occupied by acetyl-CoA, indicating that series is competitive with this substrate. This letter documents our early hit-to-lead evaluation of the chemical series and some of the findings that led to improvement in in-vitro potency against Gram-negative and Gram-positive bacterial isozymes, exemplified by compound 40. Copyright © 2012 Elsevier Ltd. All rights reserved.

Pile-up corrections in laser-driven pulsed X-ray sources

NASA Astrophysics Data System (ADS)

Hernández, G.; Fernández, F.

2018-06-01

A formalism for treating the pile-up produced in solid-state detectors by laser-driven pulsed X-ray sources has been developed. It allows the direct use of X-ray spectroscopy without artificially decreasing the number of counts in the detector, assuming the duration of a pulse is much shorter than the detector response time and the loss of counts from the energy window of the detector can be modeled or neglected. Experimental application shows that having a small amount of pile-up subsequently corrected improves the signal-to-noise ratio, which would be more beneficial than the strict single-hit condition usually imposed on this detectors.

The CERN-EU high-energy reference field (CERF) facility for dosimetry at commercial flight altitudes and in space.

PubMed

Mitaroff, A; Cern, M Silari

2002-01-01

A reference facility for the calibration and intercomparison of active and passive detectors in broad neutron fields has been available at CERN since 1992. A positively charged hadron beam (a mixture of protons and pions) with momentum of 120 GeV/c hits a copper target, 50 cm thick and 7 cm in diameter. The secondary particles produced in the interaction traverse a shield, at 90 degrees with respect to the direction of the incoming beam. made of either 80 to 160 cm of concrete or 40 cm of iron. Behind the iron shield, the resulting neutron spectrum has a maximum at about 1 MeV, with an additional high-energy component. Behind the 80 cm concrete shield, the neutron spectrum has a second pronounced maximum at about 70 MeV and resembles the high-energy component of the radiation field created by cosmic rays at commercial flight altitudes. This paper describes the facility, reports on the latest neutron spectral measurements, gives an overview of the most important experiments performed by the various collaborating institutions over recent years and briefly addresses the possible application of the facility to measurements related to the space programme.

Fragment-based drug discovery and molecular docking in drug design.

PubMed

Wang, Tao; Wu, Mian-Bin; Chen, Zheng-Jie; Chen, Hua; Lin, Jian-Ping; Yang, Li-Rong

2015-01-01

Fragment-based drug discovery (FBDD) has caused a revolution in the process of drug discovery and design, with many FBDD leads being developed into clinical trials or approved in the past few years. Compared with traditional high-throughput screening, it displays obvious advantages such as efficiently covering chemical space, achieving higher hit rates, and so forth. In this review, we focus on the most recent developments of FBDD for improving drug discovery, illustrating the process and the importance of FBDD. In particular, the computational strategies applied in the process of FBDD and molecular-docking programs are highlighted elaborately. In most cases, docking is used for predicting the ligand-receptor interaction modes and hit identification by structurebased virtual screening. The successful cases of typical significance and the hits identified most recently are discussed.

Snags hit tethered satellite mission

NASA Technical Reports Server (NTRS)

Schuiling, Roelof

1993-01-01

The processing and course of the STS-46 Space Shuttle Atlantis mission are described. Problems experienced by the astronaut team in deploying the Tethered Satellite System during the mission are recounted.

The Impact of the Geometrical Structure of the DNA on Parameters of the Track-Event Theory for Radiation Induced Cell Kill.

PubMed

Schneider, Uwe; Vasi, Fabiano; Besserer, Jürgen

2016-01-01

When fractionation schemes for hypofractionation and stereotactic body radiotherapy are considered, a reliable cell survival model at high dose is needed for calculating doses of similar biological effectiveness. An alternative to the LQ-model is the track-event theory which is based on the probabilities for one- and two two-track events. A one-track-event (OTE) is always represented by at least two simultaneous double strand breaks. A two-track-event (TTE) results in one double strand break. Therefore at least two two-track-events on the same or different chromosomes are necessary to produce an event which leads to cell sterilization. It is obvious that the probabilities of OTEs and TTEs must somehow depend on the geometrical structure of the chromatin. In terms of the track-event theory the ratio ε of the probabilities of OTEs and TTEs includes the geometrical dependence and is obtained in this work by simple Monte Carlo simulations. For this work it was assumed that the anchors of loop forming chromatin are most sensitive to radiation induced cell deaths. Therefore two adjacent tetranucleosomes representing the loop anchors were digitized. The probability ratio ε of OTEs and TTEs was factorized into a radiation quality dependent part and a geometrical part: ε = εion ∙ εgeo. εgeo was obtained for two situations, by applying Monte Carlo simulation for DNA on the tetranucleosomes itself and for linker DNA. Low energy electrons were represented by randomly distributed ionizations and high energy electrons by ionizations which were simulated on rays. εion was determined for electrons by using results from nanodosimetric measurements. The calculated ε was compared to the ε obtained from fits of the track event model to 42 sets of experimental human cell survival data. When the two tetranucleosomes are in direct contact and the hits are randomly distributed εgeo and ε are 0.12 and 0.85, respectively. When the hits are simulated on rays εgeo and ε are 0.10 and 0.71. For the linker-DNA εgeo and ε for randomly distributed hits are 0.010 and 0.073, and for hits on rays 0.0058 and 0.041, respectively. The calculated ε fits the experimentally obtained ε = 0.64±0.32 best for hits on the tetranucleosome when they are close to each other both, for high and low energy electrons. The parameter εgeo of the track event model was obtained by pure geometrical considerations of the chromatin structure and is 0.095 ± 0.022. It can be used as a fixed parameter in the track-event theory.

Fermi Large Area Telescope Observations of the Supernova Remnant GS.7-0.1

NASA Technical Reports Server (NTRS)

Ajello, M.; Allafort, A.; Baldini, L.; Ballet, J.; Barbiellini, G.; Bastieri, D.; Bechtol, K.; Bellazzini, R.; Berenji, B.; Blandford, R. D.;

Fermi Large Area Telescope Observations of the Supernova Remnant GS.7-0.1

NASA Technical Reports Server (NTRS)

Ferrara, E. C.; Hays, E.; Troja, E.; Moiseev, A. A.

2012-01-01

We present a detailed analysis of the GeV gamma-ray emission toward the supernova remnant (SNR) G8.7-0.1 with the Large Area Telescope (LAT) onboard the Fermi Gamma-ray Space Telescope. An investigation of the relationship among G8.7-0.1 and the TeV unidentified source HESS J1804-216 provides us with an important clue on diffusion process of cosmic rays if particle acceleration operates in the SNR. The GeV gamma-ray emission is extended with most of the emission in positional coincidence with the SNR G8.7-0.1 and a lesser part located outside the western boundary of G8.7-0.1. The region of the gamma-ray emission overlaps spatially-connected molecular clouds, implying a physical connection for the gamma-ray structure. The total gamma-ray spectrum measured with LAT from 200 MeV-100 GeV can be described by a broken power-law function with a break of 2.4 +/- 0.6 (stat) +/- 1.2 (sys) GeV, and photon indices of2.10 +/- 0.06 (stat) +/- 0.10 (sys) below the break and 2.70 +/- 0.12 (stat) +/- 0.14 (sys) above the break. Given the spatial association among the gamma rays, the radio emission ofG8.7-0.1, and the molecular clouds, the decay of pions produced by particles accelerated in the SNR and hitting the molecular clouds naturally explains the GeV gamma-ray spectrum. We also find that the GeV morphology is not well represented by the TeV emission from HESS Jl804-2l6 and that the spectrum in the Ge V band is not consistent with the extrapolation of the TeV gamma-ray spectrum. The spectral index of the TeV emission is consistent with the particle spectral index predicted by a theory that assumes energy-dependent diffusion of particles accelerated in an SNR. We discuss the possibility that the TeV-spectrum originates from the interaction of particles accelerated in G8.7-0.l with molecular clouds, and we constrain the diffusion coefficient of the particles.

Fermi Large Area Telescope Observations of the Supernova Remnant G8.7-0.1

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

Ajello, M.; Allafort, A.; /Stanford U., HEPL /KIPAC, Menlo Park /SLAC

We present a detailed analysis of the GeV gamma-ray emission toward the supernova remnant (SNR) G8.7-0.1 with the Large Area Telescope (LAT) on board the Fermi Gamma-ray Space Telescope. An investigation of the relationship between G8.7-0.1 and the TeV unidentified source HESS J1804-216 provides us with an important clue on diffusion process of cosmic rays if particle acceleration operates in the SNR. The GeV gamma-ray emission is extended with most of the emission in positional coincidence with the SNR G8.7-0.1 and a lesser part located outside the western boundary of G8.7-0.1. The region of the gamma-ray emission overlaps spatially connectedmore » molecular clouds, implying a physical connection for the gamma-ray structure. The total gamma-ray spectrum measured with LAT from 200 MeV-100 GeV can be described by a broken power-law function with a break of 2.4 {+-} 0.6 (stat) {+-} 1.2 (sys) GeV, and photon indices of 2.10 {+-} 0.06 (stat) {+-} 0.10 (sys) below the break and 2.70 {+-} 0.12 (stat) {+-} 0.14 (sys) above the break. Given the spatial association among the gamma rays, the radio emission of G8.7-0.1, and the molecular clouds, the decay of p0s produced by particles accelerated in the SNR and hitting the molecular clouds naturally explains the GeV gamma-ray spectrum. We also find that the GeV morphology is not well represented by the TeV emission from HESS J1804-216 and that the spectrum in the GeV band is not consistent with the extrapolation of the TeV gamma-ray spectrum. The spectral index of the TeV emission is consistent with the particle spectral index predicted by a theory that assumes energy-dependent diffusion of particles accelerated in an SNR. We discuss the possibility that the TeV spectrum originates from the interaction of particles accelerated in G8.7-0.1 with molecular clouds, and we constrain the diffusion coefficient of the particles.« less

The multiple roles of computational chemistry in fragment-based drug design

NASA Astrophysics Data System (ADS)

Law, Richard; Barker, Oliver; Barker, John J.; Hesterkamp, Thomas; Godemann, Robert; Andersen, Ole; Fryatt, Tara; Courtney, Steve; Hallett, Dave; Whittaker, Mark

2009-08-01

Fragment-based drug discovery (FBDD) represents a change in strategy from the screening of molecules with higher molecular weights and physical properties more akin to fully drug-like compounds, to the screening of smaller, less complex molecules. This is because it has been recognised that fragment hit molecules can be efficiently grown and optimised into leads, particularly after the binding mode to the target protein has been first determined by 3D structural elucidation, e.g. by NMR or X-ray crystallography. Several studies have shown that medicinal chemistry optimisation of an already drug-like hit or lead compound can result in a final compound with too high molecular weight and lipophilicity. The evolution of a lower molecular weight fragment hit therefore represents an attractive alternative approach to optimisation as it allows better control of compound properties. Computational chemistry can play an important role both prior to a fragment screen, in producing a target focussed fragment library, and post-screening in the evolution of a drug-like molecule from a fragment hit, both with and without the available fragment-target co-complex structure. We will review many of the current developments in the area and illustrate with some recent examples from successful FBDD discovery projects that we have conducted.

Discovery of covalent inhibitors for MIF tautomerase via cocrystal structures with phantom hits from virtual screening

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

McLean, Larry R.; Zhang, Ying; Li, Hua

Biochemical and X-ray crystallographic studies confirmed that hydroxyquinoline derivatives identified by virtual screening were actually covalent inhibitors of the MIF tautomerase. Adducts were formed by N-alkylation of the Pro-1 at the catalytic site with a loss of an amino group of the inhibitor.

Drug screening using model systems: some basics

PubMed Central

2016-01-01

ABSTRACT An increasing number of laboratories that focus on model systems are considering drug screening. Executing a drug screen is complicated enough. But the path for moving initial hits towards the clinic requires a different knowledge base and even a different mindset. In this Editorial I discuss the importance of doing some homework before you start screening. 'Lead hits', 'patentable chemical space' and 'druggability' are all concepts worth exploring when deciding which screening path to take. I discuss some of the lessons I learned that may be useful as you navigate the screening matrix. PMID:27821602

The in silico screening and X-ray structure analysis of the inhibitor complex of Plasmodium falciparum orotidine 5'-monophosphate decarboxylase.

PubMed

Takashima, Yasuhide; Mizohata, Eiichi; Krungkrai, Sudaratana R; Fukunishi, Yoshifumi; Kinoshita, Takayoshi; Sakata, Tsuneaki; Matsumura, Hiroyoshi; Krungkrai, Jerapan; Horii, Toshihiro; Inoue, Tsuyoshi

2012-08-01

Orotidine 5'-monophosphate decarboxylase from Plasmodium falciparum (PfOMPDC) catalyses the final step in the de novo synthesis of uridine 5'-monophosphate (UMP) from orotidine 5'-monophosphate (OMP). A defective PfOMPDC enzyme is lethal to the parasite. Novel in silico screening methods were performed to select 14 inhibitors against PfOMPDC, with a high hit rate of 9%. X-ray structure analysis of PfOMPDC in complex with one of the inhibitors, 4-(2-hydroxy-4-methoxyphenyl)-4-oxobutanoic acid, was carried out to at 2.1 Å resolution. The crystal structure revealed that the inhibitor molecule occupied a part of the active site that overlaps with the phosphate-binding region in the OMP- or UMP-bound complexes. Space occupied by the pyrimidine and ribose rings of OMP or UMP was not occupied by this inhibitor. The carboxyl group of the inhibitor caused a dramatic movement of the L1 and L2 loops that play a role in the recognition of the substrate and product molecules. Combining part of the inhibitor molecule with moieties of the pyrimidine and ribose rings of OMP and UMP represents a suitable avenue for further development of anti-malarial drugs.

Probability of cell hits in selected organs and tissues by high-LET particles at the ISS orbit

NASA Technical Reports Server (NTRS)

Yasuda, H.; Komiyama, T.; Fujitaka, K.; Badhwar, G. D. (Principal Investigator)

2002-01-01

The fluence of high-LET particles (HLP) with LET infinity H2O greater than 15 keV micrometers-1 in selected organs and tissues were measured with plastic nuclear track detectors using a life-size human phantom on the 9th Shuttle-Mir Mission (STS-91). The planar-track fluence of HLP during the 9.8-day mission ranged from 1.9 x 10(3) n cm-2 (bladder) to 5.1 x 10(3) n cm-2 (brain) by a factor of 2.7. Based on these data, a probability of HLP hits to a matured cell of each organ or tissue was roughly estimated for a 90-day ISS mission. In the calculation, all cells were assumed to be spheres with a geometric cross-sectional area of 500 micrometers2 and the cell-hit frequency from isotropic space radiation can be described by the Poisson-distribution function. As results, the probability of one or more than 1 hit to a single cell by HLP for 90 days ranged from 17% to 38%; that of two or more than 2 hits was estimated to be 1.3-8.2%. c2002 COSPAR. Published by Elsevier Science Ltd. All rights reserved.

Three-dimensional impact angle constrained distributed guidance law design for cooperative attacks.

PubMed

Wang, Xianghua; Lu, Xiao

2018-02-01

In this paper, a novel cooperative guidance law is proposed to make multiple missiles in the three-dimensional (3-D) space hit simultaneously the same target at pre-specified impact angles. Firstly, the normal accelerations which change the velocity direction (flight-path and heading angle) are designed such that all missiles will fly along the desired line of sight (LOS) after a given time which ensures the hit-to-kill interception at the desired impact angles; then the consensus variable is constructed using available information and can reach consensus under the proposed tangential acceleration which determines the velocity magnitude. Hence simultaneous hit-to-kill attack is achieved. Finally, some simulation studies are performed to verify the effectiveness of the proposed scheme. Copyright © 2017 ISA. Published by Elsevier Ltd. All rights reserved.

Space Junk Norms: US Advantages in Creating a Debris Reducing Outer Space Norm

DTIC Science & Technology

2011-05-01

and White Knight ,” http://www.scaled.com/projects/tierone/ (accessed 25 March 2011). 26 Mike Moore argues that the nearest global competitor to the...formation of norms. 27 For an explanation of the US 2008 ASAT test, see Jamie McIntyre...the Space Age. Baltimore: Johns Hopkins University Press, 1997. McIntyre, Jamie , Suzanne Malveaux and Miles O’Brien. “Navy Missile Hits Dying Spy

Comprehensive Mechanistic Analysis of Hits from High-Throughput and Docking Screens against β-Lactamase

PubMed Central

Babaoglu, Kerim; Simeonov, Anton; Irwin, John J.; Nelson, Michael E.; Feng, Brian; Thomas, Craig J.; Cancian, Laura; Costi, M. Paola; Maltby, David A.; Jadhav, Ajit; Inglese, James; Austin, Christopher P.; Shoichet, Brian K.

2009-01-01

High-throughput screening (HTS) is widely used in drug discovery. Especially for screens of unbiased libraries, false positives can dominate “hit lists”; their origins are much debated. Here we determine the mechanism of every active hit from a screen of 70,563 unbiased molecules against β-lactamase using quantitative HTS (qHTS). Of the 1274 initial inhibitors, 95% were detergent-sensitive and were classified as aggregators. Among the 70 remaining were 25 potent, covalent-acting β-lactams. Mass spectra, counter-screens, and crystallography identified 12 as promiscuous covalent inhibitors. The remaining 33 were either aggregators or irreproducible. No specific reversible inhibitors were found. We turned to molecular docking to prioritize molecules from the same library for testing at higher concentrations. Of 16 tested, 2 were modest inhibitors. Subsequent X-ray structures corresponded to the docking prediction. Analog synthesis improved affinity to 8 µM. These results suggest that it may be the physical behavior of organic molecules, not their reactivity, that accounts for most screening artifacts. Structure-based methods may prioritize weak-but-novel chemotypes in unbiased library screens. PMID:18333608

Anatomy of a cosmic-ray neutrino source and the Cygnus X-3 system

NASA Technical Reports Server (NTRS)

Stecker, F. W.; Harding, A. K.; Barnard, J. J.

1985-01-01

The effects of an intense beam of ultra-high energy cosmic rays from a compact object in the Cygnus X-3 binary system hitting the companion star, and of the subsequent production of secondary neutrinos, are examined. A maximum allowable beam luminosity of about 10 to the 42nd erg/s is found for a system containing a 1-10 solar mass main sequence target star. The proton beam must heat a relatively small area of the target star to satisfy observational constraints on the resulting stellar wind. With such a model, the neutrino to gamma-ray flux ratio of about 1000 can result from a combination of gamma-ray absorption and a large neutrino to gamma-ray duty cycle ratio. It is found that the high density of the atmosphere resulting from compression by the beam leads to pion cascading and a neutrino spectrum peaking at 1-10 GeV energies.

Free Speech in a MySpace World

ERIC Educational Resources Information Center

Baule, Steven M.; Kriha, Darcy L.

2008-01-01

In the potential shadow of a "Bong Hits for Jesus" banner, complicated student speech and discipline issues arise almost daily on the Internet. Whether it is a mock MySpace page set up to make fun of a teacher or a direct threat to an assistant principal, it is often unclear exactly where school ground discipline ends and student free speech…

Imagining the Future of the School Library. [Interview with Doug Johnson and Rolf Erikson

ERIC Educational Resources Information Center

DesignShare (NJ1), 2006

2006-01-01

For many, the library is the literal information bridge to the future. Organizations dedicate themselves to building and re-imagining school library spaces around the world by filling shelves with books and making library spaces relevant for our youngest readers. At the same time, with a fast-moving revolution of technology hitting campuses around…

JWST Program Implementation

NASA Astrophysics Data System (ADS)

Januszewski, William

2018-01-01

This poster will feature what is involved in preparing a James Webb Space Telescope program for execution on board the spacecraft. The process from when the principle investigator hits the submit button to when the observations are executed on board the spacecraft will be addressed. Although the process shares a number of sumilarities with the implementation process for the Hubble Space Telescope, there are significant differences.

Selection, application, and validation of a set of molecular descriptors for nuclear receptor ligands.

PubMed

Stewart, Eugene L; Brown, Peter J; Bentley, James A; Willson, Timothy M

2004-08-01

A methodology for the selection and validation of nuclear receptor ligand chemical descriptors is described. After descriptors for a targeted chemical space were selected, a virtual screening methodology utilizing this space was formulated for the identification of potential NR ligands from our corporate collection. Using simple descriptors and our virtual screening method, we are able to quickly identify potential NR ligands from a large collection of compounds. As validation of the virtual screening procedure, an 8, 000-membered NR targeted set and a 24, 000-membered diverse control set of compounds were selected from our in-house general screening collection and screened in parallel across a number of orphan NR FRET assays. For the two assays that provided at least one hit per set by the established minimum pEC(50) for activity, the results showed a 2-fold increase in the hit-rate of the targeted compound set over the diverse set.

Fine pattern replication on 10 x 10-mm exposure area using ETS-1 laboratory tool in HIT

NASA Astrophysics Data System (ADS)

Hamamoto, K.; Watanabe, Takeo; Hada, Hideo; Komano, Hiroshi; Kishimura, Shinji; Okazaki, Shinji; Kinoshita, Hiroo

2002-07-01

Utilizing ETS-1 laboratory tool in Himeji Institute of Technology (HIT), as for the fine pattern replicated by using the Cr mask in static exposure, it is replicated in the exposure area of 10 mm by 2 mm in size that the line and space pattern width of 60 nm, the isolated line pattern width of 40 nm, and hole pattern width of 150 nm. According to the synchronous scanning of the mass and wafer with EUVL laboratory tool with reduction optical system which consisted of three-aspherical-mirror in the NewSUBARU facilities succeeded in the line of 60 nm and the space pattern formation in the exposure region of 10mm by 10mm. From the result of exposure characteristics for positive- tone resist for KrF and EB, KrF chemically amplified resist has better characteristics than EB chemically amplified resist.

Toward Millions of File System IOPS on Low-Cost, Commodity Hardware

PubMed Central

Zheng, Da; Burns, Randal; Szalay, Alexander S.

2013-01-01

We describe a storage system that removes I/O bottlenecks to achieve more than one million IOPS based on a user-space file abstraction for arrays of commodity SSDs. The file abstraction refactors I/O scheduling and placement for extreme parallelism and non-uniform memory and I/O. The system includes a set-associative, parallel page cache in the user space. We redesign page caching to eliminate CPU overhead and lock-contention in non-uniform memory architecture machines. We evaluate our design on a 32 core NUMA machine with four, eight-core processors. Experiments show that our design delivers 1.23 million 512-byte read IOPS. The page cache realizes the scalable IOPS of Linux asynchronous I/O (AIO) and increases user-perceived I/O performance linearly with cache hit rates. The parallel, set-associative cache matches the cache hit rates of the global Linux page cache under real workloads. PMID:24402052

Toward Millions of File System IOPS on Low-Cost, Commodity Hardware.

PubMed

Zheng, Da; Burns, Randal; Szalay, Alexander S

2013-01-01

We describe a storage system that removes I/O bottlenecks to achieve more than one million IOPS based on a user-space file abstraction for arrays of commodity SSDs. The file abstraction refactors I/O scheduling and placement for extreme parallelism and non-uniform memory and I/O. The system includes a set-associative, parallel page cache in the user space. We redesign page caching to eliminate CPU overhead and lock-contention in non-uniform memory architecture machines. We evaluate our design on a 32 core NUMA machine with four, eight-core processors. Experiments show that our design delivers 1.23 million 512-byte read IOPS. The page cache realizes the scalable IOPS of Linux asynchronous I/O (AIO) and increases user-perceived I/O performance linearly with cache hit rates. The parallel, set-associative cache matches the cache hit rates of the global Linux page cache under real workloads.

Mass spectrometry for fragment screening.

PubMed

Chan, Daniel Shiu-Hin; Whitehouse, Andrew J; Coyne, Anthony G; Abell, Chris

2017-11-08

Fragment-based approaches in chemical biology and drug discovery have been widely adopted worldwide in both academia and industry. Fragment hits tend to interact weakly with their targets, necessitating the use of sensitive biophysical techniques to detect their binding. Common fragment screening techniques include differential scanning fluorimetry (DSF) and ligand-observed NMR. Validation and characterization of hits is usually performed using a combination of protein-observed NMR, isothermal titration calorimetry (ITC) and X-ray crystallography. In this context, MS is a relatively underutilized technique in fragment screening for drug discovery. MS-based techniques have the advantage of high sensitivity, low sample consumption and being label-free. This review highlights recent examples of the emerging use of MS-based techniques in fragment screening. © 2017 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society.

Discovery of Potent Non-Nucleoside Inhibitors of Dengue Viral RNA-Dependent RNA Polymerase from a Fragment Hit Using Structure-Based Drug Design.

PubMed

Yokokawa, Fumiaki; Nilar, Shahul; Noble, Christian G; Lim, Siew Pheng; Rao, Ranga; Tania, Stefani; Wang, Gang; Lee, Gladys; Hunziker, Jürg; Karuna, Ratna; Manjunatha, Ujjini; Shi, Pei-Yong; Smith, Paul W

2016-04-28

The discovery and optimization of non-nucleoside dengue viral RNA-dependent-RNA polymerase (RdRp) inhibitors are described. An X-ray-based fragment screen of Novartis' fragment collection resulted in the identification of a biphenyl acetic acid fragment 3, which bound in the palm subdomain of RdRp. Subsequent optimization of the fragment hit 3, relying on structure-based design, resulted in a >1000-fold improvement in potency in vitro and acquired antidengue activity against all four serotypes with low micromolar EC50 in cell-based assays. The lead candidate 27 interacts with a novel binding pocket in the palm subdomain of the RdRp and exerts a promising activity against all clinically relevant dengue serotypes.

Issues for Simulation of Galactic Cosmic Ray Exposures for Radiobiological Research at Ground-Based Accelerators

PubMed Central

Kim, Myung-Hee Y.; Rusek, Adam; Cucinotta, Francis A.

2015-01-01

For radiobiology research on the health risks of galactic cosmic rays (GCR) ground-based accelerators have been used with mono-energetic beams of single high charge, Z and energy, E (HZE) particles. In this paper, we consider the pros and cons of a GCR reference field at a particle accelerator. At the NASA Space Radiation Laboratory (NSRL), we have proposed a GCR simulator, which implements a new rapid switching mode and higher energy beam extraction to 1.5 GeV/u, in order to integrate multiple ions into a single simulation within hours or longer for chronic exposures. After considering the GCR environment and energy limitations of NSRL, we performed extensive simulation studies using the stochastic transport code, GERMcode (GCR Event Risk Model) to define a GCR reference field using 9 HZE particle beam–energy combinations each with a unique absorber thickness to provide fragmentation and 10 or more energies of proton and 4He beams. The reference field is shown to well represent the charge dependence of GCR dose in several energy bins behind shielding compared to a simulated GCR environment. However, a more significant challenge for space radiobiology research is to consider chronic GCR exposure of up to 3 years in relation to simulations with animal models of human risks. We discuss issues in approaches to map important biological time scales in experimental models using ground-based simulation, with extended exposure of up to a few weeks using chronic or fractionation exposures. A kinetics model of HZE particle hit probabilities suggests that experimental simulations of several weeks will be needed to avoid high fluence rate artifacts, which places limitations on the experiments to be performed. Ultimately risk estimates are limited by theoretical understanding, and focus on improving knowledge of mechanisms and development of experimental models to improve this understanding should remain the highest priority for space radiobiology research. PMID:26090339

GERMcode: A Stochastic Model for Space Radiation Risk Assessment

NASA Technical Reports Server (NTRS)

Kim, Myung-Hee Y.; Ponomarev, Artem L.; Cucinotta, Francis A.

2012-01-01

A new computer model, the GCR Event-based Risk Model code (GERMcode), was developed to describe biophysical events from high-energy protons and high charge and energy (HZE) particles that have been studied at the NASA Space Radiation Laboratory (NSRL) for the purpose of simulating space radiation biological effects. In the GERMcode, the biophysical description of the passage of HZE particles in tissue and shielding materials is made with a stochastic approach that includes both particle track structure and nuclear interactions. The GERMcode accounts for the major nuclear interaction processes of importance for describing heavy ion beams, including nuclear fragmentation, elastic scattering, and knockout-cascade processes by using the quantum multiple scattering fragmentation (QMSFRG) model. The QMSFRG model has been shown to be in excellent agreement with available experimental data for nuclear fragmentation cross sections. For NSRL applications, the GERMcode evaluates a set of biophysical properties, such as the Poisson distribution of particles or delta-ray hits for a given cellular area and particle dose, the radial dose on tissue, and the frequency distribution of energy deposition in a DNA volume. By utilizing the ProE/Fishbowl ray-tracing analysis, the GERMcode will be used as a bi-directional radiation transport model for future spacecraft shielding analysis in support of Mars mission risk assessments. Recent radiobiological experiments suggest the need for new approaches to risk assessment that include time-dependent biological events due to the signaling times for activation and relaxation of biological processes in cells and tissue. Thus, the tracking of the temporal and spatial distribution of events in tissue is a major goal of the GERMcode in support of the simulation of biological processes important in GCR risk assessments. In order to validate our approach, basic radiobiological responses such as cell survival curves, mutation, chromosomal aberrations, and representative mouse tumor induction curves are implemented into the GERMcode. Extension of these descriptions to other endpoints related to non-targeted effects and biochemical pathway responses will be discussed.

Synthesis and SAR of piperazine amides as novel c-jun N-terminal kinase (JNK) inhibitors

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

Shin, Youseung; Chen, Weiming; Habel, Jeff

2009-09-14

A novel series of c-jun N-terminal kinase (JNK) inhibitors were designed and developed from a high-throughput-screening hit. Through the optimization of the piperazine amide 1, several potent compounds were discovered. The X-ray crystal structure of 4g showed a unique binding mode different from other well known JNK3 inhibitors.

X-rays from superbubbles in the Large Magellanic Cloud

NASA Technical Reports Server (NTRS)

Chu, You-Hua; Mac Low, Mordecai-Marc

1990-01-01

Diffuse X-ray emission not associated with known supernova remnants (SNRs) are found in seven Large Magellanic Cloud H II complexes encompassing 10 OB associations: N44, N51D, N57A, N70, N154, N157 (30 Dor), and N158. Their X-ray luminosities range from 7 x 10 to the 34th ergs/s in N57A to 7 x 10 to the 36th ergs/s in 30 Dor. All, except 30 Dor, have simple ring morphologies, indicating shell structures. Modeling these as superbubbles, it is found that the X-ray luminosities expected from their hot interiors fall an order of magnitude below the observed values. SNRs close to the center of a superbubble add very little emission, but it is calculated that off-center SNRs hitting the ionized shell could explain the observed emission.

A compressed sensing X-ray camera with a multilayer architecture

NASA Astrophysics Data System (ADS)

Wang, Zhehui; Iaroshenko, O.; Li, S.; Liu, T.; Parab, N.; Chen, W. W.; Chu, P.; Kenyon, G. T.; Lipton, R.; Sun, K.-X.

2018-01-01

Recent advances in compressed sensing theory and algorithms offer new possibilities for high-speed X-ray camera design. In many CMOS cameras, each pixel has an independent on-board circuit that includes an amplifier, noise rejection, signal shaper, an analog-to-digital converter (ADC), and optional in-pixel storage. When X-ray images are sparse, i.e., when one of the following cases is true: (a.) The number of pixels with true X-ray hits is much smaller than the total number of pixels; (b.) The X-ray information is redundant; or (c.) Some prior knowledge about the X-ray images exists, sparse sampling may be allowed. Here we first illustrate the feasibility of random on-board pixel sampling (ROPS) using an existing set of X-ray images, followed by a discussion about signal to noise as a function of pixel size. Next, we describe a possible circuit architecture to achieve random pixel access and in-pixel storage. The combination of a multilayer architecture, sparse on-chip sampling, and computational image techniques, is expected to facilitate the development and applications of high-speed X-ray camera technology.

Hands in space: gesture interaction with augmented-reality interfaces.

PubMed

Billinghurst, Mark; Piumsomboon, Tham; Huidong Bai

2014-01-01

Researchers at the Human Interface Technology Laboratory New Zealand (HIT Lab NZ) are investigating free-hand gestures for natural interaction with augmented-reality interfaces. They've applied the results to systems for desktop computers and mobile devices.

KSC-04pd1770

NASA Image and Video Library

2004-09-10

KENNEDY SPACE CENTER, FLA. - Members of a hurricane assessment team from Johnson Space Center and Marshall Space Flight Center tour the Thermal Protection System (TPS) Facility at KSC after Hurricane Frances hit the east coast of Central Florida and Kennedy Space Center. At left is Martin Wilson, manager of the TPS operations. The facility, which creates the TPS tiles, blankets and all the internal thermal control systems for the Space Shuttles, is almost totally unserviceable at this time after losing approximately 35 percent of its roof. Equipment and materials that survived the storm have been relocated to the RLV hangar near the KSC Shuttle Landing Facility.

KSC-04pd1774

NASA Image and Video Library

2004-09-10

KENNEDY SPACE CENTER, FLA. - Members of a hurricane assessment team from Johnson Space Center and Marshall Space Flight Center observe the damage to the roof of the Thermal Protection System (TPS) Facility at KSC after Hurricane Frances hit the east coast of Central Florida and Kennedy Space Center. The facility, which creates the TPS tiles, blankets and all the internal thermal control systems for the Space Shuttles, is almost totally unserviceable at this time after losing approximately 35 percent of its roof. Equipment and materials that survived the storm have been relocated to the RLV hangar near the KSC Shuttle Landing Facility.

Quantum algorithms for Gibbs sampling and hitting-time estimation

DOE PAGES

Chowdhury, Anirban Narayan; Somma, Rolando D.

2017-02-01

In this paper, we present quantum algorithms for solving two problems regarding stochastic processes. The first algorithm prepares the thermal Gibbs state of a quantum system and runs in time almost linear in √Nβ/Ζ and polynomial in log(1/ϵ), where N is the Hilbert space dimension, β is the inverse temperature, Ζ is the partition function, and ϵ is the desired precision of the output state. Our quantum algorithm exponentially improves the dependence on 1/ϵ and quadratically improves the dependence on β of known quantum algorithms for this problem. The second algorithm estimates the hitting time of a Markov chain. Formore » a sparse stochastic matrix Ρ, it runs in time almost linear in 1/(ϵΔ 3/2), where ϵ is the absolute precision in the estimation and Δ is a parameter determined by Ρ, and whose inverse is an upper bound of the hitting time. Our quantum algorithm quadratically improves the dependence on 1/ϵ and 1/Δ of the analog classical algorithm for hitting-time estimation. Finally, both algorithms use tools recently developed in the context of Hamiltonian simulation, spectral gap amplification, and solving linear systems of equations.« less

Radiation leukemogenesis in mice: loss of PU.1 on chromosome 2 in CBA and C57BL/6 mice after irradiation with 1 GeV/nucleon 56Fe ions, X rays or gamma rays. Part I. Experimental observations.

PubMed

Peng, Yuanlin; Brown, Natalie; Finnon, Rosemary; Warner, Christy L; Liu, Xianan; Genik, Paula C; Callan, Matthew A; Ray, F Andrew; Borak, Thomas B; Badie, Christophe; Bouffler, Simon D; Ullrich, Robert L; Bedford, Joel S; Weil, Michael M

2009-04-01

Since deletion of the PU.1 gene on chromosome 2 is a crucial acute myeloid leukemia (AML) initiating step in the mouse model, we quantified PU.1 deleted cells in the bone marrow of gamma-, X- and 56Fe-ion-irradiated mice at various times postirradiation. Although 56Fe ions were initially some two to three times more effective than X or gamma rays in inducing PU.1 deletions, by 1 month postirradiation, the proportions of cells with PU.1 deletions were similar for the HZE particles and the sparsely ionizing radiations. These results indicate that while 56Fe ions are more effective in inducing PU.1 deletions, they are also more effective in causing collateral damage that removes hit cells from the bone marrow. After X, gamma or 56Fe-ion irradiation, AML-resistant C57BL/6 mice have fewer cells with PU.1 deletions than CBA mice, and those cells do not persist in the bone marrow of the C57B6/6 mice. Our findings suggest that quantification of PU.1 deleted bone marrow cells 1 month postirradiation can be used as surrogate for the incidence of radiation-induced AML measured in large-scale mouse studies. If so, PU.1 loss could be used to systematically assess the potential leukemogenic effects of other ions and energies in the space radiation environment.

FERMI LARGE AREA TELESCOPE OBSERVATIONS OF THE SUPERNOVA REMNANT G8.7-0.1

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

Ajello, M.; Allafort, A.; Bechtol, K.

We present a detailed analysis of the GeV gamma-ray emission toward the supernova remnant (SNR) G8.7-0.1 with the Large Area Telescope (LAT) on board the Fermi Gamma-ray Space Telescope. An investigation of the relationship between G8.7-0.1 and the TeV unidentified source HESS J1804-216 provides us with an important clue on diffusion process of cosmic rays if particle acceleration operates in the SNR. The GeV gamma-ray emission is extended with most of the emission in positional coincidence with the SNR G8.7-0.1 and a lesser part located outside the western boundary of G8.7-0.1. The region of the gamma-ray emission overlaps spatially connectedmore » molecular clouds, implying a physical connection for the gamma-ray structure. The total gamma-ray spectrum measured with LAT from 200 MeV-100 GeV can be described by a broken power-law function with a break of 2.4 {+-} 0.6 (stat) {+-} 1.2 (sys) GeV, and photon indices of 2.10 {+-} 0.06 (stat) {+-} 0.10 (sys) below the break and 2.70 {+-} 0.12 (stat) {+-} 0.14 (sys) above the break. Given the spatial association among the gamma rays, the radio emission of G8.7-0.1, and the molecular clouds, the decay of {pi}{sup 0}s produced by particles accelerated in the SNR and hitting the molecular clouds naturally explains the GeV gamma-ray spectrum. We also find that the GeV morphology is not well represented by the TeV emission from HESS J1804-216 and that the spectrum in the GeV band is not consistent with the extrapolation of the TeV gamma-ray spectrum. The spectral index of the TeV emission is consistent with the particle spectral index predicted by a theory that assumes energy-dependent diffusion of particles accelerated in an SNR. We discuss the possibility that the TeV spectrum originates from the interaction of particles accelerated in G8.7-0.1 with molecular clouds, and we constrain the diffusion coefficient of the particles.« less

Opticks : GPU Optical Photon Simulation for Particle Physics using NVIDIA® OptiX™

NASA Astrophysics Data System (ADS)

C, Blyth Simon

2017-10-01

Opticks is an open source project that integrates the NVIDIA OptiX GPU ray tracing engine with Geant4 toolkit based simulations. Massive parallelism brings drastic performance improvements with optical photon simulation speedup expected to exceed 1000 times Geant4 when using workstation GPUs. Optical photon simulation time becomes effectively zero compared to the rest of the simulation. Optical photons from scintillation and Cherenkov processes are allocated, generated and propagated entirely on the GPU, minimizing transfer overheads and allowing CPU memory usage to be restricted to optical photons that hit photomultiplier tubes or other photon detectors. Collecting hits into standard Geant4 hit collections then allows the rest of the simulation chain to proceed unmodified. Optical physics processes of scattering, absorption, scintillator reemission and boundary processes are implemented in CUDA OptiX programs based on the Geant4 implementations. Wavelength dependent material and surface properties as well as inverse cumulative distribution functions for reemission are interleaved into GPU textures providing fast interpolated property lookup or wavelength generation. Geometry is provided to OptiX in the form of CUDA programs that return bounding boxes for each primitive and ray geometry intersection positions. Some critical parts of the geometry such as photomultiplier tubes have been implemented analytically with the remainder being tessellated. OptiX handles the creation and application of a choice of acceleration structures such as boundary volume hierarchies and the transparent use of multiple GPUs. OptiX supports interoperation with OpenGL and CUDA Thrust that has enabled unprecedented visualisations of photon propagations to be developed using OpenGL geometry shaders to provide interactive time scrubbing and CUDA Thrust photon indexing to enable interactive history selection.

Cell inactivation, repair and mutation induction in bacteria after heavy ion exposure: results from experiments at accelerators and in space.

PubMed

Horneck, G; Schafer, M; Baltschukat, K; Weisbrod, U; Micke, U; Facius, R; Bucker, H

1989-01-01

To understand the mechanisms of accelerated heavy ions on biological matter, the responses of spores of B. subtilis to this structured high LET radiation was investigated applying two different approaches. 1) By the use of the Biostack concept, the inactivation probability as a function of radial distance to single particles' trajectory (i.e. impact parameter) was determined in space experiments as well as at accelerators using low fluences of heavy ions. It was found that spores can survive even a central hit and that the effective range of inactivation extends far beyond impact parameters where inactivation by delta-ray dose would be effective. Concerning the space experiment, the inactivation cross section exceeds those from comparable accelerator experiments by roughly a factor of 20. 2) From fluence effect curves, cross sections for inactivation and mutation induction, and the efficiency of repair processes were determined. They are influenced by the ions characteristics in a complex manner. According to dependence on LET, at least 3 LET ranges can be differentiated: A low LET range (app. < 200 keV/micrometers), where cross sections for inactivation and mutation induction follow a common curve for different ions and where repair processes are effective; an intermediate LET range of the so-called saturation cross section with negligible mutagenic and repair efficiency; and a high LET range (>1000 keV/micrometers) where the biological endpoints are majorly dependent on atomic mass and energy of the ion under consideration.

#MaybeHeDoesntHitYou: Social Media Underscore the Realities of Intimate Partner Violence.

PubMed

McCauley, Heather L; Bonomi, Amy E; Maas, Megan K; Bogen, Katherine W; O'Malley, Teagen L

2018-03-22

Public intimate partner violence (IPV) discourse emphasizes physical violence. In May 2016, the Twitter hashtag #MaybeHeDoesntHitYou generated a public conversation about abuse beyond physical IPV. Because of the often-disconnect between IPV research and what survivors struggle to name as abuse in their daily lives, we sought to understand how IPV discourse was unfolding as a result of the #MaybeHeDoesntHitYou hashtag. NCapture was used to collect publically available Twitter data containing the hashtag "#MaybeHeDoesntHitYou" from May 10, 2016 to May 17, 2016. Using the Duluth Power and Control Wheel (a range of tactics used by abusers to control and harm their partners) and the Women's Experience with Battering (WEB) framework (emotional and behavioral responses to being abused), we analyzed 1,229 original content tweets using qualitative content analysis. All dimensions of the Power and Control Wheel and five of six dimensions of the WEB framework were expressed via #MaybeHeDoesntHitYou; users did not express yearning for intimacy with their abusive partners. Users described one form of IPV not currently represented within the Power and Control Wheel-reproductive coercion (e.g., "#MaybeHeDoesntHitYou but he refuses to use condoms and forces you not to use contraception so you try to do it behind his back"). Two additional themes emerged; users challenged the gender pronoun of the hashtag, highlighting that abuse may happen with partners of all genders, and users provided social support for others (e.g., "#MaybeHeDoesntHitYou is real. Bruises and scars aren't the only measure of abuse! If this is you, help is there…"). Results from our study underscore the potential for social media platforms to be powerful agents for engaging public dialogue about the realities of IPV, as well as a space for seeking and providing social support about this critical women's health issue.

29 CFR 1917.152 - Welding, cutting and heating (hot work) 12 (See also § 1917.2, definition of Hazardous cargo...

Code of Federal Regulations, 2011 CFR

2011-07-01

... bars or by hitting the valve with a tool; (ix) Shall not be thawed by boiling water; (x) Shall not be... provide electrical contact. Exposed metal parts shall be insulated. (3) Ground returns and machine... the vicinity from the direct rays and sparks of the arc. (ii) Employees in areas not protected from...

The Mistaken Birth and Adoption of LNT: An Abridged Version

PubMed Central

Calabrese, Edward J.

2017-01-01

The historical foundations of cancer risk assessment were based on the discovery of X-ray-induced gene mutations by Hermann J. Muller, its transformation into the linear nonthreshold (LNT) single-hit theory, the recommendation of the model by the US National Academy of Sciences, Biological Effects of Atomic Radiation I, Genetics Panel in 1956, and subsequent widespread adoption by regulatory agencies worldwide. This article summarizes substantial recent historical revelations of this history, which profoundly challenge the standard and widely acceptable history of cancer risk assessment, showing multiple significant scientific errors and incorrect interpretations, mixed with deliberate misrepresentation of the scientific record by leading ideologically motivated radiation geneticists. These novel historical findings demonstrate that the scientific foundations of the LNT single-hit model were seriously flawed and should not have been adopted for cancer risk assessment. PMID:29051718

Bioturbo similarity searching: combining chemical and biological similarity to discover structurally diverse bioactive molecules.

PubMed

Wassermann, Anne Mai; Lounkine, Eugen; Glick, Meir

2013-03-25

Virtual screening using bioactivity profiles has become an integral part of currently applied hit finding methods in pharmaceutical industry. However, a significant drawback of this approach is that it is only applicable to compounds that have been biologically tested in the past and have sufficient activity annotations for meaningful profile comparisons. Although bioactivity data generated in pharmaceutical institutions are growing on an unprecedented scale, the number of biologically annotated compounds still covers only a minuscule fraction of chemical space. For a newly synthesized compound or an isolated natural product to be biologically characterized across multiple assays, it may take a considerable amount of time. Consequently, this chemical matter will not be included in virtual screening campaigns based on bioactivity profiles. To overcome this problem, we herein introduce bioturbo similarity searching that uses chemical similarity to map molecules without biological annotations into bioactivity space and then searches for biologically similar compounds in this reference system. In benchmark calculations on primary screening data, we demonstrate that our approach generally achieves higher hit rates and identifies structurally more diverse compounds than approaches using chemical information only. Furthermore, our method is able to discover hits with novel modes of inhibition that traditional 2D and 3D similarity approaches are unlikely to discover. Test calculations on a set of natural products reveal the practical utility of the approach for identifying novel and synthetically more accessible chemical matter.

Construction of Gallium Arsenide Solar Concentrator for Space Use.

DTIC Science & Technology

1988-03-01

electrical current from absorbed sunlight. This can only happen if the sun- light hits an electron in the valence band with enough energy to cause an... impact on its design. There are four different environments that the SCA will encounter during its lifetime, namely, terrestrial, launch, space, and...solutions are not 100 percent effective. Solder becomes porous during temperature cycling, and the adhesive absorbs water during the curing process. The

Arts: Hot tickets 2017

NASA Astrophysics Data System (ADS)

Jones, Nicola

2017-01-01

Robots, DNA and electricity bask in the limelight, as Blade Runner reboots, Kazakhstan gets energetic and a 'space tapestry' rolls out. It's quite a year -- and key anniversaries hit, too, for Canada, the anthropology dynamo the Peabody Museum and architect Frank Lloyd Wright. Nicola Jones reports.

Sensitivity to. gamma. rays of avian sarcoma and murine leukemia viruses. [/sup 60/Co, uv

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

Toyoshima, K.; Niwa, O.; Yutsudo, M.

1980-09-01

The direct inactivation of avian and murine oncoviruses by ..gamma.. rays was examined using /sup 60/Co as a ..gamma..-ray source. The inactivation of murine leukemia virus (M-MuLV) followed single-hit kinetics while the subgroup D Schmidt-Ruppin strain of avian sarcoma virus (SR-RSV D) showed multihit inactivation kinetics with an extrapolation number of 5. The two viruses showed similar uv-inactivation kinetics. The genomic RNA of the SR-RSV D strain was degraded by ..gamma.. irradiation faster than its infectivity, but viral clones isolated from the foci formed after ..gamma.. irradiation had a complete genome. These results suggest that SR-RSV D has a strongmore » repair function, possibly connected with reverse transcriptase activity.« less

Neutrinos from cosmic ray interactions in the Sun

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

Edsjö, J.; Elevant, J.; Niblaeus, C.

Cosmic rays hitting the solar atmosphere generate neutrinos that interact and oscillate in the Sun and oscillate on the way to Earth. These neutrinos could potentially be detected with neutrino telescopes and will be a background for searches for neutrinos from dark matter annihilation in the Sun. We calculate the flux of neutrinos from these cosmic ray interactions in the Sun and also investigate the interactions near a detector on Earth that give rise to muons. We compare this background with both regular Earth-atmospheric neutrinos and signals from dark matter annihilation in the Sun. Our calculation is performed with anmore » event-based Monte Carlo approach that should be suitable as a simulation tool for experimental collaborations. Our program package is released publicly along with this paper.« less

Characterization of x-ray framing cameras for the National Ignition Facility using single photon pulse height analysis.

PubMed

Holder, J P; Benedetti, L R; Bradley, D K

2016-11-01

Single hit pulse height analysis is applied to National Ignition Facility x-ray framing cameras to quantify gain and gain variation in a single micro-channel plate-based instrument. This method allows the separation of gain from detectability in these photon-detecting devices. While pulse heights measured by standard-DC calibration methods follow the expected exponential distribution at the limit of a compound-Poisson process, gain-gated pulse heights follow a more complex distribution that may be approximated as a weighted sum of a few exponentials. We can reproduce this behavior with a simple statistical-sampling model.

Acoustic Injectors for Drop-On-Demand Serial Femtosecond Crystallography.

PubMed

Roessler, Christian G; Agarwal, Rakhi; Allaire, Marc; Alonso-Mori, Roberto; Andi, Babak; Bachega, José F R; Bommer, Martin; Brewster, Aaron S; Browne, Michael C; Chatterjee, Ruchira; Cho, Eunsun; Cohen, Aina E; Cowan, Matthew; Datwani, Sammy; Davidson, Victor L; Defever, Jim; Eaton, Brent; Ellson, Richard; Feng, Yiping; Ghislain, Lucien P; Glownia, James M; Han, Guangye; Hattne, Johan; Hellmich, Julia; Héroux, Annie; Ibrahim, Mohamed; Kern, Jan; Kuczewski, Anthony; Lemke, Henrik T; Liu, Pinghua; Majlof, Lars; McClintock, William M; Myers, Stuart; Nelsen, Silke; Olechno, Joe; Orville, Allen M; Sauter, Nicholas K; Soares, Alexei S; Soltis, S Michael; Song, Heng; Stearns, Richard G; Tran, Rosalie; Tsai, Yingssu; Uervirojnangkoorn, Monarin; Wilmot, Carrie M; Yachandra, Vittal; Yano, Junko; Yukl, Erik T; Zhu, Diling; Zouni, Athina

2016-04-05

X-ray free-electron lasers (XFELs) provide very intense X-ray pulses suitable for macromolecular crystallography. Each X-ray pulse typically lasts for tens of femtoseconds and the interval between pulses is many orders of magnitude longer. Here we describe two novel acoustic injection systems that use focused sound waves to eject picoliter to nanoliter crystal-containing droplets out of microplates and into the X-ray pulse from which diffraction data are collected. The on-demand droplet delivery is synchronized to the XFEL pulse scheme, resulting in X-ray pulses intersecting up to 88% of the droplets. We tested several types of samples in a range of crystallization conditions, wherein the overall crystal hit ratio (e.g., fraction of images with observable diffraction patterns) is a function of the microcrystal slurry concentration. We report crystal structures from lysozyme, thermolysin, and stachydrine demethylase (Stc2). Additional samples were screened to demonstrate that these methods can be applied to rare samples. Copyright © 2016 Elsevier Ltd. All rights reserved.

Imaging single cells in a beam of live cyanobacteria with an X-ray laser.

PubMed

van der Schot, Gijs; Svenda, Martin; Maia, Filipe R N C; Hantke, Max; DePonte, Daniel P; Seibert, M Marvin; Aquila, Andrew; Schulz, Joachim; Kirian, Richard; Liang, Mengning; Stellato, Francesco; Iwan, Bianca; Andreasson, Jakob; Timneanu, Nicusor; Westphal, Daniel; Almeida, F Nunes; Odic, Dusko; Hasse, Dirk; Carlsson, Gunilla H; Larsson, Daniel S D; Barty, Anton; Martin, Andrew V; Schorb, Sebastian; Bostedt, Christoph; Bozek, John D; Rolles, Daniel; Rudenko, Artem; Epp, Sascha; Foucar, Lutz; Rudek, Benedikt; Hartmann, Robert; Kimmel, Nils; Holl, Peter; Englert, Lars; Duane Loh, Ne-Te; Chapman, Henry N; Andersson, Inger; Hajdu, Janos; Ekeberg, Tomas

2015-02-11

There exists a conspicuous gap of knowledge about the organization of life at mesoscopic levels. Ultra-fast coherent diffractive imaging with X-ray free-electron lasers can probe structures at the relevant length scales and may reach sub-nanometer resolution on micron-sized living cells. Here we show that we can introduce a beam of aerosolised cyanobacteria into the focus of the Linac Coherent Light Source and record diffraction patterns from individual living cells at very low noise levels and at high hit ratios. We obtain two-dimensional projection images directly from the diffraction patterns, and present the results as synthetic X-ray Nomarski images calculated from the complex-valued reconstructions. We further demonstrate that it is possible to record diffraction data to nanometer resolution on live cells with X-ray lasers. Extension to sub-nanometer resolution is within reach, although improvements in pulse parameters and X-ray area detectors will be necessary to unlock this potential.

Acoustic Injectors for Drop-On-Demand Serial Femtosecond Crystallography

DOE PAGES

Roessler, Christian G.; Agarwal, Rakhi; Allaire, Marc; ...

2016-03-17

X-ray free-electron lasers (XFELs) provide very intense X-ray pulses suitable for macromolecular crystallography. Each X-ray pulse typically lasts for tens of femtoseconds and the interval between pulses is many orders of magnitude longer. Here we describe two novel acoustic injection systems that use focused sound waves to eject picoliter to nanoliter crystal-containing droplets out of microplates and into the X-ray pulse from which diffraction data are collected. The on-demand droplet delivery is synchronized to the XFEL pulse scheme, resulting in X-ray pulses intersecting up to 88% of the droplets. We tested several types of samples in a range of crystallizationmore » conditions, wherein the overall crystal hit ratio (e.g., fraction of images with observable diffraction patterns) is a function of the microcrystal slurry concentration. Lastly, we report crystal structures from lysozyme, thermolysin, and stachydrine demethylase (Stc2). In addition, samples were screened to demonstrate that these methods can be applied to rare samples« less

Acoustic Injectors for Drop-On-Demand Serial Femtosecond Crystallography

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

Roessler, Christian G.; Agarwal, Rakhi; Allaire, Marc

X-ray free-electron lasers (XFELs) provide very intense X-ray pulses suitable for macromolecular crystallography. Each X-ray pulse typically lasts for tens of femtoseconds and the interval between pulses is many orders of magnitude longer. Here we describe two novel acoustic injection systems that use focused sound waves to eject picoliter to nanoliter crystal-containing droplets out of microplates and into the X-ray pulse from which diffraction data are collected. The on-demand droplet delivery is synchronized to the XFEL pulse scheme, resulting in X-ray pulses intersecting up to 88% of the droplets. We tested several types of samples in a range of crystallizationmore » conditions, wherein the overall crystal hit ratio (e.g., fraction of images with observable diffraction patterns) is a function of the microcrystal slurry concentration. We report crystal structures from lysozyme, thermolysin, and stachydrine demethylase (Stc2). Additional samples were screened to demonstrate that these methods can be applied to rare samples.« less

Acoustic Injectors for Drop-On-Demand Serial Femtosecond Crystallography

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

Roessler, Christian G.; Agarwal, Rakhi; Allaire, Marc

X-ray free-electron lasers (XFELs) provide very intense X-ray pulses suitable for macromolecular crystallography. Each X-ray pulse typically lasts for tens of femtoseconds and the interval between pulses is many orders of magnitude longer. Here we describe two novel acoustic injection systems that use focused sound waves to eject picoliter to nanoliter crystal-containing droplets out of microplates and into the X-ray pulse from which diffraction data are collected. The on-demand droplet delivery is synchronized to the XFEL pulse scheme, resulting in X-ray pulses intersecting up to 88% of the droplets. We tested several types of samples in a range of crystallizationmore » conditions, wherein the overall crystal hit ratio (e.g., fraction of images with observable diffraction patterns) is a function of the microcrystal slurry concentration. Lastly, we report crystal structures from lysozyme, thermolysin, and stachydrine demethylase (Stc2). In addition, samples were screened to demonstrate that these methods can be applied to rare samples« less

KSC-04pd1773

NASA Image and Video Library

2004-09-10

KENNEDY SPACE CENTER, FLA. - Members of a hurricane assessment team from Johnson Space Center and Marshall Space Flight Center observe the damage to the roof of the Thermal Protection System (TPS) Facility at KSC after Hurricane Frances hit the east coast of Central Florida and Kennedy Space Center. Near the center is astronaut Scott Altmann, a member of the team. The facility, which creates the TPS tiles, blankets and all the internal thermal control systems for the Space Shuttles, is almost totally unserviceable at this time after losing approximately 35 percent of its roof. Equipment and materials that survived the storm have been relocated to the RLV hangar near the KSC Shuttle Landing Facility.

Abbott Physicochemical Tiering (APT)--a unified approach to HTS triage.

PubMed

Cox, Philip B; Gregg, Robert J; Vasudevan, Anil

2012-07-15

The selection of the highest quality chemical matter from high throughput screening (HTS) is the ultimate aim of any triage process. Typically there are many hundreds or thousands of hits capable of modulating a given biological target in HTS with a wide range of physicochemical properties that should be taken into consideration during triage. Given the multitude of physicochemical properties that define drug-like space, a system needs to be in place that allows for a rapid selection of chemical matter based on a prioritized range of these properties. With this goal in mind, we have developed a tool, coined Abbott Physicochemical Tiering (APT) that enables hit prioritization based on ranges of these important physicochemical properties. This tool is now used routinely at Abbott to help prioritize hits out of HTS during the triage process. Herein we describe how this tool was developed and validated using Abbott internal high throughput ADME data (HT-ADME). Copyright © 2012 Elsevier Ltd. All rights reserved.

Spitzer Observations of Dust Destruction in the Puppis A Supernova Remnant

NASA Technical Reports Server (NTRS)

Arendt, Richard G.; Dweek, Eli; Blair, William P.; Ghavamian, Parviz; Hwang, Una; Long, Knox X.; Petre, Robert; Rho, Jeonghee; Winkler, P. Frank

2010-01-01

The interaction of the Puppis A supernova remnant (SNR) with a neighboring molecular cloud provides a unique opportunity to measure the amount of grain destruction in an SNR shock. Spitzer Space Telescope MIPS imaging of the entire SNR at 24, 70, and 160 micrometers shows an extremely good correlation with X-ray emission, indicating that the SNR's IR radiation is dominated by the thermal emission of swept-up interstellar dust, collisionally heated by the hot shocked gas. Spitzer IRS spectral observations targeted both the Bright Eastern Knot (BEK) of the SNR where a small cloud has been engulfed by the supernova blast wave and outlying portions of the associated molecular cloud that are yet to be hit by the shock front. Modeling the spectra from both regions reveals the composition and the grain size distribution of the interstellar dust, both in front of and behind the SNR shock front. The comparison shows that the ubiquitous polycyclic aromatic hydrocarbons of the interstellar medium are destroyed within the BEK, along with nearly 25% of the mass of graphite and silicate dust grains.

[Survivability and morphologic anomalies in higher plants wolffia arrhiza following exposure to heavy ions of the galactic space radiation].

PubMed

Nevzgodina, L V; Kaminskaia, E V; Maksimova, E N; Fatsius, R; Sherrer, K; Shtraukh, V

2000-01-01

Experimental data on the effects of spaceflight factors, space radiation in particular, on higher plant Wolffia arrhiza firstly exposed in the "Bioblock" assembly and measurements made by physical track detectors of heavy ions (HI) are presented. Death of individual Wolffia plants and morphologic anomalies were the basic evaluation criteria. The peculiar feature of this biological object consists in the possibility to reveal delayed effects after 1-2 months since space flight as Wolffia has a high rate of vegetative reproduction. German investigators through microscopic examination of track detectors performed identification of individual plants affected by HI. With specially developed software and a coordinate system of supposition of biolayers and track detectors with the accuracy of 1 micron, tracks and even separate sections of individual HI tracks were determined in biological objects. Thereafter each Wolffia plant hit by HI was examined and data were compared with other variants. As a result, correlation between Wolffia death rate and morphologic anomalies were determined at different times post flight and topography of HI tracks was found. It is hypothesized that morphological anomalies in Walffia were caused by direct hits of plant germs by heavy ions or close passage of particles.

Assessing MMOD Impacts on Seal Performance

NASA Technical Reports Server (NTRS)

deGroh, Henry C., III; Daniels, C.; Dunlap, P.; Steinetz, B.

2007-01-01

The elastomer seal needed to seal in cabin air when NASA s Crew Exploration Vehicle is docked is exposed to space prior to docking. While open to space, the seal might be hit by orbital debris or meteoroids. The likelihood of damage of this type depends on the size of the particle. Our campaign is designed to find the smallest particle that will cause seal failure resulting in loss of mission. We will then be able to estimate environmental risks to the seal. Preliminary tests indicate seals can withstand a surprising amount of damage and still function. Collaborations with internal and external partners are in place and include seal leak testing, modeling of the space environment using a computer code known as BUMPER, and hypervelocity impact (HVI) studies at Caltech. Preliminary work at White Sands Test Facility showed a 0.5 mm diameter HVI damaged areas about 7 times that diameter, boring deep (5 mm) into elastomer specimens. BUMPER simulations indicate there is a 1 in 1440 chance of getting hit by a particle of diameter 0.08 cm for current Lunar missions; and 0.27 cm for a 10 year ISS LIDS seal area exposure.

Hit to lead evaluation of 1,2,3-triazolo[4,5-b]pyridines as PIM kinase inhibitors.

PubMed

Pastor, Joaquín; Oyarzabal, Julen; Saluste, Gustavo; Alvarez, Rosa María; Rivero, Virginia; Ramos, Francisco; Cendón, Elena; Blanco-Aparicio, Carmen; Ajenjo, Nuria; Cebriá, Antonio; Albarrán, M I; Cebrián, David; Corrionero, Ana; Fominaya, Jesús; Montoya, Guillermo; Mazzorana, Marco

2012-02-15

PIM kinases have become targets of interest due to their association with biochemical mechanisms affecting survival, proliferation and cytokine production. 1,2,3-Triazolo[4,5-b]pyridines were identified as PIM inhibitors applying a scaffold hopping approach. Initial exploration around this scaffold and X-ray crystallographic data are hereby described. Copyright © 2012 Elsevier Ltd. All rights reserved.

A compressed sensing X-ray camera with a multilayer architecture

DOE PAGES

Wang, Zhehui; Laroshenko, O.; Li, S.; ...

2018-01-25

Recent advances in compressed sensing theory and algorithms offer new possibilities for high-speed X-ray camera design. In many CMOS cameras, each pixel has an independent on-board circuit that includes an amplifier, noise rejection, signal shaper, an analog-to-digital converter (ADC), and optional in-pixel storage. When X-ray images are sparse, i.e., when one of the following cases is true: (a.) The number of pixels with true X-ray hits is much smaller than the total number of pixels; (b.) The X-ray information is redundant; or (c.) Some prior knowledge about the X-ray images exists, sparse sampling may be allowed. In this work, wemore » first illustrate the feasibility of random on-board pixel sampling (ROPS) using an existing set of X-ray images, followed by a discussion about signal to noise as a function of pixel size. Next, we describe a possible circuit architecture to achieve random pixel access and in-pixel storage. The combination of a multilayer architecture, sparse on-chip sampling, and computational image techniques, is expected to facilitate the development and applications of high-speed X-ray camera technology.« less

Ray-splitting correction to the Weyl formula: Experiment versus theory

NASA Astrophysics Data System (ADS)

Blumel, Reinhold

2004-03-01

Ray splitting is a phenomenon we are all familiar with: A light ray hitting a water surface at an angle is split into a transmitted and a reflected ray. Ray splitting is not restricted to light and water, but occurs generally in all wave systems in which the properties of the propagation medium change rapidly on the scale of a wave length. It was predicted by Prange et al. [Phys. Rev. E 53, 207 (1996)] that ray splitting produces universal corrections to the Weyl formula, i.e. the average density of states. Following a brief review of Weyl's theory and the theory of ray splitting, this talk presents recent results of a first experimental confirmation of the existence of ray-splitting corrections to the Weyl formula. The experiment, a quasi two-dimensional microwave cavity loaded with two dielectric bars, has been carried out by Corrie Vaa and Peter Koch at the State University of New York at Stony Brook [C. Vaa, P. M. Koch, and R. Blumel, Phys. Rev. Lett. 90, 194102 (2003)]. This research is supported by the NSF under Grant Numbers PHY-9732443, PHY-0099398 and PHY-9984075.

Random On-Board Pixel Sampling (ROPS) X-Ray Camera

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

Wang, Zhehui; Iaroshenko, O.; Li, S.

Recent advances in compressed sensing theory and algorithms offer new possibilities for high-speed X-ray camera design. In many CMOS cameras, each pixel has an independent on-board circuit that includes an amplifier, noise rejection, signal shaper, an analog-to-digital converter (ADC), and optional in-pixel storage. When X-ray images are sparse, i.e., when one of the following cases is true: (a.) The number of pixels with true X-ray hits is much smaller than the total number of pixels; (b.) The X-ray information is redundant; or (c.) Some prior knowledge about the X-ray images exists, sparse sampling may be allowed. Here we first illustratemore » the feasibility of random on-board pixel sampling (ROPS) using an existing set of X-ray images, followed by a discussion about signal to noise as a function of pixel size. Next, we describe a possible circuit architecture to achieve random pixel access and in-pixel storage. The combination of a multilayer architecture, sparse on-chip sampling, and computational image techniques, is expected to facilitate the development and applications of high-speed X-ray camera technology.« less

A compressed sensing X-ray camera with a multilayer architecture

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

Wang, Zhehui; Laroshenko, O.; Li, S.

Recent advances in compressed sensing theory and algorithms offer new possibilities for high-speed X-ray camera design. In many CMOS cameras, each pixel has an independent on-board circuit that includes an amplifier, noise rejection, signal shaper, an analog-to-digital converter (ADC), and optional in-pixel storage. When X-ray images are sparse, i.e., when one of the following cases is true: (a.) The number of pixels with true X-ray hits is much smaller than the total number of pixels; (b.) The X-ray information is redundant; or (c.) Some prior knowledge about the X-ray images exists, sparse sampling may be allowed. In this work, wemore » first illustrate the feasibility of random on-board pixel sampling (ROPS) using an existing set of X-ray images, followed by a discussion about signal to noise as a function of pixel size. Next, we describe a possible circuit architecture to achieve random pixel access and in-pixel storage. The combination of a multilayer architecture, sparse on-chip sampling, and computational image techniques, is expected to facilitate the development and applications of high-speed X-ray camera technology.« less

The Fragment Network: A Chemistry Recommendation Engine Built Using a Graph Database.

PubMed

Hall, Richard J; Murray, Christopher W; Verdonk, Marcel L

2017-07-27

The hit validation stage of a fragment-based drug discovery campaign involves probing the SAR around one or more fragment hits. This often requires a search for similar compounds in a corporate collection or from commercial suppliers. The Fragment Network is a graph database that allows a user to efficiently search chemical space around a compound of interest. The result set is chemically intuitive, naturally grouped by substitution pattern and meaningfully sorted according to the number of observations of each transformation in medicinal chemistry databases. This paper describes the algorithms used to construct and search the Fragment Network and provides examples of how it may be used in a drug discovery context.

Hadron Cancer Therapy - relative merits of X-ray, proton and carbon beams

NASA Astrophysics Data System (ADS)

Jakel, Oliver

2014-03-01

-Heidelberg University has a long experience in radiotherapy with carbon ions, starting with a pilot project at GSI in 1997. This project was jointly run by the Dep. for Radiation Oncology of Heidelberg University, GSI and the German Cancer Research Center (DKFZ). A hospital based heavy ion center at Heidelberg University, the Heidelberg Ion Beam Therapy Center (HIT) was proposed by the same group in 1998 and started clinical operation in late 2009. Since then nearly 2000 patients were treated with beams of carbon ions and protons. Just recently the operation of the world's first and only gantry for heavy ions also started at HIT. Patient treatments are performed in three rooms. Besides that, a lot of research projects are run in the field of Medical Physics and Radiobiology using a dedicated experimental area and the possibility to use beams of protons, carbon, helium and oxygen ions being delivered with the raster scanning technique.

Radiation Testing Electronics with Heavy Ions-The Best Way to Hit a Target Moving Ever Exponentially Faster

NASA Technical Reports Server (NTRS)

Ladbury, Ray

2018-01-01

In 1972, when engineers at Hughes Aircraft Corporation discovered that errors in their satellite avionics were being caused by cosmic rays (so-called single-event effects, or SEE), Moore's Law was only 7 years old. Now, more than 45 years on, the scaling that drove Moore's Law for its first 35 years has reached its limits. However, electronics technology continues to evolve exponentially and SEE remain a formidable issue for use of electronics in space. SEE occur when a single ionizing particle passes through a sensitive volume in an active semiconductor device and generates sufficient charge to cause anomalous behavior or failure in the device. Because SEE can occur at any time during the mission, the emphasis of SEE risk management methodologies is ensuring that all SEE modes in a device under test are detected by the test. Because a particle's probability of causing an SEE generally increases as the particle becomes more ionizing, heavy-ion beams have been and remain the preferred tools for elucidating SEE vulnerabilities. In this talk we briefly discuss space radiation environments and SEE mechanisms, describe SEE test methodologies and discuss current and future challenges for use of heavy-ion beams for SEE testing in an era when the continued validity of Moore's law depends on innovation rather than CMOS scaling.

Development of confocal laser microscope system for examination of microscopic characteristics of radiophotoluminescence glass dosemeters.

PubMed

Maki, Daisuke; Ishii, Tetsuya; Sato, Fuminobu; Kato, Yushi; Yamamoto, Takayoshi; Iida, Toshiyuki

2011-03-01

A confocal laser microscope system was developed for the measurement of radiophotoluminescence (RPL) photons emitted from a minute alpha-ray-irradiated area in an RPL glass dosemeter. The system was composed mainly of an inverted-type microscope, an ultraviolet laser, an XY movable stage and photon-counting circuits. The photon-counting circuits were effective in the reduction of the background noise level in the measurement of RPL photons. The performance of this microscope system was examined by the observation of standard RPL glass samples irradiated using (241)Am alpha rays. The spatial resolution of this system was ∼ 3 μm, and with regard to the sensitivity of this system, a hit of more than four to five alpha rays in unit area produced enough amount of RPL photons to construct the image.

Hyperspectral Imager-Tracker

NASA Technical Reports Server (NTRS)

Agurok, Llya

2013-01-01

The Hyperspectral Imager-Tracker (HIT) is a technique for visualization and tracking of low-contrast, fast-moving objects. The HIT architecture is based on an innovative and only recently developed concept in imaging optics. This innovative architecture will give the Light Prescriptions Innovators (LPI) HIT the possibility of simultaneously collecting the spectral band images (hyperspectral cube), IR images, and to operate with high-light-gathering power and high magnification for multiple fast- moving objects. Adaptive Spectral Filtering algorithms will efficiently increase the contrast of low-contrast scenes. The most hazardous parts of a space mission are the first stage of a launch and the last 10 kilometers of the landing trajectory. In general, a close watch on spacecraft operation is required at distances up to 70 km. Tracking at such distances is usually associated with the use of radar, but its milliradian angular resolution translates to 100- m spatial resolution at 70-km distance. With sufficient power, radar can track a spacecraft as a whole object, but will not provide detail in the case of an accident, particularly for small debris in the onemeter range, which can only be achieved optically. It will be important to track the debris, which could disintegrate further into more debris, all the way to the ground. Such fragmentation could cause ballistic predictions, based on observations using high-resolution but narrow-field optics for only the first few seconds of the event, to be inaccurate. No optical imager architecture exists to satisfy NASA requirements. The HIT was developed for space vehicle tracking, in-flight inspection, and in the case of an accident, a detailed recording of the event. The system is a combination of five subsystems: (1) a roving fovea telescope with a wide 30 field of regard; (2) narrow, high-resolution fovea field optics; (3) a Coude optics system for telescope output beam stabilization; (4) a hyperspectral-mutispectral imaging assembly; and (5) image analysis software with effective adaptive spectral filtering algorithm for real-time contrast enhancement.

Advances in fragment-based drug discovery platforms.

PubMed

Orita, Masaya; Warizaya, Masaichi; Amano, Yasushi; Ohno, Kazuki; Niimi, Tatsuya

2009-11-01

Fragment-based drug discovery (FBDD) has been established as a powerful alternative and complement to traditional high-throughput screening techniques for identifying drug leads. At present, this technique is widely used among academic groups as well as small biotech and large pharmaceutical companies. In recent years, > 10 new compounds developed with FBDD have entered clinical development, and more and more attention in the drug discovery field is being focused on this technique. Under the FBDD approach, a fragment library of relatively small compounds (molecular mass = 100 - 300 Da) is screened by various methods and the identified fragment hits which normally weakly bind to the target are used as starting points to generate more potent drug leads. Because FBDD is still a relatively new drug discovery technology, further developments and optimizations in screening platforms and fragment exploitation can be expected. This review summarizes recent advances in FBDD platforms and discusses the factors important for the successful application of this technique. Under the FBDD approach, both identifying the starting fragment hit to be developed and generating the drug lead from that starting fragment hit are important. Integration of various techniques, such as computational technology, X-ray crystallography, NMR, surface plasmon resonance, isothermal titration calorimetry, mass spectrometry and high-concentration screening, must be applied in a situation-appropriate manner.

Isotropic microscale mechanical properties of coral skeletons

PubMed Central

Pasquini, Luca; Molinari, Alan; Fantazzini, Paola; Dauphen, Yannicke; Cuif, Jean-Pierre; Levy, Oren; Dubinsky, Zvy; Caroselli, Erik; Prada, Fiorella; Goffredo, Stefano; Di Giosia, Matteo; Reggi, Michela; Falini, Giuseppe

2015-01-01

Scleractinian corals are a major source of biogenic calcium carbonate, yet the relationship between their skeletal microstructure and mechanical properties has been scarcely studied. In this work, the skeletons of two coral species: solitary Balanophyllia europaea and colonial Stylophora pistillata, were investigated by nanoindentation. The hardness HIT and Young's modulus EIT were determined from the analysis of several load–depth data on two perpendicular sections of the skeletons: longitudinal (parallel to the main growth axis) and transverse. Within the experimental and statistical uncertainty, the average values of the mechanical parameters are independent on the section's orientation. The hydration state of the skeletons did not affect the mechanical properties. The measured values, EIT in the 76–77 GPa range, and HIT in the 4.9–5.1 GPa range, are close to the ones expected for polycrystalline pure aragonite. Notably, a small difference in HIT is observed between the species. Different from corals, single-crystal aragonite and the nacreous layer of the seashell Atrina rigida exhibit clearly orientation-dependent mechanical properties. The homogeneous and isotropic mechanical behaviour of the coral skeletons at the microscale is correlated with the microstructure, observed by electron microscopy and atomic force microscopy, and with the X-ray diffraction patterns of the longitudinal and transverse sections. PMID:25977958

Monte Carlo studies on photon interactions in radiobiological experiments

PubMed Central

Shahmohammadi Beni, Mehrdad; Krstic, D.; Nikezic, D.

2018-01-01

X-ray and γ-ray photons have been widely used for studying radiobiological effects of ionizing radiations. Photons are indirectly ionizing radiations so they need to set in motion electrons (which are a directly ionizing radiation) to perform the ionizations. When the photon dose decreases to below a certain limit, the number of electrons set in motion will become so small that not all cells in an “exposed” cell population can get at least one electron hit. When some cells in a cell population are not hit by a directly ionizing radiation (in other words not irradiated), there will be rescue effect between the irradiated cells and non-irradiated cells, and the resultant radiobiological effect observed for the “exposed” cell population will be different. In the present paper, the mechanisms underlying photon interactions in radiobiological experiments were studied using our developed NRUphoton computer code, which was benchmarked against the MCNP5 code by comparing the photon dose delivered to the cell layer underneath the water medium. The following conclusions were reached: (1) The interaction fractions decreased in the following order: 16O > 12C > 14N > 1H. Bulges in the interaction fractions (versus water medium thickness) were observed, which reflected changes in the energies of the propagating photons due to traversals of different amount of water medium as well as changes in the energy-dependent photon interaction cross-sections. (2) Photoelectric interaction and incoherent scattering dominated for lower-energy (10 keV) and high-energy (100 keV and 1 MeV) incident photons. (3) The fractions of electron ejection from different nuclei were mainly governed by the photoelectric effect cross-sections, and the fractions from the 1s subshell were the largest. (4) The penetration fractions in general decreased with increasing medium thickness, and increased with increasing incident photon energy, the latter being explained by the corresponding reduction in interaction cross-sections. (5) The areas under the angular distribution curves of photons exiting the medium layer and subsequently undergoing interactions within the cell layer became smaller for larger incident photon energies. (6) The number of cells suffering at least one electron hit increased with the administered dose. For larger incident photon energies, the numbers of cells suffering at least one electron hit became smaller, which was attributed to the reduction in the photon interaction cross-section. These results highlighted the importance of the administered dose in radiobiological experiments. In particular, the threshold administered doses at which all cells in the exposed cell array suffered at least one electron hit might provide hints on explaining the intriguing observation that radiation-induced cancers can be statistically detected only above the threshold value of ~100 mSv, and thus on reconciling controversies over the linear no-threshold model. PMID:29561871

On the Feasibility of Prefetching and Caching for Online TV Services: A Measurement Study on Hulu

NASA Astrophysics Data System (ADS)

Krishnappa, Dilip Kumar; Khemmarat, Samamon; Gao, Lixin; Zink, Michael

Lately researchers are looking at ways to reduce the delay on video playback through mechanisms like prefetching and caching for Video-on-Demand (VoD) services. The usage of prefetching and caching also has the potential to reduce the amount of network bandwidth usage, as most popular requests are served from a local cache rather than the server containing the original content. In this paper, we investigate the advantages of having such a prefetching and caching scheme for a free hosting service of professionally created video (movies and TV shows) named "hulu". We look into the advantages of using a prefetching scheme where the most popular videos of the week, as provided by the hulu website, are prefetched and compare this approach with a conventional LRU caching scheme with limited storage space and a combined scheme of prefetching and caching. Results from our measurement and analysis shows that employing a basic caching scheme at the proxy yields a hit ratio of up to 77.69%, but requires storage of about 236GB. Further analysis shows that a prefetching scheme where the top-100 popular videos of the week are downloaded to the proxy yields a hit ratio of 44% with a storage requirement of 10GB. A LRU caching scheme with a storage limitation of 20GB can achieve a hit ratio of 55% but downloads 4713 videos to achieve such high hit ratio compared to 100 videos in prefetching scheme, whereas a scheme with both prefetching and caching with the same storage yields a hit ratio of 59% with download requirement of 4439 videos. We find that employing a scheme of prefetching along with caching with trade-off on the storage will yield a better hit ratio and bandwidth saving than individual caching or prefetching schemes.

What can Space Resources do for Astronomy and Planetary Science?

NASA Astrophysics Data System (ADS)

Elvis, Martin

2016-11-01

The rapid cost growth of flagship space missions has created a crisis for astronomy and planetary science. We have hit the funding wall. For the past 3 decades scientists have not had to think much about how space technology would change within their planning horizon. However, this time around enormous improvements in space infrastructure capabilities and, especially, costs are likely on the 20-year gestation periods for large space telescopes. Commercial space will lower launch and spacecraft costs substantially, enable cost-effective on-orbit servicing, cheap lunar landers and interplanetary cubesats by the early 2020s. A doubling of flagship launch rates is not implausible. On a longer timescale it will enable large structures to be assembled and constructed in space. These developments will change how we plan and design missions.

Unique semantic space in the brain of each beholder predicts perceived similarity

PubMed Central

Charest, Ian; Kievit, Rogier A.; Schmitz, Taylor W.; Deca, Diana; Kriegeskorte, Nikolaus

2014-01-01

The unique way in which each of us perceives the world must arise from our brain representations. If brain imaging could reveal an individual’s unique mental representation, it could help us understand the biological substrate of our individual experiential worlds in mental health and disease. However, imaging studies of object vision have focused on commonalities between individuals rather than individual differences and on category averages rather than representations of particular objects. Here we investigate the individually unique component of brain representations of particular objects with functional MRI (fMRI). Subjects were presented with unfamiliar and personally meaningful object images while we measured their brain activity on two separate days. We characterized the representational geometry by the dissimilarity matrix of activity patterns elicited by particular object images. The representational geometry remained stable across scanning days and was unique in each individual in early visual cortex and human inferior temporal cortex (hIT). The hIT representation predicted perceived similarity as reflected in dissimilarity judgments. Importantly, hIT predicted the individually unique component of the judgments when the objects were personally meaningful. Our results suggest that hIT brain representational idiosyncrasies accessible to fMRI are expressed in an individual's perceptual judgments. The unique way each of us perceives the world thus might reflect the individually unique representation in high-level visual areas. PMID:25246586

Theoretical modeling of the MILES hit profiles in military weapon low-data rate simulators

NASA Astrophysics Data System (ADS)

Andrews, L. C.; Phillips, R. L.; Smith, C. A.; Belichki, S. B.; Crabbs, R.; Cofarro, J. T.; Fountain, W.; Tucker, F. M.; Parrish, B. J.

2016-09-01

Math modeling of a low-data-rate optical communication system is presented and compared with recent testing results over ranges up to 100 m in an indoor tunnel at Kennedy Space Center. Additional modeling of outdoor testing results at longer ranges in the open atmosphere is also presented. The system modeled is the Army's Multiple Integrated Laser Engagement System (MILES) that has been used as a tactical training system since the early 1980s. The objective of the current modeling and testing is to obtain target hit zone profiles for the M16A2/M4 rifles and establish a data baseline for MILES that will aid in its upgrade using more recently developed lasers and detectors.

NASA Satellite Image of Japan Captured March 11, 2011

NASA Image and Video Library

2017-12-08

NASA's Aqua satellite passed over Japan one hour and 41 minutes before the quake hit. At the time Aqua passed overhead, the Moderate Resolution Imaging Spectroradiometer (MODIS) instrument captured a visible of Japan covered by clouds. The image was taken at 0405 UTC on March 11 (1:05 p.m. local time Japan /11:05 p.m. EST March 10). The quake hit at 2:46 p.m. local time/Japan. Satellite: Aqua Credit: NASA/GSFC/Aqua NASA Goddard Space Flight Center enables NASA’s mission through four scientific endeavors: Earth Science, Heliophysics, Solar System Exploration, and Astrophysics. Goddard plays a leading role in NASA’s accomplishments by contributing compelling scientific knowledge to advance the Agency’s mission. Follow us on Twitter Join us on Facebook

Design of a multi-purpose fragment screening library using molecular complexity and orthogonal diversity metrics

NASA Astrophysics Data System (ADS)

Lau, Wan F.; Withka, Jane M.; Hepworth, David; Magee, Thomas V.; Du, Yuhua J.; Bakken, Gregory A.; Miller, Michael D.; Hendsch, Zachary S.; Thanabal, Venkataraman; Kolodziej, Steve A.; Xing, Li; Hu, Qiyue; Narasimhan, Lakshmi S.; Love, Robert; Charlton, Maura E.; Hughes, Samantha; van Hoorn, Willem P.; Mills, James E.

2011-07-01

Fragment Based Drug Discovery (FBDD) continues to advance as an efficient and alternative screening paradigm for the identification and optimization of novel chemical matter. To enable FBDD across a wide range of pharmaceutical targets, a fragment screening library is required to be chemically diverse and synthetically expandable to enable critical decision making for chemical follow-up and assessing new target druggability. In this manuscript, the Pfizer fragment library design strategy which utilized multiple and orthogonal metrics to incorporate structure, pharmacophore and pharmacological space diversity is described. Appropriate measures of molecular complexity were also employed to maximize the probability of detection of fragment hits using a variety of biophysical and biochemical screening methods. In addition, structural integrity, purity, solubility, fragment and analog availability as well as cost were important considerations in the selection process. Preliminary analysis of primary screening results for 13 targets using NMR Saturation Transfer Difference (STD) indicates the identification of uM-mM hits and the uniqueness of hits at weak binding affinities for these targets.

Design of a multi-purpose fragment screening library using molecular complexity and orthogonal diversity metrics.

PubMed

Lau, Wan F; Withka, Jane M; Hepworth, David; Magee, Thomas V; Du, Yuhua J; Bakken, Gregory A; Miller, Michael D; Hendsch, Zachary S; Thanabal, Venkataraman; Kolodziej, Steve A; Xing, Li; Hu, Qiyue; Narasimhan, Lakshmi S; Love, Robert; Charlton, Maura E; Hughes, Samantha; van Hoorn, Willem P; Mills, James E

2011-07-01

Fragment Based Drug Discovery (FBDD) continues to advance as an efficient and alternative screening paradigm for the identification and optimization of novel chemical matter. To enable FBDD across a wide range of pharmaceutical targets, a fragment screening library is required to be chemically diverse and synthetically expandable to enable critical decision making for chemical follow-up and assessing new target druggability. In this manuscript, the Pfizer fragment library design strategy which utilized multiple and orthogonal metrics to incorporate structure, pharmacophore and pharmacological space diversity is described. Appropriate measures of molecular complexity were also employed to maximize the probability of detection of fragment hits using a variety of biophysical and biochemical screening methods. In addition, structural integrity, purity, solubility, fragment and analog availability as well as cost were important considerations in the selection process. Preliminary analysis of primary screening results for 13 targets using NMR Saturation Transfer Difference (STD) indicates the identification of uM-mM hits and the uniqueness of hits at weak binding affinities for these targets.

Particle radiation transport and effects models from research to space weather operations

NASA Astrophysics Data System (ADS)

Santin, Giovanni; Nieminen, Petteri; Rivera, Angela; Ibarmia, Sergio; Truscott, Pete; Lei, Fan; Desorgher, Laurent; Ivanchenko, Vladimir; Kruglanski, Michel; Messios, Neophytos

Assessment of risk from potential radiation-induced effects to space systems requires knowledge of both the conditions of the radiation environment and of the impact of radiation on sensi-tive spacecraft elements. During sensitivity analyses, test data are complemented by models to predict how external radiation fields are transported and modified in spacecraft materials. Radiation transport is still itself a subject of research and models are continuously improved to describe the physical interactions that take place when particles pass through shielding materi-als or hit electronic systems or astronauts, sometimes down to nanometre-scale interactions of single particles with deep sub-micron technologies or DNA structures. In recent years, though, such radiation transport models are transitioning from being a research subject by itself, to being widely used in the space engineering domain and finally being directly applied in the context of operation of space weather services. A significant "research to operations" (R2O) case is offered by Geant4, an open source toolkit initially developed and used in the context of fundamental research in high energy physics. Geant4 is also being used in the space domain, e.g. for modelling detector responses in science payloads, but also for studying the radiation environment itself, with subjects ranging from cosmic rays, to solar energetic particles in the heliosphere, to geomagnetic shielding. Geant4-based tools are now becoming more and more integrated in spacecraft design procedures, also through user friendly interfaces such as SPEN-VIS. Some examples are given by MULASSIS, offering multi-layered shielding analysis capa-bilities in realistic spacecraft materials, or GEMAT, focused on micro-dosimetry in electronics, or PLANETOCOSMICS, describing the interaction of the space environment with planetary magneto-and atmospheres, or GRAS, providing a modular and easy to use interface to various analysis types in simple or complex and realistic 3D geometry models. GRAS will also be part of the space weather SEISOP system for supplying near-real-time detailed information on the interaction of the space radiation environment with selected spacecraft elements.

The joint NASA/Goddard-University of Maryland research program in charged particle and high energy photon detector technology

NASA Technical Reports Server (NTRS)

1987-01-01

The first measurements of Fe charge states in two coronal hole-association high speed streams, using the sensor on ISEE-3, are presented. Eight event intervals from the January to June 1983 timeframe were chosen for the study of magnetotail dynamics and its relationship to substorm activity and the possible formation of plasmoids. Techniques are being explored for measurement of secondary electrons which are characteristically emitted when ions hit a target material. Efforts are continuing to understand kilometer wavelength shock associated radio events. An all-sky survey of fast X-ray transients of duration of 5 to 10,000 s was completed. Research using high resolution gamma-ray spectroscopy of celestial sources in the 20 keV to 20 MeV range to search for and study narrow lines in low-energy gamma-ray spectrum continues. Research in high energy radiation from pulsars is being conducted.

Coherent soft X-ray diffraction imaging of coliphage PR772 at the Linac coherent light source

PubMed Central

Reddy, Hemanth K.N.; Yoon, Chun Hong; Aquila, Andrew; Awel, Salah; Ayyer, Kartik; Barty, Anton; Berntsen, Peter; Bielecki, Johan; Bobkov, Sergey; Bucher, Maximilian; Carini, Gabriella A.; Carron, Sebastian; Chapman, Henry; Daurer, Benedikt; DeMirci, Hasan; Ekeberg, Tomas; Fromme, Petra; Hajdu, Janos; Hanke, Max Felix; Hart, Philip; Hogue, Brenda G.; Hosseinizadeh, Ahmad; Kim, Yoonhee; Kirian, Richard A.; Kurta, Ruslan P.; Larsson, Daniel S.D.; Duane Loh, N.; Maia, Filipe R.N.C.; Mancuso, Adrian P.; Mühlig, Kerstin; Munke, Anna; Nam, Daewoong; Nettelblad, Carl; Ourmazd, Abbas; Rose, Max; Schwander, Peter; Seibert, Marvin; Sellberg, Jonas A.; Song, Changyong; Spence, John C.H.; Svenda, Martin; Van der Schot, Gijs; Vartanyants, Ivan A.; Williams, Garth J.; Xavier, P. Lourdu

2017-01-01

Single-particle diffraction from X-ray Free Electron Lasers offers the potential for molecular structure determination without the need for crystallization. In an effort to further develop the technique, we present a dataset of coherent soft X-ray diffraction images of Coliphage PR772 virus, collected at the Atomic Molecular Optics (AMO) beamline with pnCCD detectors in the LAMP instrument at the Linac Coherent Light Source. The diameter of PR772 ranges from 65–70 nm, which is considerably smaller than the previously reported ~600 nm diameter Mimivirus. This reflects continued progress in XFEL-based single-particle imaging towards the single molecular imaging regime. The data set contains significantly more single particle hits than collected in previous experiments, enabling the development of improved statistical analysis, reconstruction algorithms, and quantitative metrics to determine resolution and self-consistency. PMID:28654088

Coherent soft X-ray diffraction imaging of coliphage PR772 at the Linac coherent light source

DOE PAGES

Reddy, Hemanth K. N.; Yoon, Chun Hong; Aquila, Andrew; ...

2017-06-27

Single-particle diffraction from X-ray Free Electron Lasers offers the potential for molecular structure determination without the need for crystallization. In an effort to further develop the technique, we present a dataset of coherent soft X-ray diffraction images of Coliphage PR772 virus, collected at the Atomic Molecular Optics (AMO) beamline with pnCCD detectors in the LAMP instrument at the Linac Coherent Light Source. The diameter of PR772 ranges from 65–70 nm, which is considerably smaller than the previously reported ~600 nm diameter Mimivirus. This reflects continued progress in XFEL-based single-particle imaging towards the single molecular imaging regime. As a result, themore » data set contains significantly more single particle hits than collected in previous experiments, enabling the development of improved statistical analysis, reconstruction algorithms, and quantitative metrics to determine resolution and self-consistency.« less

Coherent soft X-ray diffraction imaging of coliphage PR772 at the Linac coherent light source.

PubMed

Reddy, Hemanth K N; Yoon, Chun Hong; Aquila, Andrew; Awel, Salah; Ayyer, Kartik; Barty, Anton; Berntsen, Peter; Bielecki, Johan; Bobkov, Sergey; Bucher, Maximilian; Carini, Gabriella A; Carron, Sebastian; Chapman, Henry; Daurer, Benedikt; DeMirci, Hasan; Ekeberg, Tomas; Fromme, Petra; Hajdu, Janos; Hanke, Max Felix; Hart, Philip; Hogue, Brenda G; Hosseinizadeh, Ahmad; Kim, Yoonhee; Kirian, Richard A; Kurta, Ruslan P; Larsson, Daniel S D; Duane Loh, N; Maia, Filipe R N C; Mancuso, Adrian P; Mühlig, Kerstin; Munke, Anna; Nam, Daewoong; Nettelblad, Carl; Ourmazd, Abbas; Rose, Max; Schwander, Peter; Seibert, Marvin; Sellberg, Jonas A; Song, Changyong; Spence, John C H; Svenda, Martin; Van der Schot, Gijs; Vartanyants, Ivan A; Williams, Garth J; Xavier, P Lourdu

2017-06-27

Single-particle diffraction from X-ray Free Electron Lasers offers the potential for molecular structure determination without the need for crystallization. In an effort to further develop the technique, we present a dataset of coherent soft X-ray diffraction images of Coliphage PR772 virus, collected at the Atomic Molecular Optics (AMO) beamline with pnCCD detectors in the LAMP instrument at the Linac Coherent Light Source. The diameter of PR772 ranges from 65-70 nm, which is considerably smaller than the previously reported ~600 nm diameter Mimivirus. This reflects continued progress in XFEL-based single-particle imaging towards the single molecular imaging regime. The data set contains significantly more single particle hits than collected in previous experiments, enabling the development of improved statistical analysis, reconstruction algorithms, and quantitative metrics to determine resolution and self-consistency.

ESA uncovers Geminga's `hot spot'

NASA Astrophysics Data System (ADS)

2004-07-01

16 July 2004 Astronomers using ESA’s X-ray observatory XMM-Newton have detected a small, bright ‘hot spot’ on the surface of the neutron star called Geminga, 500 light-years away. The hot spot is the size of a football field and is caused by the same mechanism producing Geminga’s X-ray tails. This discovery identifies the missing link between the X-ray and gamma-ray emission from Geminga. hi-res Size hi-res: 1284 kb Credits: ESA, P. Caraveo (IASF, Milan) Geminga's hot spot This figure shows the effects of charged particles accelerated in the magnetosphere of Geminga. Panel (a) shows an image taken with the EPIC instrument on board the XMM-Newton observatory. The bright tails, made of particles kicked out by Geminga’s strong magnetic field, trail the neutron star as it moves about in space. Panel (b) shows how electrically charged particles interact with Geminga’s magnetic field. For example, if electrons (blue) are kicked out by the star, positrons (in red) hit the star’s magnetic poles like in an ‘own goal’. Panel (c) illustrates the size of Geminga’s magnetic field (blue) compared to that of the star itself at the centre (purple). The magnetic field is tilted with respect to Geminga’s rotation axis (red). Panel (d) shows the magnetic poles of Geminga, where charged particles hit the surface of the star, creating a two-million degrees hot spot, a region much hotter than the surroundings. As the star spins on its rotation axis, the hot spot comes into view and then disappears, causing the periodic colour change seen by XMM-Newton. An animated version of the entire sequence can be found at: Click here for animated GIF [low resolution, animated GIF, 5536 KB] Click here for AVI [high resolution, AVI with DIVX compression, 19128 KB] hi-res Size hi-res: 371 kb Credits: ESA, P. Caraveo (IASF, Milan) Geminga's hot spot, panel (a) Panel (a) shows an image taken with the EPIC instrument on board the XMM-Newton observatory. The bright tails, made of particles kicked out by Geminga’s strong magnetic field, trail the neutron star as it moves about in space. hi-res Size hi-res: 377 kb Credits: ESA, P. Caraveo (IASF, Milan) Geminga's hot spot, panel (b) Panel (b) shows how electrically charged particles interact with Geminga’s magnetic field. For example, if electrons (blue) are kicked out by the star, positrons (red) hit the star’s magnetic poles like in an ‘own goal’. hi-res Size hi-res: 435 kb Credits: ESA, P. Caraveo (IASF, Milan) Geminga's hot spot, panel (c) Panel (c) illustrates the size of Geminga’s magnetic field (blue) compared to that of the star itself at the centre (purple). The magnetic field is tilted with respect to Geminga’s rotation axis (red). hi-res Size hi-res: 121 kb Credits: ESA, P. Caraveo (IASF, Milan) Geminga's hot spot, panel (d) Panel (d) shows the magnetic poles of Geminga, where charged particles hit the surface of the star, creating a two-million degree hot spot, a region much hotter than the surroundings. As the star spins on its rotation axis, the hot spot comes into view and then disappears, causing the periodic colour change seen by XMM-Newton. Neutron stars are the smallest kind of stars known. They are the super-dense remnants of massive stars that died in cataclysmic explosions called supernovae. They have been thrown through space like cannonballs and set spinning at a furious rate, with magnetic fields hundreds of billions of times stronger than Earth’s. In the case of Geminga, this cannonball contains one and a half times the mass of the Sun, squeezed into a sphere just 20 kilometres across and spinning four times every second. A cloud bustling with electrically charged particles surrounds Geminga. These particles are shepherded by its magnetic and electric fields. ESA’s XMM-Newton observatory had already discovered that some of these particles are ejected into space, forming tails that stream behind the neutron star as it hurtles along. Scientists did not know whether Geminga’s tails are formed by electrons or by their twin particles with an opposite electrical charge, called positrons. Nevertheless, they expected that, if for instance electrons are kicked into space, then the positrons should be funnelled down towards the neutron star itself, like in an ‘own goal’. Where these particles strike the surface of the star, they ought to create a hot spot, a region considerably hotter than the surroundings. An international team of astronomers, lead by Patrizia Caraveo, IASF-CNR, Italy, has now reported the detection of such a hot spot on Geminga using ESA’s XMM-Newton observatory. With a temperature of about two million degrees, this hot spot is considerably hotter than the one half million degrees of the surrounding surface. According to this new work, Geminga’s hot spot is just 60 metres in radius. "This hot spot is the size of a football field," said Caraveo, "and is the smallest object ever detected outside of our Solar System." Details of this size can presently be measured only on the Moon and Mars and, even then, only from a spacecraft in orbit around them. The presence of a hot spot was suspected in the late 1990s but only now can we see it ‘live’, emitting X-rays as Geminga rotates, thanks to the superior sensitivity of ESA’s X-ray observatory, XMM-Newton. The team used the European Photon Imaging Cameras (EPIC) to conduct a study of Geminga, lasting about 28 consecutive hours and recording the arrival time and energy of every X-ray photon that Geminga emitted within XMM-Newton’s grasp. "In total, this amounted to 76 850 X-ray counts - twice as many as have been collected by all previous observations of Geminga, since the time of the Roman Empire," said Caraveo. Knowing the rotation rate of Geminga and the time of each photon’s arrival meant that astronomers could identify which photons were coming from each region of the neutron star as it rotates. When they compared photons coming from different regions of the star, they found that the ‘colour’ of the X-rays, which corresponds to their energy, changed as Geminga rotated. In particular, they could clearly see a distinct colour change when the hot spot came into view and then disappeared behind the star. This research closes the gap between the X-ray and gamma-ray emission from neutron stars. XMM-Newton has shown that they both can originate through the same physical mechanism, namely the acceleration of charged particles in the magnetosphere of these degenerate stars. "XMM-Newton’s Geminga observation has been particularly fruitful," said Norbert Schartel, ESA’s Project Scientist for XMM-Newton. "Last year, it yielded the discovery of the source tails and now it has found its rotating hot spot." Caraveo is already applying this new technique to other pulsating neutron stars observed by XMM-Newton looking for hot spots. This research represents an important new tool for understanding the physics of neutron stars. Notes for editors The original paper appeared on 16 July 2004, in Science magazine, under the title 'Phase-resolved spectroscopy of Geminga shows rotating hotspot(s)'. Besides P. Caraveo, the author list includes A. De Luca, S. Mereghetti, A. Pellizzoni and G. Bignami. During the search to track down this elusive celestial object, a co-author on the paper, Giovanni Bignami, named it Geminga almost 30 years ago. He was Principal Investigator of XMM-Newton's EPIC camera from 1987 to 1997 and is now Director of the Centre d'Etude Spatiale des Rayonnements (CESR, Toulouse). Geminga was first glimpsed as a mysterious source of gamma rays, coming from somewhere in the constellation Gemini by NASA's SAS-2 spacecraft in 1973. While searching to pin down its exact location and nature, Bignami named it Geminga because it was a ‘Gemini gamma-ray source’. As an astronomer in Milan, Italy, he was also aware that in his native dialect ‘gh'èminga’ means ‘it is not there’, which he found amusing. It was also remarkably apt, for it was not until 1993 that he succeeded in finally ‘seeing’ and therefore pinpointing Geminga, using optical wavelengths. While it lacked radio emissions, the pulsating X-ray and gamma-ray emissions meant Geminga could only belong to a new class of objects, the radio-quiet neutron stars. The original announcement of the discovery of Geminga’s tails, issued on 25 July 2003, can be found at: http://www.esa.int/esaSC/Pr_11_2003_s_en.html More about XMM-Newton XMM-Newton can detect more X-ray sources than any previous observatory and is helping to solve many cosmic mysteries of the violent Universe, from black holes to the formation of galaxies. It was launched on 10 December 1999, using an Ariane-5 rocket from French Guiana. It is expected to return data for a decade. XMM-Newton’s high-tech design uses over 170 wafer-thin cylindrical mirrors spread over three telescopes. Its orbit takes it almost a third of the way to the Moon, so that astronomers can enjoy long, uninterrupted views of celestial objects. More information on XMM-Newton can be found at: http://www.esa.int/esaSC/SEMM8IGHZTD_1_spk.html

Consuming Information

ERIC Educational Resources Information Center

Bonfield, Brett

2007-01-01

While librarians and users have been inundated with advice on how to produce content for MySpace, blogs, and other Web 2.0 services, there's been much less discussion about using newer technologies to consume all this new content efficiently. These technologies are new to everyone, and the flood is hitting all people at the same time. People must…

Advanced Laser Semi-Conductor Air to Air Training Device Concept

DTIC Science & Technology

1991-12-01

The LATAGS system will allow aerial gunnery training over inhabitated areas with no live ammunition. The proposed LATAGS system will also allow free ... play of the aircraft and calculate the bullets hit and miss distances from a aerial banner. in the old system the laser is pointed to a point in space

77 FR 50956 - Exclusion of Tethered Launches From Licensing Requirements

Federal Register 2010, 2011, 2012, 2013, 2014

2012-08-23

..., but do not apply to amateur rocket activities or to space activities carried out by the United States... hitting the ground. Some of these tethered launches met the FAA's amateur rocket activity criteria,\\1\\ and thus were excluded from chapter III requirements. Those that did not meet the amateur rocket criteria...

Test apparatus to monitor time-domain signals from semiconductor-detector pixel arrays

NASA Astrophysics Data System (ADS)

Haston, Kyle; Barber, H. Bradford; Furenlid, Lars R.; Salçin, Esen; Bora, Vaibhav

2011-10-01

Pixellated semiconductor detectors, such as CdZnTe, CdTe, or TlBr, are used for gamma-ray imaging in medicine and astronomy. Data analysis for these detectors typically estimates the position (x, y, z) and energy (E) of each interacting gamma ray from a set of detector signals {Si} corresponding to completed charge transport on the hit pixel and any of its neighbors that take part in charge sharing, plus the cathode. However, it is clear from an analysis of signal induction, that there are transient signal on all pixel electrodes during the charge transport and, when there is charge trapping, small negative residual signals on all electrodes. If we wish to optimally obtain the event parameters, we should take all these signals into account. We wish to estimate x,y,z and E from the set of all electrode signals, {Si(t)}, including time dependence, using maximum-likelihood techniques[1]. To do this, we need to determine the probability of the electrode signals, given the event parameters {x, y, z, E}, i.e. Pr( {Si(t)} | {x, y, z, E} ). Thus we need to map the detector response of all pixels, {Si(t)}, for a large number of events with known x,y,z and E.In this paper we demonstrate the existence of the transient signals and residual signals and determine their magnitudes. They are typically 50-100 times smaller than the hit-pixel signals. We then describe development of an apparatus to measure the response of a 16-pixel semiconductor detector and show some preliminary results. We also discuss techniques for measuring the event parameters for individual gamma-ray interactions, a requirement for determining Pr( {Si(t)} | {x, y, z, E}).

KSC-04pd1775

NASA Image and Video Library

2004-09-10

KENNEDY SPACE CENTER, FLA. - Members of a hurricane assessment team from Johnson Space Center and Marshall Space Flight Center observe the damage to the roof of the Thermal Protection System (TPS) Facility at KSC after Hurricane Frances hit the east coast of Central Florida and Kennedy Space Center. At left is astronaut Scott Altmann, a member of the team, and at center is Martin Wilson, manager of the TPS operations. The facility, which creates the TPS tiles, blankets and all the internal thermal control systems for the Space Shuttles, is almost totally unserviceable at this time after losing approximately 35 percent of its roof. Equipment and materials that survived the storm have been relocated to the RLV hangar near the KSC Shuttle Landing Facility.

Impact! Chandra Images a Young Supernova Blast Wave

NASA Astrophysics Data System (ADS)

2000-05-01

Two images made by NASA's Chandra X-ray Observatory, one in October 1999, the other in January 2000, show for the first time the full impact of the actual blast wave from Supernova 1987A (SN1987A). The observations are the first time that X-rays from a shock wave have been imaged at such an early stage of a supernova explosion. Recent observations of SN 1987A with the Hubble Space Telescope revealed gradually brightening hot spots from a ring of matter ejected by the star thousands of years before it exploded. Chandra's X-ray images show the cause for this brightening ring. A shock wave is smashing into portions of the ring at a speed of 10 million miles per hour (4,500 kilometers per second). The gas behind the shock wave has a temperature of about ten million degrees Celsius, and is visible only with an X-ray telescope. "With Hubble we heard the whistle from the oncoming train," said David Burrows of Pennsylvania State University, University Park, the leader of the team of scientists involved in analyzing the Chandra data on SN 1987A. "Now, with Chandra, we can see the train." The X-ray observations appear to confirm the general outlines of a model developed by team member Richard McCray of the University of Colorado, Boulder, and others, which holds that a shock wave has been moving out ahead of the debris expelled by the explosion. As this shock wave collides with material outside the ring, it heats it to millions of degrees. "We are witnessing the birth of a supernova remnant for the first time," McCray said. The Chandra images clearly show the previously unseen, shock-heated matter just inside the optical ring. Comparison with observations made with Chandra in October and January, and with Hubble in February 2000, show that the X-ray emission peaks close to the newly discovered optical hot spots, and indicate that the wave is beginning to hit the ring. In the next few years, the shock wave will light up still more material in the ring, and an inward moving, or reverse, shock wave will heat the material ejected in the explosion itself. "The supernova is digging up its own past," said McCray. The observations were made on October 6, 1999, using the Advanced CCD Imaging Spectrometer (ACIS) and the High Energy Transmission Grating, and again on January 17, 2000, using ACIS. Other members of the team were Eli Michael of the University of Colorado; Dr. Una Hwang, Dr. Steven Holt and Dr. Rob Petre of NASA's Goddard Space Flight Center in Greenbelt, MD; Professor Roger Chevalier of the University of Virginia, Charlottesville; and Professors Gordon Garmire and John Nousek of Pennsylvania State University. The results will be published in an upcoming issue of the Astrophysical Journal. The ACIS instrument was built for NASA by the Massachusetts Institute of Technology, Cambridge, and Pennsylvania State University. The High Energy Transmission Grating was built by the Massachusetts Institute of Technology. NASA's Marshall Space Flight Center in Huntsville, AL, manages the Chandra program. TRW, Inc., Redondo Beach, CA, is the prime contractor for the spacecraft. The Smithsonian's Chandra X-ray Center controls science and flight operations from Cambridge, MA. More About SN 1987A Images to illustrate this release and more information on Chandra's progress can be found on the Internet at: http://chandra.harvard.edu/photo/2000/sn1987a/index.html AND http://chandra.nasa.gov More About SN 1987A

Brownian motion with adaptive drift for remaining useful life prediction: Revisited

NASA Astrophysics Data System (ADS)

Wang, Dong; Tsui, Kwok-Leung

2018-01-01

Linear Brownian motion with constant drift is widely used in remaining useful life predictions because its first hitting time follows the inverse Gaussian distribution. State space modelling of linear Brownian motion was proposed to make the drift coefficient adaptive and incorporate on-line measurements into the first hitting time distribution. Here, the drift coefficient followed the Gaussian distribution, and it was iteratively estimated by using Kalman filtering once a new measurement was available. Then, to model nonlinear degradation, linear Brownian motion with adaptive drift was extended to nonlinear Brownian motion with adaptive drift. However, in previous studies, an underlying assumption used in the state space modelling was that in the update phase of Kalman filtering, the predicted drift coefficient at the current time exactly equalled the posterior drift coefficient estimated at the previous time, which caused a contradiction with the predicted drift coefficient evolution driven by an additive Gaussian process noise. In this paper, to alleviate such an underlying assumption, a new state space model is constructed. As a result, in the update phase of Kalman filtering, the predicted drift coefficient at the current time evolves from the posterior drift coefficient at the previous time. Moreover, the optimal Kalman filtering gain for iteratively estimating the posterior drift coefficient at any time is mathematically derived. A discussion that theoretically explains the main reasons why the constructed state space model can result in high remaining useful life prediction accuracies is provided. Finally, the proposed state space model and its associated Kalman filtering gain are applied to battery prognostics.

Verification of real-time WSA-ENLIL+Cone simulations of CME arrival-time at the CCMC/SWRC from 2010-2016

NASA Astrophysics Data System (ADS)

Wold, A. M.; Mays, M. L.; Taktakishvili, A.; Odstrcil, D.; MacNeice, P. J.; Jian, L. K.

2017-12-01

The Wang-Sheeley-Arge (WSA)-ENLIL+Cone model is used extensively in space weather operations world-wide to model CME propagation. As such, it is important to assess its performance. We present validation results of the WSA-ENLIL+Cone model installed at the Community Coordinated Modeling Center (CCMC) and executed in real-time by the CCMC/Space Weather Research Center (SWRC). CCMC/SWRC uses the WSA-ENLIL+Cone model to predict CME arrivals at NASA missions throughout the inner heliosphere. In this work we compare model predicted CME arrival-times to in-situ ICME leading edge measurements near Earth, STEREO-A and STEREO-B for simulations completed between March 2010-December 2016 (over 1,800 CMEs). We report hit, miss, false alarm, and correct rejection statistics for all three spacecraft. For all predicted CME arrivals, the hit rate is 0.5, and the false alarm rate is 0.1. For the 273 events where the CME was predicted to arrive at Earth, STEREO-A, or STEREO-B and we observed an arrival (hit), the mean absolute arrival-time prediction error was 10.4 ± 0.9 hours, with a tendency to early prediction error of -4.0 hours. We show the dependence of the arrival-time error on CME input parameters. We also explore the impact of the multi-spacecraft observations used to initialize the model CME inputs by comparing model verification results before and after the STEREO-B communication loss (since September 2014) and STEREO-A side-lobe operations (August 2014-December 2015). There is an increase of 1.7 hours in the CME arrival time error during single, or limited two-viewpoint periods, compared to the three-spacecraft viewpoint period. This trend would apply to a future space weather mission at L5 or L4 as another coronagraph viewpoint to reduce CME arrival time errors compared to a single L1 viewpoint.

Nursing Information Flow in Long-Term Care Facilities.

PubMed

Wei, Quan; Courtney, Karen L

2018-04-01

 Long-term care (LTC), residential care requiring 24-hour nursing services, plays an important role in the health care service delivery system. The purpose of this study was to identify the needed clinical information and information flow to support LTC Registered Nurses (RNs) in care collaboration and clinical decision making.  This descriptive qualitative study combines direct observations and semistructured interviews, conducted at Alberta's LTC facilities between May 2014 and August 2015. The constant comparative method (CCM) of joint coding was used for data analysis.  Nine RNs from six LTC facilities participated in the study. The RN practice environment includes two essential RN information management aspects: information resources and information spaces. Ten commonly used information resources by RNs included: (1) RN-personal notes; (2) facility-specific templates/forms; (3) nursing processes/tasks; (4) paper-based resident profile; (5) daily care plans; (6) RN-notebooks; (7) medication administration records (MARs); (8) reporting software application (RAI-MDS); (9) people (care providers); and (10) references (i.e., books). Nurses used a combination of shared information spaces, such as the Nurses Station or RN-notebook, and personal information spaces, such as personal notebooks or "sticky" notes. Four essential RN information management functions were identified: collection, classification, storage, and distribution. Six sets of information were necessary to perform RN care tasks and communication, including: (1) admission, discharge, and transfer (ADT); (2) assessment; (3) care plan; (4) intervention (with two subsets: medication and care procedure); (5) report; and (6) reference. Based on the RN information management system requirements, a graphic information flow model was constructed.  This baseline study identified key components of a current LTC nursing information management system. The information flow model may assist health information technology (HIT) developers to consolidate the design of HIT solutions for LTC, and serve as a communication tool between nurses and information technology (IT) staff to refine requirements and support further LTC HIT research. Schattauer GmbH Stuttgart.

Identification of novel malarial cysteine protease inhibitors using structure-based virtual screening of a focused cysteine protease inhibitor library.

PubMed

Shah, Falgun; Mukherjee, Prasenjit; Gut, Jiri; Legac, Jennifer; Rosenthal, Philip J; Tekwani, Babu L; Avery, Mitchell A

2011-04-25

Malaria, in particular that caused by Plasmodium falciparum , is prevalent across the tropics, and its medicinal control is limited by widespread drug resistance. Cysteine proteases of P. falciparum , falcipain-2 (FP-2) and falcipain-3 (FP-3), are major hemoglobinases, validated as potential antimalarial drug targets. Structure-based virtual screening of a focused cysteine protease inhibitor library built with soft rather than hard electrophiles was performed against an X-ray crystal structure of FP-2 using the Glide docking program. An enrichment study was performed to select a suitable scoring function and to retrieve potential candidates against FP-2 from a large chemical database. Biological evaluation of 50 selected compounds identified 21 diverse nonpeptidic inhibitors of FP-2 with a hit rate of 42%. Atomic Fukui indices were used to predict the most electrophilic center and its electrophilicity in the identified hits. Comparison of predicted electrophilicity of electrophiles in identified hits with those in known irreversible inhibitors suggested the soft-nature of electrophiles in the selected target compounds. The present study highlights the importance of focused libraries and enrichment studies in structure-based virtual screening. In addition, few compounds were screened against homologous human cysteine proteases for selectivity analysis. Further evaluation of structure-activity relationships around these nonpeptidic scaffolds could help in the development of selective leads for antimalarial chemotherapy.

Targeting YAP/TAZ-TEAD protein-protein interactions using fragment-based and computational modeling approaches

PubMed Central

Verma, Chandra

2017-01-01

The Hippo signaling pathway, which is implicated in the regulation of organ size, has emerged as a potential target for the development of cancer therapeutics. YAP, TAZ (transcription co-activators) and TEAD (transcription factor) are the downstream transcriptional machinery and effectors of the pathway. Formation of the YAP/TAZ-TEAD complex leads to transcription of growth-promoting genes. Conversely, disrupting the interactions of the complex decreases cell proliferation. Herein, we screened a 1000-member fragment library using Thermal Shift Assay and identified a hit fragment. We confirmed its binding at the YAP/TAZ-TEAD interface by X-ray crystallography, and showed that it occupies the same hydrophobic pocket as a conserved phenylalanine of YAP/TAZ. This hit fragment serves as a scaffold for the development of compounds that have the potential to disrupt YAP/TAZ-TEAD interactions. Structure-activity relationship studies and computational modeling were also carried out to identify more potent compounds that may bind at this validated druggable binding site. PMID:28570566

Hit to lead account of the discovery of a new class of inhibitors of Pim kinases and crystallographic studies revealing an unusual kinase binding mode.

PubMed

Qian, Kevin; Wang, Lian; Cywin, Charles L; Farmer, Bennett T; Hickey, Eugene; Homon, Carol; Jakes, Scott; Kashem, Mohammed A; Lee, George; Leonard, Scott; Li, Jun; Magboo, Ronald; Mao, Wang; Pack, Edward; Peng, Charlene; Prokopowicz, Anthony; Welzel, Morgan; Wolak, John; Morwick, Tina

2009-04-09

A series of inhibitors of Pim-2 kinase identified by high-throughput screening is described. Details of the hit validation and lead generation process and structure-activity relationship (SAR) studies are presented. Disclosure of an unconventional binding mode for 1, as revealed by X-ray crystallography using the highly homologous Pim-1 protein, is also presented, and observed binding features are shown to correlate with the Pim-2 SAR. While highly selective within the kinase family, the series shows similar potency for both Pim-1 and Pim-2, which was expected on the basis of homology, but unusual in light of reports in the literature documenting a bias for Pim-1. A rationale for these observations based on Pim-1 and Pim-2 K(M(ATP)) values is suggested. Some interesting cross reactivity with casein kinase-2 was also identified, and structural features which may contribute to the association are discussed.

Low-dose fixed-target serial synchrotron crystallography.

PubMed

Owen, Robin L; Axford, Danny; Sherrell, Darren A; Kuo, Anling; Ernst, Oliver P; Schulz, Eike C; Miller, R J Dwayne; Mueller-Werkmeister, Henrike M

2017-04-01

The development of serial crystallography has been driven by the sample requirements imposed by X-ray free-electron lasers. Serial techniques are now being exploited at synchrotrons. Using a fixed-target approach to high-throughput serial sampling, it is demonstrated that high-quality data can be collected from myoglobin crystals, allowing room-temperature, low-dose structure determination. The combination of fixed-target arrays and a fast, accurate translation system allows high-throughput serial data collection at high hit rates and with low sample consumption.

SAR and characterization of non-substrate isoindoline urea inhibitors of nicotinamide phosphoribosyltransferase (NAMPT)

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

Curtin, Michael L.; Heyman, H. Robin; Clark, Richard F.

Herein we disclose SAR studies that led to a series of isoindoline ureas which we recently reported were first-in-class, non-substrate nicotinamide phosphoribosyltransferase (NAMPT) inhibitors. Modification of the isoindoline and/or the terminal functionality of screening hit 5 provided inhibitors such as 52 and 58 with nanomolar antiproliferative activity and preclinical pharmacokinetics properties which enabled potent antitumor activity when dosed orally in mouse xenograft models. X-ray crystal structures of two inhibitors bound in the NAMPT active-site are discussed.

Design and evaluation of 1,7-naphthyridones as novel KDM5 inhibitors.

PubMed

Labadie, Sharada S; Dragovich, Peter S; Cummings, Richard T; Deshmukh, Gauri; Gustafson, Amy; Han, Ning; Harmange, Jean-Christophe; Kiefer, James R; Li, Yue; Liang, Jun; Liederer, Bianca M; Liu, Yichin; Manieri, Wanda; Mao, Wiefeng; Murray, Lesley; Ortwine, Daniel F; Trojer, Patrick; VanderPorten, Erica; Vinogradova, Maia; Wen, Li

2016-09-15

Features from a high throughput screening (HTS) hit and a previously reported scaffold were combined to generate 1,7-naphthyridones as novel KDM5 enzyme inhibitors with nanomolar potencies. These molecules exhibited high selectivity over the related KDM4C and KDM2B isoforms. An X-ray co-crystal structure of a representative molecule bound to KDM5A showed that these inhibitors are competitive with the co-substrate (2-oxoglutarate or 2-OG). Copyright © 2016 Elsevier Ltd. All rights reserved.

Reconstruction from limited single-particle diffraction data via simultaneous determination of state, orientation, intensity, and phase

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

Donatelli, Jeffrey J.; Sethian, James A.; Zwart, Peter H.

Free-electron lasers now have the ability to collect X-ray diffraction patterns from individual molecules; however, each sample is delivered at unknown orientation and may be in one of several conformational states, each with a different molecular structure. Hit rates are often low, typically around 0.1%, limiting the number of useful images that can be collected. Determining accurate structural information requires classifying and orienting each image, accurately assembling them into a 3D diffraction intensity function, and determining missing phase information. Additionally, single particles typically scatter very few photons, leading to high image noise levels. We develop a multitiered iterative phasing algorithmmore » to reconstruct structural information from singleparticle diffraction data by simultaneously determining the states, orientations, intensities, phases, and underlying structure in a single iterative procedure. We leverage real-space constraints on the structure to help guide optimization and reconstruct underlying structure from very few images with excellent global convergence properties. We show that this approach can determine structural resolution beyond what is suggested by standard Shannon sampling arguments for ideal images and is also robust to noise.« less

Reconstruction from limited single-particle diffraction data via simultaneous determination of state, orientation, intensity, and phase

DOE PAGES

Donatelli, Jeffrey J.; Sethian, James A.; Zwart, Peter H.

2017-06-26

Free-electron lasers now have the ability to collect X-ray diffraction patterns from individual molecules; however, each sample is delivered at unknown orientation and may be in one of several conformational states, each with a different molecular structure. Hit rates are often low, typically around 0.1%, limiting the number of useful images that can be collected. Determining accurate structural information requires classifying and orienting each image, accurately assembling them into a 3D diffraction intensity function, and determining missing phase information. Additionally, single particles typically scatter very few photons, leading to high image noise levels. We develop a multitiered iterative phasing algorithmmore » to reconstruct structural information from singleparticle diffraction data by simultaneously determining the states, orientations, intensities, phases, and underlying structure in a single iterative procedure. We leverage real-space constraints on the structure to help guide optimization and reconstruct underlying structure from very few images with excellent global convergence properties. We show that this approach can determine structural resolution beyond what is suggested by standard Shannon sampling arguments for ideal images and is also robust to noise.« less

DNA-encoded chemistry: enabling the deeper sampling of chemical space.

PubMed

Goodnow, Robert A; Dumelin, Christoph E; Keefe, Anthony D

2017-02-01

DNA-encoded chemical library technologies are increasingly being adopted in drug discovery for hit and lead generation. DNA-encoded chemistry enables the exploration of chemical spaces four to five orders of magnitude more deeply than is achievable by traditional high-throughput screening methods. Operation of this technology requires developing a range of capabilities including aqueous synthetic chemistry, building block acquisition, oligonucleotide conjugation, large-scale molecular biological transformations, selection methodologies, PCR, sequencing, sequence data analysis and the analysis of large chemistry spaces. This Review provides an overview of the development and applications of DNA-encoded chemistry, highlighting the challenges and future directions for the use of this technology.

Space-atmospheric interactions of energetic cosmic rays

NASA Astrophysics Data System (ADS)

Isar, Paula Gina

2015-02-01

Ultra-high energy cosmic rays are the most energetic particles in the Universe of which origin still remain a mystery since a century from their descovery. They are unique messengers coming from far beyond our Milky Way Galaxy, which provides insights into the fundamental matter, energy, space and time. As subatomic particles flying through space to nearly light speed, the ultra-high energy cosmic rays are so rare that they strike the Earth's atmosphere at a rate of up to only one particle per square kilometer per year or century. While the atmosphere is used as a giant calorimeter where cosmic rays induced air showers are initiated and the medium through which Cherenkov or fluorescence light or radio waves propagate, all cosmic ray measurements (performed either from space or ground) rely on an accurate atmospheric monitoring and understanding of atmospheric effects. The interdisciplinary link between Astroparticle Physics and Atmospheric Environment through the ultra-high energy comic rays space - atmospheric interactions, based on the present ground- and future space-based cosmic ray observatories, will be presented.

Lexico-Semantic Structure and the Word-Frequency Effect in Recognition Memory

ERIC Educational Resources Information Center

Monaco, Joseph D.; Abbott, L. F.; Kahana, Michael J.

2007-01-01

The word-frequency effect (WFE) in recognition memory refers to the finding that more rare words are better recognized than more common words. We demonstrate that a familiarity-discrimination model operating on data from a semantic word-association space yields a robust WFE in data on both hit rates and false-alarm rates. Our modeling results…

Earth Observations taken by Expedition 41 crewmember

NASA Image and Video Library

2014-10-16

ISS041-E-078247 (16 Oct. 2014) --- One of the crew members aboard the International Space Station took this picture of Hurricane Gonzalo on Oct. 16, 2014. The storm's eye appears in the center of the frame. Gonzalo hit Bermuda on the following day, as a powerful Category 2 storm, with winds estimated at 110 miles per hour.

Earth Observations taken by Expedition 41 crewmember

NASA Image and Video Library

2014-10-16

ISS041-E-078255 (16 Oct. 2014) --- One of the crew members aboard the International Space Station took this picture of Hurricane Gonzalo on Oct. 16, 2014. The storm's eye appears in the center of the frame. Gonzalo hit Bermuda on the following day, as a powerful Category 2 storm, with winds estimated at 110 miles per hour.

Hit discovery and hit-to-lead approaches.

PubMed

Keseru, György M; Makara, Gergely M

2006-08-01

Hit discovery technologies range from traditional high-throughput screening to affinity selection of large libraries, fragment-based techniques and computer-aided de novo design, many of which have been extensively reviewed. Development of quality leads using hit confirmation and hit-to-lead approaches present their own challenges, depending on the hit discovery method used to identify the initial hits. In this paper, we summarize common industry practices adopted to tackle hit-to-lead challenges and review how the advantages and drawbacks of different hit discovery techniques could affect the various issues hit-to-lead groups face.

Terahertz Lasers Reveal Information for 3D Images

NASA Technical Reports Server (NTRS)

2013-01-01

After taking off her shoes and jacket, she places them in a bin. She then takes her laptop out of its case and places it in a separate bin. As the items move through the x-ray machine, the woman waits for a sign from security personnel to pass through the metal detector. Today, she was lucky; she did not encounter any delays. The man behind her, however, was asked to step inside a large circular tube, raise his hands above his head, and have his whole body scanned. If you have ever witnessed a full-body scan at the airport, you may have witnessed terahertz imaging. Terahertz wavelengths are located between microwave and infrared on the electromagnetic spectrum. When exposed to these wavelengths, certain materials such as clothing, thin metal, sheet rock, and insulation become transparent. At airports, terahertz radiation can illuminate guns, knives, or explosives hidden underneath a passenger s clothing. At NASA s Kennedy Space Center, terahertz wavelengths have assisted in the inspection of materials like insulating foam on the external tanks of the now-retired space shuttle. "The foam we used on the external tank was a little denser than Styrofoam, but not much," says Robert Youngquist, a physicist at Kennedy. The problem, he explains, was that "we lost a space shuttle by having a chunk of foam fall off from the external fuel tank and hit the orbiter." To uncover any potential defects in the foam covering, such as voids or air pockets, that could keep the material from staying in place, NASA employed terahertz imaging to see through the foam. For many years, the technique ensured the integrity of the material on the external tanks.

Clinical picture of heparin-induced thrombocytopenia (HIT) and its differentiation from non-HIT thrombocytopenia.

PubMed

Warkentin, Theodore E

2016-10-28

HIT is an acquired antibody-mediated disorder strongly associated with thrombosis, including microthrombosis secondary to disseminated intravascular dissemination (DIC). The clinical features of HIT are reviewed from the perspective of the 4Ts scoring system for HIT, which emphasises its characteristic timing of onset of thrombocytopenia. HIT antibodies recognize multimolecular complexes of platelet factor 4 (PF4)/heparin. However, a subset of HIT sera recognise PF4 bound to platelet chondroitin sulfate; these antibodies activate platelets in vitro and in vivo even in the absence of heparin, thus explaining: delayed-onset HIT (where HIT begins or worsens after stopping heparin); persisting HIT (where HIT takes several weeks to recover); spontaneous HIT syndrome (a disorder clinically and serologically resembling HIT but without proximate heparin exposure); and fondaparinux-associated HIT (four distinct syndromes featuring thrombocytopenia that begins or worsens during treatment with fondaparinux), with a new patient case presented with ongoing thrombocytopenia (and fatal haemorrhage) during treatment of HIT with fondaparinux, with fondaparinux-dependent platelet activation induced by patient serum ("fondaparinux cross-reactivity"). Ironically, despite existence of fondaparinux-associated HIT, this pentasaccharide anticoagulant is a frequent treatment for HIT (including one used by the author). HIT can be confused with other disorders, including those with a) timing similar to HIT (e. g. abciximab-associated thrombocytopenia of delayed-onset); b) combined thrombocytopenia/thrombosis (e. g. symmetrical peripheral gangrene secondary to acute DIC and shock liver); and c) both timing of onset and thrombosis (e. g. warfarin-associated venous limb gangrene complicating cancer-associated DIC). By understanding clinical and pathophysiological similarities and differences between HIT and non-HIT mimicking disorders, the clinician is better able to make the correct diagnosis.

An Assessment of China’s Anti-Satellite and Space Warfare Programs, Policies and Doctrines

DTIC Science & Technology

2008-01-19

selling their ballistic missile assets and space launch capabilities.” 14 8. According to Steven Lambakis, a 1994 U.S. Navy war game showed that China...of China conducted at the Naval War College in the spring of 1994. The war game , set in the year 2010, was a part of the Pentagon’s ongoing study of...enhance the effectiveness of their own forces. U.S. players in this war game were routed, their forces hit before they could throw up adequate defenses

Cosmic Rays in the Heliosphere: Requirements for Future Observations

NASA Astrophysics Data System (ADS)

Mewaldt, R. A.

2013-06-01

Since the publication of Cosmic Rays in the Heliosphere in 1998 there has been great progress in understanding how and why cosmic rays vary in space and time. This paper discusses measurements that are needed to continue advances in relating cosmic ray variations to changes in solar and interplanetary activity and variations in the local interstellar environment. Cosmic ray acceleration and transport is an important discipline in space physics and astrophysics, but it also plays a critical role in defining the radiation environment for humans and hardware in space, and is critical to efforts to unravel the history of solar activity. Cosmic rays are measured directly by balloon-borne and space instruments, and indirectly by ground-based neutron, muon and neutrino detectors, and by measurements of cosmogenic isotopes in ice cores, tree-rings, sediments, and meteorites. The topics covered here include: what we can learn from the deep 2008-2009 solar minimum, when cosmic rays reached the highest intensities of the space era; the implications of 10Be and 14C isotope archives for past and future solar activity; the effects of variations in the size of the heliosphere; opportunities provided by the Voyagers for discovering the origin of anomalous cosmic rays and measuring cosmic-ray spectra in interstellar space; and future space missions that can continue the exciting exploration of the heliosphere that has occurred over the past 50 years.

Workshop on Cosmic Ray and High Energy Gamma Ray Experiments for the Space Station Era, Louisiana State University, Baton Rouge, October 17-20, 1984, Proceedings

NASA Technical Reports Server (NTRS)

Jones, W. V. (Editor); Wefel, J. P. (Editor)

1985-01-01

The potential of the Space Station as a platform for cosmic-ray and high-energy gamma-ray astronomy is discussed in reviews, reports, and specific proposals. Topics examined include antiparticles and electrons, science facilities and new technology, high-energy nuclear interactions, nuclear composition and energy spectra, Space Shuttle experiments, Space Station facilities and detectors, high-energy gamma rays, and gamma-ray facilities and techniques. Consideration is given to universal-baryon-symmetry testing on the scale of galactic clusters, particle studies in a high-inclination orbit, balloon-borne emulsion-chamber results on ultrarelativistic nucleus-nucleus interactions, ionization states of low-energy cosmic rays, a large gamma-ray telescope for point-source studies above 1 GeV, and the possible existence of stable quark matter.

Optimization of ACC system spacing policy on curved highway

NASA Astrophysics Data System (ADS)

Ma, Jun; Qian, Kun; Gong, Zaiyan

2017-05-01

The paper optimizes the original spacing policy when adopting VTH (Variable Time Headway), proposes to introduce the road curve curvature K to the spacing policy to cope with following the wrong vehicle or failing to follow the vehicle owing to the radar limitation of curve in ACC system. By utilizing MATLAB/Simulink, automobile longitudinal dynamics model is established. At last, the paper sets up such three common cases as the vehicle ahead runs at a uniform velocity, an accelerated velocity and hits the brake suddenly, simulates these cases on the curve with different curvature, analyzes the curve spacing policy in the perspective of safety and vehicle following efficiency and draws the conclusion whether the optimization scheme is effective or not.

ASCA Observation of the Dipping X-Ray Source X1916-053

NASA Technical Reports Server (NTRS)

Ko, Yuan-Kuen; Makai, Koji; Smale, Alan P.; White, Nick E.

1997-01-01

We present the results of timing and spectral studies of the dipping X-ray source X1916-053, observed by ASCA during its Performance Verification phase. The detected dipping activity is consistent with previous observations, with a period of 3008s and an intermittent secondary dip observed roughly 0.4 out of phase with the primary dip. The energy spectra of different intensity states are fitted with a power law with partial covering fraction absorption and interstellar absorption. The increase in the hardness ratio during the primary and secondary dips, and the increase in the covering fraction and column density with decreasing X-ray intensity, all imply that the dipping is caused by the photo-absorbing materials which have been suggested to be where the accreted flow hits the outer edge of the disk materials. The spectra at all intensity levels show no apparent evidence for Fe or Ne emission lines. This may be due to the low metal abundance in the accretion flow. Alternatively, the X-ray luminosity of the central source may be too weak to excite emission lines, which are assumed to be produced by X-ray photoionization of the disk materials.

A Rapid Python-Based Methodology for Target-Focused Combinatorial Library Design.

PubMed

Li, Shiliang; Song, Yuwei; Liu, Xiaofeng; Li, Honglin

2016-01-01

The chemical space is so vast that only a small portion of it has been examined. As a complementary approach to systematically probe the chemical space, virtual combinatorial library design has extended enormous impacts on generating novel and diverse structures for drug discovery. Despite the favorable contributions, high attrition rates in drug development that mainly resulted from lack of efficacy and side effects make it increasingly challenging to discover good chemical starting points. In most cases, focused libraries, which are restricted to particular regions of the chemical space, are deftly exploited to maximize hit rate and improve efficiency at the beginning of the drug discovery and drug development pipeline. This paper presented a valid methodology for fast target-focused combinatorial library design in both reaction-based and production-based ways with the library creating rates of approximately 70,000 molecules per second. Simple, quick and convenient operating procedures are the specific features of the method. SHAFTS, a hybrid 3D similarity calculation software, was embedded to help refine the size of the libraries and improve hit rates. Two target-focused (p38-focused and COX2-focused) libraries were constructed efficiently in this study. This rapid library enumeration method is portable and applicable to any other targets for good chemical starting points identification collaborated with either structure-based or ligand-based virtual screening.

Analysis and Assessment of Peak Lightning Current Probabilities at the NASA Kennedy Space Center

NASA Technical Reports Server (NTRS)

Johnson, D. L.; Vaughan, W. W.

1999-01-01

This technical memorandum presents a summary by the Electromagnetics and Aerospace Environments Branch at the Marshall Space Flight Center of lightning characteristics and lightning criteria for the protection of aerospace vehicles. Probability estimates are included for certain lightning strikes (peak currents of 200, 100, and 50 kA) applicable to the National Aeronautics and Space Administration Space Shuttle at the Kennedy Space Center, Florida, during rollout, on-pad, and boost/launch phases. Results of an extensive literature search to compile information on this subject are presented in order to answer key questions posed by the Space Shuttle Program Office at the Johnson Space Center concerning peak lightning current probabilities if a vehicle is hit by a lightning cloud-to-ground stroke. Vehicle-triggered lightning probability estimates for the aforementioned peak currents are still being worked. Section 4.5, however, does provide some insight on estimating these same peaks.

Stars and Cosmic Rays Observed from Mars

NASA Image and Video Library

2004-03-12

In this five-minute exposure taken from the surface of Mars by NASA Spirit rover, stars appear as streaks due to the rotation of the planet, and instantaneous cosmic-ray hits appear as points of light. Spirit took the image with its panoramic camera on March 11, 2004, after waking up during the martian night for a communication session with NASA's Mars Global Surveyor orbiter. Other exposures were also taken. The images tested the capabilities of the rover for night-sky observations. Scientists will use the results to aid planning for possible future astronomical observations from Mars. The difference in Mars' rotation, compared to Earth's, gives the star trails in this image a different orientation than they would have in a comparable exposure taken from Earth. http://photojournal.jpl.nasa.gov/catalog/PIA05551

Determination of the laser intensity applied to a Ta witness plate from the measured X-ray signal using a pulsed micro-channel plate detector

DOE PAGES

Pickworth, L. A.; Rosen, M. D.; Schneider, M. B.; ...

2017-04-14

The laser intensity distribution at the surface of a high-Z material, such as Ta, can be deduced from imaging the self-emission of the produced x-ray spot using suitable calibration data. This paper presents a calibration method which uses the measured x-ray emissions from laser spots of di erent intensities hitting a Ta witness plate. The x-ray emission is measured with a micro-channel plate (MCP) based x-ray framing camera plus filters. Data from di erent positions on one MCP strip or from di erent MCP assemblies are normalized to each other using a standard candle laser beam spot at 1x10 14more » W/cm 2 intensity. The distribution of the resulting dataset agrees with results from a pseudo spectroscopic model for laser intensities between 4 and 15x10 13 W/cm 2. The model is then used to determine the absolute scaling factor between the experimental results from assemblies using two di erent x-ray filters. The data and model method also allows unique calibration factors for each MCP system and each MCP gain to be compared. We also present simulation results investigating alternate witness plate materials (Ag, Eu and Au).« less

Determination of the laser intensity applied to a Ta witness plate from the measured X-ray signal using a pulsed micro-channel plate detector

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

Pickworth, L. A.; Rosen, M. D.; Schneider, M. B.

The laser intensity distribution at the surface of a high-Z material, such as Ta, can be deduced from imaging the self-emission of the produced x-ray spot using suitable calibration data. This paper presents a calibration method which uses the measured x-ray emissions from laser spots of di erent intensities hitting a Ta witness plate. The x-ray emission is measured with a micro-channel plate (MCP) based x-ray framing camera plus filters. Data from di erent positions on one MCP strip or from di erent MCP assemblies are normalized to each other using a standard candle laser beam spot at 1x10 14more » W/cm 2 intensity. The distribution of the resulting dataset agrees with results from a pseudo spectroscopic model for laser intensities between 4 and 15x10 13 W/cm 2. The model is then used to determine the absolute scaling factor between the experimental results from assemblies using two di erent x-ray filters. The data and model method also allows unique calibration factors for each MCP system and each MCP gain to be compared. We also present simulation results investigating alternate witness plate materials (Ag, Eu and Au).« less

Stennis Day Camper

NASA Technical Reports Server (NTRS)

2005-01-01

Sara Beth Casey, 5, proudly displays her artwork, 'Planets.' Sara Beth created the art as a student of Stennis Day Camp, a free camp for Stennis Space Center employees' children whose schools have not resumed since Hurricane Katrina hit the region on Aug. 29. The camp has registered nearly 200 children and averages 100 children each day. The camp will continue until all schools are back in session.

Stennis Day Camper

NASA Image and Video Library

2005-10-05

Sara Beth Casey, 5, proudly displays her artwork, 'Planets.' Sara Beth created the art as a student of Stennis Day Camp, a free camp for Stennis Space Center employees' children whose schools have not resumed since Hurricane Katrina hit the region on Aug. 29. The camp has registered nearly 200 children and averages 100 children each day. The camp will continue until all schools are back in session.

Printmaking on a Budget

ERIC Educational Resources Information Center

Blake, Judith

2008-01-01

Want to teach printmaking on a tight budget? Try using erasers! The size and shape does not matter--they are easy to cut and print beautifully. Have students place the eraser on white paper and trace around it. They should select a design and draw it in the traced space to fit the dimensions of the eraser. It is important that the design hits at…

Earth Observations taken by Expedition 41 crewmember

NASA Image and Video Library

2014-10-16

ISS041-E-078241 (16 Oct. 2014) --- One of the crew members aboard the International Space Station photographed this oblique scene of Hurricane Gonzalo on Oct. 16, 2014. The storm's eye is barely visible just above the center of the frame. Gonzalo hit Bermuda on the following day, as a powerful Category 2 storm, with winds estimated at 110 miles per hour.

Synchrotron Radiation from Outer Space and the Chandra X-Ray Observatory

NASA Technical Reports Server (NTRS)

Weisskopf, M. C.

2006-01-01

The universe provides numerous extremely interesting astrophysical sources of synchrotron X radiation. The Chandra X-ray Observatory and other X-ray missions provide powerful probes of these and other cosmic X-ray sources. Chandra is the X-ray component of NASA's Great Observatory Program which also includes the Hubble Space telescope, the Spitzer Infrared Telescope Facility, and the now defunct Compton Gamma-Ray Observatory. The Chandra X-Ray Observatory provides the best angular resolution (sub-arcsecond) of any previous, current, or planned (for the foreseeable near future) space-based X-ray instrumentation. We present here a brief overview of the technical capability of this X-Ray observatory and some of the remarkable discoveries involving cosmic synchrotron sources.

Cassiopeia A supernova

NASA Image and Video Library

2017-12-08

NASA's Fermi Closes on Source of Cosmic Rays New images from NASA's Fermi Gamma-ray Space Telescope show where supernova remnants emit radiation a billion times more energetic than visible light. The images bring astronomers a step closer to understanding the source of some of the universe's most energetic particles -- cosmic rays. This composite shows the Cassiopeia A supernova remnant across the spectrum: Gamma rays (magenta) from NASA's Fermi Gamma-ray Space Telescope; X-rays (blue, green) from NASA's Chandra X-ray Observatory; visible light (yellow) from the Hubble Space Telescope; infrared (red) from NASA's Spitzer Space Telescope; and radio (orange) from the Very Large Array near Socorro, N.M. Credit: NASA/DOE/Fermi LAT Collaboration, CXC/SAO/JPL-Caltech/Steward/O. Krause et al., and NRAO/AUI For more information: www.nasa.gov/mission_pages/GLAST/news/cosmic-rays-source.... NASA Goddard Space Flight Center is home to the nation's largest organization of combined scientists, engineers and technologists that build spacecraft, instruments and new technology to study the Earth, the sun, our solar system, and the universe. Follow us on Twitter Join us on Facebook

The possibility of gamma-ray astronomy measurements on the Russian segment of the International Space Station.

NASA Astrophysics Data System (ADS)

Fradkin, M. I.; Gorchakov, E. V.; Kaplin, V. A.; Kaplin, D. V.; Kurnosova, L. V.; Labenskij, A. G.; Runtso, M. F.; Topchiev, N. P.

The conditions required for gamma-ray astronomy measurements at energies of 10 - 1000 GeV by a gamma-ray telescope on the International Space Station are discussed. It is shown that the properties of the detected gamma rays can be determined accurately at 30 - 1000 GeV, even if the space station solar arrays fall in the aperture of the gamma-ray telescope. Measurements of the secondary gamma-ray spectrum using a ground-based model of the gamma-ray telescope have been carried out, and the resulting spectrum at energies of 1 - 100 GeV is presented.

Phase-space evolution of x-ray coherence in phase-sensitive imaging.

PubMed

Wu, Xizeng; Liu, Hong

2008-08-01

X-ray coherence evolution in the imaging process plays a key role for x-ray phase-sensitive imaging. In this work we present a phase-space formulation for the phase-sensitive imaging. The theory is reformulated in terms of the cross-spectral density and associated Wigner distribution. The phase-space formulation enables an explicit and quantitative account of partial coherence effects on phase-sensitive imaging. The presented formulas for x-ray spectral density at the detector can be used for performing accurate phase retrieval and optimizing the phase-contrast visibility. The concept of phase-space shearing length derived from this phase-space formulation clarifies the spatial coherence requirement for phase-sensitive imaging with incoherent sources. The theory has been applied to x-ray Talbot interferometric imaging as well. The peak coherence condition derived reveals new insights into three-grating-based Talbot-interferometric imaging and gratings-based x-ray dark-field imaging.

High Energy Astronomy Observatory (HEAO)

NASA Image and Video Library

1977-06-01

This photograph is of the High Energy Astronomy Observatory (HEAO)-2 telescope being checked by engineers in the X-Ray Calibration Facility at the Marshall Space Flight Center (MSFC). The MSFC was heavily engaged in the technical and scientific aspects, testing and calibration, of the HEAO-2 telescope. The HEAO-2 was the first imaging and largest x-ray telescope built to date. The X-Ray Calibration Facility was built in 1976 for testing MSFC's HEAO-2. The facility is the world's largest, most advanced laboratory for simulating x-ray emissions from distant celestial objects. It produced a space-like environment in which components related to x-ray telescope imaging are tested and the quality of their performance in space is predicted. The original facility contained a 1,000-foot long by 3-foot diameter vacuum tube (for the x-ray path) cornecting an x-ray generator and an instrument test chamber. Recently, the facility was upgraded to evaluate the optical elements of NASA's Hubble Space Telescope, Chandra X-Ray Observatory and Compton Gamma-Ray Observatory.

Relative effectiveness of HZE iron-56 particles for the induction of cytogenetic damage in vivo

NASA Technical Reports Server (NTRS)

Brooks, A.; Bao, S.; Rithidech, K.; Couch, L. A.; Braby, L. A.

2001-01-01

One of the risks of prolonged manned space flight is the exposure of astronauts to radiation from galactic cosmic rays, which contain heavy ions such as (56)Fe. To study the effects of such exposures, experiments were conducted at the Brookhaven National Laboratory by exposing Wistar rats to high-mass, high-Z, high-energy (HZE) particles using the Alternating Gradient Synchrotron (AGS). The biological effectiveness of (56)Fe ions (1000 MeV/nucleon) relative to low-LET gamma rays and high-LET alpha particles for the induction of chromosome damage and micronuclei was determined. The mitotic index and the frequency of chromosome aberrations were evaluated in bone marrow cells, and the frequency of micronuclei was measured in cells isolated from the trachea and the deep lung. A marked delay in the entry of cells into mitosis was induced in the bone marrow cells that decreased as a function of time after the exposure. The frequencies of chromatid aberrations and micronuclei increased as linear functions of dose. The frequency of chromosome aberrations induced by HZE particles was about 3.2 times higher than that observed after exposure to (60)Co gamma rays. The frequency of micronuclei in rat lung fibroblasts, lung epithelial cells, and tracheal epithelial cells increased linearly, with slopes of 7 x 10(-4), 12 x 10(-4), and 11 x 10(-4) micronuclei/binucleated cell cGy(-1), respectively. When genetic damage induced by radiation from (56)Fe ions was compared to that from exposure to (60)Co gamma rays, (56)Fe-ion radiation was between 0.9 and 3.3 times more effective than (60)Co gamma rays. However, the HZE-particle exposures were only 10-20% as effective as radon in producing micronuclei in either deep lung or tracheal epithelial cells. Using microdosimetric techniques, we estimated that 32 cells were hit by delta rays for each cell that was traversed by the primary HZE (56)Fe particle. These calculations and the observed low relative effectiveness of the exposure to HZE particles suggest that at least part of the cytogenetic damage measured was caused by the delta rays. Much of the energy deposited by the primary HZE particles may result in cell killing and may therefore be "wasted" as far as production of detectable micronuclei is concerned. The role of wasted energy in studies of cancer induction may be important in risk estimates for exposure to HZE particles.

Mass Extinctions and Supernova Explosions

NASA Astrophysics Data System (ADS)

Korschinek, Gunther

A nearby supernova (SN) explosion could have negatively influenced life on Earth, maybe even been responsible for mass extinctions. Mass extinction poses a significant extinction of numerous species on Earth, as recorded in the paleontologic, paleoclimatic, and geological record of our planet. Depending on the distance between the Sun and the SN, different types of threats have to be considered, such as ozone depletion on Earth, causing increased exposure to the Sun's ultraviolet radiation or the direct exposure of lethal X-rays. Another indirect effect is cloud formation, induced by cosmic rays in the atmosphere which result in a drop in the Earth's temperature, causing major glaciations of the Earth. The discovery of highly intensive gamma-ray bursts (GRBs), which could be connected to SNe, initiated further discussions on possible life-threatening events in the Earth's history. The probability that GRBs hit the Earth is very low. Nevertheless, a past interaction of Earth with GRBs and/or SNe cannot be excluded and might even have been responsible for past extinction events.

42 CFR 495.344 - Approval of the State Medicaid HIT plan, the HIT PAPD and update, the HIT IAPD and update, and...

Code of Federal Regulations, 2010 CFR

2010-10-01

... 42 Public Health 5 2010-10-01 2010-10-01 false Approval of the State Medicaid HIT plan, the HIT... Health CENTERS FOR MEDICARE & MEDICAID SERVICES, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED... Requirements Specific to the Medicaid Program § 495.344 Approval of the State Medicaid HIT plan, the HIT PAPD...

MYC/BCL2/BCL6 triple hit lymphoma: a study of 40 patients with a comparison to MYC/BCL2 and MYC/BCL6 double hit lymphomas.

PubMed

Huang, Wenting; Medeiros, L Jeffrey; Lin, Pei; Wang, Wei; Tang, Guilin; Khoury, Joseph; Konoplev, Sergej; Yin, C Cameron; Xu, Jie; Oki, Yasuhiro; Li, Shaoying

2018-05-21

High-grade B-cell lymphomas with MYC, BCL2, and BCL6 rearrangements (triple hit lymphoma) are uncommon. We studied the clinicopathologic features of 40 patients with triple hit lymphoma and compared them to 157 patients with MYC/BCL2 double hit lymphoma and 13 patients with MYC/BCL6 double hit lymphoma. The triple hit lymphoma group included 25 men and 15 women with a median age of 61 years (range, 34-85). Nine patients had a history of B-cell lymphoma. Histologically, 23 (58%) cases were diffuse large B-cell lymphoma and 17 cases had features of B-cell lymphoma, unclassifiable, with features intermediate between diffuse large B-cell lymphoma and Burkitt lymphoma. Most cases of triple hit lymphoma were positive for CD10 (100%), BCL2 (95%), BCL6 (82%), MYC (74%), and 71% with MYC and BCL2 coexpression. P53 was overexpressed in 29% of triple hit lymphoma cases. The clinicopathological features of triple hit lymphoma patients were similar to patients with MYC/BCL2 and MYC/BCL6 double hit lymphoma, except that triple hit lymphoma cases were more often CD10 positive compared with MYC/BCL6 double hit lymphoma (p < 0.05). Induction chemotherapy used was similar for patients with triple hit lymphoma and double hit lymphoma and overall survival in triple hit lymphoma patients was 17.6 months, similar to the overall survival of patients with double hit lymphoma (p = 0.67). Patients with triple hit lymphoma showing P53 overexpression had significantly worse overall survival compared with those without P53 overexpression (p = 0.04). On the other hand, double expressor status and prior history of B-cell lymphoma did not correlate with overall survival. In conclusion, most patients with triple hit lymphoma have an aggressive clinical course and poor prognosis and these tumors have a germinal center B-cell immunophenotype, similar to patients with double hit lymphomas. P53 expression is a poor prognostic factor in patients with triple hit lymphoma.

Applications of particle microbeams in space radiation research.

PubMed

Durante, Marco

2009-03-01

Galactic cosmic radiation is acknowledged as one of the major barriers to human space exploration. In space, astronauts are exposed to charged particles from Z = 1 (H) up to Z = 28 (Ni), but the probability of a hit to a specific single cell in the human body is low. Particle microbeams can deliver single charged particles of different charge and energy to single cells from different tissues, and microbeam studies are therefore very useful for improving current risk estimates for long-term space travel. 2D in vitro cell cultures can be very useful for establishing basic molecular mechanisms, but they are not sufficient to extrapolate risk, given the substantial evidence proving tissue effects are key in determining the response to radiation insult. 3D tissue or animal systems represent a more promising target for space radiobiology using microbeams.

Innovative space x-ray telescopes

NASA Astrophysics Data System (ADS)

Hudec, R.; Inneman, A.; Pina, L.; Sveda, L.; Ticha, H.; Brozek, V.

2017-11-01

We report on the progress in innovative X-ray mirror development with focus on requirements of future X-ray astronomy space projects. Various future projects in X-ray astronomy and astrophysics will require large lightweight but highly accurate segments with multiple thin shells or foils. The large Wolter 1 grazing incidence multiple mirror arrays, the Kirkpatrick-Baez modules, as well as the large Lobster-Eye X-ray telescope modules in Schmidt arrangement may serve as examples. All these space projects will require high quality and light segmented shells (shaped, bent or flat foils) with high X-ray reflectivity and excellent mechanical stability.

Space program: Space debris a potential threat to Space Station and shuttle

NASA Technical Reports Server (NTRS)

Schwartz, Stephen A.; Beers, Ronald W.; Phillips, Colleen M.; Ramos, Yvette

1990-01-01

Experts estimate that more than 3.5 million man-made objects are orbiting the earth. These objects - space debris - include whole and fragmentary parts of rocket bodies and other discarded equipment from space missions. About 24,500 of these objects are 1 centimeter across or larger. A 1-centimeter man-made object travels in orbit at roughly 22,000 miles per hour. If it hit a spacecraft, it would do about the same damage as would a 400-pound safe traveling at 60 miles per hour. The Government Accounting Office (GAO) reviews NASA's plans for protecting the space station from debris, the extent and precision of current NASA and Defense Department (DOD) debris-tracking capabilities, and the extent to which debris has already affected shuttle operations. GAO recommends that the space debris model be updated, and that the findings be incorporated into the plans for protecting the space station from such debris. GAO further recommends that the increased risk from debris to the space shuttle operations be analyzed.

New two-dimensional space-resolving flux detection technique for measurement of hohlraum inner radiation in Shenguang-III prototype.

PubMed

Ren, Kuan; Liu, Shenye; Du, Huabing; Hou, Lifei; Jing, Longfei; Zhao, Yang; Yang, Zhiwen; Wei, Minxi; Deng, Keli; Yao, Li; Yang, Guohong; Li, Sanwei; Lan, Ke; Liu, Jie; Zhu, Xiaoli; Ding, Yongkun; Yi, Lin

2015-10-01

The space-resolving measurement of X-ray flux from a specific area (laser spot, re-emitting wall, or capsule) inside the hohlraum is an ongoing and critical problem in indirectly driven inertial-confinement fusion experiments. In this work, we developed a new two-dimensional space-resolving flux detection technique to measure the X-ray flux from specific areas inside the hohlraum by using the time- and space-resolving flux detector (SRFD). In two typical hohlraum experiments conducted at the Shenguang-III prototype laser facility, the X-ray flux and radiation temperature from an area 0.2 mm in diameter inside the hohlraum were measured through the laser entrance hole (LEH). The different flux intensities and radiation temperatures detected using the SRFD from the inner area of the LEH were compared with the result measured using the flat-response X-ray detector from the entire LEH. This comparison was also analyzed theoretically. The inner area detected using the SRFD was found to be the re-emitting wall area alone. This important improvement in space-resolving X-ray flux measurement will enhance the current X-ray flux space characterization techniques, thereby furthering the quantitative understanding of X-ray flux space behavior in the hohlraum.

New two-dimensional space-resolving flux detection technique for measurement of hohlraum inner radiation in Shenguang-III prototype

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

Ren, Kuan; Research Center of Laser Fusion, China Academy of Engineering Physics, P.O. Box 919-986, Mianyang 621900; Liu, Shenye, E-mail: lsye1029@163.com

2015-10-15

The space-resolving measurement of X-ray flux from a specific area (laser spot, re-emitting wall, or capsule) inside the hohlraum is an ongoing and critical problem in indirectly driven inertial-confinement fusion experiments. In this work, we developed a new two-dimensional space-resolving flux detection technique to measure the X-ray flux from specific areas inside the hohlraum by using the time- and space-resolving flux detector (SRFD). In two typical hohlraum experiments conducted at the Shenguang-III prototype laser facility, the X-ray flux and radiation temperature from an area 0.2 mm in diameter inside the hohlraum were measured through the laser entrance hole (LEH). Themore » different flux intensities and radiation temperatures detected using the SRFD from the inner area of the LEH were compared with the result measured using the flat-response X-ray detector from the entire LEH. This comparison was also analyzed theoretically. The inner area detected using the SRFD was found to be the re-emitting wall area alone. This important improvement in space-resolving X-ray flux measurement will enhance the current X-ray flux space characterization techniques, thereby furthering the quantitative understanding of X-ray flux space behavior in the hohlraum.« less

The Screening Compound Collection: A Key Asset for Drug Discovery.

PubMed

Boss, Christoph; Hazemann, Julien; Kimmerlin, Thierry; von Korff, Modest; Lüthi, Urs; Peter, Oliver; Sander, Thomas; Siegrist, Romain

2017-10-25

In this case study on an essential instrument of modern drug discovery, we summarize our successful efforts in the last four years toward enhancing the Actelion screening compound collection. A key organizational step was the establishment of the Compound Library Committee (CLC) in September 2013. This cross-functional team consisting of computational scientists, medicinal chemists and a biologist was endowed with a significant annual budget for regular new compound purchases. Based on an initial library analysis performed in 2013, the CLC developed a New Library Strategy. The established continuous library turn-over mode, and the screening library size of 300'000 compounds were maintained, while the structural library quality was increased. This was achieved by shifting the selection criteria from 'druglike' to 'leadlike' structures, enriching for non-flat structures, aiming for compound novelty, and increasing the ratio of higher cost 'Premium Compounds'. Novel chemical space was gained by adding natural compounds, macrocycles, designed and focused libraries to the collection, and through mutual exchanges of proprietary compounds with agrochemical companies. A comparative analysis in 2016 provided evidence for the positive impact of these measures. Screening the improved library has provided several highly promising hits, including a macrocyclic compound, that are currently followed up in different Hit-to-Lead and Lead Optimization programs. It is important to state that the goal of the CLC was not to achieve higher HTS hit rates, but to increase the chances of identified hits to serve as the basis of successful early drug discovery programs. The experience gathered so far legitimates the New Library Strategy.

Design of the Readout Electronics for the BGO Calorimeter of DAMPE Mission

NASA Astrophysics Data System (ADS)

Feng, Changqing; Zhang, Deliang; Zhang, Junbin; Gao, Shanshan; Yang, Di; Zhang, Yunlong; Zhang, Zhiyong; Liu, Shubin; An, Qi

2015-12-01

The DAMPE (DArk Matter Particle Explorer) is a scientific satellite being developed in China, aimed at cosmic ray study, gamma ray astronomy, and searching for the clue of dark matter particles in the near future. The BGO (Bismuth Germanate Oxide) Calorimeter, which consists of 616 PMTs (photomultiplier tubes) and 1848 dynode signals, is a crucial part of the DAMPE payload for measuring the energy of cosmic ray particles, distinguishing interesting particles from background, and providing trigger information. An electronics system, which consists of 16 FEE (Front End Electronics) modules with a total power consumption of about 26 W, has been developed. Its main functions are based on the low power, 32-channel VA160 and VATA160 ASICs (Application Specific Integrated Circuits) for precisely measuring the charge of PMT signals and providing“hit”signals as well. To assure the long-term reliability in harsh space environment, a series of critical issues such as the radiation hardness, thermal design, components and board level quality control, etc., are taken into consideration. Test result showed that the system level ENC (equivalent noise charge) for each channel is about 10 fC in RMS (root mean square), and the timing uncertainty of the hit signals is about 300 ns, both of which satisfy the physics requirements of the detector. Experiments with 60Co radioactive source proved that 20 krad(Si) TID (Total Ionizing Dose) level is achieved, while the heavy ion beam and laser beam tests indicated that its SEL (Single Event Latch-up) and SEU (Single Event Upset) performance in orbit will be acceptable by taking some hardness measures. All the readout modules successfully passed the board-level screening, the sub-system level and finally the satellite system level environmental tests, and behave well in the beam test at CERN (European Organisation for Nuclear Research).

Structure Guided Development of Novel Thymidine Mimetics targeting Pseudomonas aeruginosa Thymidylate Kinase: from Hit to Lead Generation

PubMed Central

Choi, Jun Yong; Plummer, Mark S.; Starr, Jeremy; Desbonnet, Charlene R.; Soutter, Holly; Chang, Jeanne; Miller, J. Richard; Dillman, Keith; Miller, Alita A.; Roush, William R.

2012-01-01

Thymidylate kinase (TMK) is a potential chemotherapeutic target because it is directly involved in the synthesis of an essential component, thymidine triphosphate, in DNA replication. All reported TMK inhibitors are thymidine analogs, which might retard their development as potent therapeutics due to cell permeability and off-target activity against human TMK. A small molecule hit (1, IC50 = 58 μM), which has reasonable inhibition potency against Pseudomonas aeruginosa TMK (PaTMK), was identified by the analysis of the binding mode of thymidine or TP5A in a PaTMK homology model. This hit (1) was co-crystallized with PaTMK, and several potent PaTMK inhibitors (leads, 46, 47, 48, and 56, IC50 = 100–200 nM) were synthesized using computer aided design approaches including virtual synthesis/screening, which was used to guide the design of inhibitors. The binding mode of the optimized leads in PaTMK overlaps with that of other bacterial TMKs, but not with human TMK which shares few common features with the bacterial enzymes. Therefore, the optimized TMK inhibitors described here should be useful for the development of antibacterial agents targeting TMK without undesired off-target effects. In addition, an inhibition mechanism associated with the LID loop, which mimics the process of phosphate transfer from ATP to dTMP, was proposed based on X-ray co-crystal structures, homology models, and SAR results. PMID:22243413

Spontaneous heparin-induced thrombocytopenia (HIT) syndrome: HIT without any heparin exposure.

PubMed

Miyata, Shigeki

2016-01-01

Heparin-induced thrombocytopenia (HIT) is a pro-thrombotic side effect of heparin therapy caused by HIT antibodies with platelet-activating properties. Recent advances in understanding of spontaneous HIT syndrome, which can occur even without any heparin exposure despite its clinical and serological characteristics being similar to those of HIT, reveal the following HIT clinical features atypical for an immune-mediated disease. Heparin-naïve patients can develop IgG antibodies as early as day 4, as in a secondary immune response. Evidence for an anamnestic response upon heparin re-exposure is lacking. In addition, HIT antibodies are relatively short-lived, unlike those in a secondary immune response. Antigen immunoassays are commonly used worldwide for serological diagnosis of HIT. However, such assays do not indicate whether HIT antibodies have platelet-activating properties, leading to low diagnostic specificity for HIT. The detection of platelet-activating antibodies using a washed platelet activation assay is crucial for making a HIT diagnosis. These atypical clinical and serological features should be carefully considered while appropriately diagnosing HIT, which leads to appropriate therapy such as immediate administration of an alternative anticoagulant for preventing thromboembolic events and re-administration of heparin during surgery involving cardiopulmonary bypass when HIT antibodies are no longer detectable.

Research in cosmic and gamma ray astrophysics

NASA Technical Reports Server (NTRS)

Stone, Edward C.; Mewaldt, Richard A.; Prince, Thomas A.

1992-01-01

Discussed here is research in cosmic ray and gamma ray astrophysics at the Space Radiation Laboratory (SRL) of the California Institute of Technology. The primary activities discussed involve the development of new instrumentation and techniques for future space flight. In many cases these instrumentation developments were tested in balloon flight instruments designed to conduct new investigations in cosmic ray and gamma ray astrophysics. The results of these investigations are briefly summarized. Specific topics include a quantitative investigation of the solar modulation of cosmic ray protons and helium nuclei, a study of cosmic ray positron and electron spectra in interplanetary and interstellar space, the solar modulation of cosmic rays, an investigation of techniques for the measurement and interpretation of cosmic ray isotopic abundances, and a balloon measurement of the isotopic composition of galactic cosmic ray boron, carbon, and nitrogen.

KENNEDY SPACE CENTER, FLA. - A rudder speed brake actuator sits on an air-bearing pallet to undergo X-raying. Four actuators to be installed on the orbiter Discovery are being X-rayed at the Radiographic High-Energy X-ray Facility to determine if the gears were installed correctly. Discovery has been assigned to the first Return to Flight mission, STS-114, a logistics flight to the International Space Station.

NASA Image and Video Library

2004-03-08

KENNEDY SPACE CENTER, FLA. - A rudder speed brake actuator sits on an air-bearing pallet to undergo X-raying. Four actuators to be installed on the orbiter Discovery are being X-rayed at the Radiographic High-Energy X-ray Facility to determine if the gears were installed correctly. Discovery has been assigned to the first Return to Flight mission, STS-114, a logistics flight to the International Space Station.

[Ultraviolet radiation and long term space flight].

PubMed

Wu, H B; Su, S N; Ba, F S

2000-08-01

With the prolongation of space flight, influences of various aerospace environmental factors on the astronauts become more and more severe, while ultraviolet radiation is lacking. Some studies indicated that low doses of ultraviolet rays are useful and essential for human body. In space flight, ultraviolet rays can improve the hygienic condition in the space cabin, enhance astronaut's working ability and resistance to unfavorable factors, prevent mineral metabolic disorders, cure purulent skin diseases and deallergize the allergens. So in long-term space flight, moderate amount of ultraviolet rays in the space cabin would be beneficial.

Major Hurricane Matthew Seen from Space on This Week @NASA – October 7, 2016

NASA Image and Video Library

2016-10-07

Cameras outside the International Space Station captured views of Hurricane Matthew during several passes over the major storm, as it made its way north through the Caribbean Sea during the week of Oct. 3. The storm, which reached Category 4 status with winds up to about 145 miles per hour, impacted Haiti, eastern Cuba and the Bahamas. Forecasters predicted Matthew would threaten the southeast coast of the United States, including Florida’s Space Coast. As a precaution, NASA’s Kennedy Space Center closed Oct. 5 after preparing facilities for what could be a direct hit from the storm. Also, One Mars Year of Science for MAVEN, SLS Hardware Being Stacked for Stress Test, Oceans Melting Greenland, Aspira con NASA, and NASA at White House Events!

Growth and characterization of a-axis oriented Cr-doped AlN films by DC magnetron sputtering

NASA Astrophysics Data System (ADS)

Panda, Padmalochan; Ramaseshan, R.; Krishna, Nanda Gopala; Dash, S.

2016-05-01

Wurtzite type Cr-doped AlN thin films were grown on Si (100) substrates using DC reactive magnetron sputtering with a function of N2 concentration (15 to 25%). Evolution of crystal structure of these films was studied by GIXRD where a-axis preferred orientation was observed. The electronic binding energy and concentration of Cr in these films were estimated by X-ray photoemission spectroscopy (XPS). We have observed indentation hardness (HIT) of around 28.2 GPa for a nitrogen concentration of 25%.

Space Detectors for Gamma Rays (100 MeV-100 GeV): from Egret to Fermi LAT

NASA Technical Reports Server (NTRS)

Thompson, David J.

2015-01-01

The design of spaceborne high-energy (E is greater than 100 MeV) gamma-ray detectors depends on two principal factors: (1) the basic physics of detecting and measuring the properties of the gamma rays; and (2) the constraints of operating such a detector in space for an extended period. Improvements in technology have enabled major advances in detector performance, as illustrated by two successful instruments, EGRET on the Compton Gamma Ray Observatory and LAT on the Fermi Gamma-ray Space Telescope.

The Helicity Injected Torus (HIT) Program

NASA Astrophysics Data System (ADS)

Jarboe, T. R.; Gu, P.; Hamp, W.; Izzo, V.; Jewell, P.; Liptac, J.; McCollam, K. J.; Nelson, B. A.; Raman, R.; Redd, A. J.; Shumlak, U.; Sieck, P. E.; Smith, R. J.; Jain, K. K.; Nagata, M.; Uyama, T.

2000-10-01

The purpose of the Helicity Injected Torus (HIT) program is to develop current drive techniques for low-aspect-ratio toroidal plasmas. The present HIT-II spherical tokamak experiment is capable of both Coaxial Helicity Injection (CHI) and transformer action current drive. The HIT-II device itself is modestly sized (major radius R = 0.3 m, minor radius a = 0.2 m, with an on-axis magnetic field of up to Bo = 0.5 T), but has demonstrated toroidal plasma currents of up to 200 kA, using either CHI or transformer drive. An overview of ongoing research on HIT-II plasmas, including recent results, will be presented. An electron-locking model has been developed for helicity injection current drive; a description of this model will be presented, as well as comparisons to experimental results from the HIT and HIT-II devices. Empirical results from both the HIT program and past spheromak research, buttressed by theoretical developments, have led to the design of the upcoming HIT-SI (Helicity Injected Torus with Steady Inductive helicity injection) device (T.R. Jarboe, Fusion Technology 36, p. 85, 1999). HIT-SI will be able to form a high-beta spheromak, a low aspect ratio RFP or a spherical tokamak using constant inductive helicity injection. The HIT-SI design and construction progress will be presented.

Monitoring Seawall Deformation With Repeat-Track Space-Borne SAR Images

NASA Astrophysics Data System (ADS)

Pei, Yuanyuan; Wan, Qing; Wei, Lianhuan; Fang, Zhilei; Liao, Mingsheng

2010-10-01

Seawalls are constructed to protect coastal cities from typhoon, flood and sea tide. It is necessary to monitor the deformation of seawalls in real time. Repeat-track space-borne SAR images are useful for environment monitoring, especially ground deformation monitoring. Shanghai sits on the Yangtze River Delta on China's eastern coast. Each year, the city is hit by typhoons from Pacific Ocean and threatened by the flood of the Yangtze River. PS-InSAR technique is carried out to monitor the deformation of the seawalls. Experiment exhibits that the seawalls around Pudong airport and Lingang town suffered serious deformation.

Eye light flashes on the Mir space station.

PubMed

Avdeev, S; Bidoli, V; Casolino, M; De Grandis, E; Furano, G; Morselli, A; Narici, L; De Pascale, M P; Picozza, P; Reali, E; Sparvoli, R; Boezio, M; Carlson, P; Bonvicini, W; Vacchi, A; Zampa, N; Castellini, G; Fuglesang, C; Galper, A; Khodarovich, A; Ozerov, Yu; Popov, A; Vavilov, N; Mazzenga, G; Ricci, M; Sannita, W G; Spillantini, P

2002-04-01

The phenomenon of light flashes (LF) in eyes for people in space has been investigated onboard Mir. Data on particles hitting the eye have been collected with the SilEye detectors, and correlated with human observations. It is found that a nucleus in the radiation environment of Mir has roughly a 1% probability to cause an LF, whereas the proton probability is almost three orders of magnitude less. As a function of LET, the LF probability increases above 10 keV/micrometer, reaching about 5% at around 50 keV/micrometer. c 2002 Elsevier Science Ltd. All rights reserved.

Assessment of the performances of AcuStar HIT and the combination with heparin-induced multiple electrode aggregometry: a retrospective study.

PubMed

Minet, V; Bailly, N; Douxfils, J; Osselaer, J C; Laloy, J; Chatelain, C; Elalamy, I; Chatelain, B; Dogné, J M; Mullier, F

2013-09-01

Early diagnosis of immune heparin-induced thrombocytopenia (HIT) is challenging. HemosIL® AcuStar HIT and heparin-induced multiple electrode aggregometry (HIMEA) were recently proposed as rapid diagnostic methods. We conducted a study to assess performances of AcuStar HIT-IgG (PF4-H) and AcuStar HIT-Ab (PF4-H). The secondary objective was to compare the performances of the combination of Acustar HIT and HIMEA with standardised clinical diagnosis. Sera of 104 suspected HIT patients were retrospectively tested with AcuStar HIT. HIMEA was performed on available sera (n=81). The clinical diagnosis was established by analysing in a standardized manner the patient's medical records. These tests were also compared with PF4-Enhanced®, LTA, and SRA in subsets of patients. Thresholds were determined using ROC curve analysis with clinical outcome as reference. Using the recommended thresholds (1.00AU), the negative predictive value (NPV) of HIT-IgG and HIT-Ab were 100.0% (95% CI: 95.9%-100.0% and 95.7%-100.0%). The positive predictive value (PPV) were 64.3% (95% CI: 35.1%-87.2.2%) and 45.0% (95% CI: 23.2%-68.6%), respectively. Using our thresholds (HIT-IgG: 2.89AU, HIT-Ab: 9.41AU), NPV of HIT-IgG and HIT-Ab were 100.0% (95% CI: 96.0%-100.0% and 96.1%-100.0%). PPV were 75.0% (95% CI: 42.7%-94.5%) and 81.8% (95% CI: 48.3%-97.7%), respectively. Of the 79 patients with a medium-high pretest probability score, 67 were negative using HIT-IgG (PF4-H) test at our thresholds. HIMEA was performed on HIT-IgG positive patients. Using this combination, only one patient on 79 was incorrectly diagnosed. Acustar HIT showed good performances to exclude the diagnosis of HIT. Combination with HIMEA improves PPV. Copyright © 2013 Elsevier Ltd. All rights reserved.

Heparin-induced thrombocytopenia: real-world issues.

PubMed

Linkins, Lori-Ann; Warkentin, Theodore E

2011-09-01

Heparin-induced thrombocytopenia (HIT) is a prothrombotic drug reaction caused by platelet-activating antibodies. HIT sera often activate platelets without needing heparin-such heparin-"independent" platelet activation can be associated with HIT beginning or worsening despite stopping heparin ("delayed-onset HIT"). We address important issues in HIT diagnosis and therapy, using a recent cohort of HIT patients to illustrate influences of heparin type; triggers for HIT investigation; serological features of heparin-independent platelet activation; and treatment. In our cohort of recent HIT cases ( N = 13), low-molecular-weight heparin (dalteparin) was a common causative agent ( N = 8, 62%); most patients were diagnosed after HIT-thrombosis had occurred; and danaparoid was the most frequently selected treatment. Heparin-independent platelet activation was common (7/13 [54%]) and predicted slower platelet count recovery (>1 week) among evaluable patients (5/5 vs 1/6; P = 0.015). In our experience with argatroban-treated patients, HIT-associated consumptive coagulopathy confounds anticoagulant monitoring. Our observations provide guidance on practical aspects of HIT diagnosis and management. Thieme Medical Publishers.

Verification of real-time WSA-ENLIL+Cone simulations of CME arrival-time at the CCMC from 2010 to 2016

NASA Astrophysics Data System (ADS)

Wold, Alexandra M.; Mays, M. Leila; Taktakishvili, Aleksandre; Jian, Lan K.; Odstrcil, Dusan; MacNeice, Peter

2018-03-01

The Wang-Sheeley-Arge (WSA)-ENLIL+Cone model is used extensively in space weather operations world-wide to model coronal mass ejection (CME) propagation. As such, it is important to assess its performance. We present validation results of the WSA-ENLIL+Cone model installed at the Community Coordinated Modeling Center (CCMC) and executed in real-time by the CCMC space weather team. CCMC uses the WSA-ENLIL+Cone model to predict CME arrivals at NASA missions throughout the inner heliosphere. In this work we compare model predicted CME arrival-times to in situ interplanetary coronal mass ejection leading edge measurements at Solar TErrestrial RElations Observatory-Ahead (STEREO-A), Solar TErrestrial RElations Observatory-Behind (STEREO-B), and Earth (Wind and ACE) for simulations completed between March 2010 and December 2016 (over 1,800 CMEs). We report hit, miss, false alarm, and correct rejection statistics for all three locations. For all predicted CME arrivals, the hit rate is 0.5, and the false alarm rate is 0.1. For the 273 events where the CME was predicted to arrive at Earth, STEREO-A, or STEREO-B, and was actually observed (hit event), the mean absolute arrival-time prediction error was 10.4 ± 0.9 h, with a tendency to early prediction error of -4.0 h. We show the dependence of the arrival-time error on CME input parameters. We also explore the impact of the multi-spacecraft observations used to initialize the model CME inputs by comparing model verification results before and after the STEREO-B communication loss (since September 2014) and STEREO-A sidelobe operations (August 2014-December 2015). There is an increase of 1.7 h in the CME arrival time error during single, or limited two-viewpoint periods, compared to the three-spacecraft viewpoint period. This trend would apply to a future space weather mission at L5 or L4 as another coronagraph viewpoint to reduce CME arrival time errors compared to a single L1 viewpoint.

Radiation factors in space and a system for their monitoring.

PubMed

Kovtunenko, V M; Kremnev, R S; Pichkhadze, K M; Bogomolov, V B; Kontor, N N; Filippichev, S A; Petrov, V M; Pissarenko, N F

1994-10-01

The radiation environment is of special concern when the spaceship flies in deep space. The annual fluence of the galactic cosmic rays is approximately 10(8) cm-2 and the absorbed dose of the solar cosmic rays can reach 10 Gy per event behind the shielding thickness of 3-5 g cm-2 Al. For the radiation environment monitoring it is planned to place a measuring complex on the space probes "Mars" and "Spectr" flying outside the magnetosphere. This complex is to measure: cosmic rays composition, particle flux, dose equivalent, energy and LET spectra, solar X-rays spectrum. On line data transmission by the space probes permits to obtain the radiation environment data in space.

The Next Century Astrophysics Program

NASA Technical Reports Server (NTRS)

Swanson, Paul N.

1991-01-01

The Astrophysics Division within the NASA Office of Space Science and Applications (OSSA) has defined a set of major and moderate missions that are presently under study for flight sometime within the next 20 years. These programs include the: Advanced X Ray Astrophysics Facility; X Ray Schmidt Telescope; Nuclear Astrophysics Experiment; Hard X Ray Imaging Facility; Very High Throughput Facility; Gamma Ray Spectroscopy Observatory; Hubble Space Telescope; Lunar Transit Telescope; Astrometric Interferometer Mission; Next Generation Space Telescope; Imaging Optical Interferometer; Far Ultraviolet Spectroscopic Explorer; Gravity Probe B; Laser Gravity Wave Observatory in Space; Stratospheric Observatory for Infrared Astronomy; Space Infrared Telescope Facility; Submillimeter Intermediate Mission; Large Deployable Reflector; Submillimeter Interferometer; and Next Generation Orbiting Very Long Baseline Interferometer.

Novel wide-field x-ray optics for space

NASA Astrophysics Data System (ADS)

Hudec, René; Pína, Ladislav; Inneman, Adolf

2017-11-01

We report on the program of design and development of innovative very wide field X-ray optics for space applications. We describe the idea of wide field X-ray optics of the lobster-eye type of both Angel and Schmidt arrangements. This optics was suggested in 70ies but not yet used in space experiment due to severe manufacturing problems. The lobster-eye X-ray optics may achieve up to 180 degrees (diameter) field of view at angular resolution of order of 1 arcmin. We report on various prototypes of lobster-eye X-ray lenses based on alternative technologies (replicated double sided X-ray reflecting flats, float glass, replicated square channels etc.) as well as on their optical and X-ray tests. We also discuss the importance and performance of lobster-eye X-ray telescopes in future X-ray astronomy projects.

High Energy Astronomy Observatory (HEAO)

NASA Image and Video Library

1977-01-01

This photograph is of the High Energy Astronomy Observatory (HEAO)-2 telescope being evaluated by engineers in the clean room of the X-Ray Calibration Facility at the Marshall Space Flight Center (MSFC). The MSFC was heavily engaged in the technical and scientific aspects, testing and calibration, of the HEAO-2 telescope The HEAO-2 was the first imaging and largest x-ray telescope built to date. The X-Ray Calibration Facility was built in 1976 for testing MSFC's HEAO-2. The facility is the world's largest, most advanced laboratory for simulating x-ray emissions from distant celestial objects. It produced a space-like environment in which components related to x-ray telescope imaging are tested and the quality of their performance in space is predicted. The original facility contained a 1,000-foot long by 3-foot diameter vacuum tube (for the x-ray path) cornecting an x-ray generator and an instrument test chamber. Recently, the facility was upgraded to evaluate the optical elements of NASA's Hubble Space Telescope, Chandra X-Ray Observatory and Compton Gamma-Ray Observatory.

Fixed Target combined with Spectral Mapping: Approaching 100% Hit Rates for Serial Crystallography

PubMed Central

Pare-Labrosse, Olivier; Kuo, Anling; Marx, Alexander; Epp, Sascha W.; Sherrell, Darren A.; Eger, Bryan T.; Zhong, Yinpeng; Loch, Rolf; Mariani, Valerio; Alonso-Mori, Roberto; Nelson, Silke; Lemke, Henrik T.; Owen, Robin L.; Pearson, Arwen R.; Stuart, David I.; Ernst, Oliver P.; Mueller-Werkmeister, Henrike M.; Miller, R. J. Dwayne

2018-01-01

The advent of ultrafast highly brilliant coherent X-ray Free Electron Laser sources has driven the development of novel structure determination approaches for proteins, and promises visualisation of protein dynamics on the fastest timescales with full atomic resolution. Significant efforts are being applied to the development of sample delivery systems that allow these unique sources to be most efficiently exploited for high throughput serial femtosecond crystallography. We present here the next generation of a fixed target crystallography chip designed for rapid and reliable delivery of up to 11,259 protein crystals with high spatial precision. An experimental scheme for predetermining the positions of crystals in the chip by means of in-situ spectroscopy using a fiducial system for rapid, precise alignment and registration of the crystal positions is presented. This delivers unprecedented performance in serial crystallography experiments at room temperature under atmospheric pressure with a raw hit rate approaching 100% with an effective indexing rate of approximately 50%, increasing the efficiency of beam usage, and allowing the method to be applied to systems where the number of crystals is limited. PMID:27487825

Clustered DNA damages induced by high and low LET radiation, including heavy ions

NASA Technical Reports Server (NTRS)

Sutherland, B. M.; Bennett, P. V.; Schenk, H.; Sidorkina, O.; Laval, J.; Trunk, J.; Monteleone, D.; Sutherland, J.; Lowenstein, D. I. (Principal Investigator)

2001-01-01

Clustered DNA damages--here defined as two or more lesions (strand breaks, oxidized purines, oxidized pyrimidines or abasic sites) within a few helical turns--have been postulated as difficult to repair accurately, and thus highly significant biological lesions. Further, attempted repair of clusters may produce double strand breaks (DSBs). However, until recently, there was no way to measure ionizing radiation-induced clustered damages, except DSB. We recently described an approach for measuring classes of clustered damages (oxidized purine clusters, oxidized pyrimidine clusters, abasic clusters, along with DSB). We showed that ionizing radiation (gamma rays and Fe ions, 1 GeV/amu) does induce such clusters in genomic DNA in solution and in human cells. These studies also showed that each damage cluster results from one radiation hit (and its track), thus indicating that they can be induced by very low doses of radiation, i.e. two independent hits are not required for cluster induction. Further, among all complex damages, double strand breaks comprise--at most-- 20%, with the other clustered damages being at least 80%.

Fixed target combined with spectral mapping: approaching 100% hit rates for serial crystallography.

PubMed

Oghbaey, Saeed; Sarracini, Antoine; Ginn, Helen M; Pare-Labrosse, Olivier; Kuo, Anling; Marx, Alexander; Epp, Sascha W; Sherrell, Darren A; Eger, Bryan T; Zhong, Yinpeng; Loch, Rolf; Mariani, Valerio; Alonso-Mori, Roberto; Nelson, Silke; Lemke, Henrik T; Owen, Robin L; Pearson, Arwen R; Stuart, David I; Ernst, Oliver P; Mueller-Werkmeister, Henrike M; Miller, R J Dwayne

2016-08-01

The advent of ultrafast highly brilliant coherent X-ray free-electron laser sources has driven the development of novel structure-determination approaches for proteins, and promises visualization of protein dynamics on sub-picosecond timescales with full atomic resolution. Significant efforts are being applied to the development of sample-delivery systems that allow these unique sources to be most efficiently exploited for high-throughput serial femtosecond crystallography. Here, the next iteration of a fixed-target crystallography chip designed for rapid and reliable delivery of up to 11 259 protein crystals with high spatial precision is presented. An experimental scheme for predetermining the positions of crystals in the chip by means of in situ spectroscopy using a fiducial system for rapid, precise alignment and registration of the crystal positions is presented. This delivers unprecedented performance in serial crystallography experiments at room temperature under atmospheric pressure, giving a raw hit rate approaching 100% with an effective indexing rate of approximately 50%, increasing the efficiency of beam usage and allowing the method to be applied to systems where the number of crystals is limited.

A combination of 2D similarity search, pharmacophore, and molecular docking techniques for the identification of vascular endothelial growth factor receptor-2 inhibitors.

PubMed

Ai, Guanhua; Tian, Caiping; Deng, Dawei; Fida, Guissi; Chen, Haiyan; Ma, Yuxiang; Ding, Li; Gu, Yueqing

2015-04-01

The human vascular endothelial growth factor receptor-2 (VEGFR-2) has been an attractive target for the inhibition of angiogenesis. In the current study, we used a hybrid protocol of virtual screening methods to retrieve new VEGFR-2 inhibitors from the Zinc-Specs Database (441 574 compounds). The hybrid protocol included the initial screening of candidates by comparing the 2D similarity to five reported top active inhibitors of 13 VEGFR-2 X-ray crystallography structures, followed by the pharmacophore modeling of virtual screening on the basis of receptor-ligand interactions and further narrowing by LibDOCK to obtain the final hits. Two compounds (AN-919/41439526 and AK-968/40939851) with a high libscore were selected as the final hits for a subsequent cell cytotoxicity study. The two compounds screened exerted significant inhibitory effects on the proliferation of cancer cells (U87 and MCF-7). The results indicated that the hybrid procedure is an effective approach for screening specific receptor inhibitors.

Acyl guanidine inhibitors of β-secretase (BACE-1): optimization of a micromolar hit to a nanomolar lead via iterative solid- and solution-phase library synthesis.

PubMed

Gerritz, Samuel W; Zhai, Weixu; Shi, Shuhao; Zhu, Shirong; Toyn, Jeremy H; Meredith, Jere E; Iben, Lawrence G; Burton, Catherine R; Albright, Charles F; Good, Andrew C; Tebben, Andrew J; Muckelbauer, Jodi K; Camac, Daniel M; Metzler, William; Cook, Lynda S; Padmanabha, Ramesh; Lentz, Kimberley A; Sofia, Michael J; Poss, Michael A; Macor, John E; Thompson, Lorin A

2012-11-08

This report describes the discovery and optimization of a BACE-1 inhibitor series containing an unusual acyl guanidine chemotype that was originally synthesized as part of a 6041-membered solid-phase library. The synthesis of multiple follow-up solid- and solution-phase libraries facilitated the optimization of the original micromolar hit into a single-digit nanomolar BACE-1 inhibitor in both radioligand binding and cell-based functional assay formats. The X-ray structure of representative inhibitors bound to BACE-1 revealed a number of key ligand:protein interactions, including a hydrogen bond between the side chain amide of flap residue Gln73 and the acyl guanidine carbonyl group, and a cation-π interaction between Arg235 and the isothiazole 4-methoxyphenyl substituent. Following subcutaneous administration in rats, an acyl guanidine inhibitor with single-digit nanomolar activity in cells afforded good plasma exposures and a dose-dependent reduction in plasma Aβ levels, but poor brain exposure was observed (likely due to Pgp-mediated efflux), and significant reductions in brain Aβ levels were not obtained.

Hit identification and optimization in virtual screening: practical recommendations based on a critical literature analysis.

PubMed

Zhu, Tian; Cao, Shuyi; Su, Pin-Chih; Patel, Ram; Shah, Darshan; Chokshi, Heta B; Szukala, Richard; Johnson, Michael E; Hevener, Kirk E

2013-09-12

A critical analysis of virtual screening results published between 2007 and 2011 was performed. The activity of reported hit compounds from over 400 studies was compared to their hit identification criteria. Hit rates and ligand efficiencies were calculated to assist in these analyses, and the results were compared with factors such as the size of the virtual library and the number of compounds tested. A series of promiscuity, druglike, and ADMET filters were applied to the reported hits to assess the quality of compounds reported, and a careful analysis of a subset of the studies that presented hit optimization was performed. These data allowed us to make several practical recommendations with respect to selection of compounds for experimental testing, definition of hit identification criteria, and general virtual screening hit criteria to allow for realistic hit optimization. A key recommendation is the use of size-targeted ligand efficiency values as hit identification criteria.

KENNEDY SPACE CENTER, FLA. - Workers at Cape Canaveral Air Force Station place one of four rudder speed brake actuators onto a pallet for X-ray. The actuators, to be installed on the orbiter Discovery, are being X-rayed at the Radiographic High-Energy X-ray Facility to determine if the gears were installed correctly. Discovery has been assigned to the first Return to Flight mission, STS-114, a logistics flight to the International Space Station.

NASA Image and Video Library

2004-03-08

KENNEDY SPACE CENTER, FLA. - Workers at Cape Canaveral Air Force Station place one of four rudder speed brake actuators onto a pallet for X-ray. The actuators, to be installed on the orbiter Discovery, are being X-rayed at the Radiographic High-Energy X-ray Facility to determine if the gears were installed correctly. Discovery has been assigned to the first Return to Flight mission, STS-114, a logistics flight to the International Space Station.

Analysis of nuclear resonance fluorescence excitation measured with LaBr3(Ce) detectors near 2 MeV

NASA Astrophysics Data System (ADS)

Omer, Mohamed; Negm, Hani; Ohgaki, Hideaki; Daito, Izuru; Hayakawa, Takehito; Bakr, Mahmoud; Zen, Heishun; Hori, Toshitada; Kii, Toshiteru; Masuda, Kai; Hajima, Ryoichi; Shizuma, Toshiyuki; Toyokawa, Hiroyuki; Kikuzawa, Nobuhiro

2013-11-01

The performance of LaBr3(Ce) to measure nuclear resonance fluorescence (NRF) excitations is discussed in terms of limits of detection and in comparison with high-purity germanium (HPGe) detectors near the 2 MeV region where many NRF excitation levels from special nuclear materials are located. The NRF experiment was performed at the High Intensity γ-ray Source (HIγS) facility. The incident γ-rays, of 2.12 MeV energy, hit a B4C target to excite the 11B nuclei to the first excitation level. The statistical-sensitive non-linear peak clipping (SNIP) algorithm was implemented to eliminate the background and enhance the limits of detection for the spectra measured with LaBr3(Ce). Both detection and determination limits were deduced from the experimental data.

The Rock that Hit New York

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

Meade, Roger Allen; Keksis, August Lawrence

On January 12, 1975, a rock seemed to fall from the sky over New York State’s Schoharie County hitting the tractor of a local farmer, who was “preparing his fields for spring planting.” As the farmer later described the event to a reporter from the UFO INVESTIGATOR, the object glanced off the tractor, fell to the ground, and melted its way through a patch of ice that was two and one half inches thick. The farmer, Leonard Tillapaugh, called the county sheriff, Harvey Stoddard, who recovered the rock, noting that it “was still warm.” Why and how a sample ofmore » the rock came to Los Alamos is not known. However, it captivated a wide Laboratory audience, was subjected to rigorous testing and evaluation. Los Alamos used the scientific method in the manner promoted by Hynek. Did Los Alamos solve the mystery of the rock’s origin? Not definitively. Although the exact origin could not be determined, it was shown conclusively that the rock was not from outer space. With that said, the saga of Rock that hit New York came to an end. Nothing more was said or written about it. The principals involved have long since passed from the scene. The NICAP ceased operations in 1980. And, the rock, itself, has disappeared.« less

Discovery of potent NEK2 inhibitors as potential anticancer agents using structure-based exploration of NEK2 pharmacophoric space coupled with QSAR analyses.

PubMed

Khanfar, Mohammad A; Banat, Fahmy; Alabed, Shada; Alqtaishat, Saja

2017-02-01

High expression of Nek2 has been detected in several types of cancer and it represents a novel target for human cancer. In the current study, structure-based pharmacophore modeling combined with multiple linear regression (MLR)-based QSAR analyses was applied to disclose the structural requirements for NEK2 inhibition. Generated pharmacophoric models were initially validated with receiver operating characteristic (ROC) curve, and optimum models were subsequently implemented in QSAR modeling with other physiochemical descriptors. QSAR-selected models were implied as 3D search filters to mine the National Cancer Institute (NCI) database for novel NEK2 inhibitors, whereas the associated QSAR model prioritized the bioactivities of captured hits for in vitro evaluation. Experimental validation identified several potent NEK2 inhibitors of novel structural scaffolds. The most potent captured hit exhibited an [Formula: see text] value of 237 nM.

The space shuttle payload planning working groups. Volume 3: High energy astrophysics

NASA Technical Reports Server (NTRS)

1973-01-01

The findings of the High Energy Astrophysics working group of the space shuttle payload planning activity are presented. The objectives to be accomplished during space shuttle missions are defined as: (1) X-ray astronomy, (2) hard X-ray and gamma ray astronomy, and (3) cosmic ray astronomy. The instruments and test equipment required to accomplish the mission are identified. Recommendations for managing the installation of the equipment and conducting the missions are included.

Nonlinear-drifted Brownian motion with multiple hidden states for remaining useful life prediction of rechargeable batteries

NASA Astrophysics Data System (ADS)

Wang, Dong; Zhao, Yang; Yang, Fangfang; Tsui, Kwok-Leung

2017-09-01

Brownian motion with adaptive drift has attracted much attention in prognostics because its first hitting time is highly relevant to remaining useful life prediction and it follows the inverse Gaussian distribution. Besides linear degradation modeling, nonlinear-drifted Brownian motion has been developed to model nonlinear degradation. Moreover, the first hitting time distribution of the nonlinear-drifted Brownian motion has been approximated by time-space transformation. In the previous studies, the drift coefficient is the only hidden state used in state space modeling of the nonlinear-drifted Brownian motion. Besides the drift coefficient, parameters of a nonlinear function used in the nonlinear-drifted Brownian motion should be treated as additional hidden states of state space modeling to make the nonlinear-drifted Brownian motion more flexible. In this paper, a prognostic method based on nonlinear-drifted Brownian motion with multiple hidden states is proposed and then it is applied to predict remaining useful life of rechargeable batteries. 26 sets of rechargeable battery degradation samples are analyzed to validate the effectiveness of the proposed prognostic method. Moreover, some comparisons with a standard particle filter based prognostic method, a spherical cubature particle filter based prognostic method and two classic Bayesian prognostic methods are conducted to highlight the superiority of the proposed prognostic method. Results show that the proposed prognostic method has lower average prediction errors than the particle filter based prognostic methods and the classic Bayesian prognostic methods for battery remaining useful life prediction.

Biological damage induced by ionizing cosmic rays in dry Arabidopsis seeds.

PubMed

Kranz, A R; Bork, U; Bucker, H; Reitz, G

1990-01-01

In September 1987 dry seeds containing embryos of the crucifer plant Arabidopsis thaliana (L.) Heynh, were flown in orbit for 13 days on the Kosmos 1887 satellite. The seeds were fixed on CNd detectors and stored in units of Biorack type I/O. One unit was exposed inside, another one outside the satellite. The temperature profile of the flown seeds inside the satellite was simulated on earth in an identical backup control sample (BC). An additional control (SC) was studied with the original seeds sample. By use of the CNd-detector, HZE-tracks were measured with a PC-assisted microscope. The biological damages were investigated by growing the seeds under controlled climatic conditions. The following biological endpoints of the cosmic radiation damage were studied: germination, radicle length, sublethality, morphological aberrations, flower development, tumorization, embryo lethality inside the siliques. The summarized damage (D) and the mutation frequencies of embyronic lethal genes were calculated. The following results were obtained: the damages increase significantly in orbit at all biological endpoints; germination and fiowerings especially, as well as embryo lethality of fruits and lethal mutation frequency, were maximum mostly for HZE-hit seeds. Additionally, an increase of damage was observed for the seeds of the outside-exposed Biorack in comparison to the inside ones, which was probably caused by less radiation shielding and free space vacuum. The significance of the results obtained is discussed with respect to stress and risk and, thus, the quality of the RBE-factors and heavy ionizing radiation all needed for the very definition of radiation protection standards in space.

Proportional crosstalk correction for the segmented clover at iThemba LABS

NASA Astrophysics Data System (ADS)

Bucher, T. D.; Noncolela, S. P.; Lawrie, E. A.; Dinoko, T. R. S.; Easton, J. L.; Erasmus, N.; Lawrie, J. J.; Mthembu, S. H.; Mtshali, W. X.; Shirinda, O.; Orce, J. N.

2017-11-01

Reaching new depths in nuclear structure investigations requires new experimental equipment and new techniques of data analysis. The modern γ-ray spectrometers, like AGATA and GRETINA are now built of new-generation segmented germanium detectors. These most advanced detectors are able to reconstruct the trajectory of a γ-ray inside the detector. These are powerful detectors, but they need careful characterization, since their output signals are more complex. For instance for each γ-ray interaction that occurs in a segment of such a detector additional output signals (called proportional crosstalk), falsely appearing as an independent (often negative) energy depositions, are registered on the non-interacting segments. A failure to implement crosstalk correction results in incorrectly measured energies on the segments for two- and higher-fold events. It affects all experiments which rely on the recorded segment energies. Furthermore incorrectly recorded energies on the segments cause a failure to reconstruct the γ-ray trajectories using Compton scattering analysis. The proportional crosstalk for the iThemba LABS segmented clover was measured and a crosstalk correction was successfully implemented. The measured crosstalk-corrected energies show good agreement with the true γ-ray energies independent on the number of hit segments and an improved energy resolution for the segment sum energy was obtained.

Solar and Galactic Cosmic Rays Observed by SOHO

NASA Astrophysics Data System (ADS)

Fleck, Bernhard; Curdt, Werner; Olive, Jean-Philippe; van Overbeek, Ton

2015-04-01

Both the Cosmic Ray Flux (CRF) and Solar Energetic Particles (SEPs) have left an imprint on SOHO technical systems. While the solar array efficiency degraded irreversibly down to 75% of its original level over 1 ½ solar cycles, Single Event Upsets (SEUs) in the solid state recorder (SSR) have been reversed by the memory protection mechanism. We compare the daily CRF observed by the Oulu station with the daily SOHO SEU rate and with the degradation curve of the solar arrays. The Oulu CRF and the SOHO SSR SEU rate are both modulated by the solar cycle and are highly correlated, except for sharp spikes in the SEU rate, caused by isolated SEP events, which also show up as discontinuities in the otherwise slowly decreasing solar ray efficiency. This allows to discriminate between effects with solar and non-solar origin and to compare the relative strength of both. We find that the total number of SSR SEUs with solar origin over the 17 ½ years from January 1996 through June 2013 is of the same order as those generated by cosmic ray hits. 49% of the total solar array degradation during that time can be attributed to proton events, i.e. the effect of a series of short-lived, violent events (SEPs) is comparable to the cycle-integrated damage by cosmic rays.

History of Chandra X-Ray Observatory

NASA Image and Video Library

1997-04-15

This photograph captures the installation of the Chandra X-Ray Observatory, formerly Advanced X-Ray Astrophysics Facility (AXAF), Advanced Charged-Coupled Device (CCD) Imaging Spectrometer (ACIS) into the Vacuum Chamber at the X-Ray Calibration Facility (XRCF) at Marshall Space Flight Center (MSFC). The AXAF was renamed Chandra X-Ray Observatory (CXO) in 1999. The CXO is the most sophisticated and the world's most powerful x-ray telescope ever built. It observes x-rays from high-energy regions of the universe, such as hot gas in the remnants of exploded stars. The ACIS is one of two focal plane instruments. As the name suggests, this instrument is an array of CCDs similar to those used in a camcorder. This instrument will be especially useful because it can make x-ray images and measure the energies of incoming x-rays. It is the instrument of choice for studying the temperature variation across x-ray sources, such as vast clouds of hot-gas intergalactic space. MSFC's XRCF is the world's largest, most advanced laboratory for simulating x-ray emissions from distant celestial objects. It produces a space-like environment in which components related to x-ray telescope imaging are tested and the quality of their performances in space is predicted. TRW, Inc. was the prime contractor for the development of the CXO and NASA's MSFC was responsible for its project management. The Smithsonian Astrophysical Observatory controls science and flight operations of the CXO for NASA from Cambridge, Massachusetts. The CXO was launched July 22, 1999 aboard the Space Shuttle Columbia (STS-93).

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

Anthony, Stephen

The Sandia hyperspectral upper-bound spectrum algorithm (hyper-UBS) is a cosmic ray despiking algorithm for hyperspectral data sets. When naturally-occurring, high-energy (gigaelectronvolt) cosmic rays impact the earth’s atmosphere, they create an avalanche of secondary particles which will register as a large, positive spike on any spectroscopic detector they hit. Cosmic ray spikes are therefore an unavoidable spectroscopic contaminant which can interfere with subsequent analysis. A variety of cosmic ray despiking algorithms already exist and can potentially be applied to hyperspectral data matrices, most notably the upper-bound spectrum data matrices (UBS-DM) algorithm by Dongmao Zhang and Dor Ben-Amotz which served as themore » basis for the hyper-UBS algorithm. However, the existing algorithms either cannot be applied to hyperspectral data, require information that is not always available, introduce undesired spectral bias, or have otherwise limited effectiveness for some experimentally relevant conditions. Hyper-UBS is more effective at removing a wider variety of cosmic ray spikes from hyperspectral data without introducing undesired spectral bias. In addition to the core algorithm the Sandia hyper-UBS software package includes additional source code useful in evaluating the effectiveness of the hyper-UBS algorithm. The accompanying source code includes code to generate simulated hyperspectral data contaminated by cosmic ray spikes, several existing despiking algorithms, and code to evaluate the performance of the despiking algorithms on simulated data.« less

Meteoroids are Dangerous to Spacecraft

NASA Technical Reports Server (NTRS)

Moorhead, Althea V.

2017-01-01

Meteoroids put dents in Shuttle windows much like bouncing gravel puts dents in your car's windshield. However, meteoroids move at such high speeds that they can partly vaporize the surfaces they strike! A dust particle (smaller than a meteoroid) hit the STEREO spacecraft and produced this fountain of smaller particles. When a meteoroid breaks up, its "shrapnel" can also be dangerous. Even when meteoroids don't damage a spacecraft, they can cause problems. Here, a small meteoroid bumped a camera on the Lunar Reconnaissance Orbiter (LRO), causing wiggles in this scan of the lunar surface. Meteoroids and pieces of space junk create rough edges on the outside of the Space Station that can damage space suits. The astronauts' gloves had to be thickened to help prevent them from ripping.

Space-Borne Observations of Intense Gamma-Ray Flashes (TGFs) Above Thunderstorms

NASA Technical Reports Server (NTRS)

Fishman, Gerald J.

2011-01-01

Intense millisecond flashes of MeV photons have been observed with space-borne detectors. These terrestrial gamma-ray flashes (TGFs) were discovered with the Burst and Transient Source Experiment (BATSE) aboard the Compton Gamma- Ray Observatory (CGRO) in the early 1990s. They are now being observed with several other instruments, including the Gamma-ray Burst Monitor (GBM) detectors on the Fermi Gamma-ray Space Telescope. Although Fermi-GBM was designed and optimized for the observation of cosmic gamma-ray bursts (GRBs), it has unprecedented capabilities for these TGF observations. On several occasions, intense beams of high-energy electrons and positrons have been observed at the geomagnetic conjugate points of TGFs.

Cosmic-Ray Energetics and Mass (CREAM) Processing - Bonding

NASA Image and Video Library

2017-06-20

In the Space Station Processing Facility at NASA's Kennedy Space Center in Florida, technicians and engineers inspect components for the Cosmic-Ray Energetics and Mass investigation, or CREAM, instrument. It is designed to measure the charges of cosmic rays to better understand what gives them such incredible energies, and how that effects the composition of the universe. The instrument will be launched to the space station on the SpaceX CRS-12 commercial resupply mission in August 2017.

Cosmic-Ray Energetics and Mass (CREAM) Processing - Bonding

NASA Image and Video Library

2017-06-20

In the Space Station Processing Facility at NASA's Kennedy Space Center in Florida, a technician remove a protective cover on the Cosmic-Ray Energetics and Mass investigation, or CREAM, instrument. It is designed to measure the charges of cosmic rays to better understand what gives them such incredible energies, and how that effects the composition of the universe. The instrument will be launched to the space station on the SpaceX CRS-12 commercial resupply mission in August 2017.

Cosmic-Ray Energetics and Mass (CREAM) Unbagging and Inspection

NASA Image and Video Library

2017-06-22

In the Space Station Processing Facility at NASA's Kennedy Space Center in Florida, technicians and engineers inspect the Cosmic-Ray Energetics and Mass investigation, or CREAM, instrument. It is designed to measure the charges of cosmic rays to better understand what gives them such incredible energies, and how that effects the composition of the universe. The instrument will be launched to the space station on the SpaceX CRS-12 commercial resupply mission in August 2017.

Proceedings of the Space Shuttle Sortie Workshop. Volume 2: Working group reports

NASA Technical Reports Server (NTRS)

1972-01-01

Details are presented on the mission planning progress in each of the working paper reports. The general topics covered are the following: space technology; materials processing and space manufacturing; communications and navigation; earth and ocean physics; oceanography; earth resources and surface environmental quality; meteorology and atmospheric environmental quality; life sciences; atmospheric and space physics; solar physics; high energy cosmic rays; X-ray and gamma ray astronomy; ultraviolet-optical astronomy; planetary astronomy; and infrared astronomy.

Analysis of Atmospheric Aerosols Collected in an Urban Area in Upstate NY Using Proton Induced X-ray Emission (PIXE) Spectroscopy

NASA Astrophysics Data System (ADS)

Smith, Jeremy; Ali, Salina; Nadareski, Benjamin; Safiq, Alexandrea; Yoskowitz, Joshua; Labrake, Scott; Vineyard, Michael

2013-10-01

We examined atmospheric aerosol samples collected in Schenectady NY for evidence of pollution. We collected aerosol samples using a nine stage cascade impactor which distributes the particulate matter by aerodynamic size onto 7.5 μm Kapton foils. We then used a 1MV electrostatic Pelletron accelerator to produce a 2.2 MeV proton beam to hit the impacted foils. X-ray intensity versus energy spectra were collected using an Amptek x-ray detector where the x-rays are produced from the proton beam interacting with the sample. This is called PIXE. The elemental composition and concentrations of the elements present in the aerosol samples were determined using a software package called GUPIX. We have found elements ranging from Al to Pb and in particular have found significant amounts of Pb and Br on some of our impacted foils, with a Br/Pb ratio of 0.6 +/- 0.2 which agrees with previous studies. This result suggests the presence of leaded aviation fuel perhaps due to the proximity of the collection site to a small airport with a significant amount of general aviation traffic. Union College.

CME Arrival-time Validation of Real-time WSA-ENLIL+Cone Simulations at the CCMC/SWRC

NASA Astrophysics Data System (ADS)

Wold, A. M.; Mays, M. L.; Taktakishvili, A.; Jian, L.; Odstrcil, D.; MacNeice, P. J.

2016-12-01

The Wang-Sheeley-Arge (WSA)-ENLIL+Cone model is used extensively in space weather operations worldwide to model CME propagation, as such it is important to assess its performance. We present validation results of the WSA-ENLIL+Cone model installed at the Community Coordinated Modeling Center (CCMC) and executed in real-time by the CCMC/Space Weather Research Center (SWRC). The SWRC is a CCMC sub-team that provides space weather services to NASA robotic mission operators and science campaigns, and also prototypes new forecasting models and techniques. CCMC/SWRC uses the WSA-ENLIL+Cone model to predict CME arrivals at NASA missions throughout the inner heliosphere. In this work we compare model predicted CME arrival-times to in-situ ICME shock observations near Earth (ACE, Wind), STEREO-A and B for simulations completed between March 2010 - July 2016 (over 1500 runs). We report hit, miss, false alarm, and correct rejection statistics for all three spacecraft. For hits we compute the bias, RMSE, and average absolute CME arrival time error, and the dependence of these errors on CME input parameters. We compare the predicted geomagnetic storm strength (Kp index) to the CME arrival time error for Earth-directed CMEs. The predicted Kp index is computed using the WSA-ENLIL+Cone plasma parameters at Earth with a modified Newell et al. (2007) coupling function. We also explore the impact of the multi-spacecraft observations on the CME parameters used initialize the model by comparing model validation results before and after the STEREO-B communication loss (since September 2014) and STEREO-A side-lobe operations (August 2014-December 2015). This model validation exercise has significance for future space weather mission planning such as L5 missions.

Current Perspectives in High Energy Astrophysics

NASA Technical Reports Server (NTRS)

Ormes, Jonathan F. (Editor)

1996-01-01

High energy astrophysics is a space-age discipline that has taken a quantum leap forward in the 1990s. The observables are photons and particles that are unable to penetrate the atmosphere and can only be observed from space or very high altitude balloons. The lectures presented as chapters of this book are based on the results from the Compton Gamma-Ray Observatory (CGRO) and Advanced Satellite for Cosmology and Astrophysics (ASCA) missions to which the Laboratory for High Energy Astrophysics at NASA's Goddard Space Flight Center made significant hardware contributions. These missions study emissions from very hot plasmas, nuclear processes, and high energy particle interactions in space. Results to be discussed include gamma-ray beaming from active galactic nuclei (AGN), gamma-ray emission from pulsars, radioactive elements in the interstellar medium, X-ray emission from clusters of galaxies, and the progress being made to unravel the gamma-ray burst mystery. The recently launched X-ray Timing Explorer (XTE) and prospects for upcoming Astro-E and Advanced X-ray Astronomy Satellite (AXAF) missions are also discussed.

KENNEDY SPACE CENTER, FLA. - An X-ray machine is in place to take images of four rudder speed brake actuators to be installed on the orbiter Discovery. The actuators are being X-rayed at the Cape Canaveral Air Force Station’s Radiographic High-Energy X-ray Facility to determine if the gears were installed correctly. Discovery has been assigned to the first Return to Flight mission, STS-114, a logistics flight to the International Space Station.

NASA Image and Video Library

2004-03-08

KENNEDY SPACE CENTER, FLA. - An X-ray machine is in place to take images of four rudder speed brake actuators to be installed on the orbiter Discovery. The actuators are being X-rayed at the Cape Canaveral Air Force Station’s Radiographic High-Energy X-ray Facility to determine if the gears were installed correctly. Discovery has been assigned to the first Return to Flight mission, STS-114, a logistics flight to the International Space Station.

Hit Identification and Optimization in Virtual Screening: Practical Recommendations Based Upon a Critical Literature Analysis

PubMed Central

Zhu, Tian; Cao, Shuyi; Su, Pin-Chih; Patel, Ram; Shah, Darshan; Chokshi, Heta B.; Szukala, Richard; Johnson, Michael E.; Hevener, Kirk E.

2013-01-01

A critical analysis of virtual screening results published between 2007 and 2011 was performed. The activity of reported hit compounds from over 400 studies was compared to their hit identification criteria. Hit rates and ligand efficiencies were calculated to assist in these analyses and the results were compared with factors such as the size of the virtual library and the number of compounds tested. A series of promiscuity, drug-like, and ADMET filters were applied to the reported hits to assess the quality of compounds reported and a careful analysis of a subset of the studies which presented hit optimization was performed. This data allowed us to make several practical recommendations with respect to selection of compounds for experimental testing, defining hit identification criteria, and general virtual screening hit criteria to allow for realistic hit optimization. A key recommendation is the use of size-targeted ligand efficiency values as hit identification criteria. PMID:23688234

The Helicity Injected Torus Program

NASA Astrophysics Data System (ADS)

Jarboe, T. R.; Nelson, B. A.; Jewell, P. D.; Liptac, J. E.; McCollam, K. J.; Raman, R.; Redd, A. J.; Rogers, J. A.; Sieck, P. E.; Shumlak, U.; Smith, R. J.; Nagata, M.; Uyama, T.

1999-11-01

The Helicity Injected Torus--II (HIT--II) spherical torus is capable of both Coaxial Helicity Injection (CHI) and transformer action current drive. HIT--II has a major radius R = 0.3, minor radius a = 0.2, aspect ratio A = R/a = 1.5, with an on axis magnetic field of up to Bo = 0.67 T. HIT--II provides equilibrium control, CHI flux boundary conditions, and transformer action using 28 poloidal field coils, using active flux feedback control. HIT--II has driven up to 200 kA of plasma current, using either CHI or transformer drive. An overview and recent results of the HIT--II program will be presented. The development of a locked-electron current drive model for HIT and HIT--II has led to the design of a constant inductive helicity injection method for spherical torii. This method is incorporated in the design of the Helicity Injected Torus -- Steady Inductive (HIT-- SI)(T.R. Jarboe, Fusion Technology, 36) (1), p. 85, 1999 experiment. HIT--SI can form a high-beta spheromak, a low aspect ratio RFP, or a spherical tokamak in a steady-state manner without using electrodes. The HIT--SI design and methodology will be presented.

Rapid exclusion of the diagnosis of immune HIT by AcuStar HIT and heparin-induced multiple electrode aggregometry.

PubMed

Minet, V; Baudar, J; Bailly, N; Douxfils, J; Laloy, J; Lessire, S; Gourdin, M; Devalet, B; Chatelain, B; Dogné, J M; Mullier, F

2014-06-01

Accurate diagnosis of heparin-induced thrombocytopenia (HIT) is essential but remains challenging. We have previously demonstrated, in a retrospective study, the usefulness of the combination of the 4Ts score, AcuStar HIT and heparin-induced multiple electrode aggregometry (HIMEA) with optimized thresholds. We aimed at exploring prospectively the performances of our optimized diagnostic algorithm on suspected HIT patients. The secondary objective is to evaluate performances of AcuStar HIT-Ab (PF4-H) in comparison with the clinical outcome. 116 inpatients with clinically suspected immune HIT were included. Our optimized diagnostic algorithm was applied to each patient. Sensitivity, specificity, negative predictive value (NPV), positive predictive value (PPV) of the overall diagnostic strategy as well as AcuStar HIT-Ab (at manufacturer's thresholds and at our thresholds) were calculated using clinical diagnosis as the reference. Among 116 patients, 2 patients had clinically-diagnosed HIT. These 2 patients were positive on AcuStar HIT-Ab, AcuStar HIT-IgG and HIMEA. Using our optimized algorithm, all patients were correctly diagnosed. AcuStar HIT-Ab at our cut-off (>9.41 U/mL) and at manufacturer's cut-off (>1.00 U/mL) showed both a sensitivity of 100.0% and a specificity of 99.1% and 90.4%, respectively. The combination of the 4Ts score, the HemosIL® AcuStar HIT and HIMEA with optimized thresholds may be useful for the rapid and accurate exclusion of the diagnosis of immune HIT. Copyright © 2014 Elsevier Ltd. All rights reserved.

Inappropriate documentation of heparin allergy in the medical record because of misdiagnosis of heparin-induced thrombocytopenia: frequency and consequences.

PubMed

McMahon, C M; Tanhehco, Y C; Cuker, A

2017-02-01

Essentials Misdiagnosis of heparin-induced thrombocytopenia (HIT) may be associated with adverse outcomes. We conducted a study of patients with a heparin allergy in the chart due to misdiagnosis of HIT. 42% of patients with a heparin allergy due to suspected HIT were clearly HIT-negative. 68% were unnecessarily treated with an alternative anticoagulant, 66% of whom had major bleeding. Background It is recommended that heparin be added to the allergy list of patients with heparin-induced thrombocytopenia (HIT). Misdiagnosis of HIT could lead to inappropriate documentation of a heparin allergy and adverse outcomes. Objectives To determine the frequency and consequences of inappropriate documentation of a heparin allergy because of misdiagnosis of HIT. Methods We conducted a cohort study of patients with an inappropriate heparin allergy listed in the electronic medical record (EMR) because of misdiagnosis of HIT. We searched the EMR for patients with a new heparin allergy. Patients were eligible if the reason for allergy listing was suspected acute HIT and laboratory testing for HIT was performed within 60 days. Subjects were defined as 'HIT-negative' if they had a 4Ts score of ≤ 3 or negative laboratory test results. Results Of 239 subjects with a new heparin allergy documented because of concern regarding HIT, 100 (42%) met the prespecified definition of HIT-negative. Sixty-eight (68%) HIT-negative subjects unnecessarily received an alternative parenteral anticoagulant for a median duration of 10.5 days. Among these 68 patients, 45 (66%) met criteria for major bleeding. Sixty-eight (68%) of the 100 HIT-negative subjects had an inappropriate allergy to heparin documented that persisted in the EMR for > 3 years beyond the index hospitalization. Conclusions Inappropriate listing of heparin as an allergy in the EMR because of misdiagnosis of HIT is common, is associated with substantial rates of unnecessary alternative anticoagulant use and major bleeding, and tends to persist beyond the index admission. © 2016 International Society on Thrombosis and Haemostasis.

NASA Scientists Witness a Supernova Cosmic Rite of Passage

NASA Astrophysics Data System (ADS)

2005-11-01

Scientists using NASA's Chandra X-ray Observatory have witnessed a cosmic rite of passage, the transition from a supernova to a supernova remnant, a process that has never been seen in much detail until now, leaving it poorly defined. A supernova is a massive star explosion; the remnant is the beautiful glowing shell that evolves afterwards. When does a supernova become supernova remnant? When does the shell appear and what powers its radiant glow? A science team led by Dr. Stefan Immler of NASA's Goddard Space Flight Center, Greenbelt, Md., has taken a fresh look at a supernova that exploded in 1970, called SN 1970G, just off the handle of the Big Dipper. This is the oldest supernova ever seen by X-ray telescopes. Chandra X-ray Image of SN 1970G Chandra X-ray Image of SN 1970G "Some astronomers have thought there's a moment when the supernova remnant magically turns on years after the supernova itself has faded away, when the shock wave of the explosion finally hits and lights up the interstellar medium," said Immler. "By contrast, our results show that a new supernova quickly and seamlessly evolves into a supernova remnant. The star's own debris, and not the interstellar medium gas, fuels the remnant." These results appear in The Astrophysical Journal, co-authored by Dr. Kip Kuntz, also of Goddard. They support previous Chandra observations of SN 1987A by Dr. Sangwook Park of Penn State. Using new data from Chandra and archived data from the European-led ROSAT and XMM-Newton observatories, Immler and Kuntz pieced together how SN 1970G evolved over the years. They found telltale signs of a supernova remnant - bright X-ray light - yet no evidence of interstellar gas, even across a distance around the site of the explosion 35 times larger than our solar system. Instead, the material that is heated by the supernova shock to glow in X-ray light, what we call the remnant, is from the stellar wind of the star itself and not distant gas in the interstellar medium. This wind, comprising energetic ions, was shed by the progenitor star thousands to million of years before the explosion. If this were from the interstellar medium, it would be much denser than this stellar wind. NOAO Optical Image of SN 1970G NOAO Optical Image of SN 1970G Immler and Kuntz next studied the density profiles of all other supernovae that have been detected over the past two decades. Sure enough, the low-density circumstellar matter from the stellar wind was the source of X-rays, not the interstellar medium. Immler said that historical supernova remnants such as Cassiopeia A, which exploded some 320 years ago, also show no signs of activity from the interstellar medium. This is more than just a name game, more than hypothetically changing SN 1970G to SNR 1970G. "We have to rethink this notion that a shock wave from the supernova crashes into the interstellar medium to create a supernova remnant," said Immler. "The luminous supernova remnants that we see can be created without the need of a dense interstellar medium. In fact, our study showed that all supernovae detected in X-rays over the past 25 years live in a low-density environment." SN 1970G is located in the galaxy M101, also called the Pinwheel Galaxy, a stunning spiral galaxy about 22 million light years away in the constellation Ursa Major, home of the Big Dipper. Although the galaxy itself is visible from dark skies with binoculars, telescopes cannot resolve much structure in SN 1970G, unlike for supernova remnants in our Milky Way galaxy. Discovered with an optical telescope in 1970, SN 1970G was not seen with X-ray telescopes until the 1990s. Immler's work at NASA Goddard is supported through the Universities Space Research Association. Kuntz is supported through University of Maryland, Baltimore County. NASA's Marshall Space Flight Center in Huntsville, Ala., manages the Chandra program for the Agency's Science Mission Directorate. The Smithsonian Astrophysical Observatory controls science and flight operations from the Chandra X-ray Center in Cambridge, Mass. Additional information and images are available at: http://chandra.harvard.edu and http://chandra.nasa.gov

Real-time Ensemble Forecasting of Coronal Mass Ejections using the WSA-ENLIL+Cone Model

NASA Astrophysics Data System (ADS)

Mays, M. L.; Taktakishvili, A.; Pulkkinen, A. A.; MacNeice, P. J.; Rastaetter, L.; Kuznetsova, M. M.; Odstrcil, D.

2013-12-01

Ensemble forecasting of coronal mass ejections (CMEs) provides significant information in that it provides an estimation of the spread or uncertainty in CME arrival time predictions due to uncertainties in determining CME input parameters. Ensemble modeling of CME propagation in the heliosphere is performed by forecasters at the Space Weather Research Center (SWRC) using the WSA-ENLIL cone model available at the Community Coordinated Modeling Center (CCMC). SWRC is an in-house research-based operations team at the CCMC which provides interplanetary space weather forecasting for NASA's robotic missions and performs real-time model validation. A distribution of n (routinely n=48) CME input parameters are generated using the CCMC Stereo CME Analysis Tool (StereoCAT) which employs geometrical triangulation techniques. These input parameters are used to perform n different simulations yielding an ensemble of solar wind parameters at various locations of interest (satellites or planets), including a probability distribution of CME shock arrival times (for hits), and geomagnetic storm strength (for Earth-directed hits). Ensemble simulations have been performed experimentally in real-time at the CCMC since January 2013. We present the results of ensemble simulations for a total of 15 CME events, 10 of which were performed in real-time. The observed CME arrival was within the range of ensemble arrival time predictions for 5 out of the 12 ensemble runs containing hits. The average arrival time prediction was computed for each of the twelve ensembles predicting hits and using the actual arrival time an average absolute error of 8.20 hours was found for all twelve ensembles, which is comparable to current forecasting errors. Some considerations for the accuracy of ensemble CME arrival time predictions include the importance of the initial distribution of CME input parameters, particularly the mean and spread. When the observed arrivals are not within the predicted range, this still allows the ruling out of prediction errors caused by tested CME input parameters. Prediction errors can also arise from ambient model parameters such as the accuracy of the solar wind background, and other limitations. Additionally the ensemble modeling setup was used to complete a parametric event case study of the sensitivity of the CME arrival time prediction to free parameters for ambient solar wind model and CME.

History of Chandra X-Ray Observatory

NASA Image and Video Library

1998-01-01

This photograph shows a TRW technician inspecting the completely assembled Chandra X-ray Observatory (CXO) in the Thermal Vacuum Chamber at TRW Space and Electronics Group of Redondo Beach, California. The CXO is formerly known as the Advanced X-Ray Astrophysics Facility (AXAF), which was renamed in honor of the late Indian-American Astronomer, Subrahmanyan Chandrasekhar in 1999. The CXO will help astronomers worldwide better understand the structure and evolution of the universe by studying powerful sources of x-rays such as exploding stars, matter falling into black holes and other exotic celestial objects. X-ray astronomy can only be done from space because Earth's atmosphere blocks x-rays from reaching the surface. The Observatory provides images that are 50 times more detailed than previous x-ray missions. At more than 45 feet in length and weighing more than 5 tons, it will be one of the largest objects ever placed in Earth orbit by the Space Shuttle. TRW, Inc. was the prime contractor and assembled and tested the observatory for NASA. The CXO program is managed by the Marshall Space Flight Center. The Observatory was launched on July 22, 1999 aboard the Space Shuttle Columbia, STS-93 mission. (Image courtesy of TRW)

History of Chandra X-Ray Observatory

NASA Image and Video Library

1999-01-01

This photograph shows TRW technicians preparing the assembled Chandra X-Ray Observatory (CXO) for an official unveiling at TRW Space and Electronics Group of Redondo Beach, California. The CXO is formerly known as the Advanced X-Ray Astrophysics Facility (AXAF), which was renamed in honor of the late Indian-American Astronomer, Subrahmanyan Chandrasekhar in 1999. The CXO will help astronomers world-wide better understand the structure and evolution of the universe by studying powerful sources of x-rays such as exploding stars, matter falling into black holes, and other exotic celestial objects. X-ray astronomy can only be done from space because Earth's atmosphere blocks x-rays from reaching the surface. The Observatory provides images that are 50 times more detailed than previous x-ray missions. At more than 45 feet in length and weighing more than 5 tons, it will be one of the largest objects ever placed in Earth orbit by the Space Shuttle. TRW, Inc. was the prime contractor and assembled and tested the observatory for NASA. The CXO program is managed by the Marshall Space Flight Center. The Observatory was launched on July 22, 1999 aboard the Space Shuttle Columbia, STS-93 mission. (Image courtesy of TRW)

Integrated machine learning, molecular docking and 3D-QSAR based approach for identification of potential inhibitors of trypanosomal N-myristoyltransferase.

PubMed

Singh, Nidhi; Shah, Priyanka; Dwivedi, Hemlata; Mishra, Shikha; Tripathi, Renu; Sahasrabuddhe, Amogh A; Siddiqi, Mohammad Imran

2016-11-15

N-Myristoyltransferase (NMT) catalyzes the transfer of myristate to the amino-terminal glycine of a subset of proteins, a co-translational modification involved in trafficking substrate proteins to membrane locations, stabilization and protein-protein interactions. It is a studied and validated pre-clinical drug target for fungal and parasitic infections. In the present study, a machine learning approach, docking studies and CoMFA analysis have been integrated with the objective of translation of knowledge into a pipelined workflow towards the identification of putative hits through the screening of large compound libraries. In the proposed pipeline, the reported parasitic NMT inhibitors have been used to develop predictive machine learning classification models. Simultaneously, a TbNMT complex model was generated to establish the relationship between the binding mode of the inhibitors for LmNMT and TbNMT through molecular dynamics simulation studies. A 3D-QSAR model was developed and used to predict the activity of the proposed hits in the subsequent step. The hits classified as active based on the machine learning model were assessed as the potential anti-trypanosomal NMT inhibitors through molecular docking studies, predicted activity using a QSAR model and visual inspection. In the final step, the proposed pipeline was validated through in vitro experiments. A total of seven hits have been proposed and tested in vitro for evaluation of dual inhibitory activity against Leishmania donovani and Trypanosoma brucei. Out of these five compounds showed significant inhibition against both of the organisms. The common topmost active compound SEW04173 belongs to a pyrazole carboxylate scaffold and is anticipated to enrich the chemical space with enhanced potency through optimization.

Earth Observations taken by Expedition 26 crewmember

NASA Image and Video Library

2011-03-13

ISS026-E-033648 (13 March 2011) --- From 220 miles above Japan, an Expedition 26 crew member onboard the International Space Station took this 800mm view of Sendai, and the coast mostly north on March 13. Sunglint helps to highlight the flood waters over the land, flowing out the rivers, plus the heavy oils swirling on the surface with the currents. An earthquake and subsequent tsunami hit Japan on March 11.

Why Space Telescopes Are Amazing

NASA Technical Reports Server (NTRS)

Rigby, Jane R.

2012-01-01

One of humanity's best ideas has been to put telescopes in space. The dark stillness of space allows telescopes to perform much better than they can on even the darkest and clearest of Earth's mountaintops. In addition, from space we can detect colors of light, like X-rays and gamma rays, that are blocked by the Earth's atmosphere I'll talk about NASA's team of great observatories: the Hubble Space Telescope, Spitzer Space Telescope, and Chandra X-ray Observatory} and how they've worked together to answer key questions: When did the stars form? Is there really dark matter? Is the universe really expanding ever faster and faster?

RPC based 5D tracking concept for high multiplicity tracking trigger

NASA Astrophysics Data System (ADS)

Aielli, G.; Camarri, P.; Cardarelli, R.; Di Ciaccio, A.; Distante, L.; Liberti, B.; Paolozzi, L.; Pastori, E.; Santonico, R.

2017-01-01

The recently approved High Luminosity LHC project (HL-LHC) and the future colliders proposals present a challenging experimental scenario, dominated by high pileup, radiation background and a bunch crossing time possibly shorter than 5 ns. This holds as well for muon systems, where RPCs can play a fundamental role in the design of the future experiments. The RPCs, thanks to their high space-time granularity, allows a sparse representation of the particle hits, in a very large parametric space containing, in addition to 3D spatial localization, also the pulse time and width associated to the avalanche charge. This 5D representation of the hits can be exploited to improve the performance of complex detectors such as muon systems and increase the discovery potential of a future experiment, by allowing a better track pileup rejection and sharper momentum resolution, an effective measurement of the particle velocity, to tag and trigger the non-ultrarelativistic particles, and the detection local multiple track events in close proximity without ambiguities. Moreover, due to the fast response, typically for RPCs of the order of a few ns, this information can be provided promptly to the lowest level trigger. We will discus theoretically and experimentally the principles and performance of this original method.

XMM-Newton detects X-ray 'solar cycle' in distant star

NASA Astrophysics Data System (ADS)

2004-05-01

The Sun as observed by SOHO hi-res Size hi-res: 708 Kb The Sun as observed by SOHO The Sun as observed by the ESA/NASA SOHO observatory near the minimum of the solar cycle (left) and near its maximum (right). The signs of solar activity near the maximum are clearly seen. New XMM-Newton observations suggest that this behaviour may be typical of stars like the Sun, such as HD 81809 in the constellation Hydra. Solar flare - 4 November 2003 The huge flare produced on 4 November 2003 This image of the Sun, obtained by the ESA/NASA SOHO observatory, shows the powerful X-ray flare that took place on 4 November 2003. The associated coronal mass ejection, coming out of the Sun at a speed of 8.2 million kilometres per hour, hit the Earth several hours later and caused disruptions to telecommunication and power distribution lines. New XMM-Newton observations suggest that this behaviour may be typical of stars like the Sun, such as HD 81809 in the constellation Hydra. Since the time Galileo discovered sunspots, in 1610, astronomers have measured their number, size and location on the disc of the Sun. Sunspots are relatively cooler areas on the Sun that are observed as dark patches. Their number rises and falls with the level of activity of the Sun in a cycle of about 11 years. When the Sun is very active, large-scale phenomena take place, such as the flares and coronal mass ejections observed by the ESA/NASA solar observatory SOHO. These events release a large amount of energy and charged particles that hit the Earth and can cause powerful magnetic storms, affecting radio communications, power distribution lines and even our weather and climate. During the solar cycle, the X-ray emission from the Sun varies by a large amount (about a factor of 100) and is strongest when the cycle is at its peak and the surface of the Sun is covered by the largest number of spots. ESA's X-ray observatory, XMM-Newton, has now shown for the first time that this cyclic X-ray behaviour is common to other stars as well. A team of astronomers, led by Fabio Favata, from ESA's European Space Research and Technology Centre, The Netherlands, has monitored a small number of solar-type stars since the beginning of the XMM-Newton mission in 2000. The X-ray brightness of HD 81809, a star located 90 light years away in the constellation Hydra (the water snake), has varied by more than 10 times over the past two and a half years, reaching a well defined peak in mid 2002. The star has shown the characteristic X-ray modulation (brightening and dimming) typical of the solar cycle. "This is the first clear sign of a cyclic pattern in the X-ray emission of stars other than the Sun," said Favata. Furthermore, the data show that these variations are synchronised with the starspot cycle. If HD 81809 behaves like the Sun, its X-ray brightness can vary by a factor of one hundred over a few years. "We might well have caught HD 81809 at the beginning of an X-ray activity cycle," added Favata. The existence of starspot cycles on other stars had already been established long ago, thanks to observations that began in the 1950s. However, scientists did not know whether the X-ray radiation would also vary with the number of starspots. ESA's XMM-Newton has now shown that this is indeed the case and that this cyclic X-ray pattern is not typical of the Sun alone. "This suggests that our Sun's behaviour is probably nothing exceptional," said Favata. Besides its interest for scientists, the Sun's cyclical behaviour can have an influence on everyone on Earth. Our climate is known to be significantly affected by the high-energy radiation emitted by the Sun. For instance, a temporary disappearance of the solar cycle in the 18th century corresponded with an exceptionally cold period on Earth. Similarly, in the early phases of the lifetime of a planet, this high-energy radiation has a strong influence on the conditions of the atmosphere, and thus potentially on the development of life. Finding out whether the Sun's X-ray cycle is common among other solar-type stars, and in particular among those hosting potential rocky planets, can give scientists much needed clues on whether and where other forms of life might exist outside the Solar System. At the same time, understanding how typical and long-lasting is the solar behaviour will tell us more about the evolution of the climate on Earth. Further observations of HD 81809 and other similar stars are already planned with XMM-Newton. They will allow astronomers to study whether the large modulations in X-ray brightness observed in the Sun are indeed the norm for stars of its type. Understanding how other solar-like stars behave in general will give scientists better insight into the past and future of our own Sun. Note to editors The results described here were published in the April issue of the scientific journal Astronomy and Astrophysics (Vol. 418, p. L13). The authors of the paper are F. Favata, G. Micela, S. Baliunas, J. Schmitt, M. Guedel, F. Harnden Jr., S. Sciortino and R. Stern. A reprint of the paper can be found at: http://arxiv.org/abs/astro-ph/0403142 More about XMM-Newton XMM-Newton can detect more X-ray sources than any previous satellite and is helping to solve many cosmic mysteries of the violent Universe, from black holes to the formation of galaxies. It was launched on 10 December 1999, using an Ariane-5 rocket from French Guiana. It is expected to return data for a decade. XMM-Newton's high-tech design uses over 170 wafer-thin cylindrical mirrors spread over three telescopes. Its orbit takes it almost a third of the way to the Moon, so that astronomers can enjoy long, uninterrupted views of celestial objects. More information on XMM-Newton can be found at: http://www.esa.int/esaSC/SEMM8IGHZTD_1_spk.html More about SOHO SOHO is a project of international cooperation between ESA and NASA to study the Sun, from its deep core to the outer corona, and the solar wind. Fourteen European countries, led by the European Space Agency and prime contractor Astrium (formerly Matra-Marconi), built the SOHO spacecraft. It carries twelve instruments (nine European-led and three American-led) and was launched by an NASA's Atlas II-AS rocket on 2 December 1995. Mission operations are coordinated at NASA's Goddard Space Flight Centre. The spacecraft was designed for a two-year mission but its spectacular success has led to two extensions of the mission, the first until 2003, and then again until March 2007. More information on SOHO can be found at: http://www.esa.int/esaSC/SEMJFH374OD_1_spk.html

77 FR 32639 - HIT Standards Committee and HIT Policy Committee; Call for Nominations

Federal Register 2010, 2011, 2012, 2013, 2014

2012-06-01

... with the implementation of the Federal Health IT Strategic Plan, and in accordance with policies... DEPARTMENT OF HEALTH AND HUMAN SERVICES HIT Standards Committee and HIT Policy Committee; Call for... Health Information Technology Policy Committee (HITPC). Name of Committees: HIT Standards Committee and...

An Investigation of the Relationship Between Automated Machine Translation Evaluation Metrics and User Performance on an Information Extraction Task

DTIC Science & Technology

2007-01-01

parameter dimension between the two models). 93 were tested.3 Model 1 log( pHits 1− pHits ) = α + β1 ∗ MetricScore (6.6) The results for each of the...505.67 oTERavg .357 .13 .007 log( pHits 1− pHits ), that is, log-odds of correct task performance, of 2.79 over the intercept only model. All... pHits 1− pHits ) = −1.15− .418× I[MT=2] − .527× I[MT=3] + 1.78×METEOR+ 1.28×METEOR × I[MT=2] + 1.86×METEOR × I[MT=3] (6.7) Model 3 log( pHits 1− pHits

Review of Social and Organizational Issues in Health Information Technology.

PubMed

Kuziemsky, Craig E

2015-07-01

This paper reviews organizational and social issues (OSIs) in health information technology (HIT). A review and synthesis of the literature on OSIs in HIT was conducted. Five overarching themes with respect to OSIs in HIT were identified and discussed: scope and frameworks for defining OSIs in HIT, context matters, process immaturity and complexity, trade-offs will happen and need to be discussed openly, and means of studying OSIs in HIT. There is a wide body of literature that provides insight into OSIs in HIT, even if many of the studies are not explicitly labelled as such. The two biggest research needs are more explicit and theoretical studies of OSI in HITs and more research on integrating micro and macro perspectives of HIT use in organizations.

Identifying and Synchronizing Health Information Technology (HIT) Events from FDA Medical Device Reports.

PubMed

Kang, Hong; Wang, Frank; Zhou, Sicheng; Miao, Qi; Gong, Yang

2017-01-01

Health information technology (HIT) events, a subtype of patient safety events, pose a major threat and barrier toward a safer healthcare system. It is crucial to gain a better understanding of the nature of the errors and adverse events caused by current HIT systems. The scarcity of HIT event-exclusive databases and event reporting systems indicates the challenge of identifying the HIT events from existing resources. FDA Manufacturer and User Facility Device Experience (MAUDE) database is a potential resource for HIT events. However, the low proportion and the rapid evolvement of HIT-related events present challenges for distinguishing them from other equipment failures and hazards. We proposed a strategy to identify and synchronize HIT events from MAUDE by using a filter based on structured features and classifiers based on unstructured features. The strategy will help us develop and grow an HIT event-exclusive database, keeping pace with updates to MAUDE toward shared learning.

Health information technology and dynamic capabilities.

PubMed

Leung, Ricky C

2012-01-01

Health information technology (HIT) purports to increase quality and efficiency in health care organizations. However, health care organizations are situated in constantly changing environments. They need dynamic capabilities to implement HIT effectively. This article builds on the dynamic capabilities perspective and generates propositions about implementing HIT in dynamic environments. Specifically, I identify the (1) the necessary resources and capabilities for organizations to implement HIT; (2) the organizational capabilities and benefits that can be enhanced by HIT; and (3) the similarities and differences between three distinct forms of HIT. I synthesized the literature on dynamic capabilities and HIT to identify dynamic capabilities that are associated with (1) electronic medical records, (2) telemedicine, and (3) social media. In addition, I discuss the benefits of these HITs for improving the dynamic capabilities of health care organizations. PROPOSITIONS/FINDINGS: This article generates three sets of propositions that can be tested empirically. First, I am concerned with how organizational size and human resources affect successful implementation of HIT. In addition, I argue that three technology-specific factors--hospital type, medical specialty, and socially desirable technical features--may affect the implementation of HIT. To cope with constantly changing environmental pressures, health administrators need to deploy, modify, and/or acquire organizational resources skillfully. Practitioners need to identify dynamic capabilities to support specific forms of HIT and understand how HIT enables health care organizations in turn. The concept of evolutionary fitness in the dynamic capabilities perspective may be developed to measure HIT implementation.

Health Information Technologies-Academic and Commercial Evaluation (HIT-ACE) methodology: description and application to clinical feedback systems.

PubMed

Lyon, Aaron R; Lewis, Cara C; Melvin, Abigail; Boyd, Meredith; Nicodimos, Semret; Liu, Freda F; Jungbluth, Nathaniel

2016-09-22

Health information technologies (HIT) have become nearly ubiquitous in the contemporary healthcare landscape, but information about HIT development, functionality, and implementation readiness is frequently siloed. Theory-driven methods of compiling, evaluating, and integrating information from the academic and commercial sectors are necessary to guide stakeholder decision-making surrounding HIT adoption and to develop pragmatic HIT research agendas. This article presents the Health Information Technologies-Academic and Commercial Evaluation (HIT-ACE) methodology, a structured, theory-driven method for compiling and evaluating information from multiple sectors. As an example demonstration of the methodology, we apply HIT-ACE to mental and behavioral health measurement feedback systems (MFS). MFS are a specific class of HIT that support the implementation of routine outcome monitoring, an evidence-based practice. HIT-ACE is guided by theories and frameworks related to user-centered design and implementation science. The methodology involves four phases: (1) coding academic and commercial materials, (2) developer/purveyor interviews, (3) linking putative implementation mechanisms to hit capabilities, and (4) experimental testing of capabilities and mechanisms. In the current demonstration, phase 1 included a systematic process to identify MFS in mental and behavioral health using academic literature and commercial websites. Using user-centered design, implementation science, and feedback frameworks, the HIT-ACE coding system was developed, piloted, and used to review each identified system for the presence of 38 capabilities and 18 additional characteristics via a consensus coding process. Bibliometic data were also collected to examine the representation of the systems in the scientific literature. As an example, results are presented for the application of HIT-ACE phase 1 to MFS wherein 49 separate MFS were identified, reflecting a diverse array of characteristics and capabilities. Preliminary findings demonstrate the utility of HIT-ACE to represent the scope and diversity of a given class of HIT beyond what can be identified in the academic literature. Phase 2 data collection is expected to confirm and expand the information presented and phases 3 and 4 will provide more nuanced information about the impact of specific HIT capabilities. In all, HIT-ACE is expected to support adoption decisions and additional HIT development and implementation research.

Research in space science and technology. [including X-ray astronomy and interplanetary plasma physics

NASA Technical Reports Server (NTRS)

Beckley, L. E.

1977-01-01

Progress in various space flight research programs is reported. Emphasis is placed on X-ray astronomy and interplanetary plasma physics. Topics covered include: infrared astronomy, long base line interferometry, geological spectroscopy, space life science experiments, atmospheric physics, and space based materials and structures research. Analysis of galactic and extra-galactic X-ray data from the Small Astronomy Satellite (SAS-3) and HEAO-A and interplanetary plasma data for Mariner 10, Explorers 47 and 50, and Solrad is discussed.

Cosmic-Ray Energetics and Mass (CREAM) Processing - Bonding

NASA Image and Video Library

2017-06-20

In the Space Station Processing Facility at NASA's Kennedy Space Center in Florida, technicians and engineers remove a protective cover on the Cosmic-Ray Energetics and Mass investigation, or CREAM, instrument. It is designed to measure the charges of cosmic rays to better understand what gives them such incredible energies, and how that effects the composition of the universe. The instrument will be launched to the space station on the SpaceX CRS-12 commercial resupply mission in August 2017.

TRW Ships NASA's Chandra X-ray Observatory To Kennedy Space Center

NASA Astrophysics Data System (ADS)

1999-04-01

Two U.S. Air Force C-5 Galaxy transport planes carrying the observatory and its ground support equipment landed at Kennedy's Space Shuttle Landing Facility at 2:40 p.m. EST this afternoon. REDONDO BEACH, CA.--(Business Wire)--Feb. 4, 1999--TRW has shipped NASA's Chandra X-ray Observatory ("Chandra") to the Kennedy Space Center (KSC), in Florida, in preparation for a Space Shuttle launch later this year. The 45-foot-tall, 5-ton science satellite will provide astronomers with new information on supernova remnants, the surroundings of black holes, and other celestial phenomena that produce vast quantities of X-rays. Cradled safely in the cargo hold of a tractor-trailer rig called the Space Cargo Transportation System (SCTS), NASA's newest space telescope was ferried on Feb. 4 from Los Angeles International Airport to KSC aboard an Air Force C-5 Galaxy transporter. The SCTS, an Air Force container, closely resembles the size and shape of the Shuttle cargo bay. Over the next few months, Chandra will undergo final tests at KSC and be mated to a Boeing-provided Inertial Upper Stage for launch aboard Space Shuttle Columbia. A launch date for the Space Shuttle STS-93 mission is expected to be announced later this week. The third in NASA's family of Great Observatories that includes the Hubble Space Telescope and the TRW-built Compton Gamma Ray observatory, Chandra will use the world's most powerful X-ray telescope to allow scientists to "see" and monitor cosmic events that are invisible to conventional optical telescopes. Chandra's X-ray images will yield new insight into celestial phenomena such as the temperature and extent of gas clouds that comprise clusters of galaxies and the superheating of gas and dust particles as they swirl into black holes. A TRW-led team that includes the Eastman Kodak Co., Raytheon Optical Systems Inc., and Ball Aerospace & Technologies Corp. designed and built the Chandra X-ray Observatory for NASA's Marshall Space Flight Center. The Smithsonian Astrophysical Observatory will manage the Chandra science mission for NASA from the Chandra X-ray Observatory Center in Cambridge, Mass. TRW has been developing scientific, communications and environmental satellite systems for NASA since 1958. In addition to building the Chandra X-ray Observatory, the company is currently developing the architectures and technologies needed to implement several of NASA's future space science missions, including the Next Generation Space Telescope, the Space Inteferometry Mission, both part of NASA's Origins program, and Constellation-X, the next major NASA X-ray mission after Chandra. Article courtesy of TRW. TRW news releases are available on the corporate Web site: http://www.trw.com.

Gamma-Ray Astronomy Technology Needs

NASA Technical Reports Server (NTRS)

Gehrels, N.; Cannizzo, J. K.

2012-01-01

In recent decades gamma-ray observations have become a valuable tool for studying the universe. Progress made in diverse 8re1lS such as gamma-ray bursts (GRBs), nucleosynthesis, and active galactic nuclei (AGNs) has complimented and enriched our astrophysical understanding in many ways. We present an overview of current and future planned space y-ray missions and discussion technology needs for- the next generation of space gamma-ray instruments.

Evaluation of two new automated chemiluminescent assays (HemosIL® AcuStar HIT-IgG and HemosIL® AcuStar HIT-Ab) for the detection of heparin-induced antibodies in the diagnosis of heparin-induced thrombocytopenia.

PubMed

Van Hoecke, F; Devreese, K

2012-08-01

Recently, two new, fully automated quantitative chemiluminescent immunoassays, the HemosIL(®) AcuStar HIT-IgG (PF4-H), specific for IgG anti-PF4/H antibodies, and the HemosIL(®) AcuStar HIT-Ab(PF4-H), detecting IgG, IgM and IgA anti-PF4/H antibodies, were introduced into the market. In this study, their performance was compared mutually and with the Zymutest HIA IgG and HIA IgGAM ELISA. Citrated plasmas from 87 patients with clinical suspicion of heparin-induced thrombocytopenia (HIT) were analyzed with all four assays and with a functional confirmation assay. Apart from the manufacturer's cutoffs, optimalized cutoffs were evaluated as well. Sensitivities of all assays were 100%. The Acustar HIT-IgG assay showed a higher specificity compared with the HIT-Ab assay (85%vs. 73%), using the manufacturer's cutoffs. Specificities of all assays, except for the AcuStar HIT-IgG, could be significantly improved when altering the cutoff. Titers were significantly higher for the HIT-Ab assay compared with the HIT-IgG assay (P = 0.0001). This was also the case for the patients with confirmed HIT (P = 0.0495), indicating that the one cutoff (1.0 OD) for both Acustar assays, as proposed by the manufacturer, can be adapted for the AcuStar Hit-Ab assay resulting in an increased specificity. Performance characteristics of the Acustar HIT-IgG and HIT-Ab assay are comparable to the Zymutest HIA IgG and HIA IgGAM. © 2012 Blackwell Publishing Ltd.

Cerebral High-Intensity Transient Signals during Pediatric Cardiac Catheterization: A Pilot Study Using Transcranial Doppler Ultrasonography.

PubMed

LaRovere, Kerri L; Kapur, Kush; McElhinney, Doff B; Razumovsky, Alexander; Kussman, Barry D

2017-07-01

Cerebral emboli are one potential cause of acute brain injury in children with congenital heart disease (CHD) undergoing cardiac catheterization. In this pilot study using transcranial Doppler (TCD) ultrasonography, we sought to evaluate the incidence, burden, and circumstances of cerebral high-intensity transient signals (HITS), presumably representing emboli, during pediatric cardiac catheterization. Emboli monitoring of the right middle cerebral artery was performed in five children. HITS, counted offline, were defined as unidirectional signals associated with audible "chirp" and sinusoidal correlation. HITS were grouped as single, >10 HITS ("cluster"), or HITS "with curtain effect" per 3-5 cardiac cycles. Cerebral blood flow velocity (CBFV) and pulsatility index (PI) were recorded after anesthetic induction (baseline). Total HITS in the cohort was 1,697 (790 single HITS, 606 HITS within clusters, and 301 HITS within curtains). HITS in clusters and curtains comprised 53% (907/1,697) of total HITS, and occurred in 44 clusters/curtains. Events associated with clusters/curtains included left ventricular angiography (39%; 17/44), right ventricular angiography (16%; 7/44), device placement (16%; 7/44), heparin bolus (9%; 4/44), pulmonary artery angiography (9%; 4/44), venous access (5%; 2/44), right atrial angiography (2%; 1/44), arterial access (2%; 1/44), and hemodynamic measurements (2%; 1/44). No patient had clinically detectable neurologic injury. HITS are common during pediatric cardiac catheterization, and associated with procedural factors. Whether curtains/clusters are worse than single, repetitive HITS is unknown. Larger studies are needed to determine whether HITS are a marker of risk of neurologic injury from emboli during pediatric cardiac catheterization. Copyright © 2017 by the American Society of Neuroimaging.

Future space experiments on cosmic rays and radiation on Russian segments of ISS

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

Panasyuk, Mikhail; Galper, Arkady; Stozhov, Yurii

1999-01-22

The report presents a survey of the Russian space program in the field of radiation and cosmic ray studies. The experimental projects were developed by scientists of different Russian Institutes and are intended for implementation on the future ISS. All the projects mentioned in this report have undergone various expertise stages in the Space Council of the Russian Science Academy ('Cosmic Ray Physics' section); the International Science-Technology Center of the Rocket-Space Corporation 'Energia' ('Astrophysics and radiation Measurements' section); Committee on Science-Technical Co-operation of the Russian Space Agency.

Platelet count recovery and seroreversion in immune HIT despite continuation of heparin: further observations and literature review.

PubMed

Shih, Andrew W; Sheppard, Jo-Ann I; Warkentin, Theodore E

2017-10-05

One of the standard distinctions between type 1 (non-immune) and type 2 (immune-mediated) heparin-induced thrombocytopenia (HIT) is the transience of thrombocytopenia: type 1 HIT is viewed as early-onset and transient thrombocytopenia, with platelet count recovery despite continuing heparin administration. In contrast, type 2 HIT is viewed as later-onset (i. e., 5 days or later) thrombocytopenia in which it is generally believed that platelet count recovery will not occur unless heparin is discontinued. However, older reports of type 2 HIT sometimes did include the unexpected observation that platelet counts could recover despite continued heparin administration, although without information provided regarding changes in HIT antibody levels in association with platelet count recovery. In recent years, some reports of type 2 HIT have confirmed the observation that platelet count recovery can occur despite continuing heparin administration, with serological evidence of waning levels of HIT antibodies ("seroreversion"). We now report two additional patient cases of type 2 HIT with platelet count recovery despite ongoing therapeutic-dose (1 case) or prophylactic-dose (1 case) heparin administration, in which we demonstrate concomitant waning of HIT antibody levels. We further review the literature describing this phenomenon of HIT antibody seroreversion and platelet count recovery despite continuing heparin administration. Our observations add to the concept that HIT represents a remarkably transient immune response, including sometimes even when heparin is continued.

Novel HIT antibody detection method using Sonoclot® coagulation analyzer.

PubMed

Wanaka, Keiko; Asada, Reiko; Miyashita, Kumiko; Kaneko, Makoto; Endo, Hirokazu; Yatomi, Yutaka

2015-01-01

Since heparin-induced thrombocytopenia (HIT), caused by the generation of antibodies against platelet factor 4 (PF4)/heparin complexes (HIT antibodies), may induce serious complications due to thrombosis, a prompt diagnosis is desirable. Functional tests with platelet activation to detect HIT antibodies are useful for diagnosis of HIT, in particular (14)C-selotonin release assay (SRA). However, they are complicated and so can be performed only in limited laboratories. We tested if a blood coagulation test using Sonoclot® analyzer can serve for the detection of HIT antibodies. A murine monoclonal antibody (HIT-MoAb) against PF4/heparin complexes was used as an alternative to human HIT antibodies. To the mixture of HIT-MoAb and heparin (0.5 U/mL, final), whole blood obtained from a healthy volunteer was added, and then the activated clotting time (ACT), clot rate (CR), and area under the curve (AUC) were measured with Sonoclot® analyzer for 30minutes. The HIT-MoAb (30 to 100μg/mL, final) concentration dependently suppressed the anticoagulation activity (prolongation of ACT and decrease of CR and AUC) of heparin. The suppression of anticoagulation effect of heparin by HIT-MoAb was demonstrated by measurements using Sonoclot® analyzer. This method may provide a new tool for screening of HIT antibodies. Copyright © 2014 Elsevier Ltd. All rights reserved.

Interval training in the fed or fasted state improves body composition and muscle oxidative capacity in overweight women.

PubMed

Gillen, Jenna B; Percival, Michael E; Ludzki, Alison; Tarnopolsky, Mark A; Gibala, Martin J

2013-11-01

To investigate the effects of low-volume high-intensity interval training (HIT) performed in the fasted (FAST) versus fed (FED) state on body composition, muscle oxidative capacity, and glycemic control in overweight/obese women. Sixteen women (27 ± 8 years, BMI: 29 ± 6 kg/m(2) , VO2peak : 28 ± 3 ml/kg/min) were assigned to either FAST or FED (n = 8 each) and performed 18 sessions of HIT (10× 60-s cycling efforts at ∼90% maximal heart rate, 60-s recovery) over 6 weeks. There was no significant difference between FAST and FED for any measured variable. Body mass was unchanged following training; however, dual energy X-ray absorptiometry revealed lower percent fat in abdominal and leg regions as well as the whole body level (main effects for time, P ≤ 0.05). Fat-free mass increased in leg and gynoid regions (P ≤ 0.05). Resting muscle biopsies revealed a training-induced increase in mitochondrial capacity as evidenced by increased maximal activities of citrate synthase and β-hydroxyacyl-CoA dehydrogenase (P ≤ 0.05). There was no change in insulin sensitivity, although change in insulin area under the curve was correlated with change in abdominal percent fat (r = 0.54, P ≤ 0.05). Short-term low-volume HIT is a time-efficient strategy to improve body composition and muscle oxidative capacity in overweight/obese women, but fed- versus fasted-state training does not alter this response. Copyright © 2013 The Obesity Society.

Radiation Effects on LWS Detectors and Deglitching of LWS Data

NASA Astrophysics Data System (ADS)

Burgdorf, M.; Harwood, A.; Sidher, S. D.

Glitches are caused by the effects of ionising particles (either a primary cosmic ray, interplanetary or belt electron, or a secondary generated in the spacecraft structure) on the detectors. There was roughly one glitch per ten seconds per detector during the normal period of LWS operation. These energetic particles cause a sudden jump in the ramp voltage, due to a quantity of charge being dumped on the integrating amplifier. They also cause a change in the detector responsivity which affects the following ramps. Glitches were detected in the automatic pipeline processing for each observation with the LWS that was performed with a standard Astronomical Observation Template. We describe the method with which this deglitching was carried out. Based on the findings from the deglitching algorithms we compare proton and electron fluences with average glitch rates and look for correlations. >From the glitch statistics one can also derive the energy distribution of the ionising radiation that hit the detectors. This energy spectrum agrees roughly with model predictions and therefore shows that it is in principle possible to predict the properties of the ionising radiation to which the detectors of future missions will be exposed. This is important, because for the LWS we found that the effect of an ionising radiation hit on the detectors was rather different, and more severe, than had been predicted before launch: An ionising particle could cause the detector to become unstable and spike spontaneously for some seconds following a hit, resulting in a strongly increased noise and requiring a re-adjustment of the bias levels.

How Space Radiation Risk from Galactic Cosmic Rays at the International Space Station Relates to Nuclear Cross Sections

NASA Technical Reports Server (NTRS)

Lin, Zi-Wei; Adams, J. H., Jr.

2005-01-01

Space radiation risk to astronauts is a major obstacle for long term human space explorations. Space radiation transport codes have thus been developed to evaluate radiation effects at the International Space Station (ISS) and in missions to the Moon or Mars. We study how nuclear fragmentation processes in such radiation transport affect predictions on the radiation risk from galactic cosmic rays. Taking into account effects of the geomagnetic field on the cosmic ray spectra, we investigate the effects of fragmentation cross sections at different energies on the radiation risk (represented by dose-equivalent) from galactic cosmic rays behind typical spacecraft materials. These results tell us how the radiation risk at the ISS is related to nuclear cross sections at different energies, and consequently how to most efficiently reduce the physical uncertainty in our predictions on the radiation risk at the ISS.

A complex adaptive systems perspective of health information technology implementation.

PubMed

Keshavjee, Karim; Kuziemsky, Craig; Vassanji, Karim; Ghany, Ahmad

2013-01-01

Implementing health information technology (HIT) is a challenge because of the complexity and multiple interactions that define HIT implementation. Much of the research on HIT implementation is descriptive in nature and has focused on distinct processes such as order entry or decision support. These studies fail to take into account the underlying complexity of the processes, people and settings that are typical of HIT implementations. Complex adaptive systems (CAS) is a promising field that could elucidate the complexity and non-linear interacting issues that are typical in HIT implementation. Initially we sought new models that would enable us to better understand the complex nature of HIT implementation, to proactively identify problem issues that could be a precursor to unintended consequences and to develop new models and new approaches to successful HIT implementations. Our investigation demonstrates that CAS does not provide prediction, but forces us to rethink our HIT implementation paradigms and question what we think we know. CAS provides new ways to conceptualize HIT implementation and suggests new approaches to increasing HIT implementation successes.

Adaptive CT scanning system

DOEpatents

Sampayan, Stephen E.

2016-11-22

Apparatus, systems, and methods that provide an X-ray interrogation system having a plurality of stationary X-ray point sources arranged to substantially encircle an area or space to be interrogated. A plurality of stationary detectors are arranged to substantially encircle the area or space to be interrogated, A controller is adapted to control the stationary X-ray point sources to emit X-rays one at a time, and to control the stationary detectors to detect the X-rays emitted by the stationary X-ray point sources.

Review of Social and Organizational Issues in Health Information Technology

PubMed Central

2015-01-01

Objectives This paper reviews organizational and social issues (OSIs) in health information technology (HIT). Methods A review and synthesis of the literature on OSIs in HIT was conducted. Results Five overarching themes with respect to OSIs in HIT were identified and discussed: scope and frameworks for defining OSIs in HIT, context matters, process immaturity and complexity, trade-offs will happen and need to be discussed openly, and means of studying OSIs in HIT. Conclusions There is a wide body of literature that provides insight into OSIs in HIT, even if many of the studies are not explicitly labelled as such. The two biggest research needs are more explicit and theoretical studies of OSI in HITs and more research on integrating micro and macro perspectives of HIT use in organizations. PMID:26279951

A comparison of the double hydrodistention implantation technique (HIT) and the HIT with a polyacrylate/polyalcohol copolymer (PPC) for the endoscopic treatment of primary vesicoureteral reflux.

PubMed

Akin, Melih; Erginel, Basak; Karadag, Cetin Ali; Yildiz, Abdullah; Ozçelik, Gül Sumru; Sever, Nihat; Genc, Nimetullah Mete; Dokucu, Ali Ihsan

2014-11-01

We aimed to compare the success rates of the double hydrodistention implantation technique (HIT) and the HIT with a polyacrylate/polyalcohol copolymer (PPC) for the treatment of primary vesicoureteral reflux (VUR) with a new nonbiodegradable tissue-augmenting substance (Vantris, Promedon, Cordoba, Argentina). Between January 2011 and December 2012, fifty-two children who underwent subureteric injection for primary VUR are included. The children were randomly separated into two groups, the HIT and the double HIT groups, according to the type of injection. Success was defined as no reflux on a follow-up voiding cystourethrogram (VCUG) after 6 months. The patients were evaluated according to sex, age, grade of reflux, number of injections, and injected volume, and the radiological success rates were compared. Fifty-two patients underwent an endoscopic injection for primary grade III-V VUR. The HIT group consisted of 26 patients with 33 ureters, and the double HIT group consisted of 26 patients with 35 ureters. There were no significant differences in terms of the sex, ages, VUR grades, bilaterality between the two groups. The mean injected volumes were ml 1.12 (1.02-1.22) in the HIT group and 1.24 ml (95 % CI 1.10-1.38) in the double HIT group. The reflux was resolved in 21/33 (63.6 %) ureters in the HIT group and in 30/35 (85.7 %) ureters in the double HIT group, (p < 0.05). We had only one complication. This patient in the double HIT group, developed bilateral hydronephrosis and oliguric renal failure requiring open reimplantation at the sixth month. We observed successful results double HIT method with PPC in Grade III-V reflux, but the long-term follow-up of patients is needed for hydronephrosis. As the double HIT treatment leads to a higher success rate, its use is preferable.

Design of combinatorial libraries for the exploration of virtual hits from fragment space searches with LoFT.

PubMed

Lessel, Uta; Wellenzohn, Bernd; Fischer, J Robert; Rarey, Matthias

2012-02-27

A case study is presented illustrating the design of a focused CDK2 library. The scaffold of the library was detected by a feature trees search in a fragment space based on reactions from combinatorial chemistry. For the design the software LoFT (Library optimizer using Feature Trees) was used. The special feature called FTMatch was applied to restrict the parts of the queries where the reagents are permitted to match. This way a 3D scoring function could be simulated. Results were compared with alternative designs by GOLD docking and ROCS 3D alignments.

International Students and Gender-Based Violence.

PubMed

Forbes-Mewett, Helen; McCulloch, Jude

2016-03-01

Headlines such as "Man Jailed for Train Station Attack on Indian Student," "Fatal Stabbing Hits Indian Student Hopes," and "Indian Student Bashings on the Rise in Sydney" highlight violent crimes against male international students by strangers in public spaces. The media reports run contrary to the perceptions of our interviewees who suggest that violence against female international students by known perpetrators in private spaces is common. We argue that intersecting inequalities relating to gender, race, and class are often compounded by the status of "international student." Discussions focus on various forms of gender-based violence and gender violence education and support programs in Australia and the United States. © The Author(s) 2015.

Ballistic Reconstruction of a Migrating Bullet in the Parapharyngeal Space

PubMed Central

Bächinger, David; Bolliger, Stephan; Huber, Gerhard F.; Laske, Roman D.

2015-01-01

A 21-year-old male suffering from severe throat pain after being hit by a bullet in Syria claimed that he was shot through his eye and that the bullet subsequently descended behind his throat. Even though the first medical report stated that this course is implausible, meticulous workup provided evidence that the bullet might have entered the parapharyngeal space in a more cranial position than the one it was found eight months later. Our case highlights that bullets are able to move within the body, rendering ballistic reconstruction difficult. However, after removal of the bullet the patient's symptoms completely resolved. PMID:26770857

Druggable pockets and binding site centric chemical space: a paradigm shift in drug discovery.

PubMed

Pérot, Stéphanie; Sperandio, Olivier; Miteva, Maria A; Camproux, Anne-Claude; Villoutreix, Bruno O

2010-08-01

Detection, comparison and analyses of binding pockets are pivotal to structure-based drug design endeavors, from hit identification, screening of exosites and de-orphanization of protein functions to the anticipation of specific and non-specific binding to off- and anti-targets. Here, we analyze protein-ligand complexes and discuss methods that assist binding site identification, prediction of druggability and binding site comparison. The full potential of pockets is yet to be harnessed, and we envision that better understanding of the pocket space will have far-reaching implications in the field of drug discovery, such as the design of pocket-specific compound libraries and scoring functions.

Michoud Recovering From Tornado on This Week @NASA – February 10, 2017

NASA Image and Video Library

2017-02-10

Recovery efforts are underway at NASA’s Michoud Assembly Facility in New Orleans, which was hit by a tornado Feb. 7. In accounting for all 3,500 employees at the facility, officials reported five suffered minor injuries. Buildings, structures and parked cars sustained damage, but there was no reported damage to hardware for NASA’s Space Launch System (SLS) rocket, Orion spacecraft, or the barge Pegasus docked at Michoud. NASA will release updates on the facility’s status as they become available. Also, SpaceX Launch Targeted for Mid-February, SLS Booster Hardware Arrives at KSC, and NASA Aerospace Days!

Video head impulse test: a review of the literature.

PubMed

Alhabib, Salman F; Saliba, Issam

2017-03-01

Video head impulse test (vHIT) is a new testing which able to identify the overt and covert saccades and study the gain of vestibulo-ocular reflex (VOR) of each semicircular canal. The aim of this study is to review the clinical use of vHIT in patients with vestibular disorders in different diseases. PubMed and Cochrane databases were searched for all articles that defined vHIT, compared vHIT with another clinical test, and studied the efficacy of vHIT as diagnostic tools with vestibular disease. 37 articles about vHIT were reviewed. All articles studied the vHIT in English and French languages up to May 2015 were included in the review. Editorial articles or short comments, conference abstracts, animal studies, and language restriction were excluded from the review. Four systems were used in the literature to do the vHIT. vHIT is physiological quick test, which studied the VOR at high frequency of each semicircular canal by calculating the duration ratio between the head impulse and gaze deviation. vHIT is more sensitive than clinical head impulse test (cHIT), especially in patient with isolated covert saccades. vHIT test is diagnostic of vestibular weakness by gain reduction and the appearance of overt and covert saccades. If the vHIT is normal, then caloric test is mandatory to rule out a peripheral origin of vertigo. It is recommended to test each semicircular canal, as isolated vertical canal weakness was identified in the literature. More investigation would be required to determine the evolution of the VOR gain with the progression of the vestibular disease.

Radiation Risk Projections for Space Travel

NASA Technical Reports Server (NTRS)

Cucinotta, Francis

2003-01-01

Space travelers are exposed to solar and galactic cosmic rays comprised of protons and heavy ions moving with velocities close to the speed of light. Cosmic ray heavy ions are known to produce more severe types of biomolecular damage in comparison to terrestrial forms of radiation, however the relationship between such damage and disease has not been fully elucidated. On Earth, we are protected from cosmic rays by atmospheric and magnetic shielding, and only the remnants of cosmic rays in the form of ground level muons and other secondary radiations are present. Because human epidemiology data is lacking for cosmic rays, risk projection must rely on theoretical understanding and data from experimental models exposed to space radiation using charged particle accelerators to simulate space radiation. Although the risks of cancer and other late effects from cosmic rays are currently believed to present a severe challenge to space travel, this challenge is centered on our lack of confidence in risk projections methodologies. We review biophysics and radiobiology data on the effects of the cosmic ray heavy ions, and the current methods used to project radiation risks . Cancer risk projections are described as a product of many biological and physical factors, each of which has a differential range of uncertainty due to lack of data and knowledge. Risk projections for space travel are described using Monte-Carlo sampling from subjective error di stributions that represent the lack of knowledge in each factor that contributes to the projection model in order to quantify the overall uncertainty in risk projections. This analysis is applied to space mi ssion scenarios including lunar colony, deep space outpost, and a Mars mission. Results suggest that the number of days in space where cancer mortality risks can be assured at a 95% confidence level to be below the maximum acceptable risk for radi ation workers on Earth or the International Space Station is only on the order of 100-200 days. Approaches to reduce these unceI1ainties and mitigate risks are described.

[Bio-objects and biological methods of space radiation effects evaluation].

PubMed

Kaminskaia, E V; Nevzgodina, L V; Platova, N G

2009-01-01

The unique conditions of space experiments place austere requirements to bio-objects and biological methods of radiation effects evaluation. The paper discusses suitability of a number of bio-objects varying in stage of evolution and metabolism for space researches aimed to state common patterns of the radiation damage caused by heavy ions (HI), and character of HI-cell interaction. Physical detectors in space experiments of the BIOBLOCK series make it possible to identify bio-objects hit by space HI and to set correlation between HI track topography and biological effect. The paper provides an all-round description of the bio-objects chosen for two BIOBLOCK experiments (population of hydrophyte Wolffia arrhiza (fam. duckweed) and Lactuca sativa seeds) and the method of evaluating effects from single space radiation HI. Direct effects of heavy ions on cells can be determined by the criteria of chromosomal aberrations and delayed morphologic abnormalities. The evaluation results are compared with the data about human blood lymphocytes. Consideration is being given to the procedures of test-objects' treatment and investigation.

Space Weather: The Solar Perspective

NASA Astrophysics Data System (ADS)

Schwenn, Rainer

2006-08-01

The term space weather refers to conditions on the Sun and in the solar wind, magnetosphere, ionosphere, and thermosphere that can influence the performance and reliability of space-borne and ground-based technological systems and that can affect human life and health. Our modern hi-tech society has become increasingly vulnerable to disturbances from outside the Earth system, in particular to those initiated by explosive events on the Sun: Flares release flashes of radiation that can heat up the terrestrial atmosphere such that satellites are slowed down and drop into lower orbits, solar energetic particles accelerated to near-relativistic energies may endanger astronauts traveling through interplanetary space, and coronal mass ejections are gigantic clouds of ionized gas ejected into interplanetary space that after a few hours or days may hit the Earth and cause geomagnetic storms. In this review, I describe the several chains of actions originating in our parent star, the Sun, that affect Earth, with particular attention to the solar phenomena and the subsequent effects in interplanetary space.

CSI 2264: Simultaneous Optical and Infrared Light Curves of Young Disk-Bearing Stars in NGC 2264 With CoRoT and Spitzer-Evidence For Multiple Origins of Variability

DTIC Science & Technology

2014-03-13

2005). the first position, two exposures were acquired with an 8" dither to mitigate any detector artifacts or cosmic-ray hits. Total frame time...with a ŕ/ f" trend in amplitude; two examples are provided in Figure 17. This is in contrast to typical red or " flicker " noise, which follows a 1...transitions between staring and mapping photometry. Following pixel-phase mitigation , we selected the set of ~280 by-BCD staring points lying within 1.2

In-orbit operation of the ASTRO-H SXS

NASA Astrophysics Data System (ADS)

Tsujimoto, Masahiro; Mitsuda, Kazuhisa; Kelley, Richard L.; den Herder, Jan-Willem A.; Akamatsu, Hiroki; Bialas, Thomas G.; Boyce, Kevin R.; Brown, Gregory V.; Chiao, Meng P.; Costantini, Elisa; de Vries, Cor P.; DiPirro, Michael J.; Eckart, Megan E.; Ezoe, Yuichiro; Fujimoto, Ryuichi; Haas, Daniel; Hoshino, Akio; Ishikawa, Kumi; Ishisaki, Yoshitaka; Iyomoto, Naoko; Kilbourne, Caroline A.; Kitamoto, Shunji; Koyama, Shu; Leutenegger, Maurice A.; McCammon, Dan; Mitsuishi, Ikuyuki; Murakami, Hiroshi; Murakami, Masahide; Noda, Hirofumi; Ogawa, Mina; Ota, Naomi; Paltani, Stéphane; Porter, Frederick S.; Sato, Kosuke; Sato, Yoichi; Sawada, Makoto; Seta, Hiromi; Shinozaki, Keisuke; Shirron, Peter J.; Sneiderman, Gary A.; Sugita, Hiroyuki; Szymkowiak, Andrew E.; Takei, Yoh; Tamagawa, Toru; Tashiro, Makoto S.; Terada, Yukikatsu; Yamada, Shinya; Yamasaki, Noriko Y.; Yatsu, Yoichi

2016-07-01

We summarize all the in-orbit operations of the Soft X-ray Spectrometer (SXS) onboard the ASTRO-H (Hit- omi) satellite. The satellite was launched on 2016/02/17 and the communication with the satellite ceased on 2016/03/26. The SXS was still in the commissioning phase, in which the setups were progressively changed. This article is intended to serve as a reference of the events in the orbit to properly interpret the SXS data taken during its short life time, and as a test case for planning the in-orbit operation for future micro-calorimeter missions.

High-throughput crystal-optimization strategies in the South Paris Yeast Structural Genomics Project: one size fits all?

PubMed

Leulliot, Nicolas; Trésaugues, Lionel; Bremang, Michael; Sorel, Isabelle; Ulryck, Nathalie; Graille, Marc; Aboulfath, Ilham; Poupon, Anne; Liger, Dominique; Quevillon-Cheruel, Sophie; Janin, Joël; van Tilbeurgh, Herman

2005-06-01

Crystallization has long been regarded as one of the major bottlenecks in high-throughput structural determination by X-ray crystallography. Structural genomics projects have addressed this issue by using robots to set up automated crystal screens using nanodrop technology. This has moved the bottleneck from obtaining the first crystal hit to obtaining diffraction-quality crystals, as crystal optimization is a notoriously slow process that is difficult to automatize. This article describes the high-throughput optimization strategies used in the Yeast Structural Genomics project, with selected successful examples.

2-Amino-3,4-dihydroquinazolines as inhibitors of BACE-1 (beta-site APP cleaving enzyme): Use of structure based design to convert a micromolar hit into a nanomolar lead.

PubMed

Baxter, Ellen W; Conway, Kelly A; Kennis, Ludo; Bischoff, François; Mercken, Marc H; Winter, Hans L De; Reynolds, Charles H; Tounge, Brett A; Luo, Chi; Scott, Malcolm K; Huang, Yifang; Braeken, Mirielle; Pieters, Serge M A; Berthelot, Didier J C; Masure, Stefan; Bruinzeel, Wouter D; Jordan, Alfonzo D; Parker, Michael H; Boyd, Robert E; Qu, Junya; Alexander, Richard S; Brenneman, Douglas E; Reitz, Allen B

2007-09-06

A new aspartic protease inhibitory chemotype bearing a 2-amino-3,4-dihydroquinazoline ring was identified by high-throughput screening for the inhibition of BACE-1. X-ray crystallography revealed that the exocyclic amino group participated in a hydrogen bonding array with the two catalytic aspartic acids of BACE-1 (Asp(32), Asp(228)). BACE-1 inhibitory potency was increased (0.9 microM to 11 nM K(i)) by substitution into the unoccupied S(1)' pocket.

Native State Mass Spectrometry, Surface Plasmon Resonance, and X-ray Crystallography Correlate Strongly as a Fragment Screening Combination.

PubMed

Woods, Lucy A; Dolezal, Olan; Ren, Bin; Ryan, John H; Peat, Thomas S; Poulsen, Sally-Ann

2016-03-10

Fragment-based drug discovery (FBDD) is contingent on the development of analytical methods to identify weak protein-fragment noncovalent interactions. Herein we have combined an underutilized fragment screening method, native state mass spectrometry, together with two proven and popular fragment screening methods, surface plasmon resonance and X-ray crystallography, in a fragment screening campaign against human carbonic anhydrase II (CA II). In an initial fragment screen against a 720-member fragment library (the "CSIRO Fragment Library") seven CA II binding fragments, including a selection of nonclassical CA II binding chemotypes, were identified. A further 70 compounds that comprised the initial hit chemotypes were subsequently sourced from the full CSIRO compound collection and screened. The fragment results were extremely well correlated across the three methods. Our findings demonstrate that there is a tremendous opportunity to apply native state mass spectrometry as a complementary fragment screening method to accelerate drug discovery.

Measuring the radio emission of cosmic ray air showers with LOPES

NASA Astrophysics Data System (ADS)

Schröder, F. G.; Apel, W. D.; Arteaga, J. C.; Asch, T.; Badea, F.; Bähren, L.; Bekk, K.; Bertaina, M.; Biermann, P. L.; Blümer, J.; Bozdog, H.; Brancus, I. M.; Brüggemann, M.; Buchholz, P.; Buitink, S.; Cantoni, E.; Chiavassa, A.; Cossavella, F.; Daumiller, K.; de Souza, V.; Di Pierro, F.; Doll, P.; Engel, R.; Falcke, H.; Finger, M.; Fuhrmann, D.; Gemmeke, H.; Ghia, P. L.; Glasstetter, R.; Grupen, C.; Haungs, A.; Heck, D.; Hörandel, J. R.; Horneffer, A.; Huege, T.; Isar, P. G.; Kampert, K.-H.; Kang, D.; Kickelbick, D.; Krömer, O.; Kuijpers, J.; Lafebre, S.; łuczak, P.; Ludwig, M.; Mathes, H. J.; Mayer, H. J.; Melissas, M.; Mitrica, B.; Morello, C.; Navarra, G.; Nehls, S.; Nigl, A.; Oehlschläger, J.; Over, S.; Palmieri, N.; Petcu, M.; Pierog, T.; Rautenberg, J.; Rebel, H.; Roth, M.; Saftoiu, A.; Schieler, H.; Schmidt, A.; Sima, O.; Singh, K.; Toma, G.; Trinchero, G. C.; Ulrich, H.; Weindl, A.; Wochele, J.; Wommer, M.; Zabierowski, J.; Zensus, J. A.

2010-05-01

When ultra high energy cosmic rays hit the atmosphere, they produce a shower of millions of secondary particles. Thereby the charged particles in the shower emit a radio pulse whilst deflected in the Earth's magnetic field. LOPES is a digital antenna array measuring these radio pulses in the frequency range from 40 to 80 MHz. It is located at the site of and triggered by the air shower experiment KASCADE-Grande at Karlsruhe Institute of Technology (KIT), Germany. In its present configuration, it consists of 15 east-west-polarized and 15 north-south-polarized, absolutely calibrated short dipole antennas, as well as 10 LPDAs (with two channels each). Furthermore, it serves as a test bench for technological developments, like new antenna types or a radio-based self-triggering ( LOPESSTAR). To achieve a good angular reconstruction and to digitally form a beam into the arrival direction of the shower, it has a precise time calibration.

Developing Health Information Technology (HIT) Programs and HIT Curriculum: The Southern Polytechnic State University Experience

ERIC Educational Resources Information Center

Zhang, Chi; Reichgelt, Han; Rutherfoord, Rebecca H.; Wang, Andy Ju An

2014-01-01

Health Information Technology (HIT) professionals are in increasing demand as healthcare providers need help in the adoption and meaningful use of Electronic Health Record (EHR) systems while the HIT industry needs workforce skilled in HIT and EHR development. To respond to this increasing demand, the School of Computing and Software Engineering…

Next generation of space based sensor for application in the SSA space weather domain.

NASA Astrophysics Data System (ADS)

Jansen, Frank; Kudela, Karel; Behrens, Joerg

Next generation of space based sensor for application in the SSA space weather domain. F. Jansen1, K. Kudela2, J. Behrens1 and NESTEC consortium3 1DLR, Bremen, Germany 2IEP SAS Kosice, Slovakia 3NESTEC consortium members (DLR Bremen, DESY Hamburg, MPS Katlenburg-Lindau, CTU Prague, University of Twente, IEP-SAS Kosice, UCL/MSSL, University of Manchester, University of Surrey, Hermanus Magnetic Observatory, North-West University Potchefsroom, University of Montreal) High energy solar and galactic cosmic rays have twofold importance for the SSA space weather domain. Cosmic rays have dangerous effects for space, air and ground based assets, but on the other side cosmic rays are direct measure tools for real time space weather warning. A review of space weather related SSA results from operating global cosmic ray networks (especially those by neutron monitors and by muon directional telescopes), its limitations and main questions to be solved, is presented. Especially those recent results, received in real time and with high temporal resolution, are reviewed and discussed. In addition the relevance of these monitors and telescopes in forecasting geomagnetic disturbances are checked. Based on this study result, a next generation of highly miniaturized hybrid silicon pixel device (Medipix sensor) will be described for the following, beyond state-of-the-art application: a SSA satellite for high energy solar and galactic cosmic ray spectrum measurement, with a space plasma environment data package and CME real time imaging by means of cosmic rays. All data management and processing will be carried out on the satellite in real time. Insofar a high reduction of data and transmission to ground station of finalized space weather relevant data and images are foreseen.

History of Chandra X-Ray Observatory

NASA Image and Video Library

1999-12-01

This Chandra image shows the central regions of two colliding galaxies known collectively as the Antennae (NGC-4038/4039). The dozens of bright pointy-like sources are neutron stars or black holes pulling gas off nearby stars. The bright fuzzy patches are multimillion degree gas superbubbles, thousands of light years in diameter that were produced by the accumulated power of thousands of supernovae. The remaining glow of x-ray emission could be due to many faint x-ray sources or to clouds of hot gas in the galaxies. About 60 million light years from Earth in the constellation Corvus, the Antennae Galaxies got their nickname from the wispy anntennae-like streams of gas as seen by optical telescopes. These ongoing wisps are believed to have been produced approximately 100 million years ago by the collision between the galaxies. Although it is rare for stars to hit each other during a galactic collision, clouds of dust and gas do collide. Compression of these clouds can lead to the rebirth of millions of stars, and a few million years later, to thousands of supernovae.

Forensic Evidence and Criminal Investigations: The Impact of Ballistics Information on the Investigation of Violent Crime in Nine Cities.

PubMed

King, William R; Campbell, Bradley A; Matusiak, Matthew C; Katz, Charles M

2017-07-01

We explore the impact of information from ballistics imaging hit reports on the investigation into violent crimes. Ballistics imaging hits link two crimes involving the same firearm by forensically matching tool marks on the fired bullets or cartridge cases. Interview data collected from detectives who received a hit report were used to explore the relationship between the presence of a hit report and outcomes in 65 gun-related violent crime investigations in nine U.S. police agencies. Findings indicate hit reports rarely contribute to identification, arrest, charging, or sentencing of suspects, because of delays in producing hit reports. On average, hit reports were completed 181.4 days after the focal crime. This delay forces investigations to proceed without the benefit of information from ballistics analysis. Additionally, hit reports rarely contained detailed information that was immediately useful to investigators. Instead, hit reports required additional research by the investigator to unlock useful information. © 2017 American Academy of Forensic Sciences.

Health information technology and physicians' perceptions of healthcare quality.

PubMed

Fang, Hai; Peifer, Karen L; Chen, Jie; Rizzo, John A

2011-03-01

To investigate the relationship between the use of health information technology (HIT) and physician perceptions of providing high-quality care and to determine whether this relationship has changed over time. We used 2 waves of longitudinal data from the Community Tracking Study Physician Surveys, 2000-2001 and 2004-2005. Three measures of HIT were examined: a binary variable measuring the use of at least 1 type of HIT, a continuous variable measuring the total number of HIT types, and a binary variable measuring use of all 5 HIT types related to "meaningful use" of HIT as defined by Centers for Medicare and Medicaid Services. Three multivariate models were estimated to study the effect of each HIT measure on physicians' perception of providing high-quality care. Individual fixed-effects estimation also was used to control for individual time-invariant factors. Using at least 1 type of HIT significantly enhanced physicians' perception of providing high-quality care in 2000-2001, but not in 2004-2005. The marginal effect of adding 1 extra HIT type was positive and statistically significant in both periods. The association between using all 5 HIT types related to meaningful use and perceived quality was statistically significant in 2000-2001, but not in 2004-2005. Health information technology has become a multifunctional system and appears to have enhanced physicians' perception of providing high-quality care. Physicians' perceptions of medical care quality improved as the number of HIT types used increased. This study supports more extensive use of HIT in physician practices.

LncRNA-HIT Functions as an Epigenetic Regulator of Chondrogenesis through Its Recruitment of p100/CBP Complexes.

PubMed

Carlson, Hanqian L; Quinn, Jeffrey J; Yang, Yul W; Thornburg, Chelsea K; Chang, Howard Y; Stadler, H Scott

2015-12-01

Gene expression profiling in E 11 mouse embryos identified high expression of the long noncoding RNA (lncRNA), LNCRNA-HIT in the undifferentiated limb mesenchyme, gut, and developing genital tubercle. In the limb mesenchyme, LncRNA-HIT was found to be retained in the nucleus, forming a complex with p100 and CBP. Analysis of the genome-wide distribution of LncRNA-HIT-p100/CBP complexes by ChIRP-seq revealed LncRNA-HIT associated peaks at multiple loci in the murine genome. Ontological analysis of the genes contacted by LncRNA-HIT-p100/CBP complexes indicate a primary role for these loci in chondrogenic differentiation. Functional analysis using siRNA-mediated reductions in LncRNA-HIT or p100 transcripts revealed a significant decrease in expression of many of the LncRNA-HIT-associated loci. LncRNA-HIT siRNA treatments also impacted the ability of the limb mesenchyme to form cartilage, reducing mesenchymal cell condensation and the formation of cartilage nodules. Mechanistically the LncRNA-HIT siRNA treatments impacted pro-chondrogenic gene expression by reducing H3K27ac or p100 activity, confirming that LncRNA-HIT is essential for chondrogenic differentiation in the limb mesenchyme. Taken together, these findings reveal a fundamental epigenetic mechanism functioning during early limb development, using LncRNA-HIT and its associated proteins to promote the expression of multiple genes whose products are necessary for the formation of cartilage.

LncRNA-HIT Functions as an Epigenetic Regulator of Chondrogenesis through Its Recruitment of p100/CBP Complexes

PubMed Central

Carlson, Hanqian L.; Quinn, Jeffrey J.; Yang, Yul W.; Thornburg, Chelsea K.; Chang, Howard Y.; Stadler, H. Scott

2015-01-01

Gene expression profiling in E 11 mouse embryos identified high expression of the long noncoding RNA (lncRNA), LNCRNA-HIT in the undifferentiated limb mesenchyme, gut, and developing genital tubercle. In the limb mesenchyme, LncRNA-HIT was found to be retained in the nucleus, forming a complex with p100 and CBP. Analysis of the genome-wide distribution of LncRNA-HIT-p100/CBP complexes by ChIRP-seq revealed LncRNA-HIT associated peaks at multiple loci in the murine genome. Ontological analysis of the genes contacted by LncRNA-HIT-p100/CBP complexes indicate a primary role for these loci in chondrogenic differentiation. Functional analysis using siRNA-mediated reductions in LncRNA-HIT or p100 transcripts revealed a significant decrease in expression of many of the LncRNA-HIT-associated loci. LncRNA-HIT siRNA treatments also impacted the ability of the limb mesenchyme to form cartilage, reducing mesenchymal cell condensation and the formation of cartilage nodules. Mechanistically the LncRNA-HIT siRNA treatments impacted pro-chondrogenic gene expression by reducing H3K27ac or p100 activity, confirming that LncRNA-HIT is essential for chondrogenic differentiation in the limb mesenchyme. Taken together, these findings reveal a fundamental epigenetic mechanism functioning during early limb development, using LncRNA-HIT and its associated proteins to promote the expression of multiple genes whose products are necessary for the formation of cartilage. PMID:26633036

Hyperinsulin therapy for calcium channel antagonist poisoning: a seven-year retrospective study.

PubMed

Espinoza, Tamara R; Bryant, Sean M; Aks, Steve E

2013-01-01

The use of hyperinsulin therapy (HIT) in severe calcium channel antagonist (CCA) poisoning has become a more common therapy within the last decade. The objective of this study is to report 7 years of experience recommending HIT. This was a retrospective chart review utilizing our regional poison center (RPC) data from January 1, 2002, through December 31, 2008. All cases of CCA poisoning receiving HIT were searched. Endpoints included the number of CCA cases utilizing HIT, insulin dose, time of initiation of HIT, patient outcome, adverse events, age, glucose concentration, and lowest systolic blood pressure recorded. Forty-six cases of CCA poisoning were managed with HIT over 7 years. All the patients received standard antidotal therapy (= intravenous fluids, calcium salts, glucagon, and pressors). HIT administration followed our RPC recommendation 23 times (50%), and no hypoglycemic events occurred. Means (age, highest glucose measured, and lowest systolic blood pressure measured) were 51 years, 282 mg/dL, and 74 mm Hg, respectively. Our RPC recommendations for HIT were followed 50% of the time over the last 7 years. In light of the lack of hypoglycemia associated with HIT in our study population, we recommend HIT as an early and safe antidote in significant CCA poisoning.

Patient safety goals for the proposed Federal Health Information Technology Safety Center.

PubMed

Sittig, Dean F; Classen, David C; Singh, Hardeep

2015-03-01

The Office of the National Coordinator for Health Information Technology is expected to oversee creation of a Health Information Technology (HIT) Safety Center. While its functions are still being defined, the center is envisioned as a public-private entity focusing on promotion of HIT related patient safety. We propose that the HIT Safety Center leverages its unique position to work with key administrative and policy stakeholders, healthcare organizations (HCOs), and HIT vendors to achieve four goals: (1) facilitate creation of a nationwide 'post-marketing' surveillance system to monitor HIT related safety events; (2) develop methods and governance structures to support investigation of major HIT related safety events; (3) create the infrastructure and methods needed to carry out random assessments of HIT related safety in complex HCOs; and (4) advocate for HIT safety with government and private entities. The convening ability of a federally supported HIT Safety Center could be critically important to our transformation to a safe and effective HIT enabled healthcare system. © The Author 2014. Published by Oxford University Press on behalf of the American Medical Informatics Association. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Direct oral anticoagulants for treatment of HIT: update of Hamilton experience and literature review.

PubMed

Warkentin, Theodore E; Pai, Menaka; Linkins, Lori-Ann

2017-08-31

Direct oral anticoagulants (DOACs) are attractive options for treatment of heparin-induced thrombocytopenia (HIT). We report our continuing experience in Hamilton, ON, Canada, since January 1, 2015 (when we completed our prospective study of rivaroxaban for HIT), using rivaroxaban for serologically confirmed HIT (4Ts score ≥4 points; positive platelet factor 4 [PF4]/heparin immunoassay, positive serotonin-release assay). We also performed a literature review of HIT treatment using DOACs (rivaroxaban, apixaban, dabigatran, edoxaban). We focused on patients who received DOAC therapy for acute HIT as either primary therapy (group A) or secondary therapy (group B; initial treatment using a non-DOAC/non-heparin anticoagulant with transition to a DOAC during HIT-associated thrombocytopenia). Our primary end point was occurrence of objectively documented thrombosis during DOAC therapy for acute HIT. We found that recovery without new, progressive, or recurrent thrombosis occurred in all 10 Hamilton patients with acute HIT treated with rivaroxaban. Data from the literature review plus these new data identified a thrombosis rate of 1 of 46 patients (2.2%; 95% CI, 0.4%-11.3%) in patients treated with rivaroxaban during acute HIT (group A, n = 25; group B, n = 21); major hemorrhage was seen in 0 of 46 patients. Similar outcomes in smaller numbers of patients were observed with apixaban (n = 12) and dabigatran (n = 11). DOACs offer simplified management of selected patients, as illustrated by a case of persisting (autoimmune) HIT (>2-month platelet recovery with inversely parallel waning of serum-induced heparin-independent serotonin release) with successful outpatient rivaroxaban management of HIT-associated thrombosis. Evidence supporting efficacy and safety of DOACs for acute HIT is increasing, with the most experience reported for rivaroxaban. © 2017 by The American Society of Hematology.

Evaluation of a new nanoparticle-based lateral-flow immunoassay for the exclusion of heparin-induced thrombocytopenia (HIT).

PubMed

Sachs, Ulrich J; von Hesberg, Jakob; Santoso, Sentot; Bein, Gregor; Bakchoul, Tamam

2011-12-01

Heparin-induced thrombocytopenia (HIT) is an adverse complication of heparin caused by HIT antibodies (abs) that recognise platelet factor 4-heparin (PF4/hep) complexes. Several laboratory tests are available for the confirmation and/or refutation of HIT. A reliable and rapid single-sample test is still pending. It was the objective of this study to evaluate a new lateral-flow immunoassay based on nanoparticle technology. A cohort of 452 surgical and medical patients suspected of having HIT was evaluated. All samples were tested in two IgG-specific ELISAs, in a particle gel immunoassay (PaGIA) and in a newly developed lateral-flow immunoassay (LFI-HIT) as well as in a functional test (HIPA). Clinical pre-test probability was determined using 4T's score. Platelet-activating antibodies were present in 34/452 patients, all of whom had intermediate to high clinical probability. PF4/hep abs were detected in 79, 87, 86, and 63 sera using the four different immunoassays. The negative predictive values (NPV) were 100% for both ELISA tests and LFI-HIT but only 99.2% for PaGIA. There were less false positives (n=29) in the LFI-HIT compared to any other test. Additionally, significantly less time was required to perform LFI-HIT than to perform the other immunoassays. In conclusion, a newly developed lateral-flow assay, LFI-HIT, was capable of identifying all HIT patients in a cohort in a short period of time. Beside an NPV of 100%, the rate of false-positive signals is significantly lower with LFI-HIT than with other immunoassay(s). These performance characteristics suggest a high potency in reducing the risk and costs in patients suspected of having HIT.

The Association between Health Information Technology Adoption and Family Physicians' Practice Patterns in Canada: Evidence from 2007 and 2010 National Physician Surveys

PubMed Central

Sarma, Sisira; Hajizadeh, Mohammad; Thind, Amardeep; Chan, Rick

2013-01-01

Objective: To describe the association between health information technology (HIT) adoption and family physicians' patient visit length in Canada after controlling for physician and practice characteristics. Method: HIT adoption is defined in terms of four types of HIT usage: no HIT use (NO), basic HIT use without electronic medical record system (HIT), basic HIT use with electronic medical record (EMR) and advanced HIT use (EMR + HIT). The outcome variable is the average time spent on a patient visit (visit length). The data for this study came from the 2007 and 2010 National Physician Surveys. A log-linear model was used to analyze our visit length outcome. Results: The average time worked per week was found to be in the neighbourhood of 36 hours in both 2007 and 2010, but users of EMR and EMR + HIT were undertaking fewer patient visits per week relative to NO users. Multivariable analysis showed that EMR and EMR + HIT were associated with longer average time spent per patient visit by about 7.7% (p<0.05) and 6.7% (p<0.01), respectively, compared to NO users in 2007. In 2010, EMR was not statistically significant and EMR + HIT was associated with a 4% (p<0.1) increased visit length. A variety of practice-related variables such as the mode of remuneration, work setting and interprofessional practice influenced visit length in the expected direction. Conclusion: Use of HIT is found to be associated with fewer patient visits and longer visit length among family physicians in Canada relative to NO users, but this association weakened in the multivariable analysis of 2010. PMID:23968677

Elevated circulating IGF-I promotes mammary gland development and proliferation.

PubMed

Cannata, Dara; Lann, Danielle; Wu, Yingjie; Elis, Sebastien; Sun, Hui; Yakar, Shoshana; Lazzarino, Deborah A; Wood, Teresa L; Leroith, Derek

2010-12-01

Animal studies have shown that IGF-I is essential for mammary gland development. Previous studies have suggested that local IGF-I rather than circulating IGF-I is the major mediator of mammary gland development. In the present study we used the hepatic IGF-I transgenic (HIT) and IGF-I knockout/HIT (KO-HIT) mouse models to examine the effects of enhanced circulating IGF-I on mammary development in the presence and absence of local IGF-I. HIT mice express the rat IGF-I transgene under the transthyretin promoter in the liver and have elevated circulating IGF-I and normal tissue IGF-I levels. The KO-HIT mice have no tissue IGF-I and increased circulating IGF-I. Analysis of mammary gland development reveals a greater degree of complexity in HIT mice as compared to control and KO-HIT mice, which demonstrate similar degrees of mammary gland complexity. Immunohistochemical evaluation of glands of HIT mice also suggests an enhanced degree of proliferation of the mammary gland, whereas KO-HIT mice exhibit mammary gland proliferation similar to control mice. In addition, HIT mice have a higher percentage of proliferating myoepithelial and luminal cells than control mice, whereas KO-HIT mice have an equivalent percentage of proliferating myoepithelial and luminal cells as control mice. Thus, our findings show that elevated circulating IGF-I levels are sufficient to promote normal pubertal mammary epithelial development. However, HIT mice demonstrate more pronounced mammary gland development when compared to control and KO-HIT mice. This suggests that both local and endocrine IGF-I play roles in mammary gland development and that elevated circulating IGF-I accelerates mammary epithelial proliferation.

Biological characterization of adult MYC-translocation-positive mature B-cell lymphomas other than molecular Burkitt lymphoma.

PubMed

Aukema, Sietse M; Kreuz, Markus; Kohler, Christian W; Rosolowski, Maciej; Hasenclever, Dirk; Hummel, Michael; Küppers, Ralf; Lenze, Dido; Ott, German; Pott, Christiane; Richter, Julia; Rosenwald, Andreas; Szczepanowski, Monika; Schwaenen, Carsten; Stein, Harald; Trautmann, Heiko; Wessendorf, Swen; Trümper, Lorenz; Loeffler, Markus; Spang, Rainer; Kluin, Philip M; Klapper, Wolfram; Siebert, Reiner

2014-04-01

Chromosomal translocations affecting the MYC oncogene are the biological hallmark of Burkitt lymphomas but also occur in a subset of other mature B-cell lymphomas. If accompanied by a chromosomal break targeting the BCL2 and/or BCL6 oncogene these MYC translocation-positive (MYC(+)) lymphomas are called double-hit lymphomas, otherwise the term single-hit lymphomas is applied. In order to characterize the biological features of these MYC(+) lymphomas other than Burkitt lymphoma we explored, after exclusion of molecular Burkitt lymphoma as defined by gene expression profiling, the molecular, pathological and clinical aspects of 80 MYC-translocation-positive lymphomas (31 single-hit, 46 double-hit and 3 MYC(+)-lymphomas with unknown BCL6 status). Comparison of single-hit and double-hit lymphomas revealed no difference in MYC partner (IG/non-IG), genomic complexity, MYC expression or gene expression profile. Double-hit lymphomas more frequently showed a germinal center B-cell-like gene expression profile and had higher IGH and MYC mutation frequencies. Gene expression profiling revealed 130 differentially expressed genes between BCL6(+)/MYC(+) and BCL2(+)/MYC(+) double-hit lymphomas. BCL2(+)/MYC(+) double-hit lymphomas more frequently showed a germinal center B-like gene expression profile. Analysis of all lymphomas according to MYC partner (IG/non-IG) revealed no substantial differences. In this series of lymphomas, in which immunochemotherapy was administered in only a minority of cases, single-hit and double-hit lymphomas had a similar poor outcome in contrast to the outcome of molecular Burkitt lymphoma and lymphomas without the MYC break. Our data suggest that, after excluding molecular Burkitt lymphoma and pediatric cases, MYC(+) lymphomas are biologically quite homogeneous with single-hit and double-hit lymphomas as well as IG-MYC and non-IG-MYC(+) lymphomas sharing various molecular characteristics.

Obstacles in the diagnostics and therapy of heparin-induced thrombocytopenia.

PubMed

Antonijević, Nebojsa M; Radovanović, Nebojsa; Obradović, Slobodan; Vucelić, Dragica; Stojanović, Bojan; Miković, Danijela; Kovac, Mirjana; Kocica, Tina; Tadić, Svetlana; Antonijević, Irina; Drasković, Snezana; Djordjević, Valentina; Calija, Branko; Perunicić, Jovan; Vasiljević, Zorana

2010-01-01

An immune-mediated, severe, acquired prothrombotic disorder, heparin-induced thrombocytopenia type II (HIT II) occurs in 0.5-5% of patients exposed to unfractionated heparin longer than 5-7 days. Arterial and venous thromboses are induced by HIT II in about 35-50% of patients. Typical death rate for HIT is about 29%, while 21% of HIT patients result in amputation of a limb. The trend towards the occurrence of HIT due to the administration of low molecular weight heparins (LMWH) taking ever conspicuous place in the standard venous thromboembolism (VTE) prophylaxis has been more frequently observed recently. It is considered that LMWH may cause HIT II in about 0.25-1%. The need for further modification of HIPA assays with LMWH has been imposed in the HIT laboratory diagnostics, heretofore overburdened with complexity. There are several constantly opposing problems arising in HIT laboratory diagnostics, one of which is that in a certain number of patients immunologic assays detect nonpathogenic antibodies (mainly IgM or IgA heparin-PF4 antibodies) while, on the other hand, the occurrence of HIT pathogenetically mediated by minor antigens (neutrophil-activating peptide 2 or interleukin 8) may be neglected in certain cases. The following factors play an important role in the interpretation of each laboratory HIT assays performed: 1. correlation with HIT clinical probability test, the best known of which is 4T'score, 2. the interpretation of the laboratory findings dependent on the time of the thrombocytopenia onset, as well as 3. the sensitivity and specificity of each test respectively. The HIT diagnostics in the presence of other comorbid states which may also induce thrombocytopenia, more precisely known as pseudo HIT (cancer, sepsis, disseminated intravascular coagulation, pulmonary embolism, antiphospholipid syndrome, etc), represents a specific clinical problem.

A team approach to preparing for hurricanes and other disasters.

PubMed

Kendig, Jim

2009-01-01

Applying lessons learned in Hurricane Floyd in 1999, a three-hospital system located on Florida's exposed Space Coast was able to better deal with the devastation caused by hurricanes in 2004 and make changes in its plans to better prepare for the named storms which hit its area in 2008. Each new disaster, the author points out, brings with it new challenges which have to be considered in disaster planning.

ACOSS Eleven (Active Control of Space Structures)

DTIC Science & Technology

1984-09-01

spatial integration with thresh- old level and system track threshold level reduction factor. 2.2.3 Track Acquisition In the HRAP/LRTP simulation, input ...in both row and column, however, then the track direction is determined to be diagonal. Also, as with the first * tier, multiple hits are processed...for any system track before thresholding, clustering, and centroiding can produce the next frame to be input to the two tier algorithm. As Figure 2-10

Robotics in the Construction Industry

DTIC Science & Technology

1990-06-01

accomplished through reprogramming and the attachment of different end effectors. 2.1.2.3 Manipulator I This is the mechanism for moving objects in the...other 3 types of robots), limited repeatability (ability to "hit" the same point in space time after time without reprogramming or adjustment by the... Reprogramming for a different 3 sequence of steps is generally difficult and time- consuming, as the stops must be relocated and I calibrated for the new sequence

Europe's space camera unmasks a cosmic gamma-ray machine

NASA Astrophysics Data System (ADS)

1996-11-01

The new-found neutron star is the visible counterpart of a pulsating radio source, Pulsar 1055-52. It is a mere 20 kilometres wide. Although the neutron star is very hot, at about a million degrees C, very little of its radiant energy takes the form of visible light. It emits mainly gamma-rays, an extremely energetic form of radiation. By examining it at visible wavelengths, astronomers hope to figure out why Pulsar 1055-52 is the most efficient generator of gamma-rays known so far, anywhere the Universe. The Faint Object Camera found Pulsar 1055-52 in near ultraviolet light at 3400 angstroms, a little shorter in wavelength than the violet light at the extremity of the human visual range. Roberto Mignani, Patrizia Caraveo and Giovanni Bignami of the Istituto di Fisica Cosmica in Milan, Italy, report its optical identification in a forthcoming issue of Astrophysical Journal Letters (1 January 1997). The formal name of the object is PSR 1055-52. Evading the glare of an adjacent star The Italian team had tried since 1988 to spot Pulsar 1055-52 with two of the most powerful ground-based optical telescopes in the Southern Hemisphere. These were the 3.6-metre Telescope and the 3.5-metre New Technology Telescope of the European Southern Observatory at La Silla, Chile. Unfortunately an ordinary star 100,000 times brighter lay in almost the same direction in the sky, separated from the neutron star by only a thousandth of a degree. The Earth's atmosphere defocused the star's light sufficiently to mask the glimmer from Pulsar 1055-52. The astronomers therefore needed an instrument in space. The Faint Object Camera offered the best precision and sensitivity to continue the hunt. Devised by European astronomers to complement the American wide field camera in the Hubble Space Telescope, the Faint Object Camera has a relatively narrow field of view. It intensifies the image of a faint object by repeatedly accelerating electrons from photo-electric films, so as to produce brighter flashes when the electrons hit a phosphor screen. Since Hubble's launch in 1990, the Faint Object Camera has examined many different kinds of cosmic objects, from the moons of Jupiter to remote galaxies and quasars. When the space telescope's optics were corrected at the end of 1993 the Faint Object Camera immediately celebrated the event with the discovery of primeval helium in intergalactic gas. In their search for Pulsar 1055-52, the astronomers chose a near-ultraviolet filter to sharpen the Faint Object Camera's vision and reduce the adjacent star's huge advantage in intensity. In May 1996, the Hubble Space Telescope operators aimed at the spot which radio astronomers had indicated, as the source of the radio pulsations of Pulsar 1055-52. The neutron star appeared precisely in the centre of the field of view, and it was clearly separated from the glare of the adjacent star. At magnitude 24.9, Pulsar 1055-52 was comfortably within the power of the Faint Object Camera, which can see stars 20 times fainter still. "The Faint Object Camera is the instrument of choice for looking for neutron stars," says Giovanni Bignami, speaking on behalf of the Italian team. "Whenever it points to a judiciously selected neutron star it detects the corresponding visible or ultraviolet light. The Faint Object Camera has now identified three neutron stars in that way, including Pulsar 1055-52, and it has examined a few that were first detected by other instruments." Mysteries of the neutron stars The importance of the new result can be gauged by the tally of only eight neutron stars seen so far at optical wavelengths, compared with about 760 known from their radio pulsations, and about 21 seen emitting X-rays. Since the first pulsar was detected by radio astronomers in Cambridge, England, nearly 30 years ago, theorists have come to recognize neutron stars as fantastic objects. They are veritable cosmic laboratories in which Nature reveals the behaviour of matter under extreme stress, just one step short of a black hole. A neutron star is created by the force of a supernova explosion in a large star, which crushes the star's core to an unimaginable density. A mass greater than the Sun's is squeezed into a ball no wider than a city. The gravity and magnetic fields are billions of times stronger than the Earth's. The neutron star revolves rapidly, which causes it to wink like a cosmic lighthouse as it swivels its magnetic poles towards and away from the Earth. Pulsar 1055-52 spins at five revolutions per second. At its formation in a supernova explosion, a neutron star is endowed with two main forms of energy. One is heat, at temperatures of millions of degrees, which the neutron star radiates mainly as X-rays, with only a small proportion emerging as visible light. The other power supply for the neutron star comes from its high rate of spin and a gradual slowing of the rotation. By a variety of processes involving the magnetic field and accelerated particles in the neutron star's vicinity, the spin energy of the neutron star is converted into radiation at many different wavelengths, from radio waves to gamma-rays. The exceptional gamma-ray intensity of Pulsar 1055-52 was first appreciated in observations by NASA's Compton Gamma Ray Observatory. The team in Milan recently used the Hubble Space Telescope to find the distance of the peculiar neutron star Geminga, which is not detectable by radio pulses but is a strong source of gamma-rays (see ESA Information Note 04-96, 28 March 1996). Pulsar 1055-52 is even more powerful in that respect. About 50 per cent of its radiant energy is gamma-rays, compared with 15 per cent from Geminga and 0.1 per cent from the famous Crab Pulsar, the first neutron star seen by visible light. Making the gamma-rays requires the acceleration of electrons through billions of volts. The magnetic environment of Pulsar 1055-52 fashions a natural gamma-ray machine of amazing power. The orientation of the neutron star's magnetic field with respect to the Earth may contribute to its brightness in gamma-rays. Geminga, Pulsar 1055-52 and another object, Pulsar 0656+14, make a trio that the Milanese astronomers call the Three Musketeers. All have been observed with the Faint Object Camera. They are isolated, elderly neutron stars, some hundreds of thousands of years old, contrasting with the 942 year-old Crab Pulsar which is still surrounded by dispersing debris of a supernova seen by Chinese astronomers in the 11th Century. The mysteries of the neutron stars will keep astronomers busy for years to come, and the Faint Object Camera in the Hubble Space Telescope will remain the best instrument for spotting their faint visible light. The Hubble Space Telescope is a project of international cooperation between NASA and the European Space Agency (ESA). The Space Telescope Science Institute is operated by the Association of Universities for Research in Astronomy, Inc. (AURA) for NASA, under contract with the Goddard Space Flight Center, Greenbelt, Maryland. Note to editors: An image is available of (i) PSR 1055-52 seen by ESA's Faint Object Camera in the Hubble Space Telescope, and (ii) the same region of the sky seen by the European Southern Observatory's New Technology Telescope, with the position of PSR 1055-52 indicated. The image is available on the World Wide Web at http://ecf.hq.eso.org/stecf-pubrel.html http://www.estec.esa.nl/spdwww/h2000/html/snlmain.htm

Validation of Real-time Modeling of Coronal Mass Ejections Using the WSA-ENLIL+Cone Heliospheric Model

NASA Astrophysics Data System (ADS)

Romano, M.; Mays, M. L.; Taktakishvili, A.; MacNeice, P. J.; Zheng, Y.; Pulkkinen, A. A.; Kuznetsova, M. M.; Odstrcil, D.

2013-12-01

Modeling coronal mass ejections (CMEs) is of great interest to the space weather research and forecasting communities. We present recent validation work of real-time CME arrival time predictions at different satellites using the WSA-ENLIL+Cone three-dimensional MHD heliospheric model available at the Community Coordinated Modeling Center (CCMC) and performed by the Space Weather Research Center (SWRC). SWRC is an in-house research-based operations team at the CCMC which provides interplanetary space weather forecasting for NASA's robotic missions and performs real-time model validation. The quality of model operation is evaluated by comparing its output to a measurable parameter of interest such as the CME arrival time and geomagnetic storm strength. The Kp index is calculated from the relation given in Newell et al. (2007), using solar wind parameters predicted by the WSA-ENLIL+Cone model at Earth. The CME arrival time error is defined as the difference between the predicted arrival time and the observed in-situ CME shock arrival time at the ACE, STEREO A, or STEREO B spacecraft. This study includes all real-time WSA-ENLIL+Cone model simulations performed between June 2011-2013 (over 400 runs) at the CCMC/SWRC. We report hit, miss, false alarm, and correct rejection statistics for all three spacecraft. For hits we show the average absolute CME arrival time error, and the dependence of this error on CME input parameters such as speed, width, and direction. We also present the predicted geomagnetic storm strength (using the Kp index) error for Earth-directed CMEs.

NMR screening in fragment-based drug design: a practical guide.

PubMed

Kim, Hai-Young; Wyss, Daniel F

2015-01-01

Fragment-based drug design (FBDD) comprises both fragment-based screening (FBS) to find hits and elaboration of these hits to lead compounds. Typical fragment hits have lower molecular weight (<300-350 Da) and lower initial potency but higher ligand efficiency when compared to those from high-throughput screening. NMR spectroscopy has been widely used for FBDD since it identifies and localizes the binding site of weakly interacting hits on the target protein. Here we describe ligand-based NMR methods for hit identification from fragment libraries and for functional cross-validation of primary hits.

Reflected ray retrieval from radio occultation data using radio holographic filtering of wave fields in ray space

NASA Astrophysics Data System (ADS)

Gorbunov, Michael E.; Cardellach, Estel; Lauritsen, Kent B.

2018-03-01

Linear and non-linear representations of wave fields constitute the basis of modern algorithms for analysis of radio occultation (RO) data. Linear representations are implemented by Fourier Integral Operators, which allow for high-resolution retrieval of bending angles. Non-linear representations include Wigner Distribution Function (WDF), which equals the pseudo-density of energy in the ray space. Representations allow for filtering wave fields by suppressing some areas of the ray space and mapping the field back from the transformed space to the initial one. We apply this technique to the retrieval of reflected rays from RO observations. The use of reflected rays may increase the accuracy of the retrieval of the atmospheric refractivity. Reflected rays can be identified by the visual inspection of WDF or spectrogram plots. Numerous examples from COSMIC data indicate that reflections are mostly observed over oceans or snow, in particular over Antarctica. We introduce the reflection index that characterizes the relative intensity of the reflected ray with respect to the direct ray. The index allows for the automatic identification of events with reflections. We use the radio holographic estimate of the errors of the retrieved bending angle profiles of reflected rays. A comparison of indices evaluated for a large base of events including the visual identification of reflections indicated a good agreement with our definition of reflection index.

Schematic displays for the Space Shuttle Orbiter multifunction cathode-ray-tube display system

NASA Technical Reports Server (NTRS)

Weiss, W.

1979-01-01

A standardized procedure for developing cathode ray tube displayed schematic diagrams. The displaying of Spacelab information on the space shuttle orbiter multifunction cathode ray tube display system is used to illustrate this procedure. Schematic displays with the equivalent tabular displays are compared.

Gamma ray astrophysics to the year 2000. Report of the NASA Gamma Ray Program Working Group

NASA Technical Reports Server (NTRS)

1988-01-01

Important developments in gamma-ray astrophysics up to energies of 100 GeV during the last decade are reviewed. Also, the report seeks to define the major current scientific goals of the field and proposes a vigorous program to pursue them, extending to the year 2000. The goals of gamma-ray astronomy include the study of gamma rays which provide the most direct means of studying many important problems in high energy astrophysics including explosive nucleosynthesis, accelerated particle interactions and sources, and high-energy processes around compact objects. The current research program in gamma-ray astronomy in the U.S. including the space program, balloon program and foreign programs in gamma-ray astronomy is described. The high priority recommendations for future study include an Explorer-class high resolution gamma-ray spectroscopy mission and a Get Away Special cannister (GAS-can) or Scout class multiwavelength experiment for the study of gamma-ray bursts. Continuing programs include an extended Gamma Ray Observatory mission, continuation of the vigorous program of balloon observations of the nearby Supernova 1987A, augmentation of the balloon program to provide for new instruments and rapid scientific results, and continuation of support for theoretical research. Long term recommendations include new space missions using advanced detectors to better study gamma-ray sources, the development of these detectors, continued study for the assembly of large detectors in space, collaboration with the gamma-ray astronomy missions initiated by other countries, and consideration of the Space Station attached payloads for gamma-ray experiments.

Alternative designs for space x-ray telescopes

NASA Astrophysics Data System (ADS)

Hudec, R.; Pína, L.; Maršíková, Veronika; Černá, Daniela; Inneman, A.; Tichý, V.

2017-11-01

The X-ray optics is a key element of space X-ray telescopes, as well as other X-ray imaging instruments. The grazing incidence X-ray lenses represent the important class of X-ray optics. Most of grazing incidence (reflective) X-ray imaging systems used in astronomy but also in other (laboratory) applications are based on the Wolter 1 (or modified) arrangement. But there are also other designs and configurations proposed, used and considered for future applications both in space and in laboratory. The Kirkpatrick-Baez (K-B) lenses as well as various types of Lobster-Eye optics and MCP/Micropore optics serve as an example. Analogously to Wolter lenses, the X-rays are mostly reflected twice in these systems to create focal images. Various future projects in X-ray astronomy and astrophysics will require large segments with multiple thin shells or foils. The large Kirkpatrick-Baez modules, as well as the large Lobster-Eye X-ray telescope modules in Schmidt arrangement may serve as examples. All related space projects will require high quality and light segmented shells (bent or flat foils) with high X-ray reflectivity and excellent mechanical stability. The Multi Foil Optics (MFO) approach represent a promising alternative for both LE and K-B X-ray optical modules. Several types of reflecting substrates may be considered for these applications, with emphasis on thin float glass sheets and, more recently, high quality silicon wafers. This confirms the importance of non-Wolter X-ray optics designs for the future. The alternative designs require novel reflective substrates which are also discussed in the paper.

[Diagnosis and treatment of heparin-induced thrombocytopenia (HIT) based on its atypical immunological features].

PubMed

Miyata, Shigeki; Maeda, Takuma

2016-03-01

Heparin-induced thrombocytopenia (HIT) is a prothrombotic side effect of heparin therapy caused by HIT antibodies, i.e., anti-platelet factor 4 (PF4)/heparin IgG with platelet-activating properties. For serological diagnosis, antigen immunoassays are commonly used worldwide. However, such assays do not indicate their platelet-activating properties, leading to low specificity for the HIT diagnosis. Therefore, over-diagnosis is currently the most serious problem associated with HIT. The detection of platelet-activating antibodies using a washed platelet activation assay is crucial for appropriate HIT diagnosis. Recent advances in our understanding of the pathogenesis of HIT include it having several clinical features atypical for an immune-mediated disease. Heparin-naïve patients can develop IgG antibodies as early as day 4, as in a secondary immune response. Evidence for an anamnestic response on heparin re-exposure is lacking. In addition, HIT antibodies are relatively short-lived, unlike those in a secondary immune response. These lines of evidence suggest that the mechanisms underlying HIT antibody formation may be compatible with a non-T cell-dependent immune reaction. These atypical clinical and serological features should be carefully considered while endeavoring to accurately diagnose HIT, which leads to appropriate therapies such as immediate administration of an alternative anticoagulant to prevent thromboembolic events and re-administration of heparin during surgery involving cardiopulmonary bypass when HIT antibodies are no longer detectable.

A qualitative study of health information technology in the Canadian public health system.

PubMed

Zinszer, Kate; Tamblyn, Robyn; Bates, David W; Buckeridge, David L

2013-05-25

Although the adoption of health information technology (HIT) has advanced in Canada over the past decade, considerable challenges remain in supporting the development, broad adoption, and effective use of HIT in the public health system. Policy makers and practitioners have long recognized that improvements in HIT infrastructure are necessary to support effective and efficient public health practice. The objective of this study was to identify aspects of health information technology (HIT) policy related to public health in Canada that have succeeded, to identify remaining challenges, and to suggest future directions to improve the adoption and use of HIT in the public health system. A qualitative case study was performed with 24 key stakeholders representing national and provincial organizations responsible for establishing policy and strategic direction for health information technology. Identified benefits of HIT in public health included improved communication among jurisdictions, increased awareness of the need for interoperable systems, and improvement in data standardization. Identified barriers included a lack of national vision and leadership, insufficient investment, and poor conceptualization of the priority areas for implementing HIT in public health. The application of HIT in public health should focus on automating core processes and identifying innovative applications of HIT to advance public health outcomes. The Public Health Agency of Canada should develop the expertise to lead public health HIT policy and should establish a mechanism for coordinating public health stakeholder input on HIT policy.

DoD Space Radiation Concerns.

DTIC Science & Technology

1992-07-15

cosmic - ray transport. NASA TM X-2440, 1972:117-122. DoD Space Radiation Concerns 8 2. Atkins SG, Small JT, McFarland TH. Military Man-in Space (MMIS...136. 29. Silberberg R, Tsao CH, Adams JH Jr., Letaw JR. Radiation doses and LET distributions of cosmic rays . Rad. Res., 1984, 98:209-226. 30. Stauber...levels on mission success and completion. Natural Radiation Trapped Radiation Belts Galactic Cosmic Rays (GCR) Solar Particle Events (SPEs) Man-Made

X-ray Crystallography Facility

NASA Technical Reports Server (NTRS)

1999-01-01

University of Alabama engineer Lance Weiss briefs NASA astronaut Dr. Bornie Dunbar about the design and capabilities of the X-ray Crystallography Facility under development at the Center for Macromolecular Crystallography of the University of Alabama at Birmingham, AL, April 21, 1999. The X-ray Crystallography Facility is designed to speed the collection of protein structure information from crystals grown aboard the International Space Station. By measuring and mapping the protein crystal structure in space, researchers will avoid exposing the delicate crystals to the rigors of space travel and make important research data available to scientists much faster. The X-ray Crystallography facility is being designed and developed by the Center for Macromolecular Crystallography of the University of Alabama at Birmingham, a NASA Commercial Space Center.

X-ray Crystallography Facility

NASA Technical Reports Server (NTRS)

1999-01-01

University of Alabama engineer Stacey Giles briefs NASA astronaut Dr. Bornie Dunbar about the design and capabilities of the X-ray Crystallography Facility under development at the Center for Macromolecular Crystallography of the University of Alabama at Birmingham, AL, April 21, 1999. The X-ray Crystallography Facility is designed to speed the collection of protein structure information from crystals grown aboard the International Space Station. By measuring and mapping the protein crystal structure in space, researchers will avoid exposing the delicate crystals to the rigors of space travel and make important research data available to scientists much faster. The X-ray Crystallography facility is being designed and developed by the Center for Macromolecular Crystallography of the University of Alabama at Birmingham, a NASA Commercial Space Center.

Defining health information technology-related errors: new developments since to err is human.

PubMed

Sittig, Dean F; Singh, Hardeep

2011-07-25

Despite the promise of health information technology (HIT), recent literature has revealed possible safety hazards associated with its use. The Office of the National Coordinator for HIT recently sponsored an Institute of Medicine committee to synthesize evidence and experience from the field on how HIT affects patient safety. To lay the groundwork for defining, measuring, and analyzing HIT-related safety hazards, we propose that HIT-related error occurs anytime HIT is unavailable for use, malfunctions during use, is used incorrectly by someone, or when HIT interacts with another system component incorrectly, resulting in data being lost or incorrectly entered, displayed, or transmitted. These errors, or the decisions that result from them, significantly increase the risk of adverse events and patient harm. We describe how a sociotechnical approach can be used to understand the complex origins of HIT errors, which may have roots in rapidly evolving technological, professional, organizational, and policy initiatives.

Health information technology knowledge and skills needed by HIT employers.

PubMed

Fenton, S H; Gongora-Ferraez, M J; Joost, E

2012-01-01

To evaluate the health information technology (HIT) workforce knowledge and skills needed by HIT employers. Statewide face-to-face and online focus groups of identified HIT employer groups in Austin, Brownsville, College Station, Dallas, El Paso, Houston, Lubbock, San Antonio, and webinars for rural health and nursing informatics. HIT employers reported needing an HIT workforce with diverse knowledge and skills ranging from basic to advanced, while covering information technology, privacy and security, clinical practice, needs assessment, contract negotiation, and many other areas. Consistent themes were that employees needed to be able to learn on the job and must possess the ability to think critically and problem solve. Many employers wanted persons with technical skills, yet also the knowledge and understanding of healthcare operations. The HIT employer focus groups provided valuable insight into employee skills needed in this fast-growing field. Additionally, this information will be utilized to develop a statewide HIT workforce needs assessment survey.

Early phase drug discovery: cheminformatics and computational techniques in identifying lead series.

PubMed

Duffy, Bryan C; Zhu, Lei; Decornez, Hélène; Kitchen, Douglas B

2012-09-15

Early drug discovery processes rely on hit finding procedures followed by extensive experimental confirmation in order to select high priority hit series which then undergo further scrutiny in hit-to-lead studies. The experimental cost and the risk associated with poor selection of lead series can be greatly reduced by the use of many different computational and cheminformatic techniques to sort and prioritize compounds. We describe the steps in typical hit identification and hit-to-lead programs and then describe how cheminformatic analysis assists this process. In particular, scaffold analysis, clustering and property calculations assist in the design of high-throughput screening libraries, the early analysis of hits and then organizing compounds into series for their progression from hits to leads. Additionally, these computational tools can be used in virtual screening to design hit-finding libraries and as procedures to help with early SAR exploration. Copyright © 2012 Elsevier Ltd. All rights reserved.

EFFECTS OF X-RAY BEAM ANGLE AND GEOMETRIC DISTORTION ON WIDTH OF EQUINE THORACOLUMBAR INTERSPINOUS SPACES USING RADIOGRAPHY AND COMPUTED TOMOGRAPHY-A CADAVERIC STUDY.

PubMed

Djernaes, Julie D; Nielsen, Jon V; Berg, Lise C

2017-03-01

The widths of spaces between the thoracolumbar processi spinosi (interspinous spaces) are frequently assessed using radiography in sports horses; however effects of varying X-ray beam angles and geometric distortion have not been previously described. The aim of this prospective, observational study was to determine whether X-ray beam angle has an effect on apparent widths of interspinous spaces. Thoracolumbar spine specimens were collected from six equine cadavers and left-right lateral radiographs and sagittal and dorsal reconstructed computed tomographic (CT) images were acquired. Sequential radiographs were acquired with each interspinous space in focus. Measurements were performed for each interspinous space in the focus position and up to eight angled positions as the interspinous space moved away from focus (±). Focus position measurements were compared to matching sagittal CT measurements. Effect of geometric distortion was evaluated by comparing the interspinous space in radiographs with sagittal and dorsal reconstructed CT images. A total of 49 interspinous spaces were sampled, yielding 274 measurements. X-ray beam angle significantly affected measured width of interspinous spaces in position +3 (P = 0.038). Changes in width did not follow a consistent pattern. Interspinous space widths in focus position were significantly smaller in radiographs compared to matching reconstructed CT images for backs diagnosed with kissing spine syndrome (P < 0.001). Geometric distortion markedly affected appearance of interspinous space width between planes. In conclusion, X-ray beam angle and geometric distortion influence radiographically measured widths of interspinous spaces in the equine thoracolumbar spine, and this should be taken into consideration when evaluating sport horses. © 2016 American College of Veterinary Radiology.

Space Science

NASA Image and Video Library

2003-04-09

The Eastman-Kodak mirror assembly is being tested for the James Webb Space Telescope (JWST) project at the X-Ray Calibration Facility at Marshall Space Flight Center (MSFC). In this photo, one of many segments of the mirror assembly is being set up inside the 24-ft vacuum chamber where it will undergo x-ray calibration tests. MSFC is supporting Goddard Space Flight Center (GSFC) in developing the JWST by taking numerous measurements to predict its future performance. The tests are conducted in a vacuum chamber cooled to approximate the super cold temperatures found in space. During its 27 years of operation, the facility has performed testing in support of a wide array of projects, including the Hubble Space Telescope (HST), Solar A, Chandra technology development, Chandra High Resolution Mirror Assembly and science instruments, Constellation X-Ray Mission, and Solar X-Ray Imager, currently operating on a Geostationary Operational Environment Satellite. The JWST is NASA's next generation space telescope, a successor to the Hubble Space Telescope, named in honor of NASA's second administrator, James E. Webb. It is scheduled for launch in 2010 aboard an expendable launch vehicle. It will take about 3 months for the spacecraft to reach its destination, an orbit of 940,000 miles in space.

Robust statistical methods for hit selection in RNA interference high-throughput screening experiments.

PubMed

Zhang, Xiaohua Douglas; Yang, Xiting Cindy; Chung, Namjin; Gates, Adam; Stec, Erica; Kunapuli, Priya; Holder, Dan J; Ferrer, Marc; Espeseth, Amy S

2006-04-01

RNA interference (RNAi) high-throughput screening (HTS) experiments carried out using large (>5000 short interfering [si]RNA) libraries generate a huge amount of data. In order to use these data to identify the most effective siRNAs tested, it is critical to adopt and develop appropriate statistical methods. To address the questions in hit selection of RNAi HTS, we proposed a quartile-based method which is robust to outliers, true hits and nonsymmetrical data. We compared it with the more traditional tests, mean +/- k standard deviation (SD) and median +/- 3 median of absolute deviation (MAD). The results suggested that the quartile-based method selected more hits than mean +/- k SD under the same preset error rate. The number of hits selected by median +/- k MAD was close to that by the quartile-based method. Further analysis suggested that the quartile-based method had the greatest power in detecting true hits, especially weak or moderate true hits. Our investigation also suggested that platewise analysis (determining effective siRNAs on a plate-by-plate basis) can adjust for systematic errors in different plates, while an experimentwise analysis, in which effective siRNAs are identified in an analysis of the entire experiment, cannot. However, experimentwise analysis may detect a cluster of true positive hits placed together in one or several plates, while platewise analysis may not. To display hit selection results, we designed a specific figure called a plate-well series plot. We thus suggest the following strategy for hit selection in RNAi HTS experiments. First, choose the quartile-based method, or median +/- k MAD, for identifying effective siRNAs. Second, perform the chosen method experimentwise on transformed/normalized data, such as percentage inhibition, to check the possibility of hit clusters. If a cluster of selected hits are observed, repeat the analysis based on untransformed data to determine whether the cluster is due to an artifact in the data. If no clusters of hits are observed, select hits by performing platewise analysis on transformed data. Third, adopt the plate-well series plot to visualize both the data and the hit selection results, as well as to check for artifacts.

External validation of the HIT Expert Probability (HEP) score.

PubMed

Joseph, Lee; Gomes, Marcelo P V; Al Solaiman, Firas; St John, Julie; Ozaki, Asuka; Raju, Manjunath; Dhariwal, Manoj; Kim, Esther S H

2015-03-01

The diagnosis of heparin-induced thrombocytopenia (HIT) can be challenging. The HIT Expert Probability (HEP) Score has recently been proposed to aid in the diagnosis of HIT. We sought to externally and prospectively validate the HEP score. We prospectively assessed pre-test probability of HIT for 51 consecutive patients referred to our Consultative Service for evaluation of possible HIT between August 1, 2012 and February 1, 2013. Two Vascular Medicine fellows independently applied the 4T and HEP scores for each patient. Two independent HIT expert adjudicators rendered a diagnosis of HIT likely or unlikely. The median (interquartile range) of 4T and HEP scores were 4.5 (3.0, 6.0) and 5 (3.0, 8.5), respectively. There were no significant differences between area under receiver-operating characteristic curves of 4T and HEP scores against the gold standard, confirmed HIT [defined as positive serotonin release assay and positive anti-PF4/heparin ELISA] (0.74 vs 0.73, p = 0.97). HEP score ≥ 2 was 100 % sensitive and 16 % specific for determining the presence of confirmed HIT while a 4T score > 3 was 93 % sensitive and 35 % specific. In conclusion, the HEP and 4T scores are excellent screening pre-test probability models for HIT, however, in this prospective validation study, test characteristics for the diagnosis of HIT based on confirmatory laboratory testing and expert opinion are similar. Given the complexity of the HEP scoring model compared to that of the 4T score, further validation of the HEP score is warranted prior to widespread clinical acceptance.

Recent advances in the diagnosis and treatment of heparin-induced thrombocytopenia

PubMed Central

Bakchoul, Tamam

2012-01-01

Heparin-induced thrombocytopenia (HIT) is a drug-mediated, prothrombotic disorder caused by immunization against platelet factor 4 (PF4) after complex formation with heparin or other polyanions. After their binding to PF4/heparin complexes on the platelet surface, HIT antibodies are capable of intravascular platelet activation by cross-linking Fcγ receptor IIA leading to a platelet count decrease and/or thrombosis. Diagnosis of HIT is often difficult. This, and the low specificity of the commercially available immunoassays, leads currently to substantial overdiagnosis of HIT. Timing of onset, the moderate nature of thrombocytopenia, and the common concurrence of thrombosis are very important factors, which help to differentiate HIT from other potential causes of thrombocytopenia. A combination of a clinical pretest scoring system and laboratory investigation is usually necessary to diagnose HIT. Although HIT is considered to be a rare complication of heparin treatment, the very high number of hospital inpatients, and increasingly also hospital outpatients receiving heparin, still result in a considerable number of patients developing HIT. If HIT occurs, potentially devastating complications such as life-threatening thrombosis make it one of the most serious adverse drug reactions. If HIT is strongly suspected, all heparin must be stopped and an alternative nonheparin anticoagulant started at a therapeutic dose to prevent thromboembolic complications. However, the nonheparin alternative anticoagulants bear a considerable bleeding risk, especially if given to patients with thrombocytopenia due to other reasons than HIT. While established drugs for HIT are disappearing from the market (lepirudin, danaparoid), bivalirudin, fondaparinux and potentially the new anticoagulants such as dabigatran, rivaroxaban and apixaban provide new treatment options. PMID:23606934

Is There an Association Between Heparin-Induced Thrombocytopenia (HIT) and Autoimmune Disease?

PubMed

Klinkhammer, Brent; Gruchalla, Michael

2018-03-01

Heparin-induced thrombocytopenia (HIT) is a drug-induced, immunoglobulin G medicated autoimmune disorder associated with several negative clinical outcomes including increased morbidity, mortality, and increased medical costs. Previous studies have shown associations between comorbid autoimmune diseases, but there is little known about associations between HIT and autoimmunity. To provide clinical data to suggest an association between HIT and autoimmunity. Retrospective chart review of 59 cases with a diagnosis of HIT and 251 matched controls without a HIT diagnosis, comparing the prevalence of autoimmunity in each group. A single, large upper Midwest health care system. Patients with a diagnosis of HIT were significantly more likely to have a comorbid autoimmune disease than those without a HIT diagnosis (55.9% vs 10.8%, P < 0.001). In disease-specific analyses, patients with a diagnosis of HIT were significantly more likely to have a diagnosis of antiphospholipid syndrome (15.3% vs 0.0%, P < 0.001), systemic lupus erythematous (8.5% vs 0.4%, P = 0.001), rheumatoid arthritis (5.1% vs 0.0%, P = 0.007), Hashimoto's thyroiditis (13.6% vs 3.6%, P = 0.006), or nonischemic cardiomyopathy (5.1% vs 0.0%, P = 0.007). Patients diagnosed with HIT were significantly older than controls ( P < 0.001). This novel study gives evidence to suggest an association between HIT and autoimmune disease and suggests a need for more research into the relationship between HIT and autoimmunity. These results could alter the anticoagulation management of venous thromboembolism and acute coronary syndrome in patients with a previously identified autoimmune disease. Copyright© Wisconsin Medical Society.

The effect of obesity on the rate of heparin-induced thrombocytopenia.

PubMed

Marler, Jacob L; Jones, G Morgan; Wheeler, Brian J; Alshaya, Abdulrahman; Hartmann, Jonathan L; Oliphant, Carrie S

2018-06-01

: Heparin-induced thrombocytopenia (HIT) occurs in patients receiving heparin-containing products due to the formation of platelet-activating antibodies to heparin and platelet factor 4. Diagnosis includes utilization of a scoring system known as the 4-T score, and HIT laboratory assays. Recently, obesity was identified as a potential factor associated with the development of HIT. The objective of this study was to evaluate the association of HIT with obesity in ICU and general medicine patients. We performed a chart review of adult patients within the Methodist Healthcare System, and included patients who had an ELISA and serotonin release assay laboratory tests reported within same hospital admission in which they also had documented receipt of heparin. Obese patients were compared with nonobese patients (BMI < 30) for the primary outcome of HIT occurrence, and secondary outcomes including rate of thrombosis, 4-T scores, and ELISA optical density values. We also generated a 5-T score by including one additional point for those with a BMI of 30 or more to determine the predictive value of this score in identifying HIT. Obesity was confirmed to be a risk factor for HIT, and the 5-T score model was also predictive of the development of HIT. However, the 5-T score was not statistically more predictive of HIT than the 4-T score. Predicting HIT remains challenging and novel markers of HIT are needed to improve HIT recognition. Although obesity did not improve the 4-T score, it may improve the predictability of other scoring systems, and further investigation is warranted.

Argatroban for an alternative anticoagulant in HIT during ECMO.

PubMed

Rougé, Alain; Pelen, Felix; Durand, Michel; Schwebel, Carole

2017-01-01

Extracorporeal membrane oxygenation (ECMO) have become more frequently used in daily ICU practice, heparin-induced thrombocytopenia (HIT) is a rare but life-threatening complication while on extracorporeal membrane oxygenation (ECMO). HIT confirmation directly impacts on anticoagulant strategy requiring no delay unfractionated heparin discontinuation to be replaced by alternative systemic anticoagulant treatment. We report two clinical cases of HIT occurring during ECMO in various settings with subsequent recovery with argatroban and provide literature review to help physicians treat HIT during ECMO in clinical daily practice. HIT during ECMO is uncommon, and despite the absence of recommendation, argatroban seems to be an appropriate and safe therapeutic option. Finally, there are not enough arguments favouring routine circuit change in the event of HIT during ECMO.

Current insights into the laboratory diagnosis of HIT.

PubMed

Bakchoul, T; Zöllner, H; Greinacher, A

2014-06-01

Heparin-induced thrombocytopenia (HIT) is an adverse drug reaction and prothrombotic disorder caused by immunization against platelet factor 4 (PF4) after complex formation with heparin or other polyanions. After antibody binding to PF4/heparin complexes, HIT antibodies are capable of intravascular platelet activation by cross-linking Fc gamma receptor IIa (FcγRIIa) on the platelet surface leading to a platelet count decrease and/or thrombosis. In contrast to most other immune-mediated disorders, the currently available laboratory tests for anti-PF4/heparin antibodies show a high sensitivity also for clinically irrelevant antibodies. This makes the diagnosis of HIT challenging and bears the risk to substantially overdiagnose HIT. The strength of the antigen assays for HIT is in ruling out HIT when the test is negative. Functional assays have a higher specificity for clinically relevant antibodies, but they are restricted to specialized laboratories. Currently, a Bayesian approach combining the clinical likelihood estimation for HIT with laboratory tests is the most appropriate approach to diagnose HIT. In this review, we give an overview on currently available diagnostic procedures and discuss their limitations. © 2014 John Wiley & Sons Ltd.

First Plasma Results from the HIT-SI Spheromak

NASA Astrophysics Data System (ADS)

Sieck, P. E.; Hamp, W. T.; Izzo, V. A.; Jarboe, T. R.; Nelson, B. A.; O'Neill, R. G.; Redd, A. J.; Smith, R. J.

2003-10-01

HIT-SI is the newest device in the Helicity Injected Torus (HIT) program. HIT-SI is a ``bow tie'' spheromak formed and sustained by Steady Inductive Helicity Injection (SIHI) current drive. SIHI injects helicity at a nearly constant rate with no open field lines intersecting the boundary. (T. R. Jarboe, Fusion Technology 36) (1), p. 85, 1999 HIT-SI has been designed with a bow tie geometry to achieve stable high-β (>10%) spheromak equilibria. (U. Shumlak and T. R. Jarboe, Phys. Plasmas 7) (7), p. 2959, 2000 Diagnostics currently include surface magnetic probes and flux loops, visible light imaging, H-alpha line radiation monitors, voltage measurements across insulating breaks, injector current Rogowski coils, and injector flux loops. HIT-SI is currently operating in parallel with experiments on HIT-II. At the conclusion of HIT-II operations, HIT-SI will inherit a multi-point Thomson Scattering system, a scanning two-chord FIR interferometer, and other advanced diagnostics, as well as more power supplies to extend the discharge duration. Results are presented which characterize injector operation and possible evidence for spheromak formation.

A New View of the High Energy Gamma-ray Sky with the Fermi Gamma-Ray Space Telescope

NASA Technical Reports Server (NTRS)

McEnery, Julie

2010-01-01

This slide presentation reviews some of the findings that have been made possible by the use of the Fermi Gamma-ray Space Telescope. It describes the current status of the Fermi Telescope and reviews some of the science highlights.

Global Properties of X-Ray Flashes and X-Ray-Rich Gamma-Ray Bursts Observed by Swift

NASA Astrophysics Data System (ADS)

Sakamoto, Takanori; Yamazaki, Ryo; Barthelmy, Scott; Gehrels, Neil; Osborne, Julian; Hullinger, Derek; Sato, Goro; Barbier, Louis; Cummings, Jay; Fenimore, Ed; Krimm, Hans; Lamb, Don; Markwardt, Craig; Palmer, David; Parsons, Ann; Stamatikos, Michael; Tueller, Jack

Takanori Sakamoto, Taka.Sakamoto@nasa.gov NASA Goddard Space Flight Center, Greenbelt, Maryland, United States Ryo Yamazaki, ryo@theo.phys.sci.hiroshima-u.ac.jp Hiroshima University, Higashi-Hiroshima, Japan Scott Barthelmy, scott@milkyway.gsfc.nasa.gov NASA GSFC, Greenbelt, Maryland, United States Neil Gehrels, gehrels@milkyway.gsfc.nasa.gov NASA Goddard Space Flight Center, Greenbelt, Maryland, United States Julian Osborne, julo@star.le.ac.uk University of Leicester, Leicester, United Kingdom Derek Hullinger, derek.hullinger@gmail.com Moxtek, Inc, Orem, Utah, United States Goro Sato, Goro.Sato@nasa.gov Goddard Space Flight Center, Greenbelt, Maryland, United States Louis Barbier, lmb@milkyway.gsfc.nasa.gov Goddard Space Flight Center, Greenbelt, Maryland, United States Jay Cummings, jayc@milkyway.gsfc.nasa.gov Goddard Space Flight Center, Greenbelt, Maryland, United States Ed Fenimore, efenimore@lanl.gov Los Alamos National Laboratory, Los Alamos, California, United States Hans Krimm, hans.krimm@nasa.gov Goddard Space Flight Center, Greenbelt, Maryland, United States Don Lamb, d-lamb@uchicago.edu University of Chicago, Chicago, Illinois, United States Craig Markwardt, Craig.Markwardt@nasa.gov Goddard Space Flight Center, Greenbelt, Maryland, United States David Palmer, palmer@lanl.gov Los Alamos National Laboratory, Los Alamos, California, United States Ann Parsons, Ann.M.Parsons@nasa.gov Goddard Space Flight Center, Greenbelt, Maryland, United States Michael Stamatikos, michael@milkyway.gsfc.nasa.gov Goddard Space Flight Center, Greenbelt, Maryland, United States Jack Tueller, jack.tueller@nasa.gov Goddard Space Flight Center, Greenbelt, Maryland, United States We present the spectral and temporal characteristics of the prompt emission and X-ray afterglow emission of X-ray flashes (XRFs) and X-ray-rich gamma-ray bursts (XRRs) detected and observed by Swift between December 2004 and September 2006. We compare these characteristics to a sample of conventional classical gamma-ray bursts (C-GRBs) observed during the same period. We confirm the correlation between Epeak and fluence noted by others and find further evidence that XRFs, XRRs and C-GRBs form a continuum. We also confirm that our known redshift sample is consistent with the correlation between the peak energy in the GRB rest frame (Epeak) and the isotropic radiated energy (Eiso), so called the Epeak-Eiso relation. The spectral properties of X-ray afterglows of XRFs and C-GRBs are similar, but the temporal properties of XRFs and C-GRBs are quite different. We found that the light curves of C-GRB afterglows show a break to steeper indices (shallow-to-steep break) at much earlier times than do XRF afterglows. Moreover, the overall luminosity of XRF X-ray afterglows is systematically smaller by a factor of two or more compared to that of C-GRBs. These distinct differences between the X-ray afterglows of XRFs and C-GRBs may be the key to understanding not only the mysterious shallow-to-steep break in X-ray afterglow light curves, but also the unique nature of XRFs.

Current developments and tests of small x-ray optical systems for space applications

NASA Astrophysics Data System (ADS)

Pina, L.; Hudec, R.; Inneman, A.; Doubravová, D.; Marsikova, V.

2017-05-01

The paper addresses the X-ray monitoring for astrophysical applications. A novel approach based on the use of 1D and 2D "Lobster eye" optics in combination with Timepix X-ray detector in the energy range 3 - 40 keV was further studied. Wide-field optical system of this type has not been used in space yet. Designed wide-field optical system combined with Timepix X-ray detector is described together with latest experimental results obtained during laboratory tests. Proposed project includes theoretical study and a functional sample of the Timepix X-ray detector with multifoil wide-field X-ray "Lobster eye" optics. Using optics to focus X-rays on a detector is the only solution in cases where intensity of impinging X-ray radiation is below the sensitivity of the detector, e.g. while monitoring astrophysical objects in space, or phenomena in the Earth's atmosphere. The optical system is considered to be used in a student rocket experiment.

A Ligand-observed Mass Spectrometry Approach Integrated into the Fragment Based Lead Discovery Pipeline

PubMed Central

Chen, Xin; Qin, Shanshan; Chen, Shuai; Li, Jinlong; Li, Lixin; Wang, Zhongling; Wang, Quan; Lin, Jianping; Yang, Cheng; Shui, Wenqing

2015-01-01

In fragment-based lead discovery (FBLD), a cascade combining multiple orthogonal technologies is required for reliable detection and characterization of fragment binding to the target. Given the limitations of the mainstream screening techniques, we presented a ligand-observed mass spectrometry approach to expand the toolkits and increase the flexibility of building a FBLD pipeline especially for tough targets. In this study, this approach was integrated into a FBLD program targeting the HCV RNA polymerase NS5B. Our ligand-observed mass spectrometry analysis resulted in the discovery of 10 hits from a 384-member fragment library through two independent screens of complex cocktails and a follow-up validation assay. Moreover, this MS-based approach enabled quantitative measurement of weak binding affinities of fragments which was in general consistent with SPR analysis. Five out of the ten hits were then successfully translated to X-ray structures of fragment-bound complexes to lay a foundation for structure-based inhibitor design. With distinctive strengths in terms of high capacity and speed, minimal method development, easy sample preparation, low material consumption and quantitative capability, this MS-based assay is anticipated to be a valuable addition to the repertoire of current fragment screening techniques. PMID:25666181

Thieno[3,2-b]pyrrole-5-carboxamides as New Reversible Inhibitors of Histone Lysine Demethylase KDM1A/LSD1. Part 1: High-Throughput Screening and Preliminary Exploration.

PubMed

Sartori, Luca; Mercurio, Ciro; Amigoni, Federica; Cappa, Anna; Fagá, Giovanni; Fattori, Raimondo; Legnaghi, Elena; Ciossani, Giuseppe; Mattevi, Andrea; Meroni, Giuseppe; Moretti, Loris; Cecatiello, Valentina; Pasqualato, Sebastiano; Romussi, Alessia; Thaler, Florian; Trifiró, Paolo; Villa, Manuela; Vultaggio, Stefania; Botrugno, Oronza A; Dessanti, Paola; Minucci, Saverio; Zagarrí, Elisa; Carettoni, Daniele; Iuzzolino, Lucia; Varasi, Mario; Vianello, Paola

2017-03-09

Lysine specific demethylase 1 KDM1A (LSD1) regulates histone methylation and it is increasingly recognized as a potential therapeutic target in oncology. We report on a high-throughput screening campaign performed on KDM1A/CoREST, using a time-resolved fluorescence resonance energy transfer (TR-FRET) technology, to identify reversible inhibitors. The screening led to 115 hits for which we determined biochemical IC 50 , thus identifying four chemical series. After data analysis, we have prioritized the chemical series of N-phenyl-4H-thieno[3, 2-b]pyrrole-5-carboxamide for which we obtained X-ray structures of the most potent hit (compound 19, IC 50 = 2.9 μM) in complex with the enzyme. Initial expansion of this chemical class, both modifying core structure and decorating benzamide moiety, was directed toward the definition of the moieties responsible for the interaction with the enzyme. Preliminary optimization led to compound 90, which inhibited the enzyme with a submicromolar IC 50 (0.162 μM), capable of inhibiting the target in cells.

Use of health information technology to advance evidence-based care: lessons from the VA QUERI program.

PubMed

Hynes, Denise M; Weddle, Timothy; Smith, Nina; Whittier, Erika; Atkins, David; Francis, Joseph

2010-01-01

As the Department of Veterans Affairs (VA) Health Services Research and Development Service's Quality Enhancement Research Initiative (QUERI) has progressed, health information technology (HIT) has occupied a crucial role in implementation research projects. We evaluated the role of HIT in VA QUERI implementation research, including HIT use and development, the contributions implementation research has made to HIT development, and HIT-related barriers and facilitators to implementation research. Key informants from nine disease-specific QUERI Centers. Documentation analysis of 86 implementation project abstracts followed up by semi-structured interviews with key informants from each of the nine QUERI centers. We used qualitative and descriptive analyses. We found: (1) HIT provided data and information to facilitate implementation research, (2) implementation research helped to further HIT development in a variety of uses including the development of clinical decision support systems (23 of 86 implementation research projects), and (3) common HIT barriers to implementation research existed but could be overcome by collaborations with clinical and administrative leadership. Our review of the implementation research progress in the VA revealed interdependency on an HIT infrastructure and research-based development. Collaboration with multiple stakeholders is a key factor in successful use and development of HIT in implementation research efforts and in advancing evidence-based practice.

Once an Onion, Always an Onion (Artist Concept)

NASA Technical Reports Server (NTRS)

2006-01-01

This artist's concept illustrates a massive star before and after it blew up in a cataclysmic 'supernova' explosion. NASA's Spitzer Space Telescope found evidence that this star -- the remains of which are named Cassiopeia A -- exploded with some degree of order, preserving chunks of its onion-like layers as it blasted apart.

Cassiopeia A is located 10,000 light-years away in the constellation Cassiopeia. It was once a massive star 15 to 20 times larger than our sun. Its fiery death would have been viewable from Earth about 340 years ago.

The top figure shows the star before it died, when its layers of elements were stacked neatly, with the heaviest at the core and the lightest at the top. Spitzer found evidence that these layers were preserved when the star exploded, flinging outward in all directions, but not at the same speeds. As a result, some chunks of the layered material traveled farther out than others, as illustrated in the bottom drawing.

The infrared observatory was able to see the tossed-out layers, because they light up upon ramming into a 'reverse' shock wave created in the aftermath of the explosion. When a massive star explodes, it creates two types of shock waves. The forward shock wave darts out quickest, and, in the case of Cassiopeia A, is now traveling at supersonic speeds up to 7,500 kilometers per second (4,600 miles/second). The reverse shock wave is produced when the forward shock wave slams into a shell of surrounding material expelled before the star died. It tags along behind the forward shock wave at slightly slower speeds.

Chunks of the star that were thrown out fastest hit the shock wave sooner and have had more time to heat up to scorching temperatures previously detected by X-ray and visible-light telescopes. Chunks of the star that lagged behind hit the shock wave later, so they are cooler and radiate infrared light that was not seen until Spitzer came along. These lagging chunks are made up of gas and dust containing neon, oxygen and aluminum -- elements from the middle layers of the original star.

X-ray inspection of arduous welds in rocket and space technology with the use of a microfocus X-ray apparatus

NASA Astrophysics Data System (ADS)

Potrakhov, N. N.; Potrakhov, E. N.; Usachev, E. Y.; Gnedin, M. M.; Voroschuk, D. V.; Shavrina, I. M.

2017-07-01

The article presents the design of a specialized X-ray machine to perform circumferential weld inspections various structural elements of air and space technology. Shows the main specifications of the device and describes a particular application of the apparatus. The results of the use of the device in conditions of real production on one of the local engine companies in the aircraft and space industry.

Global Positioning System (GPS) Precipitable Water in Forecasting Lightning at Spaceport Canaveral

NASA Technical Reports Server (NTRS)

Kehrer, Kristen; Graf, Brian G.; Roeder, William

2005-01-01

Using meteorology data, focusing on precipitable water (PW), obtained during the 2000-2003 thunderstorm seasons in Central Florida, this paper will, one, assess the skill and accuracy measurements of the current Mazany forecasting tool and, two, provide additional forecasting tools that can be used in predicting lightning. Kennedy Space Center (KSC) and Cape Canaveral Air Force Station (CCAFS) are located in east Central Florida. KSC and CCAFS process and launch manned (NASA Space Shuttle) and unmanned (NASA and Air Force Expendable Launch Vehicles) space vehicles. One of the biggest cost impacts is unplanned launch scrubs due to inclement weather conditions such as thunderstorms. Each launch delay/scrub costs over a quarter million dollars, and the need to land the Shuttle at another landing site and return to KSC costs approximately $ 1M. Given the amount of time lost and costs incurred, the ability to accurately forecast (predict) when lightning will occur can result in significant cost and time savings. All lightning prediction models were developed using binary logistic regression. Lightning is the dependent variable and is binary. The independent variables are the Precipitable Water (PW) value for a given time of the day, the change in PW up to 12 hours, the electric field mill value, and the K-index value. In comparing the Mazany model results for the 1999 period B against actual observations for the 2000-2003 thunderstorm seasons, differences were found in the False Alarm Rate (FAR), Probability of Detection (POD) and Hit Rate (H). On average, the False Alarm Rate (FAR) increased by 58%, the Probability of Detection (POD) decreased by 31% and the Hit Rate decreased by 20%. In comparing the performance of the 6 hour forecast period to the performance of the 1.5 hour forecast period for the Mazany model, the FAR was lower by 15% and the Hit Rate was higher by 7%. However, the POD for the 6 hour forecast period was lower by 16% as compared to the POD of the 1.5 hour forecast period. Neither forecast period performed at the accuracy measures expected. A 2-Hr Forecasting Tool was developed to support a Phase I Lightning Advisory, which requires a 30-minute lead time for predicting lightning.

Predictors of Osteopathic Medical Students' Readiness to Use Health Information Technology.

PubMed

Jacobs, Robin J; Iqbal, Hassan; Rana, Arif M; Rana, Zaid; Kane, Michael N

2017-12-01

The advent of health information technology (HIT) tools can affect the practice of modern medicine in many ways, ideally by improving quality of care and efficiency and reducing medical errors. Future physicians will play a key role in the successful implementation of HIT. However, osteopathic medical students' willingness to learn, adopt, and use technology in a health care setting is not well understood. To understand osteopathic medical students' knowledge, attitudes, and behaviors regarding HIT and to identify factors that may be related to their readiness to use HIT. Using a cross-sectional approach, quantitative surveys were collected from students attending a large osteopathic medical school. Multivariate regression modeling was used to determine whether knowledge, attitudes, behaviors, and personal characteristics were associated with students' readiness to use HIT in future clinical practice. Six hundred four students responded to at least 70% of the survey and were included in the analysis. Multivariate modeling successfully explained the 26% of variance in predicting students' readiness to use HIT (F8,506=22.6, P<.001, R2=0.263). Greater self-efficacy, openness to change (in academic/work settings), favorable attitudes toward HIT use, mobile technology use, younger age, being male, and prior exposure to technology were associated with readiness to use HIT. Understanding students' level of HIT readiness may help guide medical education intervention efforts to better prepare future osteopathic physicians for HIT engagement and use. Innovative approaches to HIT education in medical school curricula that include biomedical informatics may be necessary.

Upregulation of LncRNA-HIT promotes migration and invasion of non-small cell lung cancer cells by association with ZEB1.

PubMed

Jia, Xiaojing; Wang, Zhicheng; Qiu, Ling; Yang, Yanming; Wang, Yunlong; Chen, Zhishen; Liu, Zhongshan; Yu, Lei

2016-12-01

Lung cancer is the most common solid tumor and the leading cause of cancer-related mortality worldwide. Non-small cell lung cancer (NSCLC) accounts for approximately 80% of all lung cancer cases. The main reason of lung cancer-related deaths is due to tumor metastasis. But, the mechanisms of NSCLC metastasis remains poorly understood. LncRNAs play pivotal roles in multiple biological processes. LncRNA-HIT (HOXA transcript induced by TGFβ) was recently identified. LncRNA-HIT promotes cell migration, invasion, tumor growth, and metastasis. However, the detailed role of lncRNA-HIT in NSCLC remains unknown. In this study, for the first time, we revealed a novel role of lncRNA-HIT in the migration and invasion of NSCLC cells. The expression of lncRNA-HIT was significantly upregulated in NSCLC tissues and cell lines, and the expression level of lncRNA-HIT correlates with advanced disease stage and predicts unfavorable prognosis of NSCLC patients. Functional assays demonstrated that lncRNA-HIT markedly increased the ability of NSCLC cells to migrate and invade. Furthermore, the molecular mechanism by which lncRNA-HIT affects NSCLC cells was associated with regulation of ZEB1 stability. LncRNA-HIT functions as a prometastasis oncogene by directly associating with ZEB1 to regulate NSCLC. The interaction of lncRNA-HIT and ZEB1 may be a potential target for NSCLC therapy. © 2016 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

When does adoption of health information technology by physician practices lead to use by physicians within the practice?

PubMed Central

McClellan, Sean R; Casalino, Lawrence P; Shortell, Stephen M; Rittenhouse, Diane R

2013-01-01

Objective We sought to determine the extent to which adoption of health information technology (HIT) by physician practices may differ from the extent of use by individual physicians, and to examine factors associated with adoption and use. Materials and methods Using cross-sectional survey data from the National Study of Small and Medium-Sized Physician Practices (July 2007–March 2009), we examined the extent to which organizational capabilities and external incentives were associated with the adoption of five key HIT functionalities by physician practices and with use of those functionalities by individual physicians. Results The rate of physician practices adopting any of the five HIT functionalities was 34.1%. When practices adopted HIT functionalities, on average, about one in seven physicians did not use those functionalities. One physician in five did not use prompts and reminders following adoption by their practice. After controlling for other factors, both adoption of HIT by practices and use of HIT by individual physicians were higher in primary care practices and larger practices. Practices reporting an emphasis on patient-centered management were not more likely than others to adopt, but their physicians were more likely to use HIT. Discussion Larger practices were most likely to have adopted HIT, but other factors, including specialty mix and self-reported patient-centered management, had a stronger influence on the use of HIT once adopted. Conclusions Adoption of HIT by practices does not mean that physicians will use the HIT. PMID:23396512

KSC-08pd0613

NASA Image and Video Library

2008-03-04

KENNEDY SPACE CENTER, FLA. -- The shipping container holding NASA's Gamma-Ray Large Area Space Telescope, or GLAST, is moved into the Astrotech payload processing facility near the Kennedy Space Center to begin prelaunch activities. The GLAST will launch aboard a Delta II rocket May 16 from Launch Pad 17-B on Cape Canaveral Air Force Station. A powerful space observatory, the GLAST will explore the most extreme environments in the universe, and answer questions about supermassive black hole systems, pulsars and the origin of cosmic rays. It also will study the mystery of powerful explosions known as gamma-ray bursts. Photo credit: NASA/Kim Shiflett

KSC-08pd0610

NASA Image and Video Library

2008-03-04

KENNEDY SPACE CENTER, FLA. -- NASA's Gamma-Ray Large Area Space Telescope, or GLAST, arrives at Kennedy Space Center in a shipping container aboard a truck to begin final preparations for launch. The GLAST will launch aboard a Delta II rocket May 16 from Launch Pad 17-B on Cape Canaveral Air Force Station. A powerful space observatory, the GLAST will explore the most extreme environments in the universe, and answer questions about supermassive black hole systems, pulsars and the origin of cosmic rays. It also will study the mystery of powerful explosions known as gamma-ray bursts. Photo credit: NASA/Kim Shiflett

KSC-08pd0614

NASA Image and Video Library

2008-03-04

KENNEDY SPACE CENTER, FLA. -- In the Astrotech payload processing facility near the Kennedy Space Center, workers maneuver the shipping container holding NASA's Gamma-Ray Large Area Space Telescope, or GLAST, into place. The GLAST will launch aboard a Delta II rocket May 16 from Launch Pad 17-B on Cape Canaveral Air Force Station. A powerful space observatory, the GLAST will explore the most extreme environments in the universe, and answer questions about supermassive black hole systems, pulsars and the origin of cosmic rays. It also will study the mystery of powerful explosions known as gamma-ray bursts. Photo credit: NASA/Kim Shiflett

Conceptual Design of Tail-Research EXperiment (T-REX) on Space Plasma Environment Research Facility

NASA Astrophysics Data System (ADS)

Xiao, Qingmei; Wang, Xiaogang; E, Peng; Shen, Chao; Wang, Zhibin; Mao, Aohua; Xiao, Chijie; Ding, Weixing; Ji, Hantao; Ren, Yang

2016-10-01

Space Environment Simulation Research Infrastructure (SESRI), a scientific project for a major national facility of fundamental researches, has recently been launched at Harbin Institute of Technology (HIT). The Space Plasma Environment Research Facility (SPERF) for simulation of space plasma environment is one of the components of SESRI. It is designed to investigate fundamental issues in space plasma environment, such as energetic particles transportation and the interaction with waves in magnetosphere, magnetic reconnection at magnetopause and magnetotail, etc. Tail-Research Experiment (T-REX) is part of the SPERF for laboratory studies of space physics relevant to tail reconnection and dipolarization process. T-REX is designed to carry out two kinds of experiments: the tail plasmamoid for magnetic reconnection and magnetohydrodynamic waves excited by high speed plasma jet. In this presentation, the scientific goals and experimental plans for T-REX together with the means applied to generate the plasma with desired parameters are reviewed. Two typical scenarios of T-REX with operations of plasma sources and various magnetic configurations to study specific physical processes in space plasmas will also be presented.

Advance in multi-hit detection and quantization in atom probe tomography.

PubMed

Da Costa, G; Wang, H; Duguay, S; Bostel, A; Blavette, D; Deconihout, B

2012-12-01

The preferential retention of high evaporation field chemical species at the sample surface in atom-probe tomography (e.g., boron in silicon or in metallic alloys) leads to correlated field evaporation and pronounced pile-up effects on the detector. The latter severely affects the reliability of concentration measurements of current 3D atom probes leading to an under-estimation of the concentrations of the high-field species. The multi-hit capabilities of the position-sensitive time-resolved detector is shown to play a key role. An innovative method based on Fourier space signal processing of signals supplied by an advance delay-line position-sensitive detector is shown to drastically improve the time resolving power of the detector and consequently its capability to detect multiple events. Results show that up to 30 ions on the same evaporation pulse can be detected and properly positioned. The major impact of this new method on the quantization of chemical composition in materials, particularly in highly-doped Si(B) samples is highlighted.

Some recent advances of intelligent health monitoring systems for civil infrastructures in HIT

NASA Astrophysics Data System (ADS)

Ou, Jinping

2005-06-01

The intelligent health monitoring systems more and more become a technique for ensuring the health and safety of civil infrastructures and also an important approach for research of the damage accumulation or even disaster evolving characteristics of civil infrastructures, and attracts prodigious research interests and active development interests of scientists and engineers since a great number of civil infrastructures are planning and building each year in mainland China. In this paper, some recent advances on research, development nad implementation of intelligent health monitoring systems for civil infrastructuresin mainland China, especially in Harbin Institute of Technology (HIT), P.R.China. The main contents include smart sensors such as optical fiber Bragg grating (OFBG) and polivinyllidene fluoride (PVDF) sensors, fatigue life gauges, self-sensing mortar and carbon fiber reinforced polymer (CFRP), wireless sensor networks and their implementation in practical infrastructures such as offshore platform structures, hydraulic engineering structures, large span bridges and large space structures. Finally, the relative research projects supported by the national foundation agencies of China are briefly introduced.

COMPUTER-AIDED DRUG DISCOVERY AND DEVELOPMENT (CADDD): in silico-chemico-biological approach

PubMed Central

Kapetanovic, I.M.

2008-01-01

It is generally recognized that drug discovery and development are very time and resources consuming processes. There is an ever growing effort to apply computational power to the combined chemical and biological space in order to streamline drug discovery, design, development and optimization. In biomedical arena, computer-aided or in silico design is being utilized to expedite and facilitate hit identification, hit-to-lead selection, optimize the absorption, distribution, metabolism, excretion and toxicity profile and avoid safety issues. Commonly used computational approaches include ligand-based drug design (pharmacophore, a 3-D spatial arrangement of chemical features essential for biological activity), structure-based drug design (drug-target docking), and quantitative structure-activity and quantitative structure-property relationships. Regulatory agencies as well as pharmaceutical industry are actively involved in development of computational tools that will improve effectiveness and efficiency of drug discovery and development process, decrease use of animals, and increase predictability. It is expected that the power of CADDD will grow as the technology continues to evolve. PMID:17229415

Effective increase in beam emittance by phase-space expansion using asymmetric Bragg diffraction.

PubMed

Chu, Chia-Hung; Tang, Mau-Tsu; Chang, Shih-Lin

2015-08-24

We propose an innovative method to extend the utilization of the phase space downstream of a synchrotron light source for X-ray transmission microscopy. Based on the dynamical theory of X-ray diffraction, asymmetrically cut perfect crystals are applied to reshape the position-angle-wavelength space of the light source, by which the usable phase space of the source can be magnified by over one hundred times, thereby "phase-space-matching" the source with the objective lens of the microscope. The method's validity is confirmed using SHADOW code simulations, and aberration through an optical lens such as a Fresnel zone plate is examined via matrix optics for nano-resolution X-ray images.

High-efficiency and low-background multi-segmented proportional gas counter for β-decay spectroscopy

NASA Astrophysics Data System (ADS)

Mukai, M.; Hirayama, Y.; Watanabe, Y. X.; Schury, P.; Jung, H. S.; Ahmed, M.; Haba, H.; Ishiyama, H.; Jeong, S. C.; Kakiguchi, Y.; Kimura, S.; Moon, J. Y.; Oyaizu, M.; Ozawa, A.; Park, J. H.; Ueno, H.; Wada, M.; Miyatake, H.

2018-03-01

A multi-segmented proportional gas counter (MSPGC) with high detection efficiency and low-background event rate has been developed for β-decay spectroscopy. The MSPGC consists of two cylindrically aligned layers of 16 counters (32 counters in total). Each counter has a long active length and small trapezoidal cross-section, and the total solid angle of the 32 counters is 80% of 4 π. β-rays are distinguished from the background events including cosmic-rays by analyzing the hit patterns of independent counters. The deduced intrinsic detection efficiency of each counter was almost 100%. The measured background event rate was 0.11 counts per second using the combination of veto counters for cosmic-rays and lead block shields for background γ-rays. The MSPGC was applied to measure the β-decay half-lives of 198Ir and 199mPt. The evaluated half-lives of T1/2 = 9 . 8(7) s and 12.4(7) s for 198Ir and 199mPt, respectively, were in agreement with previously reported values. The estimated absolute detection efficiency of the MSPGC from GEANT4 simulations was consistent with the evaluated efficiency from the analysis of the β- γ spectroscopy of 199Pt, saturating at approximately 60% for Qβ > 4 MeV.

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

Deptuch, G. W.; Fahim, F.; Grybos, P.

An on-chip implementable algorithm for allocation of an X-ray photon imprint, called a hit, to a single pixel in the presence of charge sharing in a highly segmented pixel detector is described. Its proof-of-principle implementation is also given supported by the results of tests using a highly collimated X-ray photon beam from a synchrotron source. The algorithm handles asynchronous arrivals of X-ray photons. Activation of groups of pixels, comparisons of peak amplitudes of pulses within an active neighborhood and finally latching of the results of these comparisons constitute the three procedural steps of the algorithm. A grouping of pixels tomore » one virtual pixel that recovers composite signals and event driven strobes to control comparisons of fractional signals between neighboring pixels are the actuators of the algorithm. The circuitry necessary to implement the algorithm requires an extensive inter-pixel connection grid of analog and digital signals that are exchanged between pixels. A test-circuit implementation of the algorithm was achieved with a small array of 32×32 pixels and the device was exposed to an 8 keV highly collimated to a diameter of 3 μm X-ray beam. The results of these tests are given in the paper assessing physical implementation of the algorithm.« less

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

Deptuch, Grzegorz W.; Fahim, Farah; Grybos, Pawel

An on-chip implementable algorithm for allocation of an X-ray photon imprint, called a hit, to a single pixel in the presence of charge sharing in a highly segmented pixel detector is described. Its proof-of-principle implementation is also given supported by the results of tests using a highly collimated X-ray photon beam from a synchrotron source. The algorithm handles asynchronous arrivals of X-ray photons. Activation of groups of pixels, comparisons of peak amplitudes of pulses within an active neighborhood and finally latching of the results of these comparisons constitute the three procedural steps of the algorithm. A grouping of pixels tomore » one virtual pixel, that recovers composite signals and event driven strobes, to control comparisons of fractional signals between neighboring pixels are the actuators of the algorithm. The circuitry necessary to implement the algorithm requires an extensive inter-pixel connection grid of analog and digital signals, that are exchanged between pixels. A test-circuit implementation of the algorithm was achieved with a small array of 32 × 32 pixels and the device was exposed to an 8 keV highly collimated to a diameter of 3-μm X-ray beam. Furthermore, the results of these tests are given in this paper assessing physical implementation of the algorithm.« less

Exploring the Extreme Universe with the Fermi Gamma-Ray Space Telescope

NASA Technical Reports Server (NTRS)

Thompson, D. J.

2010-01-01

Because high-energy gamma rays are produced by powerful sources, the Fermi Gamma-ray Space Telescope provides a window on extreme conditions in the Universe. Some key observations of the constantly changing gamma-ray sky include: (1) Gamma-rays from pulsars appear to come from a region well above the surface of the neutron star; (2) Multiwavelength studies of blazars show that simple models of jet emission are not always adequate to explain what is seen; (3) Gamma-ray bursts can constrain models of quantum gravity; (4) Cosmic-ray electrons at energies approaching 1 TeV suggest a local source for some of these particles.

Cosmic Ray Studies with the Fermi Gamma-ray Space Telescope Large Area Telescope

NASA Technical Reports Server (NTRS)

Thompson, David J.; Baldini, L.; Uchiyama, Y.

2012-01-01

The Large Area Telescope (LAT) on the Fermi Gamma-ray Space Telescope provides both direct and indirect measurements of galactic cosmic rays (CR). The LAT high-statistics observations of the 7 GeV - 1 TeV electron plus positron spectrum and limits on spatial anisotropy constrain models for this cosmic-ray component. On a galactic scale, the LAT observations indicate that cosmic-ray sources may be more plentiful in the outer Galaxy than expected or that the scale height of the cosmic-ray diffusive halo is larger than conventional models. Production of cosmic rays in supernova remnants (SNR) is supported by the LAT gamma-ray studies of several of these, both young SNR and those interacting with molecular clouds.

Cosmic Ray Studies with the Fermi Gamma-ray Space Telescope Large Area Telescope

NASA Technical Reports Server (NTRS)

Thompson, D. J.; Baldini, L.; Uchiyama, Y.

2011-01-01

The Large Area Telescope (LAT) on the Fermi Gamma-ray Space Telescope provides both direct and indirect measurements of Galactic cosmic rays (CR). The LAT high-statistics observations of the 7 GeV - 1 TcV electron plus positron spectrum and limits on spatial anisotropy constrain models for this cosmic-ray component. On a Galactic scale, the LAT observations indicate that cosmic-ray sources may be more plentiful in the outer Galaxy than expected or that the scale height of the cosmic-ray diffusive halo is larger than conventional models. Production of cosmic rays in supernova remnants (SNR) is supported by the LAT gamma-ray studies of several of these, both young SNR and those interacting with molecular clouds.

KENNEDY SPACE CENTER, FLA. - One of four rudder speed brake actuators arrives at Cape Canaveral Air Force Station. The actuators, to be installed on the orbiter Discovery, are being X-rayed at the Radiographic High-Energy X-ray Facility to determine if the gears were installed correctly. Discovery has been assigned to the first Return to Flight mission, STS-114, a logistics flight to the International Space Station.

NASA Image and Video Library

2004-03-08

KENNEDY SPACE CENTER, FLA. - One of four rudder speed brake actuators arrives at Cape Canaveral Air Force Station. The actuators, to be installed on the orbiter Discovery, are being X-rayed at the Radiographic High-Energy X-ray Facility to determine if the gears were installed correctly. Discovery has been assigned to the first Return to Flight mission, STS-114, a logistics flight to the International Space Station.

Double-hit lymphomas constitute a highly aggressive subgroup in diffuse large B-cell lymphomas in the era of rituximab.

PubMed

Kobayashi, Tsutomu; Tsutsumi, Yasuhiko; Sakamoto, Natsumi; Nagoshi, Hisao; Yamamoto-Sugitani, Mio; Shimura, Yuji; Mizutani, Shinsuke; Matsumoto, Yosuke; Nishida, Kazuhiro; Horiike, Shigeo; Asano, Naoko; Nakamura, Shigeo; Kuroda, Junya; Taniwaki, Masafumi

2012-11-01

The incorporation of rituximab in immunochemotherapy has improved treatment outcomes for diffuse large B-cell lymphoma, but the prognosis for some diffuse large B-cell lymphomas remains dismal. Identification of adverse prognostic subgroups is essential for the choice of appropriate therapeutic strategy. We retrospectively investigated the impact of so-called 'double-hit' cytogenetic abnormalities, i.e. cytogenetic abnormalities involving c-MYC co-existing with other poor prognostic cytogenetic abnormalities involving BCL2, BCL6 or BACH2, on treatment outcomes for 93 consecutive diffuse large B-cell lymphoma patients. According to the revised international prognostic index, no patients were cytogenetically diagnosed with double-hit lymphomas in the 'very good' risk group or in the 'good' risk group, while 5 of 33 patients had double-hit lymphomas in the 'poor' risk group. All the double-hit lymphoma patients possessed both nodal and extranodal involvement. The overall complete response rate was 89.3%, overall survival 87.1% and progression-free survival 75.8% over 2 years (median observation period: 644 days). The complete response rates were 93.2% for the non-double-hit lymphoma patients and 40.0% for the double-hit lymphoma patients. Significantly longer progression-free survival and overall survival were observed for the 'very good' and the 'good' risk patients than for the 'poor' risk patients. Moreover, the progression-free survival of double-hit lymphoma was significantly shorter than that of the non-double-hit lymphoma 'poor' risk patients (P = 0.016). In addition, the overall survival of the double-hit lymphoma patients also tended to be shorter than that of the non-double-hit lymphoma 'poor' risk group. The diagnosis of double-hit lymphoma can help discriminate a subgroup of highly aggressive diffuse large B-cell lymphomas and indicate the need for the development of novel therapeutic strategies for double-hit lymphoma.

HIT-6 and MIDAS as measures of headache disability in a headache referral population.

PubMed

Sauro, Khara M; Rose, Marianne S; Becker, Werner J; Christie, Suzanne N; Giammarco, Rose; Mackie, Gordon F; Eloff, Arnoldas G; Gawel, Marek J

2010-03-01

The objective of this study was to compare the headache impact test (HIT-6) and the migraine disability assessment scale (MIDAS) as clinical measures of headache-related disability. The degree of headache-related disability is an important factor in treatment planning. Many quality of life and headache disability measures exist but it is unclear which of the available disability measures is the most helpful in planning and measuring headache management. We compared HIT-6 and MIDAS scores from 798 patients from the Canadian Headache Outpatient Registry and Database (CHORD). Correlation and regression analyses were used to examine the relationships between the HIT-6 and MIDAS total scores, headache frequency and intensity, and Beck Depression Inventory (BDI-II) scores. A positive correlation was found between HIT-6 and MIDAS scores (r = 0.52). The BDI-II scores correlated equally with the HIT-6 and the MIDAS (r = 0.42). There was a non-monotonic relationship between headache frequency and the MIDAS, and a non-linear monotonic relationship between headache frequency and the HIT-6 (r = 0.24). The correlation was higher between the intensity and the HIT-6 scores (r = 0.46), than MIDAS (r = 0.26) scores. Seventy-nine percent of patients fell into the most severe HIT-6 disability category, compared with the 57% of patients that fell into the most severe MIDAS disability category. Significantly more patients were placed in a more severe category with the HIT-6 than with the MIDAS (McNemar chi-square = 191 on 6 d.f., P < .0001). The HIT-6 and MIDAS appear to measure headache-related disability in a similar fashion. However, some important differences may exist. Headache intensity appears to influence HIT-6 score more than the MIDAS, whereas the MIDAS was influenced more by headache frequency. Using the HIT-6 and MIDAS together may give a more accurate assessment of a patient's headache-related disability.

78 FR 29135 - HIT Standards Committee Advisory Meeting

Federal Register 2010, 2011, 2012, 2013, 2014

2013-05-17

... DEPARTMENT OF HEALTH AND HUMAN SERVICES HIT Standards Committee Advisory Meeting AGENCY: Office of...: HIT Standards Committee. General Function of the Committee: To provide recommendations to the National... Federal Health IT Strategic Plan, and in accordance with policies developed by the HIT Policy Committee...

76 FR 25355 - HIT Standards Committee; Schedule for the Assessment of HIT Policy Committee Recommendations

Federal Register 2010, 2011, 2012, 2013, 2014

2011-05-04

... DEPARTMENT OF HEALTH AND HUMAN SERVICES HIT Standards Committee; Schedule for the Assessment of HIT Policy Committee Recommendations AGENCY: Office of the National Coordinator for Health Information... Committee regarding health information technology standards, implementation specifications, and/or...

Post-hit dynamics of price limit hits in the Chinese stock markets

NASA Astrophysics Data System (ADS)

Wu, Ting; Wang, Yue; Li, Ming-Xia

2017-01-01

Price limit trading rules are useful to cool off traders short-term trading mania on individual stocks. The price dynamics approaching the limit boards are known as the magnet effect. However, the price dynamics after opening price limit hits are not well investigated. Here, we provide a detailed analysis on the price dynamics after the hits of up-limit or down-limit is open based on all A-share stocks traded in the Chinese stock markets. A "W" shape is found in the expected return, which reveals high probability of a continuous price limit hit on the following day. We also find that price dynamics after opening limit hits are dependent on the market trends. The time span of continuously hitting the price limit is found to an influence factor of the expected profit after the limit hit is open. Our analysis provides a better understanding of the price dynamics around the limit boards and contributes potential practical values for investors.

Health Information Technology Knowledge and Skills Needed by HIT Employers

PubMed Central

Fenton, S.H.; Gongora-Ferraez, M.J.; Joost, E.

2012-01-01

Objective To evaluate the health information technology (HIT) workforce knowledge and skills needed by HIT employers. Methods Statewide face-to-face and online focus groups of identified HIT employer groups in Austin, Brownsville, College Station, Dallas, El Paso, Houston, Lubbock, San Antonio, and webinars for rural health and nursing informatics. Results HIT employers reported needing an HIT workforce with diverse knowledge and skills ranging from basic to advanced, while covering information technology, privacy and security, clinical practice, needs assessment, contract negotiation, and many other areas. Consistent themes were that employees needed to be able to learn on the job and must possess the ability to think critically and problem solve. Many employers wanted persons with technical skills, yet also the knowledge and understanding of healthcare operations. Conclusion The HIT employer focus groups provided valuable insight into employee skills needed in this fast-growing field. Additionally, this information will be utilized to develop a statewide HIT workforce needs assessment survey. PMID:23646090

Health Information Technology (HIT) Adaptation: Refocusing on the Journey to Successful HIT Implementation

PubMed Central

McAlearney, Ann Scheck; Sieck, Cynthia J; Hefner, Jennifer L; Huerta, Timothy R

2017-01-01

In past years, policies and regulations required hospitals to implement advanced capabilities of certified electronic health records (EHRs) in order to receive financial incentives. This has led to accelerated implementation of health information technologies (HIT) in health care settings. However, measures commonly used to evaluate the success of HIT implementation, such as HIT adoption, technology acceptance, and clinical quality, fail to account for complex sociotechnical variability across contexts and the different trajectories within organizations because of different implementation plans and timelines. We propose a new focus, HIT adaptation, to illuminate factors that facilitate or hinder the connection between use of the EHR and improved quality of care as well as to explore the trajectory of changes in the HIT implementation journey as it is impacted by frequent system upgrades and optimizations. Future research should develop instruments to evaluate the progress of HIT adaptation in both its longitudinal design and its focus on adaptation progress rather than on one cross-sectional outcome, allowing for more generalizability and knowledge transfer. PMID:28882812

Organizational factors influencing health information technology adoption in long-term-care facilities.

PubMed

Wang, Tiankai; Wang, Yangmei; Moczygemba, Jackie

2014-01-01

Long-term care (LTC) is an important sector of the health care industry. However, the adoption of health information technology (HIT) systems in LTC facilities lags behind that in other sectors of health care. Previous literature has focused on the financial and technical barriers. This study examined the organizational factors associated with HIT adoption in LTC facilities. A survey of 500 LTC facilities in Texas enabled researchers to compile HIT indexes for further statistical analyses. A general linear model was used to study the associations between the clinical/administrative HIT indexes and organizational factors. The empirical outcomes show that the size of an LTC facility has a significant association with HIT adoption. Rural LTC facilities, especially freestanding ones, adopt less HIT than their urban counterparts, whereas freestanding LTC facilities have the lowest HIT adoption overall. There is not enough evidence to support ownership status as a significant factor in HIT adoption. Some implications are proposed, but further research is necessary.

History of Chandra X-Ray Observatory

NASA Image and Video Library

1997-05-01

This photograph shows the Chandra X-Ray Observatory (CXO), formerly Advanced X-Ray Astrophysics Facility (AXAF), High Resolution Mirror Assembly (HRMA) being removed from the test structure in the X-Ray Calibration Facility (XRCF) at the Marshall Space Flight Center (MSFC). The AXAF was renamed CXO in 1999. The CXO is the most sophisticated and the world's most powerful x-ray telescope ever built. It observes x-rays from high-energy regions of the universe, such as hot gas in the remnants of exploded stars. The HRMA, the heart of the telescope system, is contained in the cylindrical "telescope" portion of the observatory. Since high-energy x-rays would penetrate a normal mirror, special cylindrical mirrors were created. The two sets of four nested mirrors resemble tubes within tubes. Incoming x-rays graze off the highly polished mirror surface and are furneled to the instrument section for detection and study. MSFC's XRCF is the world's largest, most advanced laboratory for simulating x-ray emissions from distant celestial objects. It produces a space-like environment in which components related to x-ray telescope imaging are tested and the quality of their performances in space is predicted. TRW, Inc. was the prime contractor for the development of the CXO and NASA's MSFC was responsible for its project management. The Smithsonian Astrophysical Observatory controls science and flight operations of the CXO for NASA from Cambridge, Massachusetts. The CXO was launched July 22, 1999 aboard the Space Shuttle Columbia (STS-93).

History of Chandra X-Ray Observatory

NASA Image and Video Library

1996-12-16

This is a photograph of the Chandra X-Ray Observatory (CXO), formerly Advanced X-Ray Astrophysics Facility (AXAF), High Resolution Mirror Assembly (HRMA) integration at the X-Ray Calibration Facility (XRCF) at the Marshall Space Flight Center (MSFC). The AXAF was renamed CXO in 1999. The CXO is the most sophisticated and the world's most powerful x-ray telescope ever built. It observes x-rays from high-energy regions of the universe, such as hot gas in the remnants of exploded stars. The HRMA, the heart of the telescope system, is contained in the cylindrical "telescope" portion of the observatory. Since high-energy x-rays would penetrate a normal mirror, special cylindrical mirrors were created. The two sets of four nested mirrors resemble tubes within tubes. Incoming x-rays graze off the highly polished mirror surface and are furneled to the instrument section for detection and study. MSFC's XRCF is the world's largest, most advanced laboratory for simulating x-ray emissions from distant celestial objects. It produces a space-like environment in which components related to x-ray telescope imaging are tested and the quality of their performances in space is predicted. TRW, Inc. was the prime contractor for the development of the CXO and NASA's MSFC was responsible for its project management. The Smithsonian Astrophysical Observatory controls science and flight operations of the CXO for NASA from Cambridge, Massachusetts. The CXO was launched July 22, 1999 aboard the Space Shuttle Columbia (STS-93).

History of Chandra X-Ray Observatory

NASA Image and Video Library

1997-12-16

This is a photograph of the Chandra X-Ray Observatory (CXO), formerly Advanced X-Ray Astrophysics Facility (AXAF), High Resolution Mirror Assembly (HRMA) integration at the X-Ray Calibration Facility (XRCF) at the Marshall Space Flight Center (MSFC). The AXAF was renamed CXO in 1999. The CXO is the most sophisticated and the world's most powerful x-ray telescope ever built. It observes x-rays from high-energy regions of the universe, such as hot gas in the remnants of exploded stars. The HRMA, the heart of the telescope system, is contained in the cylindrical "telescope" portion of the observatory. Since high-energy x-rays would penetrate a normal mirror, special cylindrical mirrors were created. The two sets of four nested mirrors resemble tubes within tubes. Incoming x-rays graze off the highly polished mirror surface and are furneled to the instrument section for detection and study. MSFC's XRCF is the world's largest, most advanced laboratory for simulating x-ray emissions from distant celestial objects. It produces a space-like environment in which components related to x-ray telescope imaging are tested and the quality of their performances in space is predicted. TRW, Inc. was the prime contractor for the development of the CXO and NASA's MSCF was responsible for its project management. The Smithsonian Astrophysical Observatory controls science and flight operations of the CXO for NASA from Cambridge, Massachusetts. The CXO was launched July 22, 1999 aboard the Space Shuttle Columbia (STS-93).

History of Chandra X-Ray Observatory

NASA Image and Video Library

1997-05-01

This photograph shows the Chandra X-ray Observatory (CXO), formerly Advanced X-Ray Astrophysics Facility (AXAF), High Resolution Mirror Assembly (HRMA) being removed from the test structure in the X-Ray Calibration Facility (XRCF) at the Marshall Space Flight Center (MSFC). The AXAF was renamed CXO in 1999. The CXO is the most sophisticated and the world's most powerful x-ray telescope ever built. It observes x-rays from high-energy regions of the universe, such as hot gas in the remnants of exploded stars. The HRMA, the heart of the telescope system, is contained in the cylindrical "telescope" portion of the observatory. Since high-energy x-rays would penetrate a normal mirror, special cylindrical mirrors were created. The two sets of four nested mirrors resemble tubes within tubes. Incoming x-rays graze off the highly polished mirror surface and are furneled to the instrument section for detection and study. MSFC's XRCF is the world's largest, most advanced laboratory for simulating x-ray emissions from distant celestial objects. It produces a space-like environment in which components related to x-ray telescope imaging are tested and the quality of their performances in space is predicted. TRW, Inc. was the prime contractor for the development of the CXO and NASA's MSFC was responsible for its project management. The Smithsonian Astrophysical Observatory controls science and flight operations of the CXO for NASA from Cambridge, Massachusetts. The CXO was launched July 22, 1999 aboard the Space Shuttle Columbia (STS-93).

Applying Human Factors Principles to Mitigate Usability Issues Related to Embedded Assumptions in Health Information Technology Design

PubMed Central

Lowry, Svetlana Z; Patterson, Emily S

2014-01-01

Background There is growing recognition that design flaws in health information technology (HIT) lead to increased cognitive work, impact workflows, and produce other undesirable user experiences that contribute to usability issues and, in some cases, patient harm. These usability issues may in turn contribute to HIT utilization disparities and patient safety concerns, particularly among “non-typical” HIT users and their health care providers. Health care disparities are associated with poor health outcomes, premature death, and increased health care costs. HIT has the potential to reduce these disparate outcomes. In the computer science field, it has long been recognized that embedded cultural assumptions can reduce the usability, usefulness, and safety of HIT systems for populations whose characteristics differ from “stereotypical” users. Among these non-typical users, inappropriate embedded design assumptions may contribute to health care disparities. It is unclear how to address potentially inappropriate embedded HIT design assumptions once detected. Objective The objective of this paper is to explain HIT universal design principles derived from the human factors engineering literature that can help to overcome potential usability and/or patient safety issues that are associated with unrecognized, embedded assumptions about cultural groups when designing HIT systems. Methods Existing best practices, guidance, and standards in software usability and accessibility were subjected to a 5-step expert review process to identify and summarize those best practices, guidance, and standards that could help identify and/or address embedded design assumptions in HIT that could negatively impact patient safety, particularly for non-majority HIT user populations. An iterative consensus-based process was then used to derive evidence-based design principles from the data to address potentially inappropriate embedded cultural assumptions. Results Design principles that may help identify and address embedded HIT design assumptions are available in the existing literature. Conclusions Evidence-based HIT design principles derived from existing human factors and informatics literature can help HIT developers identify and address embedded cultural assumptions that may underlie HIT-associated usability and patient safety concerns as well as health care disparities. PMID:27025349

Applying Human Factors Principles to Mitigate Usability Issues Related to Embedded Assumptions in Health Information Technology Design.

PubMed

Gibbons, Michael C; Lowry, Svetlana Z; Patterson, Emily S

2014-12-18

There is growing recognition that design flaws in health information technology (HIT) lead to increased cognitive work, impact workflows, and produce other undesirable user experiences that contribute to usability issues and, in some cases, patient harm. These usability issues may in turn contribute to HIT utilization disparities and patient safety concerns, particularly among "non-typical" HIT users and their health care providers. Health care disparities are associated with poor health outcomes, premature death, and increased health care costs. HIT has the potential to reduce these disparate outcomes. In the computer science field, it has long been recognized that embedded cultural assumptions can reduce the usability, usefulness, and safety of HIT systems for populations whose characteristics differ from "stereotypical" users. Among these non-typical users, inappropriate embedded design assumptions may contribute to health care disparities. It is unclear how to address potentially inappropriate embedded HIT design assumptions once detected. The objective of this paper is to explain HIT universal design principles derived from the human factors engineering literature that can help to overcome potential usability and/or patient safety issues that are associated with unrecognized, embedded assumptions about cultural groups when designing HIT systems. Existing best practices, guidance, and standards in software usability and accessibility were subjected to a 5-step expert review process to identify and summarize those best practices, guidance, and standards that could help identify and/or address embedded design assumptions in HIT that could negatively impact patient safety, particularly for non-majority HIT user populations. An iterative consensus-based process was then used to derive evidence-based design principles from the data to address potentially inappropriate embedded cultural assumptions. Design principles that may help identify and address embedded HIT design assumptions are available in the existing literature. Evidence-based HIT design principles derived from existing human factors and informatics literature can help HIT developers identify and address embedded cultural assumptions that may underlie HIT-associated usability and patient safety concerns as well as health care disparities.

A New View of the High Energy Gamma-Ray Sky with the Ferrni Gamma-Ray Space Telescope

NASA Technical Reports Server (NTRS)

McEnery, Julie

2009-01-01

Following its launch in June 2008, high energy gamma-ray observations by the Fermi Gamma-ray Space Telescope have opened a new and important window on a wide variety of phenomena, including pulsars, black holes and active galactic nuclei, gamma-ray bursts, supernova remnants and the origin of cosmic rays, and searches for hypothetical new phenomena such as super symmetric dark matter annihilations. In this talk I will describe the current status of the Fermi observatory and review the science highlights from the first year of observations.

HIT and brain reward function: A case of mistaken identity (theory).

PubMed

Wright, Cory; Colombo, Matteo; Beard, Alexander

2017-08-01

This paper employs a case study from the history of neuroscience-brain reward function-to scrutinize the inductive argument for the so-called 'Heuristic Identity Theory' (HIT). The case fails to support HIT, illustrating why other case studies previously thought to provide empirical support for HIT also fold under scrutiny. After distinguishing two different ways of understanding the types of identity claims presupposed by HIT and considering other conceptual problems, we conclude that HIT is not an alternative to the traditional identity theory so much as a relabeling of previously discussed strategies for mechanistic discovery. Copyright © 2017. Published by Elsevier Ltd.

Hurricane Matthew Damage Assessment

NASA Image and Video Library

2016-10-08

An aerial survey of NASA's Kennedy Space Center in Florida was conducted after Hurricane Matthew hit the Space Coast area. The survey was performed to identify structures and facilities that may have sustained damage from Hurricane Matthew as the storm passed to the east of Kennedy on Oct. 6 and 7, 2016. Officials determined that the center received some isolated roof damage, damaged support buildings, a few downed power lines, and limited water intrusion. Beach erosion also occurred, although the storm surge was less than expected. NASA closed the center ahead of the storm’s onset and only a small team of specialists known as the Rideout Team was on the center as the storm approached and passed.

PF4/heparin-antibody complex induces monocyte tissue factor expression and release of tissue factor positive microparticles by activation of FcγRI

PubMed Central

Glover, Sam L.; Jonas, William; McEachron, Troy; Pawlinski, Rafal; Arepally, Gowthami M.; Key, Nigel S.; Mackman, Nigel

2012-01-01

Heparin-induced thrombocytopenia (HIT) is a potentially devastating form of drug-induced thrombocytopenia that occurs in patients receiving heparin for prevention or treatment of thrombosis. Patients with HIT develop autoantibodies to the platelet factor 4 (PF4)/heparin complex, which is termed the HIT Ab complex. Despite a decrease in the platelet count, the most feared complication of HIT is thrombosis. The mechanism of thrombosis in HIT remains poorly understood. We investigated the effects of the HIT Ab complex on tissue factor (TF) expression and release of TF-positive microparticles in peripheral blood mononuclear cells and monocytes. To model these effects ex vivo, we used a murine mAb specific for the PF4/heparin complex (KKO), as well as plasma from patients with HIT. We found that the HIT Ab complex induced TF expression in monocytes and the release of TF-positive microparticles. Further, we found that induction of TF is mediated via engagement of the FcγRI receptor and activation of the MEK1-ERK1/2 signaling pathway. Our data suggest that monocyte TF may contribute to the development of thrombosis in patients with HIT. PMID:22394597

Acceptance of health information technology in health professionals: an application of the revised technology acceptance model.

PubMed

Ketikidis, Panayiotis; Dimitrovski, Tomislav; Lazuras, Lambros; Bath, Peter A

2012-06-01

The response of health professionals to the use of health information technology (HIT) is an important research topic that can partly explain the success or failure of any HIT application. The present study applied a modified version of the revised technology acceptance model (TAM) to assess the relevant beliefs and acceptance of HIT systems in a sample of health professionals (n = 133). Structured anonymous questionnaires were used and a cross-sectional design was employed. The main outcome measure was the intention to use HIT systems. ANOVA was employed to examine differences in TAM-related variables between nurses and medical doctors, and no significant differences were found. Multiple linear regression analysis was used to assess the predictors of HIT usage intentions. The findings showed that perceived ease of use, but not usefulness, relevance and subjective norms directly predicted HIT usage intentions. The present findings suggest that a modification of the original TAM approach is needed to better understand health professionals' support and endorsement of HIT. Perceived ease of use, relevance of HIT to the medical and nursing professions, as well as social influences, should be tapped by information campaigns aiming to enhance support for HIT in healthcare settings.

Utilizing Health Information Technology to Support Universal Healthcare Delivery: Experience of a National Healthcare System.

PubMed

Syed-Abdul, Shabbir; Hsu, Min-Huei; Iqbal, Usman; Scholl, Jeremiah; Huang, Chih-Wei; Nguyen, Phung Anh; Lee, Peisan; García-Romero, Maria Teresa; Li, Yu-Chuan Jack; Jian, Wen-Shan

2015-09-01

Recent discussions have focused on using health information technology (HIT) to support goals related to universal healthcare delivery. These discussions have generally not reflected on the experience of countries with a large amount of experience using HIT to support universal healthcare on a national level. HIT was compared globally by using data from the Ministry of the Interior, Republic of China (Taiwan). Taiwan has been providing universal healthcare since 1995 and began to strategically implement HIT on a national level at that time. Today the national-level HIT system is more extensive in Taiwan than in many other countries and is used to aid administration, clinical care, and public health. The experience of Taiwan thus can provide an illustration of how HIT can be used to support universal healthcare delivery. In this article we present an overview of some key historical developments and successes in the adoption of HIT in Taiwan over a 17-year period, as well as some more recent developments. We use this experience to offer some strategic perspectives on how it can aid in the adoption of large-scale HIT systems and on how HIT can be used to support universal healthcare delivery.

The Role of X-Rays in Future Space Navigation and Communication

NASA Technical Reports Server (NTRS)

Winternitz, Luke M. B.; Gendreau, Keith C.; Hasouneh, Monther A.; Mitchell, Jason W.; Fong, Wai H.; Lee, Wing-Tsz; Gavriil, Fotis; Arzoumanian, Zaven

2013-01-01

In the near future, applications using X-rays will enable autonomous navigation and time distribution throughout the solar system, high capacity and low-power space data links, highly accurate attitude sensing, and extremely high-precision formation flying capabilities. Each of these applications alone has the potential to revolutionize mission capabilities, particularly beyond Earth orbit. This paper will outline the NASA Goddard Space Flight Center vision and efforts toward realizing the full potential of X-ray navigation and communications.

Virtual fragment preparation for computational fragment-based drug design.

PubMed

Ludington, Jennifer L

2015-01-01

Fragment-based drug design (FBDD) has become an important component of the drug discovery process. The use of fragments can accelerate both the search for a hit molecule and the development of that hit into a lead molecule for clinical testing. In addition to experimental methodologies for FBDD such as NMR and X-ray Crystallography screens, computational techniques are playing an increasingly important role. The success of the computational simulations is due in large part to how the database of virtual fragments is prepared. In order to prepare the fragments appropriately it is necessary to understand how FBDD differs from other approaches and the issues inherent in building up molecules from smaller fragment pieces. The ultimate goal of these calculations is to link two or more simulated fragments into a molecule that has an experimental binding affinity consistent with the additive predicted binding affinities of the virtual fragments. Computationally predicting binding affinities is a complex process, with many opportunities for introducing error. Therefore, care should be taken with the fragment preparation procedure to avoid introducing additional inaccuracies.This chapter is focused on the preparation process used to create a virtual fragment database. Several key issues of fragment preparation which affect the accuracy of binding affinity predictions are discussed. The first issue is the selection of the two-dimensional atomic structure of the virtual fragment. Although the particular usage of the fragment can affect this choice (i.e., whether the fragment will be used for calibration, binding site characterization, hit identification, or lead optimization), general factors such as synthetic accessibility, size, and flexibility are major considerations in selecting the 2D structure. Other aspects of preparing the virtual fragments for simulation are the generation of three-dimensional conformations and the assignment of the associated atomic point charges.

A study of the feasibility of Internet administration of a computerized health survey: the headache impact test (HIT).

PubMed

Bayliss, M S; Dewey, J E; Dunlap, I; Batenhorst, A S; Cady, R; Diamond, M L; Sheftell, F

2003-12-01

Headache impact test (HIT) is a precise, practical tool that quantifies the impact of headache on respondents' lives. It is the first widely-available dynamic health assessment (DynHA). Applications of this brief, precise survey include population based screening for disabling headaches, tracking of individual patient scores over time, disease management programs and others. We use data from Internet HIT assessments during the fall of 2000 to (1) evaluate characteristics of respondents and assessments, (2) assess the utility of joint administration of HIT and the SF-8 Health Survey (SF-8) to screen for migraine and depression, and (3) explore associations between HIT scores and subsequent healthcare-related attitudes and behaviors. We analyzed Internet HIT surveys completed between 9/1 and 11/30/2000 (n = 19,195). Subsamples include respondents who also completed (1) a 12-item Internet survey assessing severity, frequency, cause and management of headaches; (2) an e-mail survey measuring healthcare-related behaviors; (3) the SF-8; or (4) the website registration process, providing age and gender data. We used analysis of variance (ANOVA) to evaluate HIT score differences associated with age, gender, headache severity or frequency, and healthcare-related behaviors and attitudes and chi2 tests to assess the prevalence and comorbidity of migraine and depression. Three-quarters of respondents achieved a precise HIT score in < or = 5 items. Most had moderate/severe headaches; 65% had headaches at least monthly. HIT scores were directly related to headache severity and frequency. Most respondents were females, with significantly higher HIT scores than males. Most HIT respondents were between ages 25 and 54 (HIT scores were higher for younger respondents). Sixty four percent screened positive for migraine; 20% for depression. Both conditions were more prevalent among females than males. Comorbid migraine and depression was 50% more prevalent among females and increased with age until age 50. Patients with worse headache impact were more likely to seek care, discuss headaches with their providers and find HIT useful. It is feasible to use Internet-based dynamic assessments to measure health status. These data complement previous results showing that HIT differentiates respondents according to headache characteristics (severity and frequency). HIT plus SF-8 yields a practical screen for migraine and depression in headache patients and may lead to more effective treatment for patients with these conditions. Preliminary findings suggest that the experience of taking HIT on the Internet may motivate headache patients to seek care and discuss headaches with their providers.

Approved Methods and Algorithms for DoD Risk-Based Explosives Siting

DTIC Science & Technology

2007-02-02

glass. Pgha Probability of a person being in the glass hazard area Phit Probability of hit Phit (f) Probability of hit for fatality Phit (maji...Probability of hit for major injury Phit (mini) Probability of hit for minor injury Pi Debris probability densities at the ES PMaj (pair) Individual...combined high-angle and combined low-angle tables. A unique probability of hit is calculated for the three consequences of fatality, Phit (f), major injury

Emerging Issues and Opportunities in Health Information Technology.

PubMed

Nardi, Elizabeth A; Lentz, Lisa Korin; Winckworth-Prejsnar, Katherine; Abernethy, Amy P; Carlson, Robert W

2016-10-01

When used effectively, health information technology (HIT) can transform clinical care and contribute to new research discoveries. Despite advances in HIT and increased electronic health record adoption, many challenges to optimal use, interoperability, and data sharing exist. Data standardization across systems is limited, and scanned medical note documents result in unstructured data that make reporting on quality measures for reimbursement burdensome. Different policies and initiatives, including the Health Information Technology for Economic and Clinical Health Act, the Medicare Access and CHIP Reauthorization Act, and the National Cancer Moonshot initiative, among others, all recognize the impact that HIT can have on cancer care. Given the growing role HIT plays in health care, it is vital to have effective and efficient HIT systems that can exchange information, collect credible data that is analyzable at the point of care, and improves the patient-provider relationship. In June 2016, NCCN hosted the Emerging Issues and Opportunities in Health Information Technology Policy Summit. The summit addressed challenges, issues, and opportunities in HIT as they relate to cancer care. Keynote presentations and panelists discussed moving beyond Meaningful Use, HIT readiness to support and report on quality care, the role of HIT in precision medicine, the role of HIT in the National Cancer Moonshot initiative, and leveraging HIT to improve quality of clinical care. Copyright © 2016 by the National Comprehensive Cancer Network.

Comparison of Health Information Technology Use Between American Adults With and Without Chronic Health Conditions: Findings From The National Health Interview Survey 2012

PubMed Central

Lauche, Romy; Sibbritt, David; Olaniran, Bolanle; Cook, Ronald; Adams, Jon

2017-01-01

Background Health information technology (HIT) is utilized by people with different chronic conditions such as diabetes and hypertension. However, there has been no comparison of HIT use between persons without a chronic condition, with one chronic condition, and multiple (≥2) chronic conditions (MCCs). Objective The aim of the study was to assess the difference in HIT use between persons without a chronic condition, with one chronic condition, and with MCCs, to describe the characteristics of HIT use among those with chronic conditions and to identify the predictors of HIT use of the persons with one chronic condition and MCCs. Methods A secondary data analysis was conducted in spring 2017 using the National Health Interview Survey (NHIS) 2012 Family Core and Sample Adult Core datasets that yielded 34,525 respondents aged 18 years and older. Measures included overall HIT use (ie, any use of the following five HIT on the Internet: seeking health information, ordering prescription, making appointment, emailing health provider, and using health chat groups), as well as sociodemographic and health-related characteristics. Sociodemographic and health characteristics were compared between HIT users and nonusers among those who reported having at least one chronic condition using chi-square tests. Independent predictors of HIT use were identified using multiple logistic regression analyses for those with one chronic condition, with MCCs, and without a chronic condition. Analyses were weighted and performed at significance level of .005. Results In 2012, adults with one health chronic condition (raw count 4147/8551, weighted percentage 48.54%) was significantly higher than among those with MCCs (3816/9637, 39.55%) and those with none of chronic condition (7254/16,337, 44.40%, P<.001). Seeking health information was the most prevalent HIT use. Chi-square tests revealed that among adults with chronic conditions, those who used HIT were significantly different from their counterpart peers who did not use HIT in terms of sociodemographic and health characteristics (P<.001). Overall, the significant factors related to HIT use were similar among the adults with one chronic condition, with MCCs, or without a chronic condition: younger age, female sex, non-Hispanic white, higher education level, and higher income level were shown to be positively related to the HIT use. Conclusions This study provides a snapshot of HIT use among those with chronic conditions and potential factors related to such use. Clinical care and public health communication efforts attempting to leverage more HIT use should acknowledge differential HIT usage as identified in this study to better address communication inequalities and persistent disparities in socioeconomic status. PMID:28982644

Comparison of Health Information Technology Use Between American Adults With and Without Chronic Health Conditions: Findings From The National Health Interview Survey 2012.

PubMed

Zhang, Yan; Lauche, Romy; Sibbritt, David; Olaniran, Bolanle; Cook, Ronald; Adams, Jon

2017-10-05

Health information technology (HIT) is utilized by people with different chronic conditions such as diabetes and hypertension. However, there has been no comparison of HIT use between persons without a chronic condition, with one chronic condition, and multiple (≥2) chronic conditions (MCCs). The aim of the study was to assess the difference in HIT use between persons without a chronic condition, with one chronic condition, and with MCCs, to describe the characteristics of HIT use among those with chronic conditions and to identify the predictors of HIT use of the persons with one chronic condition and MCCs. A secondary data analysis was conducted in spring 2017 using the National Health Interview Survey (NHIS) 2012 Family Core and Sample Adult Core datasets that yielded 34,525 respondents aged 18 years and older. Measures included overall HIT use (ie, any use of the following five HIT on the Internet: seeking health information, ordering prescription, making appointment, emailing health provider, and using health chat groups), as well as sociodemographic and health-related characteristics. Sociodemographic and health characteristics were compared between HIT users and nonusers among those who reported having at least one chronic condition using chi-square tests. Independent predictors of HIT use were identified using multiple logistic regression analyses for those with one chronic condition, with MCCs, and without a chronic condition. Analyses were weighted and performed at significance level of .005. In 2012, adults with one health chronic condition (raw count 4147/8551, weighted percentage 48.54%) was significantly higher than among those with MCCs (3816/9637, 39.55%) and those with none of chronic condition (7254/16,337, 44.40%, P<.001). Seeking health information was the most prevalent HIT use. Chi-square tests revealed that among adults with chronic conditions, those who used HIT were significantly different from their counterpart peers who did not use HIT in terms of sociodemographic and health characteristics (P<.001). Overall, the significant factors related to HIT use were similar among the adults with one chronic condition, with MCCs, or without a chronic condition: younger age, female sex, non-Hispanic white, higher education level, and higher income level were shown to be positively related to the HIT use. This study provides a snapshot of HIT use among those with chronic conditions and potential factors related to such use. Clinical care and public health communication efforts attempting to leverage more HIT use should acknowledge differential HIT usage as identified in this study to better address communication inequalities and persistent disparities in socioeconomic status. ©Yan Zhang, Romy Lauche, David Sibbritt, Bolanle Olaniran, Ronald Cook, Jon Adams. Originally published in the Journal of Medical Internet Research (http://www.jmir.org), 05.10.2017.

Kodak Mirror Assembly Tested at Marshall Space Flight Center

NASA Technical Reports Server (NTRS)

2003-01-01

The Eastman-Kodak mirror assembly is being tested for the James Webb Space Telescope (JWST) project at the X-Ray Calibration Facility at Marshall Space Flight Center (MSFC). In this photo, one of many segments of the mirror assembly is being set up inside the 24-ft vacuum chamber where it will undergo x-ray calibration tests. MSFC is supporting Goddard Space Flight Center (GSFC) in developing the JWST by taking numerous measurements to predict its future performance. The tests are conducted in a vacuum chamber cooled to approximate the super cold temperatures found in space. During its 27 years of operation, the facility has performed testing in support of a wide array of projects, including the Hubble Space Telescope (HST), Solar A, Chandra technology development, Chandra High Resolution Mirror Assembly and science instruments, Constellation X-Ray Mission, and Solar X-Ray Imager, currently operating on a Geostationary Operational Environment Satellite. The JWST is NASA's next generation space telescope, a successor to the Hubble Space Telescope, named in honor of NASA's second administrator, James E. Webb. It is scheduled for launch in 2010 aboard an expendable launch vehicle. It will take about 3 months for the spacecraft to reach its destination, an orbit of 940,000 miles in space.

Statistical properties and pre-hit dynamics of price limit hits in the Chinese stock markets.

PubMed

Wan, Yu-Lei; Xie, Wen-Jie; Gu, Gao-Feng; Jiang, Zhi-Qiang; Chen, Wei; Xiong, Xiong; Zhang, Wei; Zhou, Wei-Xing

2015-01-01

Price limit trading rules are adopted in some stock markets (especially emerging markets) trying to cool off traders' short-term trading mania on individual stocks and increase market efficiency. Under such a microstructure, stocks may hit their up-limits and down-limits from time to time. However, the behaviors of price limit hits are not well studied partially due to the fact that main stock markets such as the US markets and most European markets do not set price limits. Here, we perform detailed analyses of the high-frequency data of all A-share common stocks traded on the Shanghai Stock Exchange and the Shenzhen Stock Exchange from 2000 to 2011 to investigate the statistical properties of price limit hits and the dynamical evolution of several important financial variables before stock price hits its limits. We compare the properties of up-limit hits and down-limit hits. We also divide the whole period into three bullish periods and three bearish periods to unveil possible differences during bullish and bearish market states. To uncover the impacts of stock capitalization on price limit hits, we partition all stocks into six portfolios according to their capitalizations on different trading days. We find that the price limit trading rule has a cooling-off effect (object to the magnet effect), indicating that the rule takes effect in the Chinese stock markets. We find that price continuation is much more likely to occur than price reversal on the next trading day after a limit-hitting day, especially for down-limit hits, which has potential practical values for market practitioners.

Evaluation of flow cytometric HIT assays in relation to an IgG-Specific immunoassay and clinical outcome.

PubMed

Kerényi, Adrienne; Beke Debreceni, Ildikó; Oláh, Zsolt; Ilonczai, Péter; Bereczky, Zsuzsanna; Nagy, Béla; Muszbek, László; Kappelmayer, János

2017-09-01

Heparin-induced thrombocytopenia (HIT) is a severe side effect of heparin treatment caused by platelet activating IgG antibodies generated against the platelet factor 4 (PF4)-heparin complex. Thrombocytopenia and thrombosis are the leading clinical symptoms of HIT. The clinical pretest probability of HIT was evaluated by the 4T score system. Laboratory testing of HIT was performed by immunological detection of antibodies against PF4-heparin complex (EIA) and two functional assays. Heparin-dependent activation of donor platelets by patient plasma was detected by flow cytometry. Increased binding of Annexin-V to platelets and elevated number of platelet-derived microparticles (PMP) were the indicators of platelet activation. EIA for IgG isotype HIT antibodies was performed in 405 suspected HIT patients. Based on negative EIA results, HIT was excluded in 365 (90%) of cases. In 40 patients with positive EIA test result functional tests were performed. Platelet activating antibodies were detected in 17 cases by Annexin V binding. PMP count analysis provided nearly identical results. The probability of a positive flow cytometric assay result was higher in patients with elevated antibody titer. 71% of patients with positive EIA and functional assay had thrombosis. EIA is an important first line laboratory test in the diagnosis of HIT; however, HIT must be confirmed by a functional test. Annexin V binding and PMP assays using flow cytometry are functional HIT tests convenient in a clinical diagnostic laboratory. The positive results of functional assays may predict the onset of thrombosis. © 2016 International Clinical Cytometry Society. © 2016 International Clinical Cytometry Society.

Creating a safe place for pediatric care: A no hit zone.

PubMed

Frazier, Erin R; Liu, Gilbert C; Dauk, Kelly L

2014-07-01

Our goal was to create and implement a program, Kosair Children's Hospital's No Hit Zone, which trains health care workers in de-escalation techniques to address parental disruptive behaviors and physical discipline of children commonly encountered in the hospital environment. The Child Abuse Task Force, a multidisciplinary group, along with key hospital administrators developed specific content for the policy, as well as marketing and educational materials. The No Hit Zone policy designates Kosair Children's Hospital as "an environment in which no adult shall hit a child, no adult shall hit another adult, no child shall hit an adult, and no child shall hit another child. When hitting is observed, it is everyone's responsibility to interrupt the behavior as well as communicate system policy to those present." Via a multidisciplinary, collaborative approach, the No Hit Zone was successfully implemented at Kosair Children's Hospital in 2012. Cost was nominal, and the support of key hospital administrators was critical to the program's success. Education of health professionals on de-escalation techniques and intervention with families at the early signs of parental stress occurred via live sessions and online training via case-based scenarios. The No Hit Zone is an important program used to provide a safe and caring environment for all families and staff of Kosair Children's Hospital. Demand for the program continues, demonstrated by the establishment of No Hit Zones at other local hospitals and multiple outpatient clinics. This article offers information for other organizations planning to conduct similar initiatives. Copyright © 2014 by the American Academy of Pediatrics.

Protein Supplementation to Augment the Effects of High Intensity Resistance Training in Untrained Middle-Aged Males: The Randomized Controlled PUSH Trial.

PubMed

Wittke, Andreas; von Stengel, Simon; Hettchen, Michael; Fröhlich, Michael; Giessing, Jürgen; Lell, Michael; Scharf, Michael; Bebenek, Michael; Kohl, Matthias; Kemmler, Wolfgang

2017-01-01

High intensity (resistance exercise) training (HIT) defined as a "single set resistance exercise to muscular failure" is an efficient exercise method that allows people with low time budgets to realize an adequate training stimulus. Although there is an ongoing discussion, recent meta-analysis suggests the significant superiority of multiple set (MST) methods for body composition and strength parameters. The aim of this study is to determine whether additional protein supplementation may increase the effect of a HIT-protocol on body composition and strength to an equal MST-level. One hundred and twenty untrained males 30-50 years old were randomly allocated to three groups: (a) HIT, (b) HIT and protein supplementation (HIT&P), and (c) waiting-control (CG) and (after cross-over) high volume/high-intensity-training (HVHIT). HIT was defined as "single set to failure protocol" while HVHIT consistently applied two equal sets. Protein supplementation provided an overall intake of 1.5-1.7 g/kg/d/body mass. Primary study endpoint was lean body mass (LBM). LBM significantly improved in all exercise groups ( p ≤ 0.043); however only HIT&P and HVHIT differ significantly from control ( p ≤ 0.002). HIT diverges significantly from HIT&P ( p = 0.017) and nonsignificantly from HVHIT ( p = 0.059), while no differences were observed for HIT&P versus HVHIT ( p = 0.691). In conclusion, moderate to high protein supplementation significantly increases the effects of a HIT-protocol on LBM in middle-aged untrained males.

SHIELD-HIT12A - a Monte Carlo particle transport program for ion therapy research

NASA Astrophysics Data System (ADS)

Bassler, N.; Hansen, D. C.; Lühr, A.; Thomsen, B.; Petersen, J. B.; Sobolevsky, N.

2014-03-01

Purpose: The Monte Carlo (MC) code SHIELD-HIT simulates the transport of ions through matter. Since SHIELD-HIT08 we added numerous features that improves speed, usability and underlying physics and thereby the user experience. The "-A" fork of SHIELD-HIT also aims to attach SHIELD-HIT to a heavy ion dose optimization algorithm to provide MC-optimized treatment plans that include radiobiology. Methods: SHIELD-HIT12A is written in FORTRAN and carefully retains platform independence. A powerful scoring engine is implemented scoring relevant quantities such as dose and track-average LET. It supports native formats compatible with the heavy ion treatment planning system TRiP. Stopping power files follow ICRU standard and are generated using the libdEdx library, which allows the user to choose from a multitude of stopping power tables. Results: SHIELD-HIT12A runs on Linux and Windows platforms. We experienced that new users quickly learn to use SHIELD-HIT12A and setup new geometries. Contrary to previous versions of SHIELD-HIT, the 12A distribution comes along with easy-to-use example files and an English manual. A new implementation of Vavilov straggling resulted in a massive reduction of computation time. Scheduled for later release are CT import and photon-electron transport. Conclusions: SHIELD-HIT12A is an interesting alternative ion transport engine. Apart from being a flexible particle therapy research tool, it can also serve as a back end for a MC ion treatment planning system. More information about SHIELD-HIT12A and a demo version can be found on http://www.shieldhit.org.

78 FR 29134 - HIT Standards Committee; Schedule for the Assessment of HIT Policy Committee Recommendations

Federal Register 2010, 2011, 2012, 2013, 2014

2013-05-17

... quality, clinical operations, implementation, consumer technology, nationwide health information networks and privacy and security. Other groups will be convened to address specific issues as needed. HIT...) Direct the appropriate workgroup or other special group to develop a report for the HIT Standards...

42 CFR 495.332 - State Medicaid health information technology (HIT) plan requirements.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 42 Public Health 5 2014-10-01 2014-10-01 false State Medicaid health information technology (HIT... HEALTH RECORD TECHNOLOGY INCENTIVE PROGRAM Requirements Specific to the Medicaid Program § 495.332 State Medicaid health information technology (HIT) plan requirements. Each State Medicaid HIT plan must include...

42 CFR 495.332 - State Medicaid health information technology (HIT) plan requirements.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 42 Public Health 5 2013-10-01 2013-10-01 false State Medicaid health information technology (HIT... HEALTH RECORD TECHNOLOGY INCENTIVE PROGRAM Requirements Specific to the Medicaid Program § 495.332 State Medicaid health information technology (HIT) plan requirements. Each State Medicaid HIT plan must include...

42 CFR 495.332 - State Medicaid health information technology (HIT) plan requirements.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 42 Public Health 5 2012-10-01 2012-10-01 false State Medicaid health information technology (HIT... HEALTH RECORD TECHNOLOGY INCENTIVE PROGRAM Requirements Specific to the Medicaid Program § 495.332 State Medicaid health information technology (HIT) plan requirements. Each State Medicaid HIT plan must include...

42 CFR 495.332 - State Medicaid health information technology (HIT) plan requirements.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 42 Public Health 5 2011-10-01 2011-10-01 false State Medicaid health information technology (HIT... HEALTH RECORD TECHNOLOGY INCENTIVE PROGRAM Requirements Specific to the Medicaid Program § 495.332 State Medicaid health information technology (HIT) plan requirements. Each State Medicaid HIT plan must include...

77 FR 37408 - HIT Standards Committee Advisory Meeting; Notice of Meeting

Federal Register 2010, 2011, 2012, 2013, 2014

2012-06-21

... DEPARTMENT OF HEALTH AND HUMAN SERVICES HIT Standards Committee Advisory Meeting; Notice of... be open to the public. Name of Committee: HIT Standards Committee. General Function of the Committee... with policies developed by the HIT Policy Committee. Date and Time: The meeting will be held on July 19...

77 FR 65691 - HIT Standards Committee Advisory Meeting; Notice of Meeting

Federal Register 2010, 2011, 2012, 2013, 2014

2012-10-30

... DEPARTMENT OF HEALTH AND HUMAN SERVICES HIT Standards Committee Advisory Meeting; Notice of... public. Name of Committee: HIT Standards Committee. General Function of the Committee: To provide... developed by the HIT Policy Committee. Date and Time: The meeting will be held on November 13, 2012, from 9...

76 FR 70455 - HIT Standards Committee Advisory Meeting; Notice of Meeting

Federal Register 2010, 2011, 2012, 2013, 2014

2011-11-14

... DEPARTMENT OF HEALTH AND HUMAN SERVICES HIT Standards Committee Advisory Meeting; Notice of... public. Name of Committee: HIT Standards Committee. General Function of the Committee: to provide... developed by the HIT Policy Committee. Date and Time: The meeting will be held on December 14, 2011, from 9...

76 FR 79684 - HIT Standards Committee Advisory Meeting; Notice of Meeting

Federal Register 2010, 2011, 2012, 2013, 2014

2011-12-22

... DEPARTMENT OF HEALTH AND HUMAN SERVICES HIT Standards Committee Advisory Meeting; Notice of... public. Name of Committee: HIT Standards Committee. General Function of the Committee: to provide... developed by the HIT Policy Committee. Date and Time: The meeting will be held on January 25, 2012, from 9 a...

77 FR 65690 - HIT Standards Committee Advisory Meeting; Notice of Meeting

Federal Register 2010, 2011, 2012, 2013, 2014

2012-10-30

... DEPARTMENT OF HEALTH AND HUMAN SERVICES HIT Standards Committee Advisory Meeting; Notice of... public. Name of Committee: HIT Standards Committee. General Function of the Committee: To provide... developed by the HIT Policy Committee. Date and Time: The meeting will be held on December 19, 2012, from 9...

77 FR 45353 - HIT Standards Committee Advisory Meeting; Notice of Meeting

Federal Register 2010, 2011, 2012, 2013, 2014

2012-07-31

... DEPARTMENT OF HEALTH AND HUMAN SERVICES HIT Standards Committee Advisory Meeting; Notice of... public. Name of Committee: HIT Standards Committee. General Function of the Committee: To provide... developed by the HIT Policy Committee. Date and Time: The meeting will be held on August 15, 2012, from 9:00...

77 FR 2727 - HIT Standards Committee Advisory Meeting; Notice of Meeting

Federal Register 2010, 2011, 2012, 2013, 2014

2012-01-19

... DEPARTMENT OF HEALTH AND HUMAN SERVICES HIT Standards Committee Advisory Meeting; Notice of... public. Name of Committee: HIT Standards Committee. General Function of the Committee: To provide... developed by the HIT Policy Committee. Date and Time: The meeting will be held on February 29, 2012, from 9...

77 FR 73661 - HIT Standards Committee Advisory Meetings; Notice of Meetings

Federal Register 2010, 2011, 2012, 2013, 2014

2012-12-11

... DEPARTMENT OF HEALTH AND HUMAN SERVICES HIT Standards Committee Advisory Meetings; Notice of... public. Name of Committee: HIT Standards Committee. General Function of the Committee: To provide... developed by the HIT Policy Committee. Date and Time: These meetings will be held on the following dates and...

77 FR 60438 - HIT Standards Committee Advisory Meeting; Notice of Meeting

Federal Register 2010, 2011, 2012, 2013, 2014

2012-10-03

... DEPARTMENT OF HEALTH AND HUMAN SERVICES HIT Standards Committee Advisory Meeting; Notice of... public. Name of Committee: HIT Standards Committee. General Function of the Committee: To provide... developed by the HIT Policy Committee. Date and Time: The meeting will be held on October 17, 2012, from 9 a...

77 FR 50690 - HIT Standards Committee Advisory Meeting; Notice of Meeting

Federal Register 2010, 2011, 2012, 2013, 2014

2012-08-22

... DEPARTMENT OF HEALTH AND HUMAN SERVICES HIT Standards Committee Advisory Meeting; Notice of... public. Name of Committee: HIT Standards Committee. General Function of the Committee: To provide... developed by the HIT Policy Committee. Date and Time: The meeting will be held on September 19, 2012, from 9...

42 CFR 495.332 - State Medicaid health information technology (HIT) plan requirements.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 42 Public Health 5 2010-10-01 2010-10-01 false State Medicaid health information technology (HIT... HEALTH RECORD TECHNOLOGY INCENTIVE PROGRAM Requirements Specific to the Medicaid Program § 495.332 State Medicaid health information technology (HIT) plan requirements. Each State Medicaid HIT plan must include...

75 FR 62399 - Office of the National Coordinator for Health Information Technology; HIT Standards Committee...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-10-08

..., implementation, and privacy and security. HIT Standards Committee Schedule for the Assessment of HIT Policy... recommendations received from the HIT Policy Committee regarding health information technology standards...), section 3003. Erin Poetter, Office of Policy and Planning, Office of the National Coordinator for Health...

X-ray and gamma ray astronomy detectors

NASA Technical Reports Server (NTRS)

Decher, Rudolf; Ramsey, Brian D.; Austin, Robert

1994-01-01

X-ray and gamma ray astronomy was made possible by the advent of space flight. Discovery and early observations of celestial x-rays and gamma rays, dating back almost 40 years, were first done with high altitude rockets, followed by Earth-orbiting satellites> once it became possible to carry detectors above the Earth's atmosphere, a new view of the universe in the high-energy part of the electromagnetic spectrum evolved. Many of the detector concepts used for x-ray and gamma ray astronomy were derived from radiation measuring instruments used in atomic physics, nuclear physics, and other fields. However, these instruments, when used in x-ray and gamma ray astronomy, have to meet unique and demanding requirements related to their operation in space and the need to detect and measure extremely weak radiation fluxes from celestial x-ray and gamma ray sources. Their design for x-ray and gamma ray astronomy has, therefore, become a rather specialized and rapidly advancing field in which improved sensitivity, higher energy and spatial resolution, wider spectral coverage, and enhanced imaging capabilities are all sought. This text is intended as an introduction to x-ray and gamma ray astronomy instruments. It provides an overview of detector design and technology and is aimed at scientists, engineers, and technical personnel and managers associated with this field. The discussion is limited to basic principles and design concepts and provides examples of applications in past, present, and future space flight missions.

Feasibility of spectro-photometry in X-rays (SPHINX) from the moon

NASA Astrophysics Data System (ADS)

Sarkar, Ritabrata; Chakrabarti, Sandip Kumar

2010-08-01

Doing space Astronomy on lunar surface has several advantages. We present here feasibility of an All Sky Monitoring Payload for Spectro-photometry in X-rays (SPHINX) which can be placed on a lander on the moon or in a space craft orbiting around the moon. The Si-PIN photo-diodes and CdTe crystals are used to detect solar flares, bright gamma bursts, soft gamma-ray repeaters from space and also X-ray fluorescence (XRF) from lunar surface. We present the complete Geant4 simulation to study the feasibility of such an instrument in presence of Cosmic Diffused X-Ray Background (CDXRB). We find that the signal to noise ratio is sufficient for moderate to bright GRBs (above 5 keV), for the quiet sun (up to 100 keV), solar flares, soft gamma-ray repeaters, X-ray Fluorescence (XRF) of lunar surface etc. This is a low-cost system which is capable of performing multiple tasks while stationed at the natural satellite of our planet.

The nearest X-ray emitting protostellar jet (HH 154) observed with Hubble

NASA Astrophysics Data System (ADS)

Bonito, R.; Fridlund, C. V. M.; Favata, F.; Micela, G.; Peres, G.; Djupvik, A. A.; Liseau, R.

2008-06-01

Context: The jet coming from the YSO binary L1551 IRS5 is the closest astrophysical jet known. It is therefore a unique laboratory for studies of outflow mechanisms and of the shocks occurring when expanding material hits the ambient medium as well as of how the related processes influence the star- (and planet-) forming process. Aims: The optical data are related to other data covering the spectrum from the optical band to X-rays with goal of understanding the energetics of low-mass star jets, in general, and of this jet in particular. We study the time evolution of the jet, by measuring the proper motions of knots as they progress outwards from the originating source. Methods: The nebulosities associated with the jet(s) from the protostellar binary L1551 IRS5 were imaged in a number of spectral bands using the Hubble Space Telescope. This allows the proper motion to be measured and permits a simple characterization of the physical conditions in different structures. To this end we developed a reproducible method of data analysis, which allows us to define the position and shape of each substructure observed within the protostellar jet. Using this approach, we derive the proper motion of the knots in the jet, as well as their flux variability and shock emission. Results: The time base over which HST observations were carried out is now about ten years. The sub-structures within the jet undergo significant morphological variations: some knots seem to disappear in a few years and collision between different knots, ejected at different epochs and maybe with different speed, may occur. The velocities along the jet vary between ~100 km s-1 and over 400 km s-1, with the highest speed corresponding to the knots at the base of the jet. Conclusions: There are indications that the HH 154 jet has been active relatively recently. Our results suggest the presence of a new shock front at the base of the jet identified with an internal working surface. From the analysis of the terminal and internal working surfaces within the jet, we find that the more likely scenario for the HH 154 jet is that of a jet traveling through a denser ambient medium (a “light jet”). These results are consistent with the Bonito et al. (2007) model predictions. Furthermore, there is strong evidence that the knots at the base of the northern jet correspond to the location where the highest velocity and the highest excitation component are measured along the jet. More important, this is the location where the X-ray source has been discovered. Based on observations made with the NASA/ESA Hubble Space Telescope, obtained at the Space Telescope Science Institute, which is operated by the Association of Universities for Research in Astronomy, Inc., under NASA contract NAS 5-26555. These observations are associated with programs #6127, #6411 & #10351.

Funding bombshell hits UK physics

NASA Astrophysics Data System (ADS)

Banks, Michael; Durrani, Matin

2008-01-01

Physicists and astronomers in the UK are coming to terms with a massive funding crisis that engulfed one of the country's main funding agencies last month. As a result of an £80m black hole in the budget of the Science and Technology Facilities Council (STFC), it has decided to stop funding research into the International Linear Collider (ILC), withdraw from the Gemini telescopes in Hawaii and Chile, and cease all support for high-energy gamma-ray astronomy and ground-based solar-terrestrial physics. Research grants in particle physics and astronomy could also be cut by up to 25%, which may lead to job losses at university departments.

High-throughput screening for bioactive components from traditional Chinese medicine.

PubMed

Zhu, Yanhui; Zhang, Zhiyun; Zhang, Meng; Mais, Dale E; Wang, Ming-Wei

2010-12-01

Throughout the centuries, traditional Chinese medicine has been a rich resource in the development of new drugs. Modern drug discovery, which relies increasingly on automated high throughput screening and quick hit-to-lead development, however, is confronted with the challenges of the chemical complexity associated with natural products. New technologies for biological screening as well as library building are in great demand in order to meet the requirements. Here we review the developments in these techniques under the perspective of their applicability in natural product drug discovery. Methods in library building, component characterizing, biological evaluation, and other screening methods including NMR and X-ray diffraction are discussed.

Multidirectional Cosmic Ray Ion Detector for Deep Space CubeSats

NASA Technical Reports Server (NTRS)

Wrbanek, John D.; Wrbanek, Susan Y.

2016-01-01

NASA Glenn Research Center has proposed a CubeSat-based instrument to study solar and cosmic ray ions in lunar orbit or deep space. The objective of Solar Proton Anisotropy and Galactic cosmic ray High Energy Transport Instrument (SPAGHETI) is to provide multi-directional ion data to further understand anisotropies in SEP and GCR flux.

KSC-2009-1076

NASA Image and Video Library

2009-01-08

CAPE CANAVERAL, Fla. -- In the Space Station Processing Facility at NASA's Kennedy Space Center in Florida, the MAXI (Monitor of All-sky X-ray Image) has been installed next to the SEDA-AP (Space Environment Data Acquisition Equipment-Attached Payload) on the Japanese Experiment Module's Experiment Logistics Module-Exposed Section, or ELM-ES. The MAXI and SEDA-AP are part of space shuttle Endeavour's payload on the STS-127 mission. Using X-ray slit cameras with high sensitivity, the MAXI will continuously monitor astronomical X-ray objects over a broad energy band (0.5 to 30 keV). Endeavour is targeted to launch May 15. Photo credit: NASA/Jim Grossmann

KSC-08pd0615

NASA Image and Video Library

2008-03-04

KENNEDY SPACE CENTER, FLA. -- In the Astrotech payload processing facility near the Kennedy Space Center, the shipping container covering NASA's Gamma-Ray Large Area Space Telescope, or GLAST, is lifted. Workers will prepare for a complete checkout of the telescope's scientific instruments. The GLAST will launch aboard a Delta II rocket May 16 from Launch Pad 17-B on Cape Canaveral Air Force Station. A powerful space observatory, the GLAST will explore the most extreme environments in the universe, and answer questions about supermassive black hole systems, pulsars and the origin of cosmic rays. It also will study the mystery of powerful explosions known as gamma-ray bursts. Photo credit: NASA/Kim Shiflett

KSC-08pd0611

NASA Image and Video Library

2008-03-04

KENNEDY SPACE CENTER, FLA. -- The shipping container holding NASA's Gamma-Ray Large Area Space Telescope, or GLAST, is removed from the truck at the Astrotech payload processing facility near the Kennedy Space Center to begin prelaunch activities. The GLAST will launch aboard a Delta II rocket May 16 from Launch Pad 17-B on Cape Canaveral Air Force Station. A powerful space observatory, the GLAST will explore the most extreme environments in the universe, and answer questions about supermassive black hole systems, pulsars and the origin of cosmic rays. It also will study the mystery of powerful explosions known as gamma-ray bursts. Photo credit: NASA/Kim Shiflett

KSC-08pd0612

NASA Image and Video Library

2008-03-04

KENNEDY SPACE CENTER, FLA. -- The shipping container holding NASA's Gamma-Ray Large Area Space Telescope, or GLAST, is removed from the truck at the Astrotech payload processing facility near the Kennedy Space Center to begin prelaunch activities. The GLAST will launch aboard a Delta II rocket May 16 from Launch Pad 17-B on Cape Canaveral Air Force Station. A powerful space observatory, the GLAST will explore the most extreme environments in the universe, and answer questions about supermassive black hole systems, pulsars and the origin of cosmic rays. It also will study the mystery of powerful explosions known as gamma-ray bursts. Photo credit: NASA/Kim Shiflett

A Systolic Array-Based FPGA Parallel Architecture for the BLAST Algorithm

PubMed Central

Guo, Xinyu; Wang, Hong; Devabhaktuni, Vijay

2012-01-01

A design of systolic array-based Field Programmable Gate Array (FPGA) parallel architecture for Basic Local Alignment Search Tool (BLAST) Algorithm is proposed. BLAST is a heuristic biological sequence alignment algorithm which has been used by bioinformatics experts. In contrast to other designs that detect at most one hit in one-clock-cycle, our design applies a Multiple Hits Detection Module which is a pipelining systolic array to search multiple hits in a single-clock-cycle. Further, we designed a Hits Combination Block which combines overlapping hits from systolic array into one hit. These implementations completed the first and second step of BLAST architecture and achieved significant speedup comparing with previously published architectures. PMID:25969747

A large-area gamma-ray imaging telescope system

NASA Technical Reports Server (NTRS)

Koch, D. G.

1983-01-01

The concept definition of using the External Tank (ET) of the Space Shuttle as the basis for constructing a large area gamma ray imaging telescope in space is detailed. The telescope will be used to locate and study cosmic sources of gamma rays of energy greater than 100 MeV. Both the telescope properties and the means whereby an ET is used for this purpose are described. A parallel is drawn between those systems that would be common to both a Space Station and this ET application. In addition, those systems necessary for support of the telescope can form the basis for using the ET as part of the Space Station. The major conclusions of this concept definition are that the ET is ideal for making into a gamma ray telescope, and that this telescope will provide a substantial increase in collecting area.

Fermi Gamma-Ray Space Telescope: Highlights of the GeV Sky

NASA Technical Reports Server (NTRS)

Thomspon, D. J.

2011-01-01

Because high-energy gamma rays can be produced by processes that also produce neutrinos. the gamma-ray survey of the sky by the Fermi Gamma-ray Space Telescope offers a view of potenl ial targds for neutrino observations. Gamma-ray bursts. active galactic nuclei, and supernova remnants are all sites where hadronic, neutrino-producing interactions are plausible. Pulsars, pulsar wind nebulae, and binary sources are all phenomena that reveal leptonic particle acceleration through their gamma-ray emission. \\Vhile important to gamma-ray astrophysics. such sources are of less interest to neutrino studies. This talk will present a broad overview of the constantly changing sky seen with the Large Area Telescope (LAT) on the Fermi spacecraft.

Electronics for a prototype variable field of view PET camera using the PMT-quadrant-sharing detector array

NASA Astrophysics Data System (ADS)

Li, H.; Wong, Wai-Hoi; Zhang, N.; Wang, J.; Uribe, J.; Baghaei, H.; Yokoyama, S.

1999-06-01

Electronics for a prototype high-resolution PET camera with eight position-sensitive detector modules has been developed. Each module has 16 BGO (Bi/sub 4/Ge/sub 3/O/sub 12/) blocks (each block is composed of 49 crystals). The design goals are component and space reduction. The electronics is composed of five parts: front-end analog processing, digital position decoding, fast timing, coincidence processing and master data acquisition. The front-end analog circuit is a zone-based structure (each zone has 3/spl times/3 PMTs). Nine ADCs digitize integration signals of an active zone identified by eight trigger clusters; each cluster is composed of six photomultiplier tubes (PMTs). A trigger corresponding to a gamma ray is sent to a fast timing board to obtain a time-mark, and the nine digitized signals are passed to the position decoding board, where a real block (four PMTs) can be picked out from the zone for position decoding. Lookup tables are used for energy discrimination and to identify the gamma-hit crystal location. The coincidence board opens a 70-ns initial timing window, followed by two 20-ns true/accidental time-mark lookup table windows. The data output from the coincidence board can be acquired either in sinogram mode or in list mode with a Motorola/IRONICS VME-based system.

Informing the Selection of Screening Hit Series with in Silico Absorption, Distribution, Metabolism, Excretion, and Toxicity Profiles.

PubMed

Sanders, John M; Beshore, Douglas C; Culberson, J Christopher; Fells, James I; Imbriglio, Jason E; Gunaydin, Hakan; Haidle, Andrew M; Labroli, Marc; Mattioni, Brian E; Sciammetta, Nunzio; Shipe, William D; Sheridan, Robert P; Suen, Linda M; Verras, Andreas; Walji, Abbas; Joshi, Elizabeth M; Bueters, Tjerk

2017-08-24

High-throughput screening (HTS) has enabled millions of compounds to be assessed for biological activity, but challenges remain in the prioritization of hit series. While biological, absorption, distribution, metabolism, excretion, and toxicity (ADMET), purity, and structural data are routinely used to select chemical matter for further follow-up, the scarcity of historical ADMET data for screening hits limits our understanding of early hit compounds. Herein, we describe a process that utilizes a battery of in-house quantitative structure-activity relationship (QSAR) models to generate in silico ADMET profiles for hit series to enable more complete characterizations of HTS chemical matter. These profiles allow teams to quickly assess hit series for desirable ADMET properties or suspected liabilities that may require significant optimization. Accordingly, these in silico data can direct ADMET experimentation and profoundly impact the progression of hit series. Several prospective examples are presented to substantiate the value of this approach.

Acute effects of exposure to space radiation on CNS function and cognitive performance

USDA-ARS?s Scientific Manuscript database

On exploratory class missions, such as a mission to Mars, astronauts will be exposed to types and doses of radiation (cosmic rays) that are not experienced in low earth orbit where the Space Shuttle and International Space Station operate. Exposure to cosmic rays produces changes in neuronal functi...

Endeavour backdropped against space with Sun displaying rayed effect

NASA Image and Video Library

1993-12-09

STS061-105-024 (2-13 Dec. 1993) --- One of Endeavour's space walkers captured this view of Endeavour backdropped against the blackness of space, with the Sun displaying a rayed effect. The extended Remote Manipulator System (RMS) arm that the astronaut was standing on is seen on the left side of the view.

Space Science

NASA Image and Video Library

1996-01-01

In this photograph, Dr. Gerald Fishman of the Marshall Space Flight Center (MSFC), a principal investigator of the Compton Gamma-Ray Observatory's (GRO's) instrument, the Burst and Transient Source Experiment (BATSE), and Dr. Chryssa Kouveliotou of Universities Space Research Associates review data from the BATSE. For nearly 9 years, GRO's Burst and Transient Source Experiment (BATSE), designed and built by the Marshall Space Flight Center, kept a blinking watch on the universe to alert scientist to the invisible, mysterious gamma-ray bursts. By studying gamma-rays from objects like black holes, pulsars, quasars, neutron stars, and other exotic objects, scientists could discover clues to the birth, evolution, and death of stars, galaxies, and the universe. The gamma-ray instrument was one of four major science instruments aboard the Compton. It consisted of eight detectors, or modules, located at each corner of the rectangular satellite to simultaneously scan the entire universe for bursts of gamma-rays ranging in duration from fractions of a second to minutes. Because gamma-rays are so powerful, they pass through conventional telescope mirrors. Instead of a mirror, the heart of each BATSE module was a large, flat, transparent crystal that generated a tiny flash of light when struck by a gamma-ray. With an impressive list of discoveries and diverse accomplishments, BATSE could claim to have rewritten astronomy textbooks. Launched aboard the Space Shuttle Orbiter Atlantis during the STS-35 mission in April 1991, the GRO reentered the Earth's atmosphere and ended its successful 9-year mission in June 2000.

77 FR 15760 - HIT Standards Committee Advisory Meeting; Notice of Meeting

Federal Register 2010, 2011, 2012, 2013, 2014

2012-03-16

... DEPARTMENT OF HEALTH AND HUMAN SERVICES HIT Standards Committee Advisory Meeting; Notice of... public. Name of Committee: HIT Standards Committee. General Function of the Committee: to provide... developed by the HIT Policy Committee. Date and Time: The meeting will be held on April 18, 2012, from 9 a.m...

77 FR 27459 - HIT Standards Committee Advisory Meeting; Notice of Meeting

Federal Register 2010, 2011, 2012, 2013, 2014

2012-05-10

... DEPARTMENT OF HEALTH AND HUMAN SERVICES HIT Standards Committee Advisory Meeting; Notice of... public. Name of Committee: HIT Standards Committee. General Function of the Committee: To provide... developed by the HIT Policy Committee. Date and Time: The meeting will be held on June 20, 2012, from 9 a.m...

The impact of health information technology adoption by outpatient facilities on pregnancy outcomes.

PubMed

Deily, Mary E; Hu, Tianyan; Terrizzi, Sabrina; Chou, Shin-Yi; Meyerhoefer, Chad D

2013-02-01

Examine whether health information technology (HIT) at nonhospital facilities (NHFs) improves health outcomes and decreases resource use at hospitals within the same heath care network, and whether the impact of HIT varies as providers gain experience using the technologies. Administrative claims data on 491,832 births in Pennsylvania during 1998-2004 from the Pennsylvania Health Care Cost Containment Council and HIT applications data from the Dorenfest Institute. Fixed-effects regression analysis of the impact of HIT at NHFs on adverse birth outcomes and resource use. Greater use of clinical HIT applications by NHFs is associated with reduced incidence of obstetric trauma and preventable complications, as well as longer lengths of stay. In addition, the beneficial effects of HIT increase the longer that technologies have been in use. However, we find no consistent evidence on whether or how nonclinical HIT in NHFs affects either resource use or health outcomes. Clinical HIT applications at NHFs may reduce the likelihood of adverse birth outcomes, particularly after physicians and staff gain experience using the technologies. © Health Research and Educational Trust.

The Impact of Health Information Technology Adoption by Outpatient Facilities on Pregnancy Outcomes

PubMed Central

Deily, Mary E; Hu, Tianyan; Terrizzi, Sabrina; Chou, Shin-Yi; Meyerhoefer, Chad D

2013-01-01

Objective Examine whether health information technology (HIT) at nonhospital facilities (NHFs) improves health outcomes and decreases resource use at hospitals within the same heath care network, and whether the impact of HIT varies as providers gain experience using the technologies. Data Sources Administrative claims data on 491,832 births in Pennsylvania during 1998–2004 from the Pennsylvania Health Care Cost Containment Council and HIT applications data from the Dorenfest Institute. Study Design Fixed-effects regression analysis of the impact of HIT at NHFs on adverse birth outcomes and resource use. Principal Findings Greater use of clinical HIT applications by NHFs is associated with reduced incidence of obstetric trauma and preventable complications, as well as longer lengths of stay. In addition, the beneficial effects of HIT increase the longer that technologies have been in use. However, we find no consistent evidence on whether or how nonclinical HIT in NHFs affects either resource use or health outcomes. Conclusions Clinical HIT applications at NHFs may reduce the likelihood of adverse birth outcomes, particularly after physicians and staff gain experience using the technologies. PMID:22742682

Plasma exchange to remove HIT antibodies: dissociation between enzyme-immunoassay and platelet activation test reactivities.

PubMed

Warkentin, Theodore E; Sheppard, Jo-Ann I; Chu, F Victor; Kapoor, Anil; Crowther, Mark A; Gangji, Azim

2015-01-01

Repeated therapeutic plasma exchange (TPE) has been advocated to remove heparin-induced thrombocytopenia (HIT) IgG antibodies before cardiac/vascular surgery in patients who have serologically-confirmed acute or subacute HIT; for this situation, a negative platelet activation assay (eg, platelet serotonin-release assay [SRA]) has been recommended as the target serological end point to permit safe surgery. We compared reactivities in the SRA and an anti-PF4/heparin IgG-specific enzyme immunoassay (EIA), testing serial serum samples in a patient with recent (subacute) HIT who underwent serial TPE precardiac surgery, as well as for 15 other serially-diluted HIT sera. We observed that post-TPE/diluted HIT sera-when first testing SRA-negative-continue to test strongly positive by EIA-IgG. This dissociation between the platelet activation assay and a PF4-dependent immunoassay for HIT antibodies indicates that patients with subacute HIT undergoing repeated TPE before heparin reexposure should be tested by serial platelet activation assays even when their EIAs remain strongly positive. © 2015 by The American Society of Hematology.

An event-related potential study of memory for words spoken aloud or heard.

PubMed

Wilding, E L; Rugg, M D

1997-09-01

Subjects made old/new recognition judgements to visually presented words, half of which had been encountered in a prior study phase. For each word judged old, subjects made a subsequent source judgement, indicating whether they had pronounced the word aloud at study (spoken words), or whether they had heard the word spoken to them (heard words). Event-related potentials (ERPs) were compared for three classes of test item; words correctly judged to be new (correct rejections), and spoken and heard words that were correctly assigned to source (spoken hit/hit and heard hit/hit response categories). Consistent with previous findings (Wilding, E. L. and Rugg, M. D., Brain, 1996, 119, 889-905), two temporally and topographically dissociable components, with parietal and frontal maxima respectively, differentiated the ERPs to the hit/hit and correct rejection response categories. In addition, there was some evidence that the frontally distributed component could be decomposed into two distinct components, only one of which differentiated the two classes of hit/hit ERPs. The findings suggest that at least three functionally and neurologically dissociable processes can contribute to successful recovery of source information.

Factors associated with hit-and-run pedestrian fatalities and driver identification.

PubMed

MacLeod, Kara E; Griswold, Julia B; Arnold, Lindsay S; Ragland, David R

2012-03-01

As hit-and-run crashes account for a significant proportion of pedestrian fatalities, a better understanding of these crash types will assist efforts to reduce these fatalities. Of the more than 48,000 pedestrian deaths that were recorded in the United States between 1998 and 2007, 18.1% of them were caused by hit-and-run drivers. Using national data on single pedestrian-motor vehicle fatal crashes (1998-2007), logistic regression analyses were conducted to identify factors related to hit-and-run and to identify factors related to the identification of the hit-and-run driver. Results indicate an increased risk of hit-and-run in the early morning, poor light conditions, and on the weekend. There may also be an association between the type of victim and the likelihood of the driver leaving and being identified. Results also indicate that certain driver characteristics, behavior, and driving history are associated with hit-and-run. Alcohol use and invalid license were among the leading driver factor associated with an increased risk of hit-and-run. Prevention efforts that address such issues could substantially reduce pedestrian fatalities as a result of hit-and-run. However, more information about this driver population may be necessary. Copyright © 2011. Published by Elsevier Ltd.

Comparison of Video Head Impulse Test (vHIT) Gains Between Two Commercially Available Devices and by Different Gain Analytical Methods.

PubMed

Lee, Sang Hun; Yoo, Myung Hoon; Park, Jun Woo; Kang, Byung Chul; Yang, Chan Joo; Kang, Woo Suk; Ahn, Joong Ho; Chung, Jong Woo; Park, Hong Ju

2018-06-01

To evaluate whether video head impulse test (vHIT) gains are dependent on the measuring device and method of analysis. Prospective study. vHIT was performed in 25 healthy subjects using two devices simultaneously. vHIT gains were compared between these instruments and using five different methods of comparing position and velocity gains during head movement intervals. The two devices produced different vHIT gain results with the same method of analysis. There were also significant differences in the vHIT gains measured using different analytical methods. The gain analytic method that compares the areas under the velocity curve (AUC) of the head and eye movements during head movements showed lower vHIT gains than a method that compared the peak velocities of the head and eye movements. The former method produced the vHIT gain with the smallest standard deviation among the five procedures tested in this study. vHIT gains differ in normal subjects depending on the device and method of analysis used, suggesting that it is advisable for each device to have its own normal values. Gain calculations that compare the AUC of the head and eye movements during the head movements show the smallest variance.

Think of HIT.

PubMed

Warkentin, Theodore E

2006-01-01

Heparin-induced thrombocytopenia, or HIT, can present in many ways, ranging from common-isolated thrombocytopenia, venous thromboembolism, acute limb ischemia-to less common but specific presentations-necrotizing skin lesions at heparin injection sites, post-bolus acute systemic reactions, and adrenal hemorrhagic necrosis (secondary to adrenal vein thrombosis). Many patients with HIT have mild or moderate thrombocytopenia: the median platelet count nadir is 60 x 10(9)/L, and ranges from 15 to 150 x 10(9)/L in 90% of patients, most of whom evince a 50% or greater fall in the platelet count. HIT that begins after stopping heparin ("delayed-onset HIT") is increasingly recognized. Factors influencing risk of HIT include type of heparin (unfractionated heparin > low-molecular-weight heparin), type of patient (surgical > medical), and gender (female > male). Since timely diagnosis and treatment of HIT may reduce the risk of adverse outcomes, this review focuses on those clinical circumstances that should prompt the clinician to "think of HIT." Coumarin anticoagulants such as warfarin are ineffective in acute HIT and can even be deleterious by predisposing to micro-thrombosis via protein C depletion (venous limb gangrene and skin necrosis syndromes). Thus, it is important to avoid or postpone coumarin while managing HIT hypercoagulability, focusing on agents that inhibit thrombin directly (lepirudin, argatroban) or that inhibit its generation (danaparoid, fondaparinux). Post-marketing experience suggests that standard dosing of lepirudin is too high; current recommendations are to avoid the initial lepirudin bolus and to begin with lower infusion rates, even in patients without overt renal dysfunction.

Prospective evaluation of automatized PF4/heparin immunoassays HemosIL HIT-ab (PF4-H) for the diagnosis of heparin-induced thrombocytopenia.

PubMed

Jourdy, Y; Nougier, C; Rugeri, L; Bordet, J C; Sobas, F; Negrier, C

2015-04-01

Recently, rapid immunoassays have been developed to allow the detection of antibodies anti-PF4/heparin. In this prospective study, we evaluated the performances of a automatized immunoassay (HemosIL HIT-Ab) in comparison with an ELISA (Zymutest HIA IgG) used for the diagnosis of heparin-induced thrombocytopenia (HIT) in association with the 4T's score. According to the 4T's score, samples with score ≤3 had no further analysis. Two immunological assays Zymutest HIA IgG and HemosIL HIT-Ab were performed in samples with score ≥4. In patients with at least one positive immunological assay or two negative immunological assays but with high-pretest probability (4T's score ≥6), HIT was screened by one functional assay using washed platelets. The sensitivities of both assays were excellent and comparable (100%). The specificity was 92.3% for ELISA and 91.2% for HemosIL HIT-Ab. The analysis of the operating characteristics showed that both assays have almost identical ROCs (AUROC, 0.9951 and 0.9853, respectively, for ELISA and HemosIL HIT-Ab) and the calculating of the κ coefficient revealed a good agreement (0.67). Performance characteristics of the HemosIL HIT-Ab are comparable to the Zymutest HIA IgG. The HemosIL HIT-Ab can be used in association with the 4T's score to rule out HIT. © 2014 John Wiley & Sons Ltd.

Reliability and Validity of the Persian HIT-6 Questionnaire in Migraine and Tension-type Headache.

PubMed

Zandifar, Alireza; Banihashemi, Mahboobeh; Haghdoost, Faraidoon; Masjedi, Samaneh S; Manouchehri, Navid; Asgari, Fatemeh; Najafi, Mohammad R; Ghorbani, Abbas; Zandifar, Samaneh; Saadatnia, Mohammad; White, Michelle K

2014-09-01

Headache Impact Test (HIT-6) measures the impact headaches in a 1-month period. We validated the Persian translation of HIT-6, compared the HIT-6 psychometric analysis between migraine and tension-type headache (TTH) patients, and evaluated the capability of HIT-6 to differentiate between TTH, chronic migraine, and episodic migraine. Qualified participants, including 274 patients diagnosed with migraine or TTH, were required to complete HIT-6, SF-36v2, and a symptoms questionnaire on their first visit. At 3 and 8 weeks from first visit, participants completed HIT-6. Internal consistency (Cronbach's α) and test-retest reproducibility (Pearson's correlation coefficient) were used to assess reliability. Convergent validity was also assessed. Tension-type headache, episodic, and chronic migraines included 24.5%, 61.9%, and 13.6% of the participants, respectively. Internal consistency among all patients, TTH, and migraine in the first visit were 0.74, 0.77, and 0.73, respectively. Test-retest reliability for HIT-6 between visit 1 and 2 showed a moderate level of correlation (r = 0.50). Convergent validity and also item total correlation were acceptable. There was no significant difference in HIT-6 total score between TTH and migraine. Persian HIT-6 is a valid and reliable questionnaire for the evaluation of headache. However, it cannot differentiate between chronic migraine, episodic migraine, and TTH in Iranian population. © 2013 World Institute of Pain.

NIMROD Simulations of the HIT-SI and HIT-SI3 Devices

NASA Astrophysics Data System (ADS)

Morgan, Kyle; Jarboe, Tom; Hossack, Aaron; Chandra, Rian; Everson, Chris

2017-10-01

The Helicity Injected Torus with Steady Inductive helicity injection (HIT-SI) experiment uses a set of inductively driven helicity injectors to apply non-axisymmetric current drive on the edge of the plasma, driving an axisymmetric spheromak equilibrium in a central confinement volume. Significant improvements have been made to extended MHD modeling of HIT-SI, with both the resolution of disagreement at high injector frequencies in HIT-SI in addition to successes with the new upgraded HIT-SI3 device. Previous numerical studies of HIT-SI, using a zero-beta eMHD model, focused on operations with a drive frequency of 14.5 kHz, and found reduced agreement with both the magnetic profile and current amplification at higher frequencies (30-70 kHz). HIT-SI3 has three helicity injectors which are able to operate with different mode structures of perturbations through the different relative temporal phasing of the injectors. Simulations that allow for pressure gradients have been performed in the parameter regimes of both devices using the NIMROD code and show improved agreement with experimental results, most notably capturing the observed Shafranov-shift due to increased beta observed at higher finj in HIT-SI and the variety of toroidal perturbation spectra available in HIT-SI3. This material is based upon work supported by the U.S. Department of Energy, Office of Science, Office of Fusion Energy Sciences under Award Number DE-FG02- 96ER54361.

Space Science

NASA Image and Video Library

2002-02-01

This photograph depicts the Solar X-Ray Imager (SXI) being installed in the X-Ray Calibration Facility (XRCF) vacuum chamber for testing at the Marshall Space Flight Center (MSFC). The XRCF vacuum chamber simulates a space environment with low temperature and pressure. The x-ray images from SXI on the Geostationary Operational Environmental Satellite-12 (GOES-12) will be used by the National Oceanic and Atmospheric Administration (NOAA) and U.S. Air Force to forecast the intensity and speed of solar disturbances that could destroy satellite electronics or disrupt long-distance radio communications. The SXI will observe solar flares, coronal mass ejections, coronal holes, and active regions in the x-ray region of the electromagnetic spectrum. These features are the dominant sources of disturbances in space weather. The imager instrument consists of a telescope assembly with a 6.3-inch (16-centimeter) diameter grazing incidence mirror and a detector system. The imager was developed, tested, and calibrated by MSFC, in conjunction with the NASA Goddard Space Flight Center and U.S. Air Force.

The role of health information technology in advancing care management and coordination in accountable care organizations.

PubMed

Wu, Frances M; Shortell, Stephen M; Rundall, Thomas G; Bloom, Joan R

To be successful, accountable care organizations (ACOs) must effectively manage patient care. Health information technology (HIT) can support care delivery by providing various degrees of coordination. Few studies have examined the role of HIT functionalities or the role of different levels of coordination enabled by HIT on care management processes. We examine HIT functionalities in ACOs, categorized by the level of coordination they enable in terms of information and work flow, to determine which specific HIT functionalities and levels of coordination are most strongly associated with care management processes. Retrospective cross-sectional analysis was done using 2012 data from the National Survey of Accountable Care Organizations. HIT functionalities are categorized into coordination levels: information capture, the lowest level, which coordinates through standardization; information provision, which supports unidirectional activities; and information exchange, which reflects the highest level of coordination allowing for bidirectional exchange. The Care Management Process index (CMP index) includes 13 questions about the extent to which care is planned, monitored, and supported by providers and patients. Multiple regressions adjusting for organizational and ACO contractual factors are used to assess relationships between HIT functionalities and the CMP index. HIT functionality coordinating the most complex interdependences (information exchange) was associated with a 0.41 standard deviation change in the CMP index (β = .41, p < .001), but the associations for information capture (β = -.01, p = .97) and information provision (β = .15, p = .48) functionalities were not significant. The current study has shed some light on the relationship between HIT and care management processes by specifying the coordination roles that HIT may play and, in particular, the importance of information exchange functionalities. Although these represent early findings, further research can help policy makers and clinical leaders understand how to prioritize HIT development given resource constraints.

Statistical Properties and Pre-Hit Dynamics of Price Limit Hits in the Chinese Stock Markets

PubMed Central

Wan, Yu-Lei; Xie, Wen-Jie; Gu, Gao-Feng; Jiang, Zhi-Qiang; Chen, Wei; Xiong, Xiong; Zhang, Wei; Zhou, Wei-Xing

2015-01-01

Price limit trading rules are adopted in some stock markets (especially emerging markets) trying to cool off traders’ short-term trading mania on individual stocks and increase market efficiency. Under such a microstructure, stocks may hit their up-limits and down-limits from time to time. However, the behaviors of price limit hits are not well studied partially due to the fact that main stock markets such as the US markets and most European markets do not set price limits. Here, we perform detailed analyses of the high-frequency data of all A-share common stocks traded on the Shanghai Stock Exchange and the Shenzhen Stock Exchange from 2000 to 2011 to investigate the statistical properties of price limit hits and the dynamical evolution of several important financial variables before stock price hits its limits. We compare the properties of up-limit hits and down-limit hits. We also divide the whole period into three bullish periods and three bearish periods to unveil possible differences during bullish and bearish market states. To uncover the impacts of stock capitalization on price limit hits, we partition all stocks into six portfolios according to their capitalizations on different trading days. We find that the price limit trading rule has a cooling-off effect (object to the magnet effect), indicating that the rule takes effect in the Chinese stock markets. We find that price continuation is much more likely to occur than price reversal on the next trading day after a limit-hitting day, especially for down-limit hits, which has potential practical values for market practitioners. PMID:25874716

Heparin-induced thrombocytopenia: reducing misdiagnosis via collaboration between an inpatient anticoagulation pharmacy service and hospital reference laboratory.

PubMed

Burnett, Allison E; Bowles, Harmony; Borrego, Matthew E; Montoya, Tiffany N; Garcia, David A; Mahan, Charles

2016-11-01

Misdiagnosis of heparin-induced thrombocytopenia (HIT) is common and exposes patients to high-risk therapies and potentially serious adverse events. The primary objective of this study was to evaluate the impact of collaboration between an inpatient pharmacy-driven anticoagulation management service (AMS) and hospital reference laboratory to reduce inappropriate HIT antibody testing via pharmacist intervention and use of the 4T pre-test probability score. Secondary objectives included clinical outcomes and cost-savings realized through reduced laboratory testing and decreased unnecessary treatment of HIT. This was a single center, pre-post, observational study. The hospital reference laboratory contacted the AMS when they received a blood sample for an enzyme-linked immunosorbent HIT antibody (HIT Ab). Trained pharmacists prospectively scored each HIT Ab ordered by using the 4T score with subsequent communication to physicians recommending for or against processing and reporting of lab results. Utilizing retrospective chart review and a database for all patients with a HIT Ab ordered during the study period, we compared the incidence of HIT Ab testing before and after implementation of the pharmacy-driven 4T score intervention. Our intervention significantly reduced the number of inappropriate HIT Ab tests processed (176 vs. 63, p < 0.0001), with no increase in thrombotic or hemorrhagic events. Overall incidence of suspected and confirmed HIT was <3 and <0.005 %, respectively. Overall cost savings were $75,754 (US) or 62 % per patient exposed to heparin between the pre and post intervention groups. Collaboration between inpatient pharmacy AMS and hospital reference laboratories can result in reduction of misdiagnosis of HIT and significant cost savings with similar safety.

Implementation of a rapid HIT immunoassay at a university hospital - Retrospective analysis of HIT laboratory orders in patients with thrombocytopenia.

PubMed

Black, Anne; Heimerl, Susanne; Oertli, Linnéa; Wilczek, Wolf; Greinacher, Andreas; Spannagl, Michael; Herr, Wolfgang; Hart, Christina

2017-10-01

Heparin-induced thrombocytopenia (HIT) is a rare cause of thrombocytopenia and a potentially life-threatening adverse drug reaction. Clinical overdiagnosis of HIT results in costly laboratory tests and anticoagulation. Criteria and algorithms for diagnosis are established, but their translation into clinical practice is still challenging. In a retrospective approach we studied all HIT related laboratory test requests within four years and evaluated data before (1st period, 24month) and after (2nd period, 24month) replacing particle gel immunoassay (PaGIA) and enzyme-linked immunosorbent assay (ELISA) by a chemiluminescent immunoassay (CLIA). HIT was confirmed by heparin-induced platelet activation (HIPA) test. Clinical pretest probability for HIT using an implemented simplified 4Ts score and platelet count were evaluated. Costs for laboratory tests and alternative anticoagulation were calculated. In 1850 patients with suspected HIT, 2327 laboratory orders were performed. In 87.2% of these orders an intermediate/high simplified 4Ts score was found. Thrombocytopenia was present in 87.1%. After replacing PaGIA and ELISA by CLIA the number of immunological and functional laboratory tests was reduced by 38.2%. The number of positive HIT immunoassays declined from 22.6% to 6.0%, while the number of positive HIPA tests among positive immunological tests increased by 19%. Altogether, acute HIT was confirmed in 59 patients. A decline in the use of alternative anticoagulants was observed in the 2nd period. Our study shows that in a university hospital setting HIT is well-known, but diagnosis requires a precise laboratory confirmation. Replacing PaGIA and ELISA by CLIA did not influence laboratory order behavior but results in reduced overall costs for laboratory diagnostics and alternative anticoagulation. Copyright © 2017 Elsevier Ltd. All rights reserved.

Increased Health Information Technology Adoption and Use Among Small Primary Care Physician Practices Over Time: A National Cohort Study.

PubMed

Rittenhouse, Diane R; Ramsay, Patricia P; Casalino, Lawrence P; McClellan, Sean; Kandel, Zosha K; Shortell, Stephen M

2017-01-01

Implementation and meaningful use of health information technology (HIT) has been shown to facilitate delivery system transformation, yet implementation is far from universal. This study examined correlates of greater HIT implementation over time among a national cohort of small primary care practices in the United States. We used data from a 40-minute telephone panel survey of 566 small primary care practices having 8 or fewer physicians to investigate adoption and use of HIT in 2007-2010 and 2012-2013. We used generalized estimating equations (GEE) to estimate the association of practice characteristics and external incentives with the adoption and use of HIT. We studied 18 measures of HIT functionalities, including record keeping, clinical decision support, patient communication, and health information exchange with hospitals and pharmacies. Overall, use of 16 HIT functionalities increased significantly over time, whereas use of 2 decreased significantly. On average, compared with physician-owned practices, hospital-owned practices used 1.48 (95% CI, 1.07-1.88; P <.001) more HIT processes. And relative to smaller practices, practices with 3 to 8 physicians used 2.49 (95% CI, 2.26-2.72; P <.001) more HIT processes. Participation in pay-for-performance programs, participation in public reporting of clinical quality data, and a larger proportion of revenue from Medicare were also associated with greater adoption and use of HIT. The new Medicare Access and CHIP Reauthorization Act (MACRA) will provide payment incentives and technical support to speed HIT adoption and use by small practices. We found that external incentives were, indeed, positively associated with greater adoption and use of HIT. Our findings also support a strategy of targeting assistance to smaller physician practices and those that are physician owned. © 2017 Annals of Family Medicine, Inc.

The costs of heparin-induced thrombocytopenia: a patient-based cost of illness analysis.

PubMed

Wilke, T; Tesch, S; Scholz, A; Kohlmann, T; Greinacher, A

2009-05-01

SUMMARY BACKGROUND AND OBJECTIVES: Due to the complexity of heparin-induced thrombocytopenia (HIT), currently available cost analyses are rough estimates. The objectives of this study were quantification of costs involved in HIT and identification of main cost drivers based on a patient-oriented approach. Patients diagnosed with HIT (1995-2004, University-hospital Greifswald, Germany) based on a positive functional assay (HIPA test) were retrieved from the laboratory records and scored (4T-score) by two medical experts using the patient file. For cost of illness analysis, predefined HIT-relevant cost parameters (medication costs, prolonged in-hospital stay, diagnostic and therapeutic interventions, laboratory tests, blood transfusions) were retrieved from the patient files. The data were analysed by linear regression estimates with the log of costs and a gamma regression model. Mean length of stay data of non-HIT patients were obtained from the German Federal Statistical Office, adjusted for patient characteristics, comorbidities and year of treatment. Hospital costs were provided by the controlling department. One hundred and thirty HIT cases with a 4T-score >or=4 and a positive HIPA test were analyzed. Mean additional costs of a HIT case were 9008 euro. The main cost drivers were prolonged in-hospital stay (70.3%) and costs of alternative anticoagulants (19.7%). HIT was more costly in surgical patients compared with medical patients and in patients with thrombosis. Early start of alternative anticoagulation did not increase HIT costs despite the high medication costs indicating prevention of costly complications. An HIT cost calculator is provided, allowing online calculation of HIT costs based on local cost structures and different currencies.

The use and role of open source software applications in public and not-for-profit hospitals in the United States.

PubMed

Vest, Joshua R; Stephens, James H

2013-01-01

The potential cost savings and customizability of open source software (OSS) may be particularly attractive for hospitals. However, numerous health-care-specific OSS applications exist, the adoption of OSS health information technology (HIT) applications is not widespread in the United States. This disconnect between the availability of promising software and low adoption raises the basic question: If OSS HIT is so advantageous, why are more health care organizations not using it? We interviewed the chief information officer, or equivalent position, at 17 not-for-profit and public hospitals across the United States. Through targeted recruitment, our sample included nine hospitals using OSS HIT and eight hospitals not using OSS HIT. The open-ended interview questions were guided by domains included in the fit-viability theory, an organizational-level innovation adoption framework, and those suggested by a review of the literature. Transcripts were analyzed using an inductive and comparative approach, which involved an open coding for relevant themes. Interviews described the state of OSS use in hospitals. Specifically, general OSS applications were widely used by IT professionals. In addition, hospitals using OSS HIT still relied heavily on vendor support. In terms of why decisions arose to use OSS HIT, several hospitals using OSS HIT noted the cost advantages. In contrast, hospitals avoiding OSS HIT were clear, OSS as a class did not fit with clinical work and posed too much risk. Perceptions of OSS HIT ranged from enthusiastic embracement to resigned adoption, to refusal, to abandonment. Some organizations were achieving success with their OSS HIT choices, but they still relied on vendors for significant support. The decision to adopt OSS HIT was not uniform but contingent upon views of the risk posed by the technology, economic factors, and the hospital's existing capabilities.

Recovery of Vestibulo-Ocular Reflex Symmetry After an Acute Unilateral Peripheral Vestibular Deficit: Time Course and Correlation With Canal Paresis.

PubMed

Allum, John H J; Cleworth, T; Honegger, Flurin

2016-07-01

We investigated how response asymmetries and deficit side response amplitudes for head accelerations used clinically to test the vestibular ocular reflex (VOR) are correlated with caloric canal paresis (CP) values. 30 patients were examined at onset of an acute unilateral peripheral vestibular deficit (aUPVD) and 3, 6, and 13 weeks later with three different VOR tests: caloric, rotating chair (ROT), and video head impulse tests (vHIT). Response changes over time were fitted with an exponential decay model and compared with using linear regression analysis. Recovery times (to within 10% of steady state) were similar for vHIT-asymmetry and CP (>10 weeks) but shorter for ROT asymmetry (<4 weeks). Regressions with CP were similar (vHIT asymmetry, R = 0.68, ROT, R = 0.62). Responses to the deficit side were also equally well correlated with CP values (R = 0.71). Specificity for vHIT and 20 degrees/s ROT deficit side responses was 100% in comparison to CP values, sensitivity was 74% for vHIT, 75% for ROT. A decrease in normal side responses occurred for ROT but not for vHIT at 3 weeks. Normal side responses were weekly correlated with CP for ROT (R = 0.49) but not for vHIT (R = 0.17). These results indicate that vHIT deficit side VOR gains are slightly better correlated with CP values than ROT, probably because of similar recovery time courses of vHIT and caloric responses and the lack of normal side vHIT changes. However, specificity and sensitivity is the same for vHIT and ROT tests.

Temporal characteristic analysis of laser-modulated pulsed X-ray source for space X-ray communication

NASA Astrophysics Data System (ADS)

Hang, Shuang; Liu, Yunpeng; Li, Huan; Tang, Xiaobin; Chen, Da

2018-04-01

X-ray communication (XCOM) is a new communication type and is expected to realize high-speed data transmission in some special communication scenarios, such as deep space communication and blackout communication. This study proposes a high-speed modulated X-ray source scheme based on the laser-to-X-ray conversion. The temporal characteristics of the essential components of the proposed laser-modulated pulsed X-ray source (LMPXS) were analyzed to evaluate its pulse emission performance. Results show that the LMPXS can provide a maximum modulation rate up to 100 Mbps which is expected to significantly improve the data rate of XCOM.

ISPAE Research Highlights 1995-1997

NASA Technical Reports Server (NTRS)

Harwell, Ken

1997-01-01

This paper presents ISPAE (Institute for Space Physics, Astrophysics and Education) research highlights from 1995-1997. The topics include: 1) High-Energy Astrophysics (Finding the smoking gun in gamma-ray bursts, Playing peekaboo with gamma ray bursts, and Spectral pulses muddle burst source study, Einstein was right: Black holes do spin, Astronomers find "one-man X-ray band", and Cosmic rays from the supernova next door?); 2) Solar Physics (Bright burst confirms solar storm model, Model predicts speed of solar wind in space, and Angry sunspots snap under the strain); 3) Gravitational Physics; 4) Tether Dynamics; and 5) Space Physics (Plasma winds blow form polar regions, De-SCIFERing thermal electrons, and UVI lets scientists see daytime aurora).

Spaced-based Cosmic Ray Astrophysics

NASA Astrophysics Data System (ADS)

Seo, Eun-Suk

2016-03-01

The bulk of cosmic ray data has been obtained with great success by balloon-borne instruments, particularly with NASA's long duration flights over Antarctica. More recently, PAMELA on a Russian Satellite and AMS-02 on the International Space Station (ISS) started providing exciting measurements of particles and anti-particles with unprecedented precision upto TeV energies. In order to address open questions in cosmic ray astrophysics, future missions require spaceflight exposures for rare species, such as isotopes, ultra-heavy elements, and high (the ``knee'' and above) energies. Isotopic composition measurements up to about 10 GeV/nucleon that are critical for understanding interstellar propagation and origin of the elements are still to be accomplished. The cosmic ray composition in the knee (PeV) region holds a key to understanding the origin of cosmic rays. Just last year, the JAXA-led CALET ISS mission, and the DAMPE Chinese Satellite were launched. NASA's ISS-CREAM completed its final verification at GSFC, and was delivered to KSC to await launch on SpaceX. In addition, a EUSO-like mission for ultrahigh energy cosmic rays and an HNX-like mission for ultraheavy nuclei could accomplish a vision for a cosmic ray observatory in space. Strong support of NASA's Explorer Program category of payloads would be needed for completion of these missions over the next decade.

Low-Volume High-Intensity Interval Training in a Gym Setting Improves Cardio-Metabolic and Psychological Health.

PubMed

Shepherd, Sam O; Wilson, Oliver J; Taylor, Alexandra S; Thøgersen-Ntoumani, Cecilie; Adlan, Ahmed M; Wagenmakers, Anton J M; Shaw, Christopher S

2015-01-01

Within a controlled laboratory environment, high-intensity interval training (HIT) elicits similar cardiovascular and metabolic benefits as traditional moderate-intensity continuous training (MICT). It is currently unclear how HIT can be applied effectively in a real-world environment. To investigate the hypothesis that 10 weeks of HIT, performed in an instructor-led, group-based gym setting, elicits improvements in aerobic capacity (VO2max), cardio-metabolic risk and psychological health which are comparable to MICT. Ninety physically inactive volunteers (42±11 y, 27.7±4.8 kg.m-2) were randomly assigned to HIT or MICT group exercise classes. HIT consisted of repeated sprints (15-60 seconds, >90% HRmax) interspersed with periods of recovery cycling (≤25 min.session-1, 3 sessions.week-1). MICT participants performed continuous cycling (~70% HRmax, 30-45 min.session-1, 5 sessions.week-1). VO2max, markers of cardio-metabolic risk, and psychological health were assessed pre and post-intervention. Mean weekly training time was 55±10 (HIT) and 128±44 min (MICT) (p<0.05), with greater adherence to HIT (83±14% vs. 61±15% prescribed sessions attended, respectively; p<0.05). HIT improved VO2max, insulin sensitivity, reduced abdominal fat mass, and induced favourable changes in blood lipids (p<0.05). HIT also induced beneficial effects on health perceptions, positive and negative affect, and subjective vitality (p<0.05). No difference between HIT and MICT was seen for any of these variables. HIT performed in a real-world gym setting improves cardio-metabolic risk factors and psychological health in physically inactive adults. With a reduced time commitment and greater adherence than MICT, HIT offers a viable and effective exercise strategy to target the growing incidence of metabolic disease and psychological ill-being associated with physical inactivity.

High-Intensity Interval Training with Vibration as Rest Intervals Attenuates Fiber Atrophy and Prevents Decreases in Anaerobic Performance

PubMed Central

Mueller, Sandro Manuel; Aguayo, David; Zuercher, Matthias; Fleischmann, Oliver; Boutellier, Urs; Auer, Maria; Jung, Hans H.; Toigo, Marco

2015-01-01

Aerobic high-intensity interval training (HIT) improves cardiovascular capacity but may reduce the finite work capacity above critical power (W′) and lead to atrophy of myosin heavy chain (MyHC)-2 fibers. Since whole-body vibration may enhance indices of anaerobic performance, we examined whether side-alternating whole-body vibration as a replacement for the active rest intervals during a 4x4 min HIT prevents decreases in anaerobic performance and capacity without compromising gains in aerobic function. Thirty-three young recreationally active men were randomly assigned to conduct either conventional 4x4 min HIT, HIT with 3 min of WBV at 18 Hz (HIT+VIB18) or 30 Hz (HIT+VIB30) in lieu of conventional rest intervals, or WBV at 30 Hz (VIB30). Pre and post training, critical power (CP), W′, cellular muscle characteristics, as well as cardiovascular and neuromuscular variables were determined. W′ (−14.3%, P = 0.013), maximal voluntary torque (−8.6%, P = 0.001), rate of force development (−10.5%, P = 0.018), maximal jumping power (−6.3%, P = 0.007) and cross-sectional areas of MyHC-2A fibers (−6.4%, P = 0.044) were reduced only after conventional HIT. CP, V̇O2peak, peak cardiac output, and overall capillary-to-fiber ratio were increased after HIT, HIT+VIB18, and HIT+VIB30 without differences between groups. HIT-specific reductions in anaerobic performance and capacity were prevented by replacing active rest intervals with side-alternating whole-body vibration, notably without compromising aerobic adaptations. Therefore, competitive cyclists (and potentially other endurance-oriented athletes) may benefit from replacing the active rest intervals during aerobic HIT with side-alternating whole-body vibration. Trial Registration ClinicalTrials.gov Identifier: NCT01875146 PMID:25679998

Low-Volume High-Intensity Interval Training in a Gym Setting Improves Cardio-Metabolic and Psychological Health

PubMed Central

Shepherd, Sam O.; Wilson, Oliver J.; Taylor, Alexandra S.; Thøgersen-Ntoumani, Cecilie; Adlan, Ahmed M.; Wagenmakers, Anton J. M.; Shaw, Christopher S.

2015-01-01

Background Within a controlled laboratory environment, high-intensity interval training (HIT) elicits similar cardiovascular and metabolic benefits as traditional moderate-intensity continuous training (MICT). It is currently unclear how HIT can be applied effectively in a real-world environment. Purpose To investigate the hypothesis that 10 weeks of HIT, performed in an instructor-led, group-based gym setting, elicits improvements in aerobic capacity (VO2max), cardio-metabolic risk and psychological health which are comparable to MICT. Methods Ninety physically inactive volunteers (42±11 y, 27.7±4.8 kg.m-2) were randomly assigned to HIT or MICT group exercise classes. HIT consisted of repeated sprints (15–60 seconds, >90% HRmax) interspersed with periods of recovery cycling (≤25 min.session-1, 3 sessions.week-1). MICT participants performed continuous cycling (~70% HRmax, 30–45 min.session-1, 5 sessions.week-1). VO2max, markers of cardio-metabolic risk, and psychological health were assessed pre and post-intervention. Results Mean weekly training time was 55±10 (HIT) and 128±44 min (MICT) (p<0.05), with greater adherence to HIT (83±14% vs. 61±15% prescribed sessions attended, respectively; p<0.05). HIT improved VO2max, insulin sensitivity, reduced abdominal fat mass, and induced favourable changes in blood lipids (p<0.05). HIT also induced beneficial effects on health perceptions, positive and negative affect, and subjective vitality (p<0.05). No difference between HIT and MICT was seen for any of these variables. Conclusions HIT performed in a real-world gym setting improves cardio-metabolic risk factors and psychological health in physically inactive adults. With a reduced time commitment and greater adherence than MICT, HIT offers a viable and effective exercise strategy to target the growing incidence of metabolic disease and psychological ill-being associated with physical inactivity. PMID:26402859