Highly specific targeting of the TMPRSS2/ERG fusion gene using liposomal nanovectors.

PubMed

Shao, Longjiang; Tekedereli, Ibrahim; Wang, Jianghua; Yuca, Erkan; Tsang, Susan; Sood, Anil; Lopez-Berestein, Gabriel; Ozpolat, Bulent; Ittmann, Michael

2012-12-15

The TMPRSS2/ERG (T/E) fusion gene is present in half of all prostate cancer tumors. Fusion of the oncogenic ERG gene with the androgen-regulated TMPRSS2 gene promoter results in expression of fusion mRNAs in prostate cancer cells. The junction of theTMPRSS2- and ERG-derived portions of the fusion mRNA constitutes a cancer-specific target in cells containing the T/E fusion gene. Targeting the most common alternatively spliced fusion gene mRNA junctional isoforms in vivo using siRNAs in liposomal nanovectors may potentially be a novel, low-toxicity treatment for prostate cancer. We designed and optimized siRNAs targeting the two most common T/E fusion gene mRNA junctional isoforms (type III or type VI). Specificity of siRNAs was assessed by transient co-transfection in vitro. To test their ability to inhibit growth of prostate cancer cells expressing these fusion gene isoforms in vivo, specific siRNAs in liposomal nanovectors were used to treat mice bearing orthotopic or subcutaneous xenograft tumors expressing the targeted fusion isoforms. The targeting siRNAs were both potent and highly specific in vitro. In vivo they significantly inhibited tumor growth. The degree of growth inhibition was variable and was correlated with the extent of fusion gene knockdown. The growth inhibition was associated with marked inhibition of angiogenesis and, to a lesser degree, proliferation and a marked increase in apoptosis of tumor cells. No toxicity was observed. Targeting the T/E fusion junction in vivo with specific siRNAs delivered via liposomal nanovectors is a promising therapy for men with prostate cancer. ©2012 AACR.

High degree-of-freedom dynamic manipulation

NASA Astrophysics Data System (ADS)

Murphy, Michael P.; Stephens, Benjamin; Abe, Yeuhi; Rizzi, Alfred A.

2012-06-01

The creation of high degree of freedom dynamic mobile manipulation techniques and behaviors will allow robots to accomplish difficult tasks in the field. We are investigating the use of the body and legs of legged robots to improve the strength, velocity, and workspace of an integrated manipulator to accomplish dynamic manipulation. This is an especially challenging task, as all of the degrees of freedom are active at all times, the dynamic forces generated are high, and the legged system must maintain robust balance throughout the duration of the tasks. To accomplish this goal, we are utilizing trajectory optimization techniques to generate feasible open-loop behaviors for our 28 dof quadruped robot (BigDog) by planning the trajectories in a 13 dimensional space. Covariance Matrix Adaptation techniques are utilized to optimize for several criteria such as payload capability and task completion speed while also obeying constraints such as torque and velocity limits, kinematic limits, and center of pressure location. These open-loop behaviors are then used to generate feed-forward terms, which are subsequently used online to improve tracking and maintain low controller gains. Some initial results on one of our existing balancing quadruped robots with an additional human-arm-like manipulator are demonstrated on robot hardware, including dynamic lifting and throwing of heavy objects 16.5kg cinder blocks, using motions that resemble a human athlete more than typical robotic motions. Increased payload capacity is accomplished through coordinated body motion.

ACCURATE CHARACTERIZATION OF HIGH-DEGREE MODES USING MDI OBSERVATIONS

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

Korzennik, S. G.; Rabello-Soares, M. C.; Schou, J.

2013-08-01

We present the first accurate characterization of high-degree modes, derived using the best Michelson Doppler Imager (MDI) full-disk full-resolution data set available. A 90 day long time series of full-disk 2 arcsec pixel{sup -1} resolution Dopplergrams was acquired in 2001, thanks to the high rate telemetry provided by the Deep Space Network. These Dopplergrams were spatially decomposed using our best estimate of the image scale and the known components of MDI's image distortion. A multi-taper power spectrum estimator was used to generate power spectra for all degrees and all azimuthal orders, up to l = 1000. We used a largemore » number of tapers to reduce the realization noise, since at high degrees the individual modes blend into ridges and thus there is no reason to preserve a high spectral resolution. These power spectra were fitted for all degrees and all azimuthal orders, between l = 100 and l = 1000, and for all the orders with substantial amplitude. This fitting generated in excess of 5.2 Multiplication-Sign 10{sup 6} individual estimates of ridge frequencies, line widths, amplitudes, and asymmetries (singlets), corresponding to some 5700 multiplets (l, n). Fitting at high degrees generates ridge characteristics, characteristics that do not correspond to the underlying mode characteristics. We used a sophisticated forward modeling to recover the best possible estimate of the underlying mode characteristics (mode frequencies, as well as line widths, amplitudes, and asymmetries). We describe in detail this modeling and its validation. The modeling has been extensively reviewed and refined, by including an iterative process to improve its input parameters to better match the observations. Also, the contribution of the leakage matrix on the accuracy of the procedure has been carefully assessed. We present the derived set of corrected mode characteristics, which includes not only frequencies, but line widths, asymmetries, and amplitudes. We present and

Realized Potential or Lost Talent: High School Variables and Bachelor's Degree Completion

ERIC Educational Resources Information Center

Trusty, Jerry; Niles, Spencer G.

2004-01-01

This study examined how background and high school variables affected participants in either realizing their potential by completing a bachelor's degree or experiencing lost talent by not completing a bachelor's degree. A sample of participants who had demonstrated above average cognitive ability and had high postsecondary educational goals when…

Drugs targeting high-density lipoprotein cholesterol for coronary artery disease management.

PubMed

Katz, Pamela M; Leiter, Lawrence A

2012-01-01

Many patients remain at high risk for future cardiovascular events despite levels of low-density lipoprotein cholesterol (LDL-C) at, or below, target while taking statin therapy. Much effort is therefore being focused on strategies to reduce this residual risk. High-density lipoprotein cholesterol (HDL-C) is a strong, independent, inverse predictor of coronary heart disease risk and is therefore an attractive therapeutic target. Currently available agents that raise HDL-C have only modest effects and there is limited evidence of additional cardiovascular risk reduction on top of background statin therapy associated with their use. It was hoped that the use of cholesteryl ester transfer protein (CETP) inhibitors would provide additional benefit, but the results of clinical outcome studies to date have been disappointing. The results of ongoing trials with other CETP inhibitors that raise HDL-C to a greater degree and also lower LDL-C, as well as with other emerging therapies are awaited. Copyright © 2012 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.

A high yield neutron target

NASA Technical Reports Server (NTRS)

Alger, D. L.; Steinberg, R.; Weisenbach, P.

1974-01-01

Target, in cylinder form, rotates rapidly in front of beam. Titanium tritide film is much thicker than range of accelerated deutron. Sputtering electrode permits full use of thick film. Stream of high-velocity coolant provides efficient transfer of heat from target.

Educational Engagement and Degree Attainment among High School Dropouts

ERIC Educational Resources Information Center

Suh, Suhyun; Suh, Jingyo

2006-01-01

This research investigates the relationship between educational engagement and high school degree attainment among school dropouts. Educational engagement considered in this article focuses on student factors such as educational aspiration, organizational skills, and locus of control. Findings of this study show that self-concept engagement…

Field Testing of High Degree Revenue Service Track for Buckling Safety Assessment

DOT National Transportation Integrated Search

1995-01-01

This report presents the results of a field study of high degree curves in continuous welded rail (CWR) territory. This program was conducted at two test sites: a 10 degree curve on the Atchison, Topeka, and Santa Fe (ATSF) Railroad near Sante Fe, NM...

28 CFR 570.43 - Inmates requiring a high degree of control and supervision.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 28 Judicial Administration 2 2010-07-01 2010-07-01 false Inmates requiring a high degree of control and supervision. 570.43 Section 570.43 Judicial Administration BUREAU OF PRISONS, DEPARTMENT OF JUSTICE COMMUNITY PROGRAMS AND RELEASE COMMUNITY PROGRAMS Escorted Trips § 570.43 Inmates requiring a high degree of control and supervision. Only the...

The relationship between the target effective site concentration of rocuronium and the degree of recovery from neuromuscular blockade in elderly patients

PubMed Central

Fan, Xiaochong; Ma, Minyu; Li, Zhisong; Gong, Shengkai; Zhang, Wei; Wen, Yuanyuan

2015-01-01

Objective: To study the relationship between the target effective site concentration (Ce) of rocuronium and the degree of recovery from neuromuscular blockade in elderly patients. Methods: 50 elderly patients (ASA grade II) scheduled for selective surgical procedure under general anaesthesia were randomly divided into two groups, A and B, with 25 cases in each group. The Ce of rocuronium for intubation was 3 μg·ml-1 in both groups, and the Ce during operation were 0.8 and 1.0 μg·ml-1 in group A and B, respectively. When target controlled infusion of rocuronium was stopped, without the administration of reversal agents for neuromuscular blockade, the relationship between Ce and the first twitch height (T1) was studied by regression analysis. Results: There was a significant linear relationship between Ce and T1, and there was no statistical difference in regression coefficient and interception between group A and B (P>0.05). Conclusion: The degree of recovery from neuromuscular blockade could be judged by the target effective site concentration of rocuronium at the time of reversal from neuromuscular blockade in the elderly patients. PMID:26629159

Low-enriched uranium high-density target project. Compendium report

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

Vandegrift, George; Brown, M. Alex; Jerden, James L.

2016-09-01

At present, most 99Mo is produced in research, test, or isotope production reactors by irradiation of highly enriched uranium targets. To achieve the denser form of uranium needed for switching from high to low enriched uranium (LEU), targets in the form of a metal foil (~125-150 µm thick) are being developed. The LEU High Density Target Project successfully demonstrated several iterations of an LEU-fission-based Mo-99 technology that has the potential to provide the world’s supply of Mo-99, should major producers choose to utilize the technology. Over 50 annular high density targets have been successfully tested, and the assembly and disassemblymore » of targets have been improved and optimized. Two target front-end processes (acidic and electrochemical) have been scaled up and demonstrated to allow for the high-density target technology to mate up to the existing producer technology for target processing. In the event that a new target processing line is started, the chemical processing of the targets is greatly simplified. Extensive modeling and safety analysis has been conducted, and the target has been qualified to be inserted into the High Flux Isotope Reactor, which is considered above and beyond the requirements for the typical use of this target due to high fluence and irradiation duration.« less

A Targeting Microbubble for Ultrasound Molecular Imaging

PubMed Central

Yeh, James Shue-Min; Sennoga, Charles A.; McConnell, Ellen; Eckersley, Robert; Tang, Meng-Xing; Nourshargh, Sussan; Seddon, John M.; Haskard, Dorian O.; Nihoyannopoulos, Petros

2015-01-01

Rationale Microbubbles conjugated with targeting ligands are used as contrast agents for ultrasound molecular imaging. However, they often contain immunogenic (strept)avidin, which impedes application in humans. Although targeting bubbles not employing the biotin-(strept)avidin conjugation chemistry have been explored, only a few reached the stage of ultrasound imaging in vivo, none were reported/evaluated to show all three of the following properties desired for clinical applications: (i) low degree of non-specific bubble retention in more than one non-reticuloendothelial tissue; (ii) effective for real-time imaging; and (iii) effective for acoustic quantification of molecular targets to a high degree of quantification. Furthermore, disclosures of the compositions and methodologies enabling reproduction of the bubbles are often withheld. Objective To develop and evaluate a targeting microbubble based on maleimide-thiol conjugation chemistry for ultrasound molecular imaging. Methods and Results Microbubbles with a previously unreported generic (non-targeting components) composition were grafted with anti-E-selectin F(ab’)2 using maleimide-thiol conjugation, to produce E-selectin targeting microbubbles. The resulting targeting bubbles showed high specificity to E-selectin in vitro and in vivo. Non-specific bubble retention was minimal in at least three non-reticuloendothelial tissues with inflammation (mouse heart, kidneys, cremaster). The bubbles were effective for real-time ultrasound imaging of E-selectin expression in the inflamed mouse heart and kidneys, using a clinical ultrasound scanner. The acoustic signal intensity of the targeted bubbles retained in the heart correlated strongly with the level of E-selectin expression (|r|≥0.8), demonstrating a high degree of non-invasive molecular quantification. Conclusions Targeting microbubbles for ultrasound molecular imaging, based on maleimide-thiol conjugation chemistry and the generic composition described

High density laser-driven target

DOEpatents

Lindl, John D.

1981-01-01

A high density target for implosion by laser energy composed of a central quantity of fuel surrounded by a high-Z pusher shell with a low-Z ablator-pusher shell spaced therefrom forming a region filled with low-density material.

Apollo 8 Mission image,Target of Opportunity (T/O) 10

NASA Image and Video Library

1968-12-21

Apollo 8,Moon,Target of Opportunity (T/O) 10, Various targets. Latitude 18 degrees South,Longitude 163.50 degrees West. Camera Tilt Mode: High Oblique. Direction: South. Sun Angle 12 degrees. Original Film Magazine was labeled E. Camera Data: 70mm Hasselblad; F-Stop: F-5.6; Shutter Speed: 1/250 second. Film Type: Kodak SO-3400 Black and White,ASA 40. Other Photographic Coverage: Lunar Orbiter 1 (LO I) S-3. Flight Date: December 21-27,1968.

Liquid lithium target as a high intensity, high energy neutron source

DOEpatents

Parkin, Don M.; Dudey, Norman D.

1976-01-01

This invention provides a target jet for charged particles. In one embodiment the charged particles are high energy deuterons that bombard the target jet to produce high intensity, high energy neutrons. To this end, deuterons in a vacuum container bombard an endlessly circulating, free-falling, sheet-shaped, copiously flowing, liquid lithium jet that gushes by gravity from a rectangular cross-section vent on the inside of the container means to form a moving web in contact with the inside wall of the vacuum container. The neutrons are produced via break-up of the beam in the target by stripping, spallation and compound nuclear reactions in which the projectiles (deuterons) interact with the target (Li) to produce excited nuclei, which then "boil off" or evaporate a neutron.

High purity tungsten targets

NASA Technical Reports Server (NTRS)

1975-01-01

High purity tungsten, which is used for targets in X-ray tubes was considered for space processing. The demand for X-ray tubes was calculated using the growth rates for dental and medical X-ray machines. It is concluded that the cost benefits are uncertain.

Polarized targets in high energy physics

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

Cates, G.D. Jr.

1994-12-01

Various approaches are discussed for producing polarized nuclear targets for high energy physics experiments. As a unifying theme, examples are drawn from experiments to measure spin dependent structure functions of nucleons in deep inelastic scattering. This single physics goal has, over roughly two decades, been a driving force in advances in target technology. Actual or planned approaches have included solid targets polarized by dynamic nuclear polarization (DNP), several types of internal targets for use in storage rings, and gaseous {sup 3}He targets polarized by spin-exchange optical pumping. This last approach is the type of target adopted for SLAC E-142, anmore » experiment to measure the spin structure function of the neutron, and is described in detail.« less

Negative Emotion Weakens the Degree of Self-Reference Effect: Evidence from ERPs

PubMed Central

Fan, Wei; Zhong, Yiping; Li, Jin; Yang, Zilu; Zhan, Youlong; Cai, Ronghua; Fu, Xiaolan

2016-01-01

We investigated the influence of negative emotion on the degree of self-reference effect using event-related potentials (ERPs). We presented emotional pictures and self-referential stimuli (stimuli that accelerate and improve processing and improve memory of information related to an individual’s self-concept) in sequence. Participants judged the color of the target stimulus (self-referential stimuli). ERP results showed that the target stimuli elicited larger P2 amplitudes under neutral conditions than under negative emotional conditions. Under neutral conditions, N2 amplitudes for highly self-relevant names (target stimulus) were smaller than those for any other names. Under negative emotional conditions, highly and moderately self-referential stimuli activated smaller N2 amplitudes. P3 amplitudes activated by self-referential processing under negative emotional conditions were smaller than neutral conditions. In the left and central sites, highly self-relevant names activated larger P3 amplitudes than any other names. But in the central sites, moderately self-relevant names activated larger P3 amplitudes than non-self-relevant names. The findings indicate that negative emotional processing could weaken the degree of self-reference effect. PMID:27733836

De-Trending K2 Exoplanet Targets for High Spacecraft Motion

NASA Astrophysics Data System (ADS)

Saunders, Nicholas; Luger, Rodrigo; Barnes, Rory

2018-01-01

After the failure of two reaction wheels, the Kepler space telescope lost its fine pointing ability and entered a new phase of observation, K2. Targets observed by K2 have high motion relative to the detector and K2 light curves have higher noise than Kepler observations. Despite the increased noise, systematics removal pipelines such as K2SFF and EVEREST have enabled continued high-precision transiting planet science with the telescope, resulting in the detection of hundreds of new exoplanets. However, as the spacecraft begins to run out of fuel, sputtering will drive large and random variations in pointing that can prevent detection of exoplanets during the remaining 5 campaigns. In general, higher motion will spread the stellar point spread function (PSF) across more pixels during a campaign, which increases the number of degrees of freedom in the noise component and significantly reduces the de-trending power of traditional systematics removal methods. We use a model of the Kepler CCD combined with pixel-level information of a large number of stars across the detector to improve the performance of the EVEREST pipeline at high motion. We also consider the problem of increased crowding for static apertures in the high-motion regime and develop pixel response function (PRF)-fitting techniques to mitigate contamination and maximize the de-trending power. We assess the performance of our code by simulating sputtering events and assessing exoplanet detection efficiency with transit injection/recovery tests. We find that targets with roll amplitudes of up to 8 pixels, approximately 15 times K2 roll, can be de-trended within 2 to 3 factors of current K2 photometric precision for stars up to 14th magnitude. Achieved recovery precision allows detection of small planets around 11th and 12th magnitude stars. These methods can be applied to the light curves of K2 targets for existing and future campaigns to ensure that precision exoplanet science can still be performed

Neutron-rich nuclei produced at zero degrees in damped collisions induced by a beam of 18O on a 238U target

NASA Astrophysics Data System (ADS)

Stefan, I.; Fornal, B.; Leoni, S.; Azaiez, F.; Portail, C.; Thomas, J. C.; Karpov, A. V.; Ackermann, D.; Bednarczyk, P.; Blumenfeld, Y.; Calinescu, S.; Chbihi, A.; Ciemala, M.; Cieplicka-Oryńczak, N.; Crespi, F. C. L.; Franchoo, S.; Hammache, F.; Iskra, Ł. W.; Jacquot, B.; Janssens, R. V. F.; Kamalou, O.; Lauritsen, T.; Lewitowicz, M.; Olivier, L.; Lukyanov, S. M.; Maccormick, M.; Maj, A.; Marini, P.; Matea, I.; Naumenko, M. A.; de Oliveira Santos, F.; Petrone, C.; Penionzhkevich, Yu. E.; Rotaru, F.; Savajols, H.; Sorlin, O.; Stanoiu, M.; Szpak, B.; Tarasov, O. B.; Verney, D.

2018-04-01

Cross sections and corresponding momentum distributions have been measured for the first time at zero degrees for the exotic nuclei obtained from a beam of 18O at 8.5 MeV/A impinging on a 1 mg/cm2238U target. Sizable cross sections were found for the production of exotic species arising from the neutron transfer and proton removal from the projectile. Comparisons of experimental results with calculations based on deep-inelastic reaction models, taking into account the particle evaporation process, indicate that zero degree is a scattering angle at which the differential reaction cross section for production of exotic nuclei is at its maximum. This result is important in view of the new generation of zero degrees spectrometers under construction, such as the S3 separator at GANIL, for example.

High volume fabrication of laser targets using MEMS techniques

NASA Astrophysics Data System (ADS)

Spindloe, C.; Arthur, G.; Hall, F.; Tomlinson, S.; Potter, R.; Kar, S.; Green, J.; Higginbotham, A.; Booth, N.; Tolley, M. K.

2016-04-01

The latest techniques for the fabrication of high power laser targets, using processes developed for the manufacture of Micro-Electro-Mechanical System (MEMS) devices are discussed. These laser targets are designed to meet the needs of the increased shot numbers that are available in the latest design of laser facilities. Traditionally laser targets have been fabricated using conventional machining or coarse etching processes and have been produced in quantities of 10s to low 100s. Such targets can be used for high complexity experiments such as Inertial Fusion Energy (IFE) studies and can have many complex components that need assembling and characterisation with high precision. Using the techniques that are common to MEMS devices and integrating these with an existing target fabrication capability we are able to manufacture and deliver targets to these systems. It also enables us to manufacture novel targets that have not been possible using other techniques. In addition, developments in the positioning systems that are required to deliver these targets to the laser focus are also required and a system to deliver the target to a focus of an F2 beam at 0.1Hz is discussed.

Increasingly Global: Combining an International Business Degree with a Post-Degree Designation

ERIC Educational Resources Information Center

Smith, Rachel; Terry, Andy; Vibhakar, Ashvin

2006-01-01

In the increasingly complex and competitive global marketplace, many students seek to gain multiple skills and credentials that can aid them in their career goals. One such career strategy weds a general overarching comprehensive degree with a specific and targeted skill set. This paper provides a viable curriculum path for students who seek…

The Complex Case of Positioning the Foundation Degree: Making Sense of a Degree That Is Not a Degree

ERIC Educational Resources Information Center

Kadembo, Ernest

2008-01-01

The Foundation degree was launched in 2001 and has enjoyed growth but remains a controversial qualification. Foundation Degree Forward, the body charged by the UK government with providing a "national network or expertise to support the development and validation of high-quality Foundation degrees" is championing the marketing of the…

High affinity ligands from in vitro selection: Complex targets

PubMed Central

Morris, Kevin N.; Jensen, Kirk B.; Julin, Carol M.; Weil, Michael; Gold, Larry

1998-01-01

Human red blood cell membranes were used as a model system to determine if the systematic evolution of ligands by exponential enrichment (SELEX) methodology, an in vitro protocol for isolating high-affinity oligonucleotides that bind specifically to virtually any single protein, could be used with a complex mixture of potential targets. Ligands to multiple targets were generated simultaneously during the selection process, and the binding affinities of these ligands for their targets are comparable to those found in similar experiments against pure targets. A secondary selection scheme, deconvolution-SELEX, facilitates rapid isolation of the ligands to targets of special interest within the mixture. SELEX provides high-affinity compounds for multiple targets in a mixture and might allow a means for dissecting complex biological systems. PMID:9501188

High-frequency ultrasound-guided disruption of glycoprotein VI-targeted microbubbles targets atheroprogressison in mice.

PubMed

Metzger, Katja; Vogel, Sebastian; Chatterjee, Madhumita; Borst, Oliver; Seizer, Peter; Schönberger, Tanja; Geisler, Tobias; Lang, Florian; Langer, Harald; Rheinlaender, Johannes; Schäffer, Tilman E; Gawaz, Meinrad

2015-01-01

Targeted contrast-enhanced ultrasound (CEU) using microbubble agents is a promising non-invasive imaging technique to evaluate atherosclerotic lesions. In this study, we decipher the diagnostic and therapeutic potential of targeted-CEU with soluble glycoprotein (GP)-VI in vivo. Microbubbles were conjugated with the recombinant fusion protein GPVI-Fc (MBGPVI) that binds with high affinity to atherosclerotic lesions. MBGPVI or control microbubbles (MBC) were intravenously administered into ApoE(-/-) or wild type mice and binding of the microbubbles to the vessel wall was visualized by high-resolution CEU. CEU molecular imaging signals of MBGPVI were substantially enhanced in the aortic arch and in the truncus brachiocephalicus in ApoE(-/-) as compared to wild type mice. High-frequency ultrasound (HFU)-guided disruption of MBGPVI enhanced accumulation of GPVI in the atherosclerotic lesions, which may interfere with atheroprogression. Thus, we establish targeted-CEU with soluble GPVI as a novel non-invasive molecular imaging method for atherosclerosis. Further, HFU-guided disruption of GPVI-targeted microbubbles is an innovate therapeutic approach that potentially prevents progression of atherosclerotic disease. Copyright © 2014 Elsevier Ltd. All rights reserved.

The SPES High Power ISOL production target

NASA Astrophysics Data System (ADS)

Andrighetto, A.; Corradetti, S.; Ballan, M.; Borgna, F.; Manzolaro, M.; Scarpa, D.; Monetti, A.; Rossignoli, M.; Silingardi, R.; Mozzi, A.; Vivian, G.; Boratto, E.; De Ruvo, L.; Sattin, N.; Meneghetti, G.; Oboe, R.; Guerzoni, M.; Margotti, A.; Ferrari, M.; Zenoni, A.; Prete, G.

2016-11-01

SPES (Selective Production of Exotic Species) is a facility under construction at INFN-LNL (Istituto Nazionale di Fisica Nucleare - Laboratori Nazionali di Legnaro), aimed to produce intense neutron-rich radioactive ion beams (RIBs). These will be obtained using the ISOL (Isotope Separation On-Line) method, bombarding a uranium carbide target with a proton beam of 40MeV energy and currents up to 200μA. The target configuration was designed to obtain a high number of fissions, up to 1013 per second, low power deposition and fast release of the produced isotopes. The exotic isotopes generated in the target are ionized, mass separated and re-accelerated by the ALPI superconducting LINAC at energies of 10AMeV and higher, for masses in the region of A = 130 amu , with an expected rate on the secondary target up to 109 particles per second. In this work, recent results on the R&D activities regarding the SPES RIB production target-ion source system are reported.

Identification of tissue-specific targeting peptide

NASA Astrophysics Data System (ADS)

Jung, Eunkyoung; Lee, Nam Kyung; Kang, Sang-Kee; Choi, Seung-Hoon; Kim, Daejin; Park, Kisoo; Choi, Kihang; Choi, Yun-Jaie; Jung, Dong Hyun

2012-11-01

Using phage display technique, we identified tissue-targeting peptide sets that recognize specific tissues (bone-marrow dendritic cell, kidney, liver, lung, spleen and visceral adipose tissue). In order to rapidly evaluate tissue-specific targeting peptides, we performed machine learning studies for predicting the tissue-specific targeting activity of peptides on the basis of peptide sequence information using four machine learning models and isolated the groups of peptides capable of mediating selective targeting to specific tissues. As a representative liver-specific targeting sequence, the peptide "DKNLQLH" was selected by the sequence similarity analysis. This peptide has a high degree of homology with protein ligands which can interact with corresponding membrane counterparts. We anticipate that our models will be applicable to the prediction of tissue-specific targeting peptides which can recognize the endothelial markers of target tissues.

Development of high resolution target monitor.

DOT National Transportation Integrated Search

2008-01-01

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

Greenhouse-gas emission targets for limiting global warming to 2 degrees C.

PubMed

Meinshausen, Malte; Meinshausen, Nicolai; Hare, William; Raper, Sarah C B; Frieler, Katja; Knutti, Reto; Frame, David J; Allen, Myles R

2009-04-30

More than 100 countries have adopted a global warming limit of 2 degrees C or below (relative to pre-industrial levels) as a guiding principle for mitigation efforts to reduce climate change risks, impacts and damages. However, the greenhouse gas (GHG) emissions corresponding to a specified maximum warming are poorly known owing to uncertainties in the carbon cycle and the climate response. Here we provide a comprehensive probabilistic analysis aimed at quantifying GHG emission budgets for the 2000-50 period that would limit warming throughout the twenty-first century to below 2 degrees C, based on a combination of published distributions of climate system properties and observational constraints. We show that, for the chosen class of emission scenarios, both cumulative emissions up to 2050 and emission levels in 2050 are robust indicators of the probability that twenty-first century warming will not exceed 2 degrees C relative to pre-industrial temperatures. Limiting cumulative CO(2) emissions over 2000-50 to 1,000 Gt CO(2) yields a 25% probability of warming exceeding 2 degrees C-and a limit of 1,440 Gt CO(2) yields a 50% probability-given a representative estimate of the distribution of climate system properties. As known 2000-06 CO(2) emissions were approximately 234 Gt CO(2), less than half the proven economically recoverable oil, gas and coal reserves can still be emitted up to 2050 to achieve such a goal. Recent G8 Communiqués envisage halved global GHG emissions by 2050, for which we estimate a 12-45% probability of exceeding 2 degrees C-assuming 1990 as emission base year and a range of published climate sensitivity distributions. Emissions levels in 2020 are a less robust indicator, but for the scenarios considered, the probability of exceeding 2 degrees C rises to 53-87% if global GHG emissions are still more than 25% above 2000 levels in 2020.

Study on the influence factors of camouflage target polarization detection

NASA Astrophysics Data System (ADS)

Huang, Yanhua; Chen, Lei; Li, Xia; Wu, Wenyuan

2016-10-01

The degree of linear polarization (DOLP) expressions at any polarizer direction (PD) was deduced based on the Stokes vector and Mueller matrix. The outdoors experiments were carried out to demonstrate the expressions. This paper mainly explored the DOLP-image-Contrast (DOLPC) between the target image and the background image, and the PD and RGB waveband that be considered two important influence factors were studied for camouflage target polarization detection. It was found that the DOLPC of target and background was obviously higher than intensity image. When setting the reference direction that polarizer was perpendicular to the incident face, the DOLP image of interval angle 60 degree between PD and reference direction had relatively high DOLPC, the interval angle 45 degree was the second, and the interval angle 35 degree was the third. The outdoors polarization detection experiment of controlling waveband showed that the DOLPC results was significantly different to use 650nm, 550nm and 450nm waveband, and the polarization detection performance by using 650nm band was an optimization method.

High power neutron production targets

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

Wender, S.

1996-06-01

The author describes issues of concern in the design of targets and associated systems for high power neutron production facilities. The facilities include uses for neutron scattering, accelerator driven transmutation, accelerator production of tritium, short pulse spallation sources, and long pulse spallation sources. Each of these applications requires a source with different design needs and consequently different implementation in practise.

HIGH POWER BEAM DUMP AND TARGET / ACCELERATOR INTERFACE PROCEDURES

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

Blokland, Willem; Plum, Michael A; Peters, Charles C

Satisfying operational procedures and limits for the beam target interface is a critical concern for high power operation at spallation neutron sources. At the Oak Ridge Spallation Neutron Source (SNS) a number of protective measures are instituted to ensure that the beam position, beam size and peak intensity are within acceptable limits at the target and high power Ring Injection Dump (RID). The high power beam dump typically handles up to 50 100 kW of beam power and its setup is complicated by the fact that there are two separate beam components simultaneously directed to the dump. The beam onmore » target is typically in the 800-1000 kW average power level, delivered in sub- s 60 Hz pulses. Setup techniques using beam measurements to quantify the beam parameters at the target and dump will be described. However, not all the instrumentation used for the setup and initial qualification is available during high power operation. Additional techniques are used to monitor the beam during high power operation to ensure the setup conditions are maintained, and these are also described.« less

Professional Learning Communities and the Degree of Teamness in Riverside County High Schools

ERIC Educational Resources Information Center

Roberts, Benjamin A.

2013-01-01

Purpose. The purpose of this study was to determine if a significant difference in the degree of teamness in high school teams whose schools have strong evidence of the five dimensions of a Professional Learning Community, compared to high school teams in schools that do not have strong evidence of the five dimensions of a Professional Learning…

Mass Media Strategies Targeting High Sensation Seekers: What Works and Why

ERIC Educational Resources Information Center

Stephenson, Michael T.

2003-01-01

Objectives: To examine strategies for using the mass media effectively in drug prevention campaigns targeting high sensation seekers. Methods: Both experimental lab and field studies were used to develop a comprehensive audience segmentation strategy targeting high sensation seekers. Results: A 4-pronged targeting strategy employed in an…

Transition from High School to Associate Degree Nursing Education: A Qualitative Study

ERIC Educational Resources Information Center

Mitchell, Kathy Jessee

2012-01-01

Nursing is facing a critical shortage and retention of nursing students is of paramount importance. Much research has been completed related to retention in nursing education and student success, but there is very little in current literature related to issues associated with the transition from high school to associate degree nursing (ADN)…

High-power liquid-lithium jet target for neutron production

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

Halfon, S.; Feinberg, G.; Racah Institute of Physics, Hebrew University, Jerusalem 91904

2013-12-15

A compact liquid-lithium target (LiLiT) was built and tested with a high-power electron gun at the Soreq Nuclear Research Center. The lithium target, to be bombarded by the high-intensity proton beam of the Soreq Applied Research Accelerator Facility (SARAF), will constitute an intense source of neutrons produced by the {sup 7}Li(p,n){sup 7}Be reaction for nuclear astrophysics research and as a pilot setup for accelerator-based Boron Neutron Capture Therapy. The liquid-lithium jet target acts both as neutron-producing target and beam dump by removing the beam thermal power (>5 kW, >1 MW/cm{sup 3}) with fast transport. The target was designed based onmore » a thermal model, accompanied by a detailed calculation of the {sup 7}Li(p,n) neutron yield, energy distribution, and angular distribution. Liquid lithium is circulated through the target loop at ∼200 °C and generates a stable 1.5 mm-thick film flowing at a velocity up to 7 m/s onto a concave supporting wall. Electron beam irradiation demonstrated that the liquid-lithium target can dissipate electron power areal densities of >4 kW/cm{sup 2} and volume power density of ∼2 MW/cm{sup 3} at a lithium flow of ∼4 m/s while maintaining stable temperature and vacuum conditions. The LiLiT setup is presently in online commissioning stage for high-intensity proton beam irradiation (1.91–2.5 MeV, 1–2 mA) at SARAF.« less

Tech-Prep/Associate Degree Program Guide: Tech Prep Associate Degree Program, Business Administration Associate Degree Program, Office Administration Associate Degree Program, Allied Health Associate Degree Program.

ERIC Educational Resources Information Center

Marmaras, Judy; Neri, Pat

The Tech-Prep Associate Degree Program (TPAD) at the Community College of Rhode Island (CCRI) in Warwick, is a high school/community college partnership providing high school students with an alternative program of study focused on goal setting, basic academic skills development, and the skills needed to pursue a career in a technical, business or…

The drug target genes show higher evolutionary conservation than non-target genes.

PubMed

Lv, Wenhua; Xu, Yongdeng; Guo, Yiying; Yu, Ziqi; Feng, Guanglong; Liu, Panpan; Luan, Meiwei; Zhu, Hongjie; Liu, Guiyou; Zhang, Mingming; Lv, Hongchao; Duan, Lian; Shang, Zhenwei; Li, Jin; Jiang, Yongshuai; Zhang, Ruijie

2016-01-26

Although evidence indicates that drug target genes share some common evolutionary features, there have been few studies analyzing evolutionary features of drug targets from an overall level. Therefore, we conducted an analysis which aimed to investigate the evolutionary characteristics of drug target genes. We compared the evolutionary conservation between human drug target genes and non-target genes by combining both the evolutionary features and network topological properties in human protein-protein interaction network. The evolution rate, conservation score and the percentage of orthologous genes of 21 species were included in our study. Meanwhile, four topological features including the average shortest path length, betweenness centrality, clustering coefficient and degree were considered for comparison analysis. Then we got four results as following: compared with non-drug target genes, 1) drug target genes had lower evolutionary rates; 2) drug target genes had higher conservation scores; 3) drug target genes had higher percentages of orthologous genes and 4) drug target genes had a tighter network structure including higher degrees, betweenness centrality, clustering coefficients and lower average shortest path lengths. These results demonstrate that drug target genes are more evolutionarily conserved than non-drug target genes. We hope that our study will provide valuable information for other researchers who are interested in evolutionary conservation of drug targets.

High-efficiency-release targets for use at ISOL facilities: computational design

NASA Astrophysics Data System (ADS)

Liu, Y.; Alton, G. D.

1999-12-01

This report describes efforts made at the Oak Ridge National Laboratory to design high-efficiency-release targets that simultaneously incorporate the short diffusion lengths, high permeabilities, controllable temperatures, and heat-removal properties required for the generation of useful radioactive ion beam (RIB) intensities for nuclear physics and astrophysics research using the isotope separation on-line (ISOL) technique. Short diffusion lengths are achieved either by using thin fibrous target materials or by coating thin layers of selected target material onto low-density carbon fibers such as reticulated-vitreous-carbon fiber (RVCF) or carbon-bonded-carbon fiber (CBCF) to form highly permeable composite target matrices. Computational studies that simulate the generation and removal of primary beam deposited heat from target materials have been conducted to optimize the design of target/heat-sink systems for generating RIBs. The results derived from diffusion release-rate simulation studies for selected targets and thermal analyses of temperature distributions within a prototype target/heat-sink system subjected to primary ion beam irradiation are presented in this report.

Robustness of network of networks under targeted attack.

PubMed

Dong, Gaogao; Gao, Jianxi; Du, Ruijin; Tian, Lixin; Stanley, H Eugene; Havlin, Shlomo

2013-05-01

The robustness of a network of networks (NON) under random attack has been studied recently [Gao et al., Phys. Rev. Lett. 107, 195701 (2011)]. Understanding how robust a NON is to targeted attacks is a major challenge when designing resilient infrastructures. We address here the question how the robustness of a NON is affected by targeted attack on high- or low-degree nodes. We introduce a targeted attack probability function that is dependent upon node degree and study the robustness of two types of NON under targeted attack: (i) a tree of n fully interdependent Erdős-Rényi or scale-free networks and (ii) a starlike network of n partially interdependent Erdős-Rényi networks. For any tree of n fully interdependent Erdős-Rényi networks and scale-free networks under targeted attack, we find that the network becomes significantly more vulnerable when nodes of higher degree have higher probability to fail. When the probability that a node will fail is proportional to its degree, for a NON composed of Erdős-Rényi networks we find analytical solutions for the mutual giant component P(∞) as a function of p, where 1-p is the initial fraction of failed nodes in each network. We also find analytical solutions for the critical fraction p(c), which causes the fragmentation of the n interdependent networks, and for the minimum average degree k[over ¯](min) below which the NON will collapse even if only a single node fails. For a starlike NON of n partially interdependent Erdős-Rényi networks under targeted attack, we find the critical coupling strength q(c) for different n. When q>q(c), the attacked system undergoes an abrupt first order type transition. When q≤q(c), the system displays a smooth second order percolation transition. We also evaluate how the central network becomes more vulnerable as the number of networks with the same coupling strength q increases. The limit of q=0 represents no dependency, and the results are consistent with the classical

Parallel Reaction Monitoring: A Targeted Experiment Performed Using High Resolution and High Mass Accuracy Mass Spectrometry

PubMed Central

Rauniyar, Navin

2015-01-01

The parallel reaction monitoring (PRM) assay has emerged as an alternative method of targeted quantification. The PRM assay is performed in a high resolution and high mass accuracy mode on a mass spectrometer. This review presents the features that make PRM a highly specific and selective method for targeted quantification using quadrupole-Orbitrap hybrid instruments. In addition, this review discusses the label-based and label-free methods of quantification that can be performed with the targeted approach. PMID:26633379

ACCELERATOR TARGET POSITIONER AND CONTROL CIRCUIT THEREFOR

DOEpatents

Stone, K.F.; Force, R.J.; Olson, W.W.; Cagle, D.S.

1959-12-15

An apparatus is described for inserting and retracting a target material with respect to the internal beam of a charged particle accelerator and to circuitry for controlling the timing and motion of the target placement. Two drive coils are mounted on the shaft of a target holder arm and disposed within the accelerator magnetic field with one coil at right angles to the other. Control circuitry alternately connects each coil to a current source and to a varying shorting resistance whereby the coils interchangeably produce driving and braking forces which swing the target arm within a ninety degree arc. The target is thus moved into the beam and away from it at high speeds and is brought to rest after each movement without whiplash or vibration.

Topological robustness analysis of protein interaction networks reveals key targets for overcoming chemotherapy resistance in glioma

NASA Astrophysics Data System (ADS)

Azevedo, Hátylas; Moreira-Filho, Carlos Alberto

2015-11-01

Biological networks display high robustness against random failures but are vulnerable to targeted attacks on central nodes. Thus, network topology analysis represents a powerful tool for investigating network susceptibility against targeted node removal. Here, we built protein interaction networks associated with chemoresistance to temozolomide, an alkylating agent used in glioma therapy, and analyzed their modular structure and robustness against intentional attack. These networks showed functional modules related to DNA repair, immunity, apoptosis, cell stress, proliferation and migration. Subsequently, network vulnerability was assessed by means of centrality-based attacks based on the removal of node fractions in descending orders of degree, betweenness, or the product of degree and betweenness. This analysis revealed that removing nodes with high degree and high betweenness was more effective in altering networks’ robustness parameters, suggesting that their corresponding proteins may be particularly relevant to target temozolomide resistance. In silico data was used for validation and confirmed that central nodes are more relevant for altering proliferation rates in temozolomide-resistant glioma cell lines and for predicting survival in glioma patients. Altogether, these results demonstrate how the analysis of network vulnerability to topological attack facilitates target prioritization for overcoming cancer chemoresistance.

High strength nickel-base alloy with improved oxidation resistance up to 2200 degrees F

NASA Technical Reports Server (NTRS)

Freche, J. C.; Waters, W. J.

1968-01-01

Modifying the chemistry of the NASA TAZ-8 alloy and utilizing vacuum melting techniques provides a high strength, workable nickel base superalloy with improved oxidation resistance for use up to 2200 degrees F.

High degree of supervision improves adherence to inhaled corticosteroids in children with asthma

PubMed Central

Park, Geun Mi; Han, Hye Won; Kim, Hee Se; Kim, Jae Youn; Lee, Eun; Cho, Hyun-Ju; Yang, Song-I; Jung, Young-Ho; Hong, Soo-Jong; Kim, Hyung Young; Seo, Ju-Hee

2015-01-01

Purpose Adherence to treatment with inhaled corticosteroids (ICS) is a critical determinant of asthma control. The objective of this study was to assess factors that determine adherence to ICS therapy in children with asthma. Methods Fifty-eight children with asthma, aged 5 to 16 years, used ICS with or without a spacer for 3 months. Adherence rates as measured from questionnaires and canisters, asthma symptom scores, and inhalation technique scores were assessed every 30 days. The degree of supervision by caregivers was assessed at day 30. Results Adherence rates measured using canisters were lower at day 60 than at day 30 (P=0.044) and did not change thereafter (74.4%±17.4% at day 30, 66.5%±18.4% at day 60, and 67.4%±22.2% at day 90). Adherence rates at days 60 and 90 and during the total study period were significantly different when measured by using questionnaires versus canisters (P<0.001, P=0.022, and P=0.001, respectively). In the comparison of adherence rates repeatedly measured at days 30, 60, and 90 and adherence rates during the total study period among the 3 groups, adherence rates in the high-degree supervision group were significantly higher than those in the low-degree supervision group (82.0±16.0 vs. 66.1±14.5, 75.4±14.4 vs. 56.2±18.4, 75.0±18.3 vs. 55.0±19.7 [P=0.027]; 77.9±12.2 vs. 59.1±11.4 [P=0.021]) after adjustment for sex and age. Conclusion The level of caregiver supervision is an important factor affecting adherence to ICS therapy in children with asthma. Therefore, a high degree of supervision may be required to increase adherence to ICS therapy in children with asthma. PMID:26770222

High-Speed Incoming Infrared Target Detection by Fusion of Spatial and Temporal Detectors

PubMed Central

Kim, Sungho

2015-01-01

This paper presents a method for detecting high-speed incoming targets by the fusion of spatial and temporal detectors to achieve a high detection rate for an active protection system (APS). The incoming targets have different image velocities according to the target-camera geometry. Therefore, single-target detector-based approaches, such as a 1D temporal filter, 2D spatial filter and 3D matched filter, cannot provide a high detection rate with moderate false alarms. The target speed variation was analyzed according to the incoming angle and target velocity. The speed of the distant target at the firing time is almost stationary and increases slowly. The speed varying targets are detected stably by fusing the spatial and temporal filters. The stationary target detector is activated by an almost zero temporal contrast filter (TCF) and identifies targets using a spatial filter called the modified mean subtraction filter (M-MSF). A small motion (sub-pixel velocity) target detector is activated by a small TCF value and finds targets using the same spatial filter. A large motion (pixel-velocity) target detector works when the TCF value is high. The final target detection is terminated by fusing the three detectors based on the threat priority. The experimental results of the various target sequences show that the proposed fusion-based target detector produces the highest detection rate with an acceptable false alarm rate. PMID:25815448

Pathways to a Four-Year Degree: Determinants of Degree Completion among Socioeconomically Disadvantaged Students.

ERIC Educational Resources Information Center

Cabrera, Alberto F.; Burkum, Kurt R.; La Nasa, Steven M.

The High School Sophomore Cohort of 1980 followed nine different pathways to a 4-year college degree. These paths were formed by a combination of different levels of academic preparation secured in high school and the first type of postsecondary institution attended. The pathway most likely to lead to a 4-year degree is one defined by acquiring…

A high content, high throughput cellular thermal stability assay for measuring drug-target engagement in living cells.

PubMed

Massey, Andrew J

2018-01-01

Determining and understanding drug target engagement is critical for drug discovery. This can be challenging within living cells as selective readouts are often unavailable. Here we describe a novel method for measuring target engagement in living cells based on the principle of altered protein thermal stabilization / destabilization in response to ligand binding. This assay (HCIF-CETSA) utilizes high content, high throughput single cell immunofluorescent detection to determine target protein levels following heating of adherent cells in a 96 well plate format. We have used target engagement of Chk1 by potent small molecule inhibitors to validate the assay. Target engagement measured by this method was subsequently compared to target engagement measured by two alternative methods (autophosphorylation and CETSA). The HCIF-CETSA method appeared robust and a good correlation in target engagement measured by this method and CETSA for the selective Chk1 inhibitor V158411 was observed. However, these EC50 values were 23- and 12-fold greater than the autophosphorylation IC50. The described method is therefore a valuable advance in the CETSA method allowing the high throughput determination of target engagement in adherent cells.

Why do different people choose different university degrees? Motivation and the choice of degree

PubMed Central

Skatova, Anya; Ferguson, Eamonn

2014-01-01

Different people choose undergraduate degrees to study at university for different reasons. To date, there have been limited attempts to identify individual differences in motivation that drive undergraduate degree choice. We identified that people choose university degrees for four reasons: career concerns (Career), intrinsic interest in the subject (Interest), an opportunity to help others (Helping) and because they are looking for an easy option to get into higher education (Loafing). We investigated whether these motivations apply to the choice of undergraduate degree in two samples: (1) undergraduate (N = 989) and (2) prospective (N = 896) students. We developed the Motivations Influencing Course Choice (MICC) questionnaire to measure these motivations. Scales of Helping, Career, Loafing, and Interest showed good psychometric properties, showed validity with respect to general life goals and personality traits, and predicted actual and prospective degree choices. We demonstrated that medical degrees were chosen due to a mixture of Helping and Career, while engineering degrees were associated with Career and low Interest in the degree. The choice of arts and humanities degrees was driven by Interest and low concern about future career, accompanied with high Loafing. We also demonstrated gender differences: females were high in Helping (both samples) and Interest (only in the undergraduate sample) motivation, while males scored higher in Career (only in the undergraduate sample) and Loafing (both samples). The findings can feed into both theoretical accounts of proximal motivation as well as provide help to improve degree programmes at universities and support better career advice. PMID:25431561

Computational design of high efficiency release targets for use at ISOL facilities

NASA Astrophysics Data System (ADS)

Liu, Y.; Alton, G. D.; Middleton, J. W.

1999-06-01

This report describes efforts made at the Oak Ridge National Laboratory to design high-efficiency-release targets that simultaneously incorporate the short diffusion lengths, high permeabilities, controllable temperatures, and heat removal properties required for the generation of useful radioactive ion beam (RIB) intensities for nuclear physics and astrophysics research using the isotope separation on-line (ISOL) technique. Short diffusion lengths are achieved either by using thin fibrous target materials or by coating thin layers of selected target material onto low-density carbon fibers such as reticulated vitreous carbon fiber (RVCF) or carbon-bonded-carbon-fiber (CBCF) to form highly permeable composite target matrices. Computational studies which simulate the generation and removal of primary beam deposited heat from target materials have been conducted to optimize the design of target/heat-sink systems for generating RIBs. The results derived from diffusion release-rate simulation studies for selected targets and thermal analyses of temperature distributions within a prototype target/heat-sink system subjected to primary ion beam irradiation will be presented in this report.

Target geometry and rigidity determines laser-induced cavitation bubble transport and nanoparticle productivity - a high-speed videography study.

PubMed

Kohsakowski, Sebastian; Gökce, Bilal; Tanabe, Rie; Wagener, Philipp; Plech, Anton; Ito, Yoshiro; Barcikowski, Stephan

2016-06-28

Laser-induced cavitation has mostly been studied in bulk liquid or at a two-dimensional wall, although target shapes for the particle synthesis may strongly affect bubble dynamics and interfere with particle productivity. We investigated the dynamics of the cavitation bubble induced by pulsed-laser ablation in liquid for different target geometries with high-speed laser microsecond videography and focus on the collapse behaviour. This method enables us observations in a high time resolution (intervals of 1 μs) and single-pulse experiments. Further, we analyzed the nanoparticle productivity, the sizes of the synthesized nanoparticles and the evolution of the bubble volume for each different target shape and geometry. For the ablation of metal (Ag, Cu, Ni) wire tips a springboard-like behaviour after the first collapse is observed which can be correlated with vertical projectile motion. Its turbulent friction in the liquid causes a very efficient transport and movement of the bubble and ablated material into the bulk liquid and prevents particle redeposition. This effect is influenced by the degree of freedom of the wire as well as the material properties and dimensions, especially the Young's modulus. The most efficient and largest bubble movement away from the wire was observed for a thin (500 μm) silver wire with velocities up to 19.8 m s(-1) and for materials with a small Young's modulus and flexural rigidity. We suggest that these observations may contribute to upscaling strategies and increase of particle yield towards large synthesis of colloids based on targets that may continuously be fed.

Microkeratome-Assisted Anterior Lamellar Keratoplasty for the Correction of High-Degree Postkeratoplasty Astigmatism.

PubMed

Gutfreund, Shay; Leon, Pia; Busin, Massimo

2017-07-01

To describe the surgical technique and report the outcomes of patients treated with microkeratome-assisted anterior lamellar keratoplasty (MALK) for the correction of high-degree postkeratoplasty astigmatism. Four eyes of 2 patients with extremely high (>10 D) and irregular [surface asymmetry index >1.0 D] post-penetrating keratoplasty astigmatism occurring after complete suture removal underwent MALK and were followed for at least 3 years after the procedure. In all cases, 250-µm lamellar keratectomy was performed, followed by 2 full-thickness incisions through the penetrating keratoplasty scar and the placement of an appropriately sized donor graft, which was secured with a double-running 10-0 nylon suture. All sutures were removed in all eyes within 1 year from surgery. Corrected distance visual acuity, refraction, corneal topography, and endothelial cell density were noted at each examination. At the last follow-up examination (3 years or longer after MALK), corrected distance visual acuity had improved to 20/20, refractive astigmatism had decreased to an average of 2.1 D (in all cases within 4.5 D), and the average surface asymmetry index had reduced from 2.27 to 0.56. MALK is an effective and safe technique for the correction of high-degree postkeratoplasty astigmatism.

High Costs, Uncertain Benefits: What Do Americans without a College Degree Think about Postsecondary Education?

ERIC Educational Resources Information Center

Kelly, Andrew P.

2015-01-01

The path to economic mobility increasingly runs through postsecondary education. Although the combination of rising tuition prices and a difficult labor market have raised questions about the value of education after high school, degree and certificate holders are still better off than those with just a high school diploma. As a group, young…

A high density field reversed configuration (FRC) target for magnetized target fusion: First internal profile measurements of a high density FRC

NASA Astrophysics Data System (ADS)

Intrator, T.; Zhang, S. Y.; Degnan, J. H.; Furno, I.; Grabowski, C.; Hsu, S. C.; Ruden, E. L.; Sanchez, P. G.; Taccetti, J. M.; Tuszewski, M.; Waganaar, W. J.; Wurden, G. A.

2004-05-01

Magnetized target fusion (MTF) is a potentially low cost path to fusion, intermediate in plasma regime between magnetic and inertial fusion energy. It requires compression of a magnetized target plasma and consequent heating to fusion relevant conditions inside a converging flux conserver. To demonstrate the physics basis for MTF, a field reversed configuration (FRC) target plasma has been chosen that will ultimately be compressed within an imploding metal liner. The required FRC will need large density, and this regime is being explored by the FRX-L (FRC-Liner) experiment. All theta pinch formed FRCs have some shock heating during formation, but FRX-L depends further on large ohmic heating from magnetic flux annihilation to heat the high density (2-5×1022m-3), plasma to a temperature of Te+Ti≈500 eV. At the field null, anomalous resistivity is typically invoked to characterize the resistive like flux dissipation process. The first resistivity estimate for a high density collisional FRC is shown here. The flux dissipation process is both a key issue for MTF and an important underlying physics question.

Microstructured snow targets for high energy quasi-monoenergetic proton acceleration

NASA Astrophysics Data System (ADS)

Schleifer, E.; Nahum, E.; Eisenmann, S.; Botton, M.; Baspaly, A.; Pomerantz, I.; Abricht, F.; Branzel, J.; Priebe, G.; Steinke, S.; Andreev, A.; Schnuerer, M.; Sandner, W.; Gordon, D.; Sprangle, P.; Ledingham, K. W. D.; Zigler, A.

2013-05-01

Compact size sources of high energy protons (50-200MeV) are expected to be key technology in a wide range of scientific applications 1-8. One promising approach is the Target Normal Sheath Acceleration (TNSA) scheme 9,10, holding record level of 67MeV protons generated by a peta-Watt laser 11. In general, laser intensity exceeding 1018 W/cm2 is required to produce MeV level protons. Another approach is the Break-Out Afterburner (BOA) scheme which is a more efficient acceleration scheme but requires an extremely clean pulse with contrast ratio of above 10-10. Increasing the energy of the accelerated protons using modest energy laser sources is a very attractive task nowadays. Recently, nano-scale targets were used to accelerate ions 12,13 but no significant enhancement of the accelerated proton energy was measured. Here we report on the generation of up to 20MeV by a modest (5TW) laser system interacting with a microstructured snow target deposited on a Sapphire substrate. This scheme relax also the requirement of high contrast ratio between the pulse and the pre-pulse, where the latter produces the highly structured plasma essential for the interaction process. The plasma near the tip of the snow target is subject to locally enhanced laser intensity with high spatial gradients, and enhanced charge separation is obtained. Electrostatic fields of extremely high intensities are produced, and protons are accelerated to MeV-level energies. PIC simulations of this targets reproduce the experimentally measured energy scaling and predict the generation of 150 MeV protons from laser power of 100TW laser system18.

Target R and D for high power proton beam applications

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

Fabich, A.

High power targets are one of the major issues in an accelerator complex for future HEP physic studies. The paper will review status of studies worldwide. It will focus on the status of the MERIT mercury-jet target experiment at CERN.

Targeting high-risk employees may reduce cardiovascular racial disparities.

PubMed

Burke, James F; Vijan, Sandeep; Chekan, Lynette A; Makowiec, Ted M; Thomas, Laurita; Morgenstern, Lewis B

2014-09-01

A possible remedy for health disparities is for employers to promote cardiovascular health among minority employees. We sought to quantify the financial return to employers of interventions to improve minority health, and to determine whether a race- or risk-targeted strategy was better. Retrospective claims-based cohort analysis. Unconditional per-person costs attributable to stroke and myocardial infarction (MI) were estimated for University of Michigan employees from 2006 to 2009 using a 2-part model. The model was then used to predict the costs of cardiovascular disease to the University for 2 subgroups of employees-minorities and high-risk patients-and to calculate cost-savings thresholds: the point at which the costs of hypothetical interventions (eg, workplace fitness programs) would equal the cost savings from stroke/ MI prevention. Of the 38,314 enrollees, 10% were African American. Estimated unconditional payments for stroke/MI were almost the same in African Americans ($128 per employee per year; 95% CI, $79-$177) and whites ($128 per employee per year; 95% CI, $101- $156), including higher event rates and lower payments per event in African Americans. Targeting the highest risk decile with interventions to reduce stroke/MI would result in a substantially higher cost-savings threshold ($81) compared with targeting African Americans ($13). An unanticipated consequence of risk-based targeting is that African Americans would substantially benefit: an intervention targeted at the top risk decile would prevent 75% of the events in African Americans, just as would an intervention that exclusively targeted African Americans. Targeting all high-risk employees for cardiovascular risk reduction may be a win-win-win situation for employers: improving health, decreasing costs, and reducing disparities.

An Event to Encourage High School Students to Pursue College Degrees in Physics and Math

NASA Astrophysics Data System (ADS)

Bukiet, Bruce; Thomas, Gordon

2003-04-01

We discuss a Math and Physics Day for high school students and teachers, with hands-on activities and seminars involving mathematics and physics. Participants also learn about careers for those who go on to major in physics and mathematics in college. The New York State Section of the APS has provided generous support for this workshop through its Outreach grant program. Approximately a dozen high schools and 100 students attend each year. The program, which runs from 9:15 AM until 2:15 PM, includes an introduction to undergraduate degree programs in Mathematics, Statistics, Optics, Actuarial Science and Applied Physics, a group physics experiment/contest, brief talks over lunch by speakers from industry who have degrees in Math or Physics, and an afternoon seminar. Teachers earn Professional Development credit.

Studies of uranium carbide targets of a high density

NASA Astrophysics Data System (ADS)

Panteleev, V. N.; Alyakrinskiy, O.; Barbui, M.; Barzakh, A. E.; Dubois, M.; Eleon, C.; Essabaa, S.; Fedorov, D. V.; Gaubert, G.; Ionan, A. M.; Ivanov, V. S.; Jardin, P.; Lau, C.; Leroy, R.; Lhersonneau, G.; Mezilev, K. A.; Mhamed, C.; Molkanov, P. L.; Moroz, F. V.; Orlov, S. Yu.; Saint Laurent, M. G.; Stroe, L.; Tecchio, L. B.; Tonezzer, M.; Villari, A. C. C.; Volkov, Yu. M.

2008-10-01

Production of Cs and Fr isotopes from uranium carbide targets of a high density has been investigated at IRIS (Investigation Radioactive Isotopes at Synchrocyclotron), Gatchina. The UC target material with a density of 12 g/cm3 was prepared in a form of pellets. Two targets were tested on-line under the same temperature conditions: (a) a reference small target with a thickness of 4.5 g/cm2; (b) a heavier (so called intermediate) target with a thickness of 91 g/cm2. Yields and release efficiencies of nuclides with half-lives from some minutes to some milliseconds produced by 1 GeV protons in these targets are presented. It is remarkable that yields, even those of very short-lived isotopes such as 214Fr (T1/2 = 5 ms) and 219Fr (T1/2 = 20 ms), increase proportionally to the target thickness. A one month off-line heating test of the 91 g/cm2 target at a temperature of 2000 °C has been carried out successfully. The yields and release efficiencies of Cs and Fr measured on-line before and after the heating test coincided within the limits of measurement errors, thereby demonstrating the conservation of the target unit parameters. Based on these very promising results, a heavier target with a mass about 0.7 kg is prepared presently at IRIS.

Compound Structure-Independent Activity Prediction in High-Dimensional Target Space.

PubMed

Balfer, Jenny; Hu, Ye; Bajorath, Jürgen

2014-08-01

Profiling of compound libraries against arrays of targets has become an important approach in pharmaceutical research. The prediction of multi-target compound activities also represents an attractive task for machine learning with potential for drug discovery applications. Herein, we have explored activity prediction in high-dimensional target space. Different types of models were derived to predict multi-target activities. The models included naïve Bayesian (NB) and support vector machine (SVM) classifiers based upon compound structure information and NB models derived on the basis of activity profiles, without considering compound structure. Because the latter approach can be applied to incomplete training data and principally depends on the feature independence assumption, SVM modeling was not applicable in this case. Furthermore, iterative hybrid NB models making use of both activity profiles and compound structure information were built. In high-dimensional target space, NB models utilizing activity profile data were found to yield more accurate activity predictions than structure-based NB and SVM models or hybrid models. An in-depth analysis of activity profile-based models revealed the presence of correlation effects across different targets and rationalized prediction accuracy. Taken together, the results indicate that activity profile information can be effectively used to predict the activity of test compounds against novel targets. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Impact of High-Z Coatings on the Ablation Pressure of Laser Driven Targets.

NASA Astrophysics Data System (ADS)

Mostovych, Andrew; Oh, Jaechul; Schmitt, Andrew; Weaver, James

2007-11-01

Recent hydrodynamic experiments [1] with planar high-Z coated targets at the Naval Research Laboratory and spherical implosion experiments with high-Z coated shell targets [2] at the Omega facility all show significant improvement in target stability as a result of the high-Z coatings. For better understanding of the hydrodynamic processes it is important to know the changes in ablation pressure as a result of the high-Z layers. Using the Nike Laser, we have conducted new experiments to measure the change in shock speed of planar CH targets that are irradiated with and without the presence of a 200 Ang. gold high-Z coating. The evolution of shock propagation inside the targets is diagnosed with VISAR probing while average shock velocities are also measured by shock breakout detection from the stepped rear surface of the targets. We find that the high-Z layers produce a time dependent ablation pressure which is detected via the observation of non-steady shocks in the targets. Experimental results and comparisons to hydrodynamic simulations will be presented. Work supported by U. S. Department of Energy. [1] S.P. Obenschain et al., Phys. Plasmas 9, 2234 (2002). [2] A.N. Mostovych et al., APS Abstracts DPPFO3002M, (2005).

Target modelling for SAR image simulation

NASA Astrophysics Data System (ADS)

Willis, Chris J.

2014-10-01

This paper examines target models that might be used in simulations of Synthetic Aperture Radar imagery. We examine the basis for scattering phenomena in SAR, and briefly review the Swerling target model set, before considering extensions to this set discussed in the literature. Methods for simulating and extracting parameters for the extended Swerling models are presented. It is shown that in many cases the more elaborate extended Swerling models can be represented, to a high degree of fidelity, by simpler members of the model set. Further, it is shown that it is quite unlikely that these extended models would be selected when fitting models to typical data samples.

Strong electromagnetic pulses generated in high-intensity short-pulse laser interactions with thin foil targets

NASA Astrophysics Data System (ADS)

Rączka, P.; Dubois, J.-L.; Hulin, S.; Tikhonchuk, V.; Rosiński, M.; Zaraś-Szydłowska, A.; Badziak, J.

2017-12-01

Measurements are reported of the target neutralization current, the target charge, and the tangential component of the magnetic field generated as a result of laser-target interaction by pulses with the energy in the range of 45 mJ to 92 mJ on target and the pulse duration from 39 fs to 1000 fs. The experiment was performed at the Eclipse facility in CELIA, Bordeaux. The aim of the experiment was to extend investigations performed for the thick (mm scale) targets to the case of thin (micrometer thickness) targets in a way that would allow for a straightforward comparison of the results. We found that thin foil targets tend to generate 20 to 50 percent higher neutralization current and the target charge than the thick targets. The measurement of the tangential component of the magnetic field had shown that the initial spike is dominated by the 1 ns pulse consistent with the 1 ns pulse of the neutralization current, but there are some differences between targets of different type on sub-ns scale, which is an effect going beyond a simple picture of the target acting as an antenna. The sub-ns structure appears to be reproducible to surprising degree. We found that there is in general a linear correlation between the maximum value of the magnetic field and the maximum neutralization current, which supports the target-antenna picture, except for pulses hundreds of fs long.

High-current fast electron beam propagation in a dielectric target.

PubMed

Klimo, Ondrej; Tikhonchuk, V T; Debayle, A

2007-01-01

Recent experiments demonstrate an efficient transformation of high intensity laser pulse into a relativistic electron beam with a very high current density exceeding 10(12) A cm(-2). The propagation of such a beam inside the target is possible if its current is neutralized. This phenomenon is not well understood, especially in dielectric targets. In this paper, we study the propagation of high current density electron beam in a plastic target using a particle-in-cell simulation code. The code includes both ionization of the plastic and collisions of newborn electrons. The numerical results are compared with a relatively simple analytical model and a reasonable agreement is found. The temporal evolution of the beam velocity distribution, the spatial density profile, and the propagation velocity of the ionization front are analyzed and their dependencies on the beam density and energy are discussed. The beam energy losses are mainly due to the target ionization induced by the self-generated electric field and the return current. For the highest beam density, a two-stream instability is observed to develop in the plasma behind the ionization front and it contributes to the beam energy losses.

GLRS-R 2-colour retroreflector target design and predicted performance

NASA Technical Reports Server (NTRS)

Lund, Glenn

1993-01-01

This paper reports on the retroreflector ground-target design for the GLRS-R spaceborne dual-wavelength laser ranging system. The described passive design flows down from the requirements of high station autonomy, high global FOV (up to 60 degrees zenith angle), little or no multiple pulse returns, and adequate optical cross section for most ranging geometries. The proposed solution makes use of 5 hollow cube-corner retroreflectors of which one points to the zenith and the remaining four are inclined from the vertical at uniform azimuthal spacings. The need for fairly large (is approximately 10 cm) retroreflectors is expected (within turbulence limitations) to generate quite narrow diffraction lobes, thus placing non-trivial requirements on the vectorial accuracy of velocity aberration corrections. A good compromise solution is found by appropriately spoiling just one of the retroreflector dihedral angles from 90 degrees, thus generating two symmetrically oriented diffraction lobes in the return beam. The required spoil angles are found to have little dependence on ground target latitude. Various link budget analyses are presented, showing the influence of such factors as point-ahead optimization, turbulence, ranging angle, atmospheric visibility and ground target thermal deformations.

GLRS-R 2-colour retroreflector target design and predicted performance

NASA Astrophysics Data System (ADS)

Lund, Glenn

1993-06-01

This paper reports on the retroreflector ground-target design for the GLRS-R spaceborne dual-wavelength laser ranging system. The described passive design flows down from the requirements of high station autonomy, high global FOV (up to 60 degrees zenith angle), little or no multiple pulse returns, and adequate optical cross section for most ranging geometries. The proposed solution makes use of 5 hollow cube-corner retroreflectors of which one points to the zenith and the remaining four are inclined from the vertical at uniform azimuthal spacings. The need for fairly large (is approximately 10 cm) retroreflectors is expected (within turbulence limitations) to generate quite narrow diffraction lobes, thus placing non-trivial requirements on the vectorial accuracy of velocity aberration corrections. A good compromise solution is found by appropriately spoiling just one of the retroreflector dihedral angles from 90 degrees, thus generating two symmetrically oriented diffraction lobes in the return beam. The required spoil angles are found to have little dependence on ground target latitude. Various link budget analyses are presented, showing the influence of such factors as point-ahead optimization, turbulence, ranging angle, atmospheric visibility and ground target thermal deformations.

Representing high throughput expression profiles via perturbation barcodes reveals compound targets.

PubMed

Filzen, Tracey M; Kutchukian, Peter S; Hermes, Jeffrey D; Li, Jing; Tudor, Matthew

2017-02-01

High throughput mRNA expression profiling can be used to characterize the response of cell culture models to perturbations such as pharmacologic modulators and genetic perturbations. As profiling campaigns expand in scope, it is important to homogenize, summarize, and analyze the resulting data in a manner that captures significant biological signals in spite of various noise sources such as batch effects and stochastic variation. We used the L1000 platform for large-scale profiling of 978 representative genes across thousands of compound treatments. Here, a method is described that uses deep learning techniques to convert the expression changes of the landmark genes into a perturbation barcode that reveals important features of the underlying data, performing better than the raw data in revealing important biological insights. The barcode captures compound structure and target information, and predicts a compound's high throughput screening promiscuity, to a higher degree than the original data measurements, indicating that the approach uncovers underlying factors of the expression data that are otherwise entangled or masked by noise. Furthermore, we demonstrate that visualizations derived from the perturbation barcode can be used to more sensitively assign functions to unknown compounds through a guilt-by-association approach, which we use to predict and experimentally validate the activity of compounds on the MAPK pathway. The demonstrated application of deep metric learning to large-scale chemical genetics projects highlights the utility of this and related approaches to the extraction of insights and testable hypotheses from big, sometimes noisy data.

Resilience of antagonistic networks with regard to the effects of initial failures and degree-degree correlations

NASA Astrophysics Data System (ADS)

Watanabe, Shunsuke; Kabashima, Yoshiyuki

2016-09-01

In this study we investigate the resilience of duplex networked layers α and β coupled with antagonistic interlinks, each layer of which inhibits its counterpart at the microscopic level, changing the following factors: whether the influence of the initial failures in α remains [quenched (case Q )] or not [free (case F )]; the effect of intralayer degree-degree correlations in each layer and interlayer degree-degree correlations; and the type of the initial failures, such as random failures or targeted attacks (TAs). We illustrate that the percolation processes repeat in both cases Q and F , although only in case F are nodes that initially failed reactivated. To analytically evaluate the resilience of each layer, we develop a methodology based on the cavity method for deriving the size of a giant component (GC). Strong hysteresis, which is ignored in the standard cavity analysis, is observed in the repetition of the percolation processes particularly in case F . To handle this, we heuristically modify interlayer messages for macroscopic analysis, the utility of which is verified by numerical experiments. The percolation transition in each layer is continuous in both cases Q and F . We also analyze the influences of degree-degree correlations on the robustness of layer α , in particular for the case of TAs. The analysis indicates that the critical fraction of initial failures that makes the GC size in layer α vanish depends only on its intralayer degree-degree correlations. Although our model is defined in a somewhat abstract manner, it may have relevance to ecological systems that are composed of endangered species (layer α ) and invaders (layer β ), the former of which are damaged by the latter whereas the latter are exterminated in the areas where the former are active.

High degree of genetic differentiation in marine three-spined sticklebacks (Gasterosteus aculeatus).

PubMed

Defaveri, Jacquelin; Shikano, Takahito; Shimada, Yukinori; Merilä, Juha

2013-09-01

Populations of widespread marine organisms are typically characterized by a low degree of genetic differentiation in neutral genetic markers, but much less is known about differentiation in genes whose functional roles are associated with specific selection regimes. To uncover possible adaptive population divergence and heterogeneous genomic differentiation in marine three-spined sticklebacks (Gasterosteus aculeatus), we used a candidate gene-based genome-scan approach to analyse variability in 138 microsatellite loci located within/close to (<6 kb) functionally important genes in samples collected from ten geographic locations. The degree of genetic differentiation in markers classified as neutral or under balancing selection-as determined with several outlier detection methods-was low (F(ST) = 0.033 or 0.011, respectively), whereas average FST for directionally selected markers was significantly higher (F(ST) = 0.097). Clustering analyses provided support for genomic and geographic heterogeneity in selection: six genetic clusters were identified based on allele frequency differences in the directionally selected loci, whereas four were identified with the neutral loci. Allelic variation in several loci exhibited significant associations with environmental variables, supporting the conjecture that temperature and salinity, but not optic conditions, are important drivers of adaptive divergence among populations. In general, these results suggest that in spite of the high degree of physical connectivity and gene flow as inferred from neutral marker genes, marine stickleback populations are strongly genetically structured in loci associated with functionally relevant genes. © 2013 John Wiley & Sons Ltd.

Bar coded retroreflective target

DOEpatents

Vann, Charles S.

2000-01-01

This small, inexpensive, non-contact laser sensor can detect the location of a retroreflective target in a relatively large volume and up to six degrees of position. The tracker's laser beam is formed into a plane of light which is swept across the space of interest. When the beam illuminates the retroreflector, some of the light returns to the tracker. The intensity, angle, and time of the return beam is measured to calculate the three dimensional location of the target. With three retroreflectors on the target, the locations of three points on the target are measured, enabling the calculation of all six degrees of target position. Until now, devices for three-dimensional tracking of objects in a large volume have been heavy, large, and very expensive. Because of the simplicity and unique characteristics of this tracker, it is capable of three-dimensional tracking of one to several objects in a large volume, yet it is compact, light-weight, and relatively inexpensive. Alternatively, a tracker produces a diverging laser beam which is directed towards a fixed position, and senses when a retroreflective target enters the fixed field of view. An optically bar coded target can be read by the tracker to provide information about the target. The target can be formed of a ball lens with a bar code on one end. As the target moves through the field, the ball lens causes the laser beam to scan across the bar code.

Transformation between surface spherical harmonic expansion of arbitrary high degree and order and double Fourier series on sphere

NASA Astrophysics Data System (ADS)

Fukushima, Toshio

2018-02-01

In order to accelerate the spherical harmonic synthesis and/or analysis of arbitrary function on the unit sphere, we developed a pair of procedures to transform between a truncated spherical harmonic expansion and the corresponding two-dimensional Fourier series. First, we obtained an analytic expression of the sine/cosine series coefficient of the 4 π fully normalized associated Legendre function in terms of the rectangle values of the Wigner d function. Then, we elaborated the existing method to transform the coefficients of the surface spherical harmonic expansion to those of the double Fourier series so as to be capable with arbitrary high degree and order. Next, we created a new method to transform inversely a given double Fourier series to the corresponding surface spherical harmonic expansion. The key of the new method is a couple of new recurrence formulas to compute the inverse transformation coefficients: a decreasing-order, fixed-degree, and fixed-wavenumber three-term formula for general terms, and an increasing-degree-and-order and fixed-wavenumber two-term formula for diagonal terms. Meanwhile, the two seed values are analytically prepared. Both of the forward and inverse transformation procedures are confirmed to be sufficiently accurate and applicable to an extremely high degree/order/wavenumber as 2^{30} {≈ } 10^9. The developed procedures will be useful not only in the synthesis and analysis of the spherical harmonic expansion of arbitrary high degree and order, but also in the evaluation of the derivatives and integrals of the spherical harmonic expansion.

Dielectric properties of ferroelectric betaine phosphite crystals with a high degree of deuteration

NASA Astrophysics Data System (ADS)

Balashova, E. V.; Krichevtsov, B. B.; Yurko, E. I.; Svinarev, F. B.; Pankova, G. A.

2015-12-01

The dielectric properties of deuterated betaine phosphite crystals with a high degree of deuteration in the region of the antiferrodistorsive (at T = T c1) and ferroelectric (at T = T c2) phase transitions have been investigated. The temperature behavior of the dielectric permittivity of betaine phosphite and deuterated betaine phosphite has been described within the framework of the Landau thermodynamic model taking into account the biquadratic coupling between the polar order parameter of the ferroelectric transition and the nonpolar order parameter of the antiferrodistorsive phase transition. It has been shown that an increase in the degree of deuteration leads to a decrease in the coupling between the order parameters. An increase in the temperature of the ferroelectric phase transition due to the deuteration of betaine phosphite is caused by an increase in the dielectric permittivity in the symmetric phase above the temperature of the antiferrodistorsive phase transition.

High Degree and Order Gravity Fields of the Moon Derived from GRAIL Data

NASA Technical Reports Server (NTRS)

Lemoine, F. G.; Goossens, S. J.; Sabaka, T. J.; Nicholas, J. B.; Mazarico, E.; Rowlands, D. D.; Loomis, B. D.; Chinn, D. S.; Caprette, D. S.; McCarthy, J. J.;

The Role of High Dose Interleukin-2 in the Era of Targeted Therapy.

PubMed

Gills, Jessie; Parker, William P; Pate, Scott; Niu, Sida; Van Veldhuizen, Peter; Mirza, Moben; Holzbeierlein, Jeffery M; Lee, Eugene K

2017-09-01

We assessed survival outcomes following high dose interleukin-2 in a contemporary cohort of patients during the era of targeted agents. We retrospectively reviewed the records of patients with metastatic renal cell carcinoma treated with high dose interleukin-2 between July 2007 and September 2014. Clinicopathological data were abstracted and patient response to therapy was based on RECIST (Response Evaluation Criteria In Solid Tumors), version 1.1 criteria. The Kaplan-Meier method was used to estimate progression-free and overall survival in the entire cohort, the response to high dose interleukin-2 in regard to previous targeted agent therapy and the response to the targeted agent in relation to the response to high dose interleukin-2. We identified 92 patients, of whom 87 had documentation of a response to high dose interleukin-2. Median overall survival was 34.4 months from the initiation of high dose interleukin-2 therapy in the entire cohort. Patients who received targeted therapy before high dose interleukin-2 had overall survival (median 34.4 and 30.0 months, p = 0.88) and progression-free survival (median 1.5 and 1.7 months, p = 0.8) similar to those in patients who received no prior therapy, respectively. Additionally, patients with a complete or partial response to high dose interleukin-2 had similar outcomes for subsequent targeted agents compared to patients whose best response was stable or progressive disease (median overall survival 30.1 vs 25.4 months, p = 0.4). Our data demonstrate that patient responses to high dose interleukin-2 and to targeted agents before and after receiving high dose interleukin-2 are independent. As such, carefully selected patients should be offered high dose interleukin-2 for the possibility of a complete and durable response without the fear of limiting the treatment benefit of targeted agents. Copyright © 2017 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Improving Robotic Assembly of Planar High Energy Density Targets

NASA Astrophysics Data System (ADS)

Dudt, D.; Carlson, L.; Alexander, N.; Boehm, K.

2016-10-01

Increased quantities of planar assemblies for high energy density targets are needed with higher shot rates being implemented at facilities such as the National Ignition Facility and the Matter in Extreme Conditions station of the Linac Coherent Light Source. To meet this growing demand, robotics are used to reduce assembly time. This project studies how machine vision and force feedback systems can be used to improve the quantity and quality of planar target assemblies. Vision-guided robotics can identify and locate parts, reducing laborious manual loading of parts into precision pallets and associated teaching of locations. On-board automated inspection can measure part pickup offsets to correct part drop-off placement into target assemblies. Force feedback systems can detect pickup locations and apply consistent force to produce more uniform glue bond thickness, thus improving the performance of the targets. System designs and performance evaluations will be presented. Work supported in part by the US DOE under the Science Undergraduate Laboratory Internships Program (SULI) and ICF Target Fabrication DE-NA0001808.

Strategies for Maintaining Associate Degree Nursing Programs.

ERIC Educational Resources Information Center

Tilton, Theodore

As part of the national campaign of the American Nurses Association (ANA) to create two levels of nursing, one for bachelor of science nurses (BSN's) and one for associate degree nurses (ADN's), Illinois has been targeted for a legislative push to change the laws governing nurse licensure, which, if successful, would signal the beginning of the…

Detection technology of polarization target based on curvelet transform in turbid liquid

NASA Astrophysics Data System (ADS)

Zhang, Su; Duan, Jin; Fu, Qiang; Zhan, Juntong; Ma, Wanzhuo

2015-08-01

To suppress the interference of the target detecting in the turbid medium, a kind of polarization detection technology based on Curvelet transform was applied. This method firstly adjusts the angles of polarizing film to get the intensity images of the situations at 0°,60° and 120°, then deduces the images of Stokes vectors, degree of polarization (DOP) and polarization angle (PA) according to the Mueller matrix. At last the DOP and intensity images can be decomposed by Curvelet transform to realize the fusion of the high and low coefficients respectively, after the processed coefficients are reconstructed, the target which is easier to detect can be achieved. To prove this method, many targets in turbid medium have been detected by polarization method and fused their DOP and intensity images with Curvelet transform algorithm. As an example screws in moderate and high concentration liquid are presented respectively, from which we can see the unpolarized targets are less obvious in higher concentration liquid. When the DOP and intensity images are fused by Curvelet transform, the targets are emerged clearly out of the turbid medium, and the values of the quality evaluation parameters in clarity, degree of contract and spatial frequency are prominently enhanced comparing with the unpolarized images, which can show the feasibility of this method.

A free-jet Hg target operating in a high magnetic field intersecting a high-power proton beam

NASA Astrophysics Data System (ADS)

Graves, Van; Spampinato, Philip; Gabriel, Tony; Kirk, Harold; Simos, Nicholas; Tsang, Thomas; McDonald, Kirk; Peter Titus; Fabich, Adrian; Haseroth, Helmut; Lettry, Jacques

2006-06-01

A proof-of-principal experiment to investigate the interaction of a proton beam, high magnetic field, and high-Z target is planned to take place at CERN in early 2007. This experiment is part of the Muon Collider Collaboration, with participants from Brookhaven National Laboratory, Princeton University, Massachusetts Institute Of Technology, European Organization for Nuclear Research-CERN, Rutherford Appleton Laboratory, and Oak Ridge National Laboratory. An unconstrained mercury jet target system that interacts with a high power (1 MW) proton beam in a high magnetic field (15 T) is being designed. The Hg jet diameter is 1-cm with a velocity up to 20 m/s. A laser optical diagnostic system will be incorporated into the target design to permit observation of the dispersal of the jet resulting from interaction with a 24 GeV proton beam with up to 20×1012 ppp. The target system includes instruments for sensing mercury vapor, temperature, flow rate, and sump tank level, and the means to position the jet relative to the magnetic axis of a solenoid and the proton beam. The design considerations for the system include all issues dealing with safely handling approximately 23 l of Hg, transporting the target system and the mercury to CERN, decommissioning the experiment, and returning the mildly activated equipment and Hg to the US.

A free-jet Hg target operating in a high magnetic field intersecting a high-power proton beam

NASA Astrophysics Data System (ADS)

Van Graves; Spampinato, Philip; Gabriel, Tony; Kirk, Harold; Simos, Nicholas; Tsang, Thomas; McDonald, Kirk; Peter Titus; Fabich, Adrian; Haseroth, Helmut; Lettry, Jacques

2006-06-01

A proof-of-principal experiment to investigate the interaction of a proton beam, high magnetic field, and high- Z target is planned to take place at CERN in early 2007. This experiment is part of the Muon Collider Collaboration, with participants from Brookhaven National Laboratory, Princeton University, Massachusetts Institute Of Technology, European Organization for Nuclear Research-CERN, Rutherford Appleton Laboratory, and Oak Ridge National Laboratory. An unconstrained mercury jet target system that interacts with a high power (1 MW) proton beam in a high magnetic field (15 T) is being designed. The Hg jet diameter is 1-cm with a velocity up to 20 m/s. A laser optical diagnostic system will be incorporated into the target design to permit observation of the dispersal of the jet resulting from interaction with a 24 GeV proton beam with up to 20×10 12 ppp. The target system includes instruments for sensing mercury vapor, temperature, flow rate, and sump tank level, and the means to position the jet relative to the magnetic axis of a solenoid and the proton beam. The design considerations for the system include all issues dealing with safely handling approximately 23 l of Hg, transporting the target system and the mercury to CERN, decommissioning the experiment, and returning the mildly activated equipment and Hg to the US.

Passive damping enhancement of a two-degree-of-freedom system through a strongly nonlinear two-degree-of-freedom attachment

NASA Astrophysics Data System (ADS)

Wierschem, Nicholas E.; Quinn, D. Dane; Hubbard, Sean A.; Al-Shudeifat, Mohammad A.; McFarland, D. Michael; Luo, Jie; Fahnestock, Larry A.; Spencer, Billie F.; Vakakis, Alexander F.; Bergman, Lawrence A.

2012-12-01

This work reports on the first experimental study of the broadband targeted energy transfer properties of a two-degree-of-freedom (two-DOF) essentially nonlinear energy absorber. In particular, proper design of the absorber allows for an extended range of energy over which it serves to significantly enhance the damping observed in the structural system to which it is attached. Comparisons of computational and experimental results validate the proposed design as a means of drastically enhancing the damping properties of a structure by passive broadband targeted energy transfers to a strongly nonlinear, multidegree-of-freedom attachment.

The Physics of Advanced High-Gain Targets for Inertial Fusion Energy

NASA Astrophysics Data System (ADS)

Perkins, L. John

2010-11-01

In ca. 2011-2012, the National Ignition Facility is poised to demonstrate fusion ignition and gain in the laboratory for the first time. This key milestone in the development of inertial confinement fusion (ICF) can be expected to engender interest in the development of inertial fusion energy (IFE) and expanded efforts on a number of advanced targets that may achieve high fusion energy gain at lower driver energies. In this tutorial talk, we will discuss the physics underlying ICF ignition and thermonuclear burn, examine the requirements for high gain, and outline candidate R&D programs that will be required to assess the performance of these target concepts under various driver systems including lasers, heavy-ions and pulsed power. Such target concepts include those operating by fast ignition, shock ignition, impact ignition, dual-density, magnetically-insulated, one- and two-sided drive, etc., some of which may have potential to burn advanced, non-DT fusion fuels. We will then delineate the role of such targets in their application to the production of high average fusion power. Here, systems studies of IFE economics suggest that we should strive for target fusion gains of around 100 at drive energies of 1MJ, together with corresponding rep-rates of up to 10Hz and driver electrical efficiencies around 15%. In future years, there may be exciting opportunities to study such ``innovative confinement concepts'' with prospects of fielding them on facilities such as NIF to obtain high fusion energy gains on a single shot basis.

Measurement of high-degree solar oscillation frequencies

NASA Technical Reports Server (NTRS)

Bachmann, K. T.; Duvall, T. L., Jr.; Harvey, J. W.; Hill, F.

1995-01-01

We present m-averaged solar p- and f-mode oscillation frequencies over the frequency range nu greater than 1.8 and less than 5.0 mHz and the spherical harmonic degree range l greater than or equal to 100 and less than or equal to 1200 from full-disk, 1000 x 1024 pixel, Ca II intensity images collected 1993 June 22-25 with a temporal cadence of 60 s. We itemize the sources and magnitudes of statistical and systematic uncertainties and of small frequency corrections, and we show that our frequencies represent an improvement in accuracy and coverage over previous measurements. Our frequencies agree at the 2 micro Hz level with Mount Wilson frequencies determined for l less than or equal to 600 from full-disk images, and we find systematic offsets of 10-20 micro Hz with respect to frequencies measured from Big Bear and La Palma observations. We give evidence that these latter offsets are indicative of spatial scaling uncertainties associated with the analysis of partial-disk images. In comparison with theory, our p-mode frequencies agree within 10 micro Hz of frequencies predicted by the Los Alamos model but are as much as 100 micro Hz smaller than frequencies predicted by the Denmark and Yale models at degrees near 1000. We also find systematic differences between our n = 0 frequencies and the frequencies closely agreed upon by all three models.

Representing high throughput expression profiles via perturbation barcodes reveals compound targets

PubMed Central

Kutchukian, Peter S.; Li, Jing; Tudor, Matthew

2017-01-01

High throughput mRNA expression profiling can be used to characterize the response of cell culture models to perturbations such as pharmacologic modulators and genetic perturbations. As profiling campaigns expand in scope, it is important to homogenize, summarize, and analyze the resulting data in a manner that captures significant biological signals in spite of various noise sources such as batch effects and stochastic variation. We used the L1000 platform for large-scale profiling of 978 representative genes across thousands of compound treatments. Here, a method is described that uses deep learning techniques to convert the expression changes of the landmark genes into a perturbation barcode that reveals important features of the underlying data, performing better than the raw data in revealing important biological insights. The barcode captures compound structure and target information, and predicts a compound’s high throughput screening promiscuity, to a higher degree than the original data measurements, indicating that the approach uncovers underlying factors of the expression data that are otherwise entangled or masked by noise. Furthermore, we demonstrate that visualizations derived from the perturbation barcode can be used to more sensitively assign functions to unknown compounds through a guilt-by-association approach, which we use to predict and experimentally validate the activity of compounds on the MAPK pathway. The demonstrated application of deep metric learning to large-scale chemical genetics projects highlights the utility of this and related approaches to the extraction of insights and testable hypotheses from big, sometimes noisy data. PMID:28182661

Constrained target controllability of complex networks

NASA Astrophysics Data System (ADS)

Guo, Wei-Feng; Zhang, Shao-Wu; Wei, Ze-Gang; Zeng, Tao; Liu, Fei; Zhang, Jingsong; Wu, Fang-Xiang; Chen, Luonan

2017-06-01

It is of great theoretical interest and practical significance to study how to control a system by applying perturbations to only a few driver nodes. Recently, a hot topic of modern network researches is how to determine driver nodes that allow the control of an entire network. However, in practice, to control a complex network, especially a biological network, one may know not only the set of nodes which need to be controlled (i.e. target nodes), but also the set of nodes to which only control signals can be applied (i.e. constrained control nodes). Compared to the general concept of controllability, we introduce the concept of constrained target controllability (CTC) of complex networks, which concerns the ability to drive any state of target nodes to their desirable state by applying control signals to the driver nodes from the set of constrained control nodes. To efficiently investigate the CTC of complex networks, we further design a novel graph-theoretic algorithm called CTCA to estimate the ability of a given network to control targets by choosing driver nodes from the set of constrained control nodes. We extensively evaluate the CTC of numerous real complex networks. The results indicate that biological networks with a higher average degree are easier to control than biological networks with a lower average degree, while electronic networks with a lower average degree are easier to control than web networks with a higher average degree. We also show that our CTCA can more efficiently produce driver nodes for target-controlling the networks than existing state-of-the-art methods. Moreover, we use our CTCA to analyze two expert-curated bio-molecular networks and compare to other state-of-the-art methods. The results illustrate that our CTCA can efficiently identify proven drug targets and new potentials, according to the constrained controllability of those biological networks.

Moving target feature phenomenology data collection at China Lake

NASA Astrophysics Data System (ADS)

Gross, David C.; Hill, Jeff; Schmitz, James L.

2002-08-01

This paper describes the DARPA Moving Target Feature Phenomenology (MTFP) data collection conducted at the China Lake Naval Weapons Center's Junction Ranch in July 2001. The collection featured both X-band and Ku-band radars positioned on top of Junction Ranch's Parrot Peak. The test included seven targets used in eleven configurations with vehicle motion consisting of circular, straight-line, and 90-degree turning motion. Data was collected at 10-degree and 17-degree depression angles. Key parameters in the collection were polarization, vehicle speed, and road roughness. The collection also included a canonical target positioned at Junction Ranch's tilt-deck turntable. The canonical target included rotating wheels (military truck tire and civilian pick-up truck tire) and a flat plate with variable positioned corner reflectors. The canonical target was also used to simulate a rotating antenna and a vibrating plate. The target vehicles were instrumented with ARDS pods for differential GPS and roll, pitch and yaw measurements. Target motion was also documented using a video camera slaved to the X-band radar antenna and by a video camera operated near the target site.

Astronautics Degrees for Space Industry

NASA Astrophysics Data System (ADS)

Gruntman, M.; Brodsky, R.; Erwin, D.; Kunc, J.

The Astronautics Program (http://astronautics.usc.edu) of the University of Southern California (USC) offers a full set of undergraduate and graduate degree programs in Aerospace Engineering with emphasis in Astronautics. The Bachelor of Science degree program in Astronautics combines basic science and engineering classes with specialized astronautics classes. The Master of Science degree program in Astronautics offers classes in various areas of space technology. The Certificate in Astronautics targets practicing engineers and scientists who enter space-related fields and/or who want to obtain training in specific space-related areas. Many specialized graduate classes are taught by adjunct faculty working at the leading space companies. The Master of Science degree and Certificate are available through the USC Distance Education Network (DEN). Today, the Internet allows us to reach students anywhere in the world through webcasting. The majority of our graduate students, as well as those pursuing the Certificate, work full time as engineers in the space industry and government research and development centers. The new world of distance learning presents new challenges and opens new opportunities. We show how the transformation of distance learning and particularly the introduction of webcasting transform organization of the program and class delivery. We will describe in detail the academic focus of the program, student reach, and structure of program components. Program development is illustrated by the student enrollment dynamics and related industrial trends; the lessons learned emphasize the importance of feedback from the students and from the space industry.

CarPrice versus CarpRice: Word Boundary Ambiguity Influences Saccade Target Selection during the Reading of Chinese Sentences

ERIC Educational Resources Information Center

Yan, Ming; Kliegl, Reinhold

2016-01-01

As a contribution to a theoretical debate about the degree of high-level influences on saccade targeting during sentence reading, we investigated eye movements during the reading of structurally ambiguous Chinese character strings and examined whether parafoveal word segmentation could influence saccade-target selection. As expected, ambiguous…

Self-esteem and self-efficacy as predictors of attrition in associate degree nursing students.

PubMed

Peterson-Graziose, Virginia; Bryer, Jennifer; Nikolaidou, Maria

2013-06-01

There is a serious and growing shortage of nurses in the United States, and the high rate of student attrition from nursing programs has further added to this problem. The challenge for schools of nursing is to recruit increased numbers of qualified candidates into their programs and to determine ways to decrease the rate of student attrition. The purpose of this study was to determine whether self-esteem, self-efficacy, and life stressors were significantly related to student attrition in first-semester associate degree nursing students. A descriptive correlational design and nonprobability convenience sample of first-semester associate degree nursing students was used. Data were gathered using the Rosenberg Self-Esteem Scale, the General Self-Efficacy Scale, and the Holmes and Rahe Social Readjustment Rating Scale. Findings indicated that self-esteem was significantly associated with student attrition. Results from this study provide the basis for targeted interventions designed to decrease student attrition rates in associate degree nursing programs. Copyright 2013, SLACK Incorporated.

High-degree Gravity Models from GRAIL Primary Mission Data

NASA Technical Reports Server (NTRS)

Lemoine, Frank G.; Goossens, Sander J.; Sabaka, Terence J.; Nicholas, Joseph B.; Mazarico, Erwan; Rowlands, David D.; Loomis, Bryant D.; Chinn, Douglas S.; Caprette, Douglas S.; Neumann, Gregory A.;

Packaging Technology for SiC High Temperature Circuits Operable up to 500 Degrees Centigrade

NASA Technical Reports Server (NTRS)

Chen, Lian-Yu

2002-01-01

New high temperature low power 8-pin packages have been fabricated using commercial fabrication service. These packages are made of aluminum nitride and 96 percent alumina with Au metallization. The new design of these packages provides the chips inside with EM shielding. Wirebond geometry control has been achieved for precise mechanical tests. Au wirebond samples with 45 degree heel-angle have been tested using wireloop test module. The geometry control improves the consistency of measurement of the wireloop breaking point.Also reported on is a parametric study of the thermomechanical reliability of a Au thick-film based SiC die-attach assembly using nonlinear finite element analysis (FEA) was conducted to optimize the die-attach thermo-mechanical performance for operation at temperatures from room temperature to 500 degrees Centigrade. This parametric study centered on material selection, structure design and process control.

The efficiency of ceramic-faced metal targets at high-velocity impact

NASA Astrophysics Data System (ADS)

Tolkachev, V. F.; Konyaev, A. A.; Pakhnutova, N. V.

2017-11-01

The paper represents experimental results and engineering evaluation concerning the efficiency of composite materials to be used as an additional protection during the high- velocity interaction of a tungsten rod with a target in the velocity range of 1...5 km/s. The main parameter that characterizes the high-velocity interaction of a projectile with a layered target is the penetration depth. Experimental data, numerical simulation and engineering evaluation by modified models are used to determine the penetration depth. Boron carbide, aluminum oxide, and aluminum nickelide are applied as a front surface of targets. Based on experimental data and numerical simulation, the main characteristics of ceramics are determined, which allows composite materials to be effectively used as additional elements of protection.

Targeted Capture and High-Throughput Sequencing Using Molecular Inversion Probes (MIPs).

PubMed

Cantsilieris, Stuart; Stessman, Holly A; Shendure, Jay; Eichler, Evan E

2017-01-01

Molecular inversion probes (MIPs) in combination with massively parallel DNA sequencing represent a versatile, yet economical tool for targeted sequencing of genomic DNA. Several thousand genomic targets can be selectively captured using long oligonucleotides containing unique targeting arms and universal linkers. The ability to append sequencing adaptors and sample-specific barcodes allows large-scale pooling and subsequent high-throughput sequencing at relatively low cost per sample. Here, we describe a "wet bench" protocol detailing the capture and subsequent sequencing of >2000 genomic targets from 192 samples, representative of a single lane on the Illumina HiSeq 2000 platform.

High-intensity laser-accelerated ion beam produced from cryogenic micro-jet target

DOE PAGES

Gauthier, M.; Kim, J. B.; Curry, C. B.; ...

2016-08-24

Here, we report on the successful operation of a newly developed cryogenic jet target at high intensity laser-irradiation. Using the frequency-doubled Titan short pulse laser system at Jupiter Laser Facility, Lawrence Livermore National Laboratory, we demonstrate the generation of a pure proton beam a with maximum energy of 2 MeV. Furthermore, we record a quasi-monoenergetic peak at 1.1 MeV in the proton spectrum emitted in the laser forward direction suggesting an alternative acceleration mechanism. Using a solid-density mixed hydrogen-deuterium target, we are also able to produce pure proton-deuteron ion beams. With its high purity, limited size, near-critical density, and high-repetitionmore » rate capability, this target is promising for future applications.« less

High-intensity laser-accelerated ion beam produced from cryogenic micro-jet target

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

Gauthier, M., E-mail: maxence.gauthier@stanford.edu; Kim, J. B.; Curry, C. B.

2016-11-15

We report on the successful operation of a newly developed cryogenic jet target at high intensity laser-irradiation. Using the frequency-doubled Titan short pulse laser system at Jupiter Laser Facility, Lawrence Livermore National Laboratory, we demonstrate the generation of a pure proton beam a with maximum energy of 2 MeV. Furthermore, we record a quasi-monoenergetic peak at 1.1 MeV in the proton spectrum emitted in the laser forward direction suggesting an alternative acceleration mechanism. Using a solid-density mixed hydrogen-deuterium target, we are also able to produce pure proton-deuteron ion beams. With its high purity, limited size, near-critical density, and high-repetition ratemore » capability, this target is promising for future applications.« less

A Qualitative Study of Tribal Colleges and Universities that Have Transitioned: From Two-Year Associate Degree Granting Institutions to Targeted Four-Year Bachelor Degree Granting Institutions

ERIC Educational Resources Information Center

Chandler, Lynette

2010-01-01

The purpose of this qualitative case study was to analyze how tribal colleges and Universities have transitioned from two-year associate degree granting institutions to offering four-year bachelor degree granting institutions. This case study includes three tribal colleges: Sitting Bull College, Salish Kootenai College and Turtle Mountain…

Enhanced Membrane Pore Formation through High-Affinity Targeted Antimicrobial Peptides

PubMed Central

Arnusch, Christopher J.; Pieters, Roland J.; Breukink, Eefjan

2012-01-01

Many cationic antimicrobial peptides (AMPs) target the unique lipid composition of the prokaryotic cell membrane. However, the micromolar activities common for these peptides are considered weak in comparison to nisin, which follows a targeted, pore-forming mode of action. Here we show that AMPs can be modified with a high-affinity targeting module, which enables membrane permeabilization at low concentration. Magainin 2 and a truncated peptide analog were conjugated to vancomycin using click chemistry, and could be directed towards specific membrane embedded receptors both in model membrane systems and whole cells. Compared with untargeted vesicles, a gain in permeabilization efficacy of two orders of magnitude was reached with large unilamellar vesicles that included lipid II, the target of vancomycin. The truncated vancomycin-peptide conjugate showed an increased activity against vancomycin resistant Enterococci, whereas the full-length conjugate was more active against a targeted eukaryotic cell model: lipid II containing erythrocytes. This study highlights that AMPs can be made more selective and more potent against biological membranes that contain structures that can be targeted. PMID:22768121

Dynamic accommodation with simulated targets blurred with high order aberrations

PubMed Central

Gambra, Enrique; Wang, Yinan; Yuan, Jing; Kruger, Philip B.; Marcos, Susana

2010-01-01

High order aberrations have been suggested to play a role in determining the direction of accommodation. We have explored the effect of retinal blur induced by high order aberrations on dynamic accommodation by measuring the accommodative response to sinusoidal variations in accommodative demand (1–3 D). The targets were blurred with 0.3 and 1 μm (for a 3-mm pupil) of defocus, coma, trefoil and spherical aberration. Accommodative gain decreased significantly when 1-μm of aberration was induced. We found a strong correlation between the relative accommodative gain (and phase lag) and the contrast degradation imposed on the target at relevant spatial frequencies. PMID:20600230

High-resolution remotely sensed small target detection by imitating fly visual perception mechanism.

PubMed

Huang, Fengchen; Xu, Lizhong; Li, Min; Tang, Min

2012-01-01

The difficulty and limitation of small target detection methods for high-resolution remote sensing data have been a recent research hot spot. Inspired by the information capture and processing theory of fly visual system, this paper endeavors to construct a characterized model of information perception and make use of the advantages of fast and accurate small target detection under complex varied nature environment. The proposed model forms a theoretical basis of small target detection for high-resolution remote sensing data. After the comparison of prevailing simulation mechanism behind fly visual systems, we propose a fly-imitated visual system method of information processing for high-resolution remote sensing data. A small target detector and corresponding detection algorithm are designed by simulating the mechanism of information acquisition, compression, and fusion of fly visual system and the function of pool cell and the character of nonlinear self-adaption. Experiments verify the feasibility and rationality of the proposed small target detection model and fly-imitated visual perception method.

High-flux neutron source based on a liquid-lithium target

NASA Astrophysics Data System (ADS)

Halfon, S.; Feinberg, G.; Paul, M.; Arenshtam, A.; Berkovits, D.; Kijel, D.; Nagler, A.; Eliyahu, I.; Silverman, I.

2013-04-01

A prototype compact Liquid Lithium Target (LiLiT), able to constitute an accelerator-based intense neutron source, was built. The neutron source is intended for nuclear astrophysical research, boron neutron capture therapy (BNCT) in hospitals and material studies for fusion reactors. The LiLiT setup is presently being commissioned at Soreq Nuclear research Center (SNRC). The lithium target will produce neutrons through the 7Li(p,n)7Be reaction and it will overcome the major problem of removing the thermal power generated by a high-intensity proton beam, necessary for intense neutron flux for the above applications. The liquid-lithium loop of LiLiT is designed to generate a stable lithium jet at high velocity on a concave supporting wall with free surface toward the incident proton beam (up to 10 kW). During off-line tests, liquid lithium was flown through the loop and generated a stable jet at velocity higher than 5 m/s on the concave supporting wall. The target is now under extensive test program using a high-power electron-gun. Up to 2 kW electron beam was applied on the lithium flow at velocity of 4 m/s without any flow instabilities or excessive evaporation. High-intensity proton beam irradiation will take place at SARAF (Soreq Applied Research Accelerator Facility) superconducting linear accelerator currently in commissioning at SNRC.

Targeted Therapeutics in Patients With High-Grade Gliomas: Past, Present, and Future.

PubMed

Chen, Ricky; Cohen, Adam L; Colman, Howard

2016-08-01

High-grade gliomas remain incurable despite current therapies, which are plagued by high morbidity and mortality. Molecular categorization of glioma subtypes using mutations in isocitrate dehydrogenase 1/2 (IDH1/2), TP53, and ATRX; codeletion of chromosomes 1p and 19q; DNA methylation; and amplification of genes such as epidermal growth factor receptor (EGFR) and platelet-derived growth factor receptor, alpha polypeptide provides a more accurate prognostication and biologic classification than classical histopathological diagnoses, and a number of molecular markers are being incorporated in the new World Health Organization classification of gliomas. However, despite the improved understanding of the molecular subtypes of gliomas and the underlying alterations in specific signaling pathways, these observations have so far failed to result in the successful application of targeted therapies, as has occurred in other solid tumors. To date, the only targeted therapy for gliomas approved by the US Food and Drug Administration is bevacizumab, which targets vascular endothelial growth factor. EGFR remains a dominant molecular alteration in specific glioma subtypes and represents a potentially promising target, with drugs of multiple types targeting EGFR in development including vaccines, antibody drug conjugates, and chimeric antigen receptor (CAR) T cells, despite the prior failures of EGFR tyrosine kinase inhibitors. Immune therapies under investigation include checkpoint inhibitors, vaccines against tumor-associated antigens and tumor-specific antigens, pulsed dendritic cells, heat shock protein-tumor conjugates, and CAR T cells. Mutations in the IDH1/2 genes are central to gliomagenesis in a high proportion of grade II and III gliomas, and ongoing trials are examining vaccines against IDH1, small molecular inhibitors of IDH1 and IDH2, and metabolic components including NAD+ depletion to target IDH-mutated gliomas. The central role of DNA methylation in a subset of

Characterizing EPR-mediated passive drug targeting using contrast-enhanced functional ultrasound imaging.

PubMed

Theek, Benjamin; Gremse, Felix; Kunjachan, Sijumon; Fokong, Stanley; Pola, Robert; Pechar, Michal; Deckers, Roel; Storm, Gert; Ehling, Josef; Kiessling, Fabian; Lammers, Twan

2014-05-28

The Enhanced Permeability and Retention (EPR) effect is extensively used in drug delivery research. Taking into account that EPR is a highly variable phenomenon, we have here set out to evaluate if contrast-enhanced functional ultrasound (ceUS) imaging can be employed to characterize EPR-mediated passive drug targeting to tumors. Using standard fluorescence molecular tomography (FMT) and two different protocols for hybrid computed tomography-fluorescence molecular tomography (CT-FMT), the tumor accumulation of a ~10 nm-sized near-infrared-fluorophore-labeled polymeric drug carrier (pHPMA-Dy750) was evaluated in CT26 tumor-bearing mice. In the same set of animals, two different ceUS techniques (2D MIOT and 3D B-mode imaging) were employed to assess tumor vascularization. Subsequently, the degree of tumor vascularization was correlated with the degree of EPR-mediated drug targeting. Depending on the optical imaging protocol used, the tumor accumulation of the polymeric drug carrier ranged from 5 to 12% of the injected dose. The degree of tumor vascularization, determined using ceUS, varied from 4 to 11%. For both hybrid CT-FMT protocols, a good correlation between the degree of tumor vascularization and the degree of tumor accumulation was observed, within the case of reconstructed CT-FMT, correlation coefficients of ~0.8 and p-values of <0.02. These findings indicate that ceUS can be used to characterize and predict EPR, and potentially also to pre-select patients likely to respond to passively tumor-targeted nanomedicine treatments. Copyright © 2014 Elsevier B.V. All rights reserved.

Initiated chemical vapor deposition polymers for high peak-power laser targets

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

Baxamusa, Salmaan H.; Lepro, Xavier; Lee, Tom

2016-12-05

Here, we report two examples of initiated chemical vapor deposition (iCVD) polymers being developed for use in laser targets for high peak-power laser systems. First, we show that iCVD poly(divinylbenzene) is more photo-oxidatively stable than the plasma polymers currently used in laser targets. Thick layers (10–12 μm) of this highly crosslinked polymer can be deposited with near-zero intrinsic film stress. Second, we show that iCVD epoxy polymers can be crosslinked after deposition to form thin adhesive layers for assembling precision laser targets. The bondlines can be made as thin as ~ 1 μm, approximately a factor of 2 thinner thanmore » achievable using viscous resin-based adhesives. These bonds can withstand downstream coining and stamping processes.« less

Efficient visualization of high-throughput targeted proteomics experiments: TAPIR.

PubMed

Röst, Hannes L; Rosenberger, George; Aebersold, Ruedi; Malmström, Lars

2015-07-15

Targeted mass spectrometry comprises a set of powerful methods to obtain accurate and consistent protein quantification in complex samples. To fully exploit these techniques, a cross-platform and open-source software stack based on standardized data exchange formats is required. We present TAPIR, a fast and efficient Python visualization software for chromatograms and peaks identified in targeted proteomics experiments. The input formats are open, community-driven standardized data formats (mzML for raw data storage and TraML encoding the hierarchical relationships between transitions, peptides and proteins). TAPIR is scalable to proteome-wide targeted proteomics studies (as enabled by SWATH-MS), allowing researchers to visualize high-throughput datasets. The framework integrates well with existing automated analysis pipelines and can be extended beyond targeted proteomics to other types of analyses. TAPIR is available for all computing platforms under the 3-clause BSD license at https://github.com/msproteomicstools/msproteomicstools. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Spherical harmonic modelling to ultra-high degree of Bouguer and isostatic anomalies

NASA Astrophysics Data System (ADS)

Balmino, G.; Vales, N.; Bonvalot, S.; Briais, A.

2012-07-01

The availability of high-resolution global digital elevation data sets has raised a growing interest in the feasibility of obtaining their spherical harmonic representation at matching resolution, and from there in the modelling of induced gravity perturbations. We have therefore estimated spherical Bouguer and Airy isostatic anomalies whose spherical harmonic models are derived from the Earth's topography harmonic expansion. These spherical anomalies differ from the classical planar ones and may be used in the context of new applications. We succeeded in meeting a number of challenges to build spherical harmonic models with no theoretical limitation on the resolution. A specific algorithm was developed to enable the computation of associated Legendre functions to any degree and order. It was successfully tested up to degree 32,400. All analyses and syntheses were performed, in 64 bits arithmetic and with semi-empirical control of the significant terms to prevent from calculus underflows and overflows, according to IEEE limitations, also in preserving the speed of a specific regular grid processing scheme. Finally, the continuation from the reference ellipsoid's surface to the Earth's surface was performed by high-order Taylor expansion with all grids of required partial derivatives being computed in parallel. The main application was the production of a 1' × 1' equiangular global Bouguer anomaly grid which was computed by spherical harmonic analysis of the Earth's topography-bathymetry ETOPO1 data set up to degree and order 10,800, taking into account the precise boundaries and densities of major lakes and inner seas, with their own altitude, polar caps with bedrock information, and land areas below sea level. The harmonic coefficients for each entity were derived by analyzing the corresponding ETOPO1 part, and free surface data when required, at one arc minute resolution. The following approximations were made: the land, ocean and ice cap gravity spherical

High-Energy Space Propulsion Based on Magnetized Target Fusion

NASA Technical Reports Server (NTRS)

Thio, Y. C. F.; Landrum, D. B.; Freeze, B.; Kirkpatrick, R. C.; Gerrish, H.; Schmidt, G. R.

1999-01-01

Magnetized target fusion is an approach in which a magnetized target plasma is compressed inertially by an imploding material wall. A high energy plasma liner may be used to produce the required implosion. The plasma liner is formed by the merging of a number of high momentum plasma jets converging towards the center of a sphere where two compact toroids have been introduced. Preliminary 3-D hydrodynamics modeling results using the SPHINX code of Los Alamos National Laboratory have been very encouraging and confirm earlier theoretical expectations. The concept appears ready for experimental exploration and plans for doing so are being pursued. In this talk, we explore conceptually how this innovative fusion approach could be packaged for space propulsion for interplanetary travel. We discuss the generally generic components of a baseline propulsion concept including the fusion engine, high velocity plasma accelerators, generators of compact toroids using conical theta pinches, magnetic nozzle, neutron absorption blanket, tritium reprocessing system, shock absorber, magnetohydrodynamic generator, capacitor pulsed power system, thermal management system, and micrometeorite shields.

Fully Bayesian Analysis of High-throughput Targeted Metabolomics Assays

EPA Science Inventory

High-throughput metabolomic assays that allow simultaneous targeted screening of hundreds of metabolites have recently become available in kit form. Such assays provide a window into understanding changes to biochemical pathways due to chemical exposure or disease, and are usefu...

Effects of Relative Platform and Target Motion on Propagation of High Energy Lasers

DTIC Science & Technology

2016-06-01

RELATIVE PLATFORM AND TARGET MOTION ON PROPAGATION OF HIGH ENERGY LASERS by Hayati Emir June 2016 Thesis Advisor: Joseph Blau Co-Advisor...COVERED Master’s thesis 4. TITLE AND SUBTITLE EFFECTS OF RELATIVE PLATFORM AND TARGET MOTION ON PROPAGATION OF HIGH ENERGY LASERS 5. FUNDING...distribution is unlimited 12b. DISTRIBUTION CODE 13. ABSTRACT (maximum 200 words) To facilitate the study of engagement scenarios with high

Performance and microbial community composition dynamics of aerobic granular sludge from sequencing batch bubble column reactors operated at 20 degrees C, 30 degrees C, and 35 degrees C.

PubMed

Ebrahimi, Sirous; Gabus, Sébastien; Rohrbach-Brandt, Emmanuelle; Hosseini, Maryam; Rossi, Pierre; Maillard, Julien; Holliger, Christof

2010-07-01

Two bubble column sequencing batch reactors fed with an artificial wastewater were operated at 20 degrees C, 30 degrees C, and 35 degrees C. In a first stage, stable granules were obtained at 20 degrees C, whereas fluffy structures were observed at 30 degrees C. Molecular analysis revealed high abundance of the operational taxonomic unit 208 (OTU 208) affiliating with filamentous bacteria Leptothrix spp. at 30 degrees C, an OTU much less abundant at 20 degrees C. The granular sludge obtained at 20 degrees C was used for the second stage during which one reactor was maintained at 20 degrees C and the second operated at 30 degrees C and 35 degrees C after prior gradual increase of temperature. Aerobic granular sludge with similar physical properties developed in both reactors but it had different nutrient elimination performances and microbial communities. At 20 degrees C, acetate was consumed during anaerobic feeding, and biological phosphorous removal was observed when Rhodocyclaceae-affiliating OTU 214 was present. At 30 degrees C and 35 degrees C, acetate was mainly consumed during aeration and phosphorous removal was insignificant. OTU 214 was almost absent but the Gammaproteobacteria-affiliating OTU 239 was more abundant than at 20 degrees C. Aerobic granular sludge at all temperatures contained abundantly the OTUs 224 and 289 affiliating with Sphingomonadaceae indicating that this bacterial family played an important role in maintaining stable granular structures.

High-frequency waves following PKP-C sub diff at distances greater than 155 degree

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

Nakanishi, Ichiro

Using a seismic network in Hokkaido-Tohoku region, Japan the author observes PKP waves in the distance range 152 to 157{degree} from a deep earthquake in Argentina. The seismic network consists of 26 stations and provides a data set of dense distance sampling. The examination of amplitude variation of PKP-BC and PKP-C{sub diff} with distance locates the C-cusp at about 155.5{degree} for a surface source for the path from Argentina to Japan. This C-cusp position suggests a P velocity of 10.27 km/s at the bottom of the outer core. The bandpass filtering of the data shows that high-frequency waves are observedmore » following PKP-C{sub diff} at distances beyond the C-cusp. The waves are characterized by a dominant frequency of about 29 to 3 Hz, a long duration of oscillation until the arrival of PKP-AB, and an apparent onset slowness of about 4 s/deg, which is approximately equal to that of PKP-AB in the distance range. The onset time of the high-frequency waves seems to be consistent with the least time of the scattering of PKP-BC on the receiver side near the bottom of the upper mantle.« less

[EFFICACY OF STANDARD TWO-YEAR COMPREHENSIVE THERAPY TO ACHIEVE TARGET BLOOD PRESSURE AND REGRESSION DEGREES OF REMODELING OF THE LEFT VENTRICULAR HYPERTROPHY IN PATIENTS AFTER ACUTE MYOCARDIAL INFARCTION WITH COMORBID HYPERTENSION].

PubMed

Denesiuk, E V

2015-01-01

The study involved 23 men after acute myocardial infarction (AMI) with comorbid arterial hypertension (AH). Mean age of patients was 56.7 years. Recurrent myocardial infarction was determined in 38.4%, cardiac failure I-III functional classes--100% of the cases. All patients underwent clinical examination, electrocardiography and echocardiography, blood lipid profile. Standard comprehensive treatment for two years included an perindopril 5-10 mg/day, beta-blocker bisoprolol--5-10 mg/day, antisclerotic drug atorvastatin--20 mg/day and aspirin--75 mg/day. The patients after treatment was determined by a gradual increase towards the target of AT at 3, 6 and 12 to 24 months. Concentric left ventricular hypertrophy (LVH) before treatment was determined in 47.8%, eccentric--in 52.2% of patients. In the study of degrees of LVH I (initial) the extent to treatment was determined by 4.3%, II (moderate)--26.1%, III (large)--at 69.6%, indicating the development of cardiac remodeling. After the treatment was determined by marked reduction III (large) degree and transfer it in the II (moderate) and I (small) degree of left ventricular hypertrophy due to more or less pronounced changes remodeling left ventricular. The obtained data allow a more detailed and adequately assess the structural and functional outcome variables and determine the regression of myocardial hypertrophy in the background to achieve target blood pressure, which is important in practical cardiology.

Binary-encounter electrons observed at 0 degree in collisions of 1--2-MeV/amu H sup + , C sup 6+ , N sup 7+ , O sup 8+ , and F sup 9+ ions with H sub 2 and He targets

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

Lee, D.H.; Richard, P.; Zouros, T.J.M.

The energy distribution of binary-encounter electrons (BEE) produced in collisions of 1--2 MeV/amu H{sup +} and bare C, N, O, and F ions with H{sub 2} and He gas targets is reported at 0{degree} with respect to the beam direction. These electrons result from ionization of the target due to hard collisions with the projectile and can thus be considered to be produced in a process analogous to elastic scattering of a free electron from a highly charged ion. An impulse-approximation (IA) model has been developed to describe this process in which quasifree'' target electrons undergo 180{degree} Rutherford scattering inmore » the projectile frame. The measured BEE double-differential production cross sections for bare ions were well described by this model and were found to scale with {ital Z}{sub {ital p}}{sup 2} and {ital E}{sub {ital p}}{sup {minus}({similar to}2.6--2.7)} where {ital Z}{sub {ital p}} and {ital E}{sub {ital p}} are the charge and energy of the projectile, respectively. An energy shift of the BEE below 4{ital t}, where {ital t} is the cusp electron energy, is observed and is also predicted by the IA treatment. A plane-wave Born approximation (PWBA) calculation for BEE production is also found to be in overall agreement with our data. However, the energy shift of the BEE peak could not be fully accounted for within this PWBA calculation.« less

Does Structure of Content Delivery or Degree of Professional Development Support Matter for Student Reading Growth in High-Poverty Settings?

ERIC Educational Resources Information Center

Amendum, Steven J.; Fitzgerald, Jill

2013-01-01

We addressed whether the degree of structure of reading content delivery to the children or degree of professional development support for the teachers was related to kindergarten through second-grade students' 2-year reading growth in high-poverty, low-performing schools. There were four categories of data sources: (a) classroom,…

Discrimination of relationships with the same degree of kinship using chromosomal sharing patterns estimated from high-density SNPs.

PubMed

Morimoto, Chie; Manabe, Sho; Fujimoto, Shuntaro; Hamano, Yuya; Tamaki, Keiji

2018-03-01

Distinguishing relationships with the same degree of kinship (e.g., uncle-nephew and grandfather-grandson) is generally difficult in forensic genetics by using the commonly employed short tandem repeat loci. In this study, we developed a new method for discerning such relationships between two individuals by examining the number of chromosomal shared segments estimated from high-density single nucleotide polymorphisms (SNPs). We computationally generated second-degree kinships (i.e., uncle-nephew and grandfather-grandson) and third-degree kinships (i.e., first cousins and great-grandfather-great-grandson) for 174,254 autosomal SNPs considering the effect of linkage disequilibrium and recombination for each SNP. We investigated shared chromosomal segments between two individuals that were estimated based on identity by state regions. We then counted the number of segments in each pair. Based on our results, the number of shared chromosomal segments in collateral relationships was larger than that in lineal relationships with both the second-degree and third-degree kinships. This was probably caused by differences involving chromosomal transitions and recombination between relationships. As we probabilistically evaluated the relationships between simulated pairs based on the number of shared segments using logistic regression, we could determine accurate relationships in >90% of second-degree relatives and >70% of third-degree relatives, using a probability criterion for the relationship ≥0.9. Furthermore, we could judge the true relationships of actual sample pairs from volunteers, as well as simulated data. Therefore, this method can be useful for discerning relationships between two individuals with the same degree of kinship. Copyright © 2017 Elsevier B.V. All rights reserved.

Distributed MIMO Radar for Imaging and High Resolution Target Localization

DTIC Science & Technology

2012-02-02

Reduction in Distributed MIMO Radar with Multi-Carrier OFDM Signals Carl Georgeson 11/23/2010 Approved 17 • 10-019 Algorithms for Target Location and...28-2012 Final Report 04/15/2009 - 11/30/2011 Distributed MIMO Radar for Imaging and High Resolution Target Localization FA9550-09-1-0303 Alexander M...error for the general case of MIMO radar with multiple waveforms with non-coherent and coherent observations; (b) finds a closed-form solution for the

Combining high-speed SVM learning with CNN feature encoding for real-time target recognition in high-definition video for ISR missions

NASA Astrophysics Data System (ADS)

Kroll, Christine; von der Werth, Monika; Leuck, Holger; Stahl, Christoph; Schertler, Klaus

2017-05-01

For Intelligence, Surveillance, Reconnaissance (ISR) missions of manned and unmanned air systems typical electrooptical payloads provide high-definition video data which has to be exploited with respect to relevant ground targets in real-time by automatic/assisted target recognition software. Airbus Defence and Space is developing required technologies for real-time sensor exploitation since years and has combined the latest advances of Deep Convolutional Neural Networks (CNN) with a proprietary high-speed Support Vector Machine (SVM) learning method into a powerful object recognition system with impressive results on relevant high-definition video scenes compared to conventional target recognition approaches. This paper describes the principal requirements for real-time target recognition in high-definition video for ISR missions and the Airbus approach of combining an invariant feature extraction using pre-trained CNNs and the high-speed training and classification ability of a novel frequency-domain SVM training method. The frequency-domain approach allows for a highly optimized implementation for General Purpose Computation on a Graphics Processing Unit (GPGPU) and also an efficient training of large training samples. The selected CNN which is pre-trained only once on domain-extrinsic data reveals a highly invariant feature extraction. This allows for a significantly reduced adaptation and training of the target recognition method for new target classes and mission scenarios. A comprehensive training and test dataset was defined and prepared using relevant high-definition airborne video sequences. The assessment concept is explained and performance results are given using the established precision-recall diagrams, average precision and runtime figures on representative test data. A comparison to legacy target recognition approaches shows the impressive performance increase by the proposed CNN+SVM machine-learning approach and the capability of real-time high

High-flux neutron source based on a liquid-lithium target

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

Halfon, S.; Feinberg, G.; Paul, M.

2013-04-19

A prototype compact Liquid Lithium Target (LiLiT), able to constitute an accelerator-based intense neutron source, was built. The neutron source is intended for nuclear astrophysical research, boron neutron capture therapy (BNCT) in hospitals and material studies for fusion reactors. The LiLiT setup is presently being commissioned at Soreq Nuclear research Center (SNRC). The lithium target will produce neutrons through the {sup 7}Li(p,n){sup 7}Be reaction and it will overcome the major problem of removing the thermal power generated by a high-intensity proton beam, necessary for intense neutron flux for the above applications. The liquid-lithium loop of LiLiT is designed to generatemore » a stable lithium jet at high velocity on a concave supporting wall with free surface toward the incident proton beam (up to 10 kW). During off-line tests, liquid lithium was flown through the loop and generated a stable jet at velocity higher than 5 m/s on the concave supporting wall. The target is now under extensive test program using a high-power electron-gun. Up to 2 kW electron beam was applied on the lithium flow at velocity of 4 m/s without any flow instabilities or excessive evaporation. High-intensity proton beam irradiation will take place at SARAF (Soreq Applied Research Accelerator Facility) superconducting linear accelerator currently in commissioning at SNRC.« less

Online virtual isocenter based radiation field targeting for high performance small animal microirradiation

NASA Astrophysics Data System (ADS)

Stewart, James M. P.; Ansell, Steve; Lindsay, Patricia E.; Jaffray, David A.

2015-12-01

Advances in precision microirradiators for small animal radiation oncology studies have provided the framework for novel translational radiobiological studies. Such systems target radiation fields at the scale required for small animal investigations, typically through a combination of on-board computed tomography image guidance and fixed, interchangeable collimators. Robust targeting accuracy of these radiation fields remains challenging, particularly at the millimetre scale field sizes achievable by the majority of microirradiators. Consistent and reproducible targeting accuracy is further hindered as collimators are removed and inserted during a typical experimental workflow. This investigation quantified this targeting uncertainty and developed an online method based on a virtual treatment isocenter to actively ensure high performance targeting accuracy for all radiation field sizes. The results indicated that the two-dimensional field placement uncertainty was as high as 1.16 mm at isocenter, with simulations suggesting this error could be reduced to 0.20 mm using the online correction method. End-to-end targeting analysis of a ball bearing target on radiochromic film sections showed an improved targeting accuracy with the three-dimensional vector targeting error across six different collimators reduced from 0.56+/- 0.05 mm (mean  ±  SD) to 0.05+/- 0.05 mm for an isotropic imaging voxel size of 0.1 mm.

Child-targeted TV advertising and preschoolers' consumption of high-sugar breakfast cereals.

PubMed

Longacre, Meghan R; Drake, Keith M; Titus, Linda J; Harris, Jennifer; Cleveland, Lauren P; Langeloh, Gail; Hendricks, Kristy; Dalton, Madeline A

2017-01-01

Breakfast cereals represent the most highly advertised packaged food on child-targeted television, and most ads are for cereals high in sugar. This study examined whether children's TV exposure to child-targeted, high-sugar breakfast cereal (SBC) ads was associated with their consumption of those SBC brands. Parents of 3- to 5-year-old children were recruited from pediatric and Women, Infants, and Children (WIC) clinics in Southern New Hampshire, USA, and completed a cross-sectional survey between April-December 2013. Parents reported their child's consumption of SBC brands; whether their child had watched any of 11 kids' channels in the past week; their child's TV viewing time; and socio-demographics. Children's exposure to child-targeted SBC TV ads was calculated by combining TV channel and viewing time with advertising data for SBC ads aired on kids' TV channels during the same timeframe. Five hundred forty-eight parents completed surveys; 52.7% had an annual household income of $50,000 or less. Children's mean age was 4.4 years, 51.6% were female, and 72.5% were non-Hispanic white. In the past week, 56.9% (N = 312) of children ate SBCs advertised on kids' channels. Overall, 40.6% of children were exposed to child-targeted SBC TV ads in the past week. In fully adjusted analyses, the number of SBC brands children consumed was positively associated with their exposure to child-targeted SBC ads. Children consumed 14% (RR = 1.14, 95% CI: 1.02, 1.27) more SBC brands for every 10 SBC ads seen in the past 7 days. Exposure to child-targeted SBC TV advertising is positively associated with SBC brand consumption among preschool-aged children. These findings support recommendations to limit the marketing of high-sugar foods to young children. Copyright © 2016 Elsevier Ltd. All rights reserved.

Drivers' detection of roadside targets when driving vehicles with three headlight systems during high beam activation.

PubMed

Reagan, Ian J; Brumbelow, Matthew L

2017-02-01

A previous open-road experiment indicated that curve-adaptive HID headlights driven with low beams improved drivers' detection of low conspicuity targets compared with fixed halogen and fixed HID low beam systems. The current study used the same test environment and targets to assess whether drivers' detection of targets was affected by the same three headlight systems when using high beams. Twenty drivers search and responded for 60 8×12inch targets of high or low reflectance that were distributed evenly across straight and curved road sections as they drove at 30 mph on an unlit two-lane rural road. The results indicate that target detection performance was generally similar across the three systems. However, one interaction indicated that drivers saw low reflectance targets on straight road sections from further away when driving with the fixed halogen high beam condition compared with curve-adaptive HID high beam headlights and also indicated a possible benefit for the curve-adaptive HID high beams for high reflectance targets placed on the inside of curves. The results of this study conflict with the previous study of low beams, which showed a consistent benefit for the curve-adaptive HID low beams for targets placed on curves compared with fixed HID and fixed halogen low beam conditions. However, a comparison of mean detection distances from the two studies indicated uniformly longer mean target detection distances for participants driving with high beams and implicates the potential visibility benefits for systems that optimize proper high beam use. Copyright © 2016 Elsevier Ltd. All rights reserved.

A novel algorithm for finding optimal driver nodes to target control complex networks and its applications for drug targets identification.

PubMed

Guo, Wei-Feng; Zhang, Shao-Wu; Shi, Qian-Qian; Zhang, Cheng-Ming; Zeng, Tao; Chen, Luonan

2018-01-19

The advances in target control of complex networks not only can offer new insights into the general control dynamics of complex systems, but also be useful for the practical application in systems biology, such as discovering new therapeutic targets for disease intervention. In many cases, e.g. drug target identification in biological networks, we usually require a target control on a subset of nodes (i.e., disease-associated genes) with minimum cost, and we further expect that more driver nodes consistent with a certain well-selected network nodes (i.e., prior-known drug-target genes). Therefore, motivated by this fact, we pose and address a new and practical problem called as target control problem with objectives-guided optimization (TCO): how could we control the interested variables (or targets) of a system with the optional driver nodes by minimizing the total quantity of drivers and meantime maximizing the quantity of constrained nodes among those drivers. Here, we design an efficient algorithm (TCOA) to find the optional driver nodes for controlling targets in complex networks. We apply our TCOA to several real-world networks, and the results support that our TCOA can identify more precise driver nodes than the existing control-fucus approaches. Furthermore, we have applied TCOA to two bimolecular expert-curate networks. Source code for our TCOA is freely available from http://sysbio.sibcb.ac.cn/cb/chenlab/software.htm or https://github.com/WilfongGuo/guoweifeng . In the previous theoretical research for the full control, there exists an observation and conclusion that the driver nodes tend to be low-degree nodes. However, for target control the biological networks, we find interestingly that the driver nodes tend to be high-degree nodes, which is more consistent with the biological experimental observations. Furthermore, our results supply the novel insights into how we can efficiently target control a complex system, and especially many evidences on the

Astronomy Enrollments and Degrees: Results from the 2012 Survey of Astronomy Enrollments and Degrees. Focus On

ERIC Educational Resources Information Center

Mulvey, Patrick; Nicholson, Starr

2014-01-01

Interest in astronomy degrees in the U.S. remains strong, with astronomy enrollments at or near all-time highs for the 2012-13 academic year. The total number of students taking an introductory astronomy course at a degree-granting physics or astronomy department is approaching 200,000. Enrollments in introductory astronomy courses have been…

Drug Target Validation Methods in Malaria - Protein Interference Assay (PIA) as a Tool for Highly Specific Drug Target Validation.

PubMed

Meissner, Kamila A; Lunev, Sergey; Wang, Yuan-Ze; Linzke, Marleen; de Assis Batista, Fernando; Wrenger, Carsten; Groves, Matthew R

2017-01-01

The validation of drug targets in malaria and other human diseases remains a highly difficult and laborious process. In the vast majority of cases, highly specific small molecule tools to inhibit a proteins function in vivo are simply not available. Additionally, the use of genetic tools in the analysis of malarial pathways is challenging. These issues result in difficulties in specifically modulating a hypothetical drug target's function in vivo. The current "toolbox" of various methods and techniques to identify a protein's function in vivo remains very limited and there is a pressing need for expansion. New approaches are urgently required to support target validation in the drug discovery process. Oligomerisation is the natural assembly of multiple copies of a single protein into one object and this self-assembly is present in more than half of all protein structures. Thus, oligomerisation plays a central role in the generation of functional biomolecules. A key feature of oligomerisation is that the oligomeric interfaces between the individual parts of the final assembly are highly specific. However, these interfaces have not yet been systematically explored or exploited to dissect biochemical pathways in vivo. This mini review will describe the current state of the antimalarial toolset as well as the potentially druggable malarial pathways. A specific focus is drawn to the initial efforts to exploit oligomerisation surfaces in drug target validation. As alternative to the conventional methods, Protein Interference Assay (PIA) can be used for specific distortion of the target protein function and pathway assessment in vivo. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Imprinting of Pre-Imposed Laser Perturbations on Targets With a High-Z Overcoat

NASA Astrophysics Data System (ADS)

Karasik, Max; Weaver, J. L.; Aglitskiy, Y.; Oh, J.; Schmitt, A. J.; Bates, J. W.; Serlin, V.; Obenschain, S. P.

2014-10-01

In direct drive ICF, most of the laser imprint is expected to occur during the initial part of the laser pulse, which generates the first shocks necessary to compress the target to achieve high gain. Previous experiments found that a thin (400-800Å) high-Z (Au or Pd) overcoat on the laser side of the target is effective in suppressing broadband imprint. The overcoat initially absorbs the laser and emits soft x-rays that ablate the target, forming a large stand-off distance between laser absorption and ablation and smoothing the drive perturbations. We investigate the effectiveness of imprint suppression for different spatial wavelengths via perturbations imposed on top of the beams smoothed by Induced Spatial Incoherence (ISI). Measurements of areal mass non-uniformity on planar targets driven by the Nike KrF laser are made by curved crystal x-ray radiography. Simultaneous side-on radiography allows observation of the layer dynamics and monitoring of the laser absorption - target ablation stand-off. X-ray flux from the high-Z layer is monitored using absolutely calibrated time-resolved x-ray spectrometers. Work supported by the Department of Energy/NNSA.

An interdimensional correlation framework for real-time estimation of six degree of freedom target motion using a single x-ray imager during radiotherapy

NASA Astrophysics Data System (ADS)

Nguyen, D. T.; Bertholet, J.; Kim, J.-H.; O'Brien, R.; Booth, J. T.; Poulsen, P. R.; Keall, P. J.

2018-01-01

Increasing evidence suggests that intrafraction tumour motion monitoring needs to include both 3D translations and 3D rotations. Presently, methods to estimate the rotation motion require the 3D translation of the target to be known first. However, ideally, translation and rotation should be estimated concurrently. We present the first method to directly estimate six-degree-of-freedom (6DoF) motion from the target’s projection on a single rotating x-ray imager in real-time. This novel method is based on the linear correlations between the superior-inferior translations and the motion in the other five degrees-of-freedom. The accuracy of the method was evaluated in silico with 81 liver tumour motion traces from 19 patients with three implanted markers. The ground-truth motion was estimated using the current gold standard method where each marker’s 3D position was first estimated using a Gaussian probability method, and the 6DoF motion was then estimated from the 3D positions using an iterative method. The 3D position of each marker was projected onto a gantry-mounted imager with an imaging rate of 11 Hz. After an initial 110° gantry rotation (200 images), a correlation model between the superior-inferior translations and the five other DoFs was built using a least square method. The correlation model was then updated after each subsequent frame to estimate 6DoF motion in real-time. The proposed algorithm had an accuracy (±precision) of  -0.03  ±  0.32 mm, -0.01  ±  0.13 mm and 0.03  ±  0.52 mm for translations in the left-right (LR), superior-inferior (SI) and anterior-posterior (AP) directions respectively; and, 0.07  ±  1.18°, 0.07  ±  1.00° and 0.06  ±  1.32° for rotations around the LR, SI and AP axes respectively on the dataset. The first method to directly estimate real-time 6DoF target motion from segmented marker positions on a 2D imager was devised. The algorithm was evaluated using 81

High-stringency screening of target-binding partners using a microfluidic device

DOEpatents

Soh, Hyongsok; Lou, Xinhui; Lagally, Eric

2015-12-01

The invention provides a method of screening a library of candidate agents by contacting the library with a target in a reaction mixture under a condition of high stringency, wherein the target includes a tag that responds to a controllable force applied to the tag, and passing the members of the library through a microfluidic device in a manner that exposes the library members to the controllable force, thereby displacing members of the library that are bound to the target relative to their unbound counterparts. Kits and systems for use with the methods of the invention are also provided.

Thermal treatment of galactose-branched polyelectrolyte microcapsules to improve drug delivery with reserved targetability.

PubMed

Zhang, Fu; Wu, Qi; Liu, Li-Jun; Chen, Zhi-Chun; Lin, Xian-Fu

2008-06-05

A novel multilayered drug delivery system by LbL assembly of galactosylated polyelectrolyte, which is possible to have the potential in hepatic targeting by the presence of galactose residues at the microcapsule's surface, is designed. Thermal treatment was performed on the capsules and a dramatic thermal shrinkage up to 60% decrease of capsule diameter above 50 degrees C was observed. This thermal behavior was then used to manipulate drug loading capacity and release rate. Heating after drug loading could seal the capsule shell, enhancing the loading capacity and reducing the release rate significantly. Excellent affinity between galactose-binding lectin and heated galactose-containing microcapsules were observed, indicating a stable targeting potential even after high temperature elevating up to 90 degrees C.

Astronautics degrees for the space industry

NASA Astrophysics Data System (ADS)

Gruntman, M.; Brodsky, R. F.; Erwin, D. A.; Kunc, J. A.

2004-01-01

The Astronautics Program (http://astronautics.usc.edu) of the University of Southern California (USC) offers a full set of undergraduate and graduate degree programs in Aerospace Engineering with emphasis in Astronautics. The Bachelor of Science and Master of Science degree programs in Astronautics combine basic science and engineering classes with specialized classes in space technology. The Certificate in Astronautics targets practicing engineers and scientists who enter space-related fields and/or who want to obtain training in specific space-related areas. Many specialized graduate classes are taught by adjunct faculty working at the leading space companies. The Master of Science degree and Certificate are available entirely through the USC Distance Education Network (DEN). Today, the Internet allows us to reach students anywhere in the world through webcasting. The majority of our graduate students, as well as those pursuing the Certificate, work full time as engineers in the space industry and government research and development centers while earning their degrees. The new world of distance learning presents new challenges and opens new opportunities. Distance learning, and particularly the introduction of webcasting, transform the organization of the graduate program and class delivery. We describe in detail the program's academic focus, student reach, and structure of program components. Program development is illustrated by the student enrollment dynamics and related industrial trends; the lessons learned emphasize the importance of feedback from the students and from the space industry.

Toward high-efficiency and detailed Monte Carlo simulation study of the granular flow spallation target

NASA Astrophysics Data System (ADS)

Cai, Han-Jie; Zhang, Zhi-Lei; Fu, Fen; Li, Jian-Yang; Zhang, Xun-Chao; Zhang, Ya-Ling; Yan, Xue-Song; Lin, Ping; Xv, Jian-Ya; Yang, Lei

2018-02-01

The dense granular flow spallation target is a new target concept chosen for the Accelerator-Driven Subcritical (ADS) project in China. For the R&D of this kind of target concept, a dedicated Monte Carlo (MC) program named GMT was developed to perform the simulation study of the beam-target interaction. Owing to the complexities of the target geometry, the computational cost of the MC simulation of particle tracks is highly expensive. Thus, improvement of computational efficiency will be essential for the detailed MC simulation studies of the dense granular target. Here we present the special design of the GMT program and its high efficiency performance. In addition, the speedup potential of the GPU-accelerated spallation models is discussed.

High degree of polymerization in a fullerene-containing supramolecular polymer.

PubMed

Isla, Helena; Pérez, Emilio M; Martín, Nazario

2014-05-26

Supramolecular polymers based on dispersion forces typically show lower molecular weights (MW) than those based on hydrogen bonding or metal-ligand coordination. We present the synthesis and self-assembling properties of a monomer featuring two complementary units, a C60 derivative and an exTTF-based macrocycle, that interact mainly through π-π, charge-transfer, and van der Waals interactions. Thanks to the preorganization in the host part, a remarkable log K(a)=5.1±0.5 in CHCl3 at room temperature is determined for the host-guest couple. In accordance with the large binding constant, the monomer self-assembles in the gas phase, in solution, and in the solid state to form linear supramolecular polymers with a very high degree of polymerization. A MW above 150 kDa has been found experimentally in solution, while in the solid state the monomer forms extraordinarily long, straight, and uniform fibers with lengths reaching several microns. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Vocational Certificates and College Degrees. ERIC Digest No. 212.

ERIC Educational Resources Information Center

Brown, Bettina Lankard

Many studies have verified that education beyond high school results in higher earnings. The highest earnings benefits depend upon certification or degree achievement. Not obtaining a degree results in some penalty: individuals who have some college credit but no degree earn less than associate degree holders. Professional and vocational…

Directional enhancement of selected high-order-harmonics from intense laser irradiated blazed grating targets.

PubMed

Zhang, Guobo; Chen, Min; Liu, Feng; Yuan, Xiaohui; Weng, Suming; Zheng, Jun; Ma, Yanyun; Shao, Fuqiu; Sheng, Zhengming; Zhang, Jie

2017-10-02

Relativistically intense laser solid target interaction has been proved to be a promising way to generate high-order harmonics, which can be used to diagnose ultrafast phenomena. However, their emission direction and spectra still lack tunability. Based upon two-dimensional particle-in-cell simulations, we show that directional enhancement of selected high-order-harmonics can be realized using blazed grating targets. Such targets can select harmonics with frequencies being integer times of the grating frequency. Meanwhile, the radiation intensity and emission area of the harmonics are increased. The emission direction is controlled by tailoring the local blazed structure. Theoretical and electron dynamics analysis for harmonics generation, selection and directional enhancement from the interaction between multi-cycle laser and grating target are carried out. These studies will benefit the generation and application of laser plasma-based high order harmonics.

Pose measurement method and experiments for high-speed rolling targets in a wind tunnel.

PubMed

Jia, Zhenyuan; Ma, Xin; Liu, Wei; Lu, Wenbo; Li, Xiao; Chen, Ling; Wang, Zhengqu; Cui, Xiaochun

2014-12-12

High-precision wind tunnel simulation tests play an important role in aircraft design and manufacture. In this study, a high-speed pose vision measurement method is proposed for high-speed and rolling targets in a supersonic wind tunnel. To obtain images with high signal-to-noise ratio and avoid impacts on the aerodynamic shape of the rolling targets, a high-speed image acquisition method based on ultrathin retro-reflection markers is presented. Since markers are small-sized and some of them may be lost when the target is rolling, a novel markers layout with which markers are distributed evenly on the surface is proposed based on a spatial coding method to achieve highly accurate pose information. Additionally, a pose acquisition is carried out according to the mentioned markers layout after removing mismatching points by Case Deletion Diagnostics. Finally, experiments on measuring the pose parameters of high-speed targets in the laboratory and in a supersonic wind tunnel are conducted to verify the feasibility and effectiveness of the proposed method. Experimental results indicate that the position measurement precision is less than 0.16 mm, the pitching and yaw angle precision less than 0.132° and the roll angle precision 0.712°.

Pose Measurement Method and Experiments for High-Speed Rolling Targets in a Wind Tunnel

PubMed Central

Jia, Zhenyuan; Ma, Xin; Liu, Wei; Lu, Wenbo; Li, Xiao; Chen, Ling; Wang, Zhengqu; Cui, Xiaochun

2014-01-01

High-precision wind tunnel simulation tests play an important role in aircraft design and manufacture. In this study, a high-speed pose vision measurement method is proposed for high-speed and rolling targets in a supersonic wind tunnel. To obtain images with high signal-to-noise ratio and avoid impacts on the aerodynamic shape of the rolling targets, a high-speed image acquisition method based on ultrathin retro-reflection markers is presented. Since markers are small-sized and some of them may be lost when the target is rolling, a novel markers layout with which markers are distributed evenly on the surface is proposed based on a spatial coding method to achieve highly accurate pose information. Additionally, a pose acquisition is carried out according to the mentioned markers layout after removing mismatching points by Case Deletion Diagnostics. Finally, experiments on measuring the pose parameters of high-speed targets in the laboratory and in a supersonic wind tunnel are conducted to verify the feasibility and effectiveness of the proposed method. Experimental results indicate that the position measurement precision is less than 0.16 mm, the pitching and yaw angle precision less than 0.132° and the roll angle precision 0.712°. PMID:25615732

Predicting the Noise of High Power Fluid Targets Using Computational Fluid Dynamics

NASA Astrophysics Data System (ADS)

Moore, Michael; Covrig Dusa, Silviu

The 2.5 kW liquid hydrogen (LH2) target used in the Qweak parity violation experiment is the highest power LH2 target in the world and the first to be designed with Computational Fluid Dynamics (CFD) at Jefferson Lab. The Qweak experiment determined the weak charge of the proton by measuring the parity-violating elastic scattering asymmetry of longitudinally polarized electrons from unpolarized liquid hydrogen at small momentum transfer (Q2 = 0 . 025 GeV2). This target satisfied the design goals of < 1 % luminosity reduction and < 5 % contribution to the total asymmetry width (the Qweak target achieved 2 % or 55ppm). State of the art time dependent CFD simulations are being developed to improve the predictions of target noise on the time scale of the electron beam helicity period. These predictions will be bench-marked with the Qweak target data. This work is an essential component in future designs of very high power low noise targets like MOLLER (5 kW, target noise asymmetry contribution < 25 ppm) and MESA (4.5 kW).

Epidermal growth factor receptor-targeted lipid nanoparticles retain self-assembled nanostructures and provide high specificity

NASA Astrophysics Data System (ADS)

Zhai, Jiali; Scoble, Judith A.; Li, Nan; Lovrecz, George; Waddington, Lynne J.; Tran, Nhiem; Muir, Benjamin W.; Coia, Gregory; Kirby, Nigel; Drummond, Calum J.; Mulet, Xavier

2015-02-01

Next generation drug delivery utilising nanoparticles incorporates active targeting to specific sites. In this work, we combined targeting with the inherent advantages of self-assembled lipid nanoparticles containing internal nano-structures. Epidermal growth factor receptor (EGFR)-targeting, PEGylated lipid nanoparticles using phytantriol and 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-PEG-maleimide amphiphiles were created. The self-assembled lipid nanoparticles presented here have internal lyotropic liquid crystalline nano-structures, verified by synchrotron small angle X-ray scattering and cryo-transmission electron microscopy, that offer the potential of high drug loading and enhanced cell penetration. Anti-EGFR Fab' fragments were conjugated to the surface of nanoparticles via a maleimide-thiol reaction at a high conjugation efficiency and retained specificity following conjugation to the nanoparticles. The conjugated nanoparticles were demonstrated to have high affinity for an EGFR target in a ligand binding assay.Next generation drug delivery utilising nanoparticles incorporates active targeting to specific sites. In this work, we combined targeting with the inherent advantages of self-assembled lipid nanoparticles containing internal nano-structures. Epidermal growth factor receptor (EGFR)-targeting, PEGylated lipid nanoparticles using phytantriol and 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-PEG-maleimide amphiphiles were created. The self-assembled lipid nanoparticles presented here have internal lyotropic liquid crystalline nano-structures, verified by synchrotron small angle X-ray scattering and cryo-transmission electron microscopy, that offer the potential of high drug loading and enhanced cell penetration. Anti-EGFR Fab' fragments were conjugated to the surface of nanoparticles via a maleimide-thiol reaction at a high conjugation efficiency and retained specificity following conjugation to the nanoparticles. The conjugated nanoparticles

Modeling real shim fields for very high degree (and order) B0 shimming of the human brain at 9.4 T.

PubMed

Chang, Paul; Nassirpour, Sahar; Henning, Anke

2018-01-01

To describe the process of calibrating a B 0 shim system using high-degree (or high order) spherical harmonic models of the measured shim fields, to provide a method that considers amplitude dependency of these models, and to show the advantage of very high-degree B 0 shimming for whole-brain and single-slice applications at 9.4 Tesla (T). An insert shim with up to fourth and partial fifth/sixth degree (order) spherical harmonics was used with a Siemens 9.4T scanner. Each shim field was measured and modeled as input for the shimming algorithm. Optimal shim currents can therefore be calculated in a single iteration. A range of shim currents was used in the modeling to account for possible amplitude nonlinearities. The modeled shim fields were used to compare different degrees of whole-brain B 0 shimming on healthy subjects. The ideal shim fields did not correctly shim the subject brains. However, using the modeled shim fields improved the B 0 homogeneity from 55.1 (second degree) to 44.68 Hz (partial fifth/sixth degree) on the whole brains of 9 healthy volunteers, with a total applied current of 0.77 and 6.8 A, respectively. The necessity of calibrating the shim system was shown. Better B 0 homogeneity drastically reduces signal dropout and distortions for echo-planar imaging, and significantly improves the linewidths of MR spectroscopy imaging. Magn Reson Med 79:529-540, 2018. © 2017 International Society for Magnetic Resonance in Medicine. © 2017 International Society for Magnetic Resonance in Medicine.

Increased importance of methane reduction for a 1.5 degree target

NASA Astrophysics Data System (ADS)

Collins, William J.; Webber, Christopher P.; Cox, Peter M.; Huntingford, Chris; Lowe, Jason; Sitch, Stephen; Chadburn, Sarah E.; Comyn-Platt, Edward; Harper, Anna B.; Hayman, Garry; Powell, Tom

2018-04-01

To understand the importance of methane on the levels of carbon emission reductions required to achieve temperature goals, a processed-based approach is necessary rather than reliance on the transient climate response to emissions. We show that plausible levels of methane (CH4) mitigation can make a substantial difference to the feasibility of achieving the Paris climate targets through increasing the allowable carbon emissions. This benefit is enhanced by the indirect effects of CH4 on ozone (O3). Here the differing effects of CH4 and CO2 on land carbon storage, including the effects of surface O3, lead to an additional increase in the allowable carbon emissions with CH4 mitigation. We find a simple robust relationship between the change in the 2100 CH4 concentration and the extra allowable cumulative carbon emissions between now and 2100 (0.27 ± 0.05 GtC per ppb CH4). This relationship is independent of modelled climate sensitivity and precise temperature target, although later mitigation of CH4 reduces its value and thus methane reduction effectiveness. Up to 12% of this increase in allowable emissions is due to the effect of surface ozone. We conclude early mitigation of CH4 emissions would significantly increase the feasibility of stabilising global warming below 1.5 °C, alongside having co-benefits for human and ecosystem health.

All-reflective optical target illumination system with high numerical aperture

DOEpatents

Sigler, Robert D.

1978-01-01

An all-reflective optical system for providing illumination of a target focal region at high numerical aperture from a pair of co-axially, confluent collimated light beams. A target cavity is defined by a pair of opposed inner ellipsoidal reflectors having respective first focal points within a target region and second focal points at a vertex opening in the opposing reflector. Outwardly of each inner reflector is the opposed combination of a spherical reflector, and an outer generally ellipsoidal reflector having an aberrated first focal point coincident with the focus of the opposing spherical reflector and a second focal point coincident with the second focal point of the opposing inner ellipsoidal reflector through a vertex opening in the spherical reflector. The confluent collimated beams are incident through vertex openings in the outer ellipsoidal reflectors onto respective opposing spherical reflectors. Each beam is reflected by the associated spherical reflector onto the opposing outer ellipsoidal reflector and focused thereby onto the opposing inner ellipsoidal reflector, and then onto the target region.

Measurements of Laser Imprint with High-Z Coated targets on Omega EP

NASA Astrophysics Data System (ADS)

Karasik, Max; Oh, J.; Stoeckl, C.; Aglitskiy, Y.; Schmitt, A. J.; Bates, J. W.; Obenschain, S. P.

2015-11-01

Previous experiments on Nike KrF laser (λ = 248nm) at NRL found that a thin (400-800 Å) high-Z (Au or Pd) overcoat on the laser side of the target is effective in suppressing broadband imprint and reducing ablative Richtmyer-Meshkov growth. The overcoat initially absorbs the laser and emits soft x-rays that ablate the target, forming a large stand-off distance between laser absorption and ablation and driving the target at higher mass ablation rate. Implementation of this technique on the frequency-tripled Nd:glass (351 nm) NIF would enable a wider range direct drive experiments there. To this end, we are carrying out experiments using the NIF-like beams of Omega EP. Analogous to experiments on Nike, areal mass perturbations due to RT-amplified laser imprint are measured using curved crystal imaging coupled to a streak camera. High-Z coating dynamics and target trajectory are imaged side-on. First results indicate that imprint suppression is observed, albeit with thicker coatings. Work supported by the Department of Energy/NNSA.

Smoluchowski Equation for Networks: Merger Induced Intermittent Giant Node Formation and Degree Gap

NASA Astrophysics Data System (ADS)

Goto, Hayato; Viegas, Eduardo; Jensen, Henrik Jeldtoft; Takayasu, Hideki; Takayasu, Misako

2018-06-01

The dynamical phase diagram of a network undergoing annihilation, creation, and coagulation of nodes is found to exhibit two regimes controlled by the combined effect of preferential attachment for initiator and target nodes during coagulation and for link assignment to new nodes. The first regime exhibits smooth dynamics and power law degree distributions. In the second regime, giant degree nodes and gaps in the degree distribution are formed intermittently. Data for the Japanese firm network in 1994 and 2014 suggests that this network is moving towards the intermittent switching region.

A Flexure-Based Mechanism for Precision Adjustment of National Ignition Facility Target Shrouds in Three Rotational Degrees of Freedom

DOE PAGES

Boehm, K. -J.; Gibson, C. R.; Hollaway, J. R.; ...

2016-09-01

This study presents the design of a flexure-based mount allowing adjustment in three rotational degrees of freedom (DOFs) through high-precision set-screw actuators. The requirements of the application called for small but controlled angular adjustments for mounting a cantilevered beam. The proposed design is based on an array of parallel beams to provide sufficiently high stiffness in the translational directions while allowing angular adjustment through the actuators. A simplified physical model in combination with standard beam theory was applied to estimate the deflection profile and maximum stresses in the beams. A finite element model was built to calculate the stresses andmore » beam profiles for scenarios in which the flexure is simultaneously actuated in more than one DOF.« less

Thermal Test on Target with Pressed Disks

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

Woloshun, Keith Albert; Dale, Gregory E.; Olivas, Eric Richard

A thorough test of the thermal performance of a target for Mo 99 production using solid Mo 100 target to produce the Mo 99 via a gamma-n reaction has previously been conducted at Argonne National Laboratory (ANL). The results are reported in “Zero Degree Line Mo Target Thermal Test Results and Analysis,” LANL report Number LA-UR-15-23134 dated 3/27/15. This target was comprised of 25 disks 1 mm thick and 12 mm in diameter, separated by helium coolant gaps 0.5 mm wide. The test reported in the above referenced report was conducted with natural Mo disks all cut from commercial rod.more » The production plant will have Mo 100 disks pressed and sintered using a process being developed at Oak Ridge National Laboratory (ORNL). The structural integrity of press-and-sinter disks is of some concern. The test reported herein included 4 disks made by the ORNL process and placed in the high heat, and therefore high thermal stress, region of the target. The electron beam energy was 23 MeV for these tests. Beam spot size was 3.5 mm horizontal and 3 mm vertical, FWHM. The thermal stress test of pressed-and-sintered disks resulted in no mechanical failures. The induced thermal stresses were below yield stress for natural Mo, indicating that up to that stress state no inherent deficiencies in the mechanical properties of the fabricated disks were evident.« less

The Potential of Targeting Ribosome Biogenesis in High-Grade Serous Ovarian Cancer

PubMed Central

Yan, Shunfei; Frank, Daniel; Son, Jinbae; Hannan, Katherine M.; Hannan, Ross D.; Chan, Keefe T.; Pearson, Richard B.; Sanij, Elaine

2017-01-01

Overall survival for patients with ovarian cancer (OC) has shown little improvement for decades meaning new therapeutic options are critical. OC comprises multiple histological subtypes, of which the most common and aggressive subtype is high-grade serous ovarian cancer (HGSOC). HGSOC is characterized by genomic structural variations with relatively few recurrent somatic mutations or dominantly acting oncogenes that can be targeted for the development of novel therapies. However, deregulation of pathways controlling homologous recombination (HR) and ribosome biogenesis has been observed in a high proportion of HGSOC, raising the possibility that targeting these basic cellular processes may provide improved patient outcomes. The poly (ADP-ribose) polymerase (PARP) inhibitor olaparib has been approved to treat women with defects in HR due to germline BRCA mutations. Recent evidence demonstrated the efficacy of targeting ribosome biogenesis with the specific inhibitor of ribosomal RNA synthesis, CX-5461 in v-myc avian myelocytomatosis viral oncogene homolog (MYC)-driven haematological and prostate cancers. CX-5461 has now progressed to a phase I clinical trial in patients with haematological malignancies and phase I/II trial in breast cancer. Here we review the currently available targeted therapies for HGSOC and discuss the potential of targeting ribosome biogenesis as a novel therapeutic approach against HGSOC. PMID:28117679

Transitioning from Targeted to Comprehensive Mass Spectrometry Using Genetic Algorithms.

PubMed

Jaffe, Jacob D; Feeney, Caitlin M; Patel, Jinal; Lu, Xiaodong; Mani, D R

2016-11-01

Targeted proteomic assays are becoming increasingly popular because of their robust quantitative applications enabled by internal standardization, and they can be routinely executed on high performance mass spectrometry instrumentation. However, these assays are typically limited to 100s of analytes per experiment. Considerable time and effort are often expended in obtaining and preparing samples prior to targeted analyses. It would be highly desirable to detect and quantify 1000s of analytes in such samples using comprehensive mass spectrometry techniques (e.g., SWATH and DIA) while retaining a high degree of quantitative rigor for analytes with matched internal standards. Experimentally, it is facile to port a targeted assay to a comprehensive data acquisition technique. However, data analysis challenges arise from this strategy concerning agreement of results from the targeted and comprehensive approaches. Here, we present the use of genetic algorithms to overcome these challenges in order to configure hybrid targeted/comprehensive MS assays. The genetic algorithms are used to select precursor-to-fragment transitions that maximize the agreement in quantification between the targeted and the comprehensive methods. We find that the algorithm we used provided across-the-board improvement in the quantitative agreement between the targeted assay data and the hybrid comprehensive/targeted assay that we developed, as measured by parameters of linear models fitted to the results. We also found that the algorithm could perform at least as well as an independently-trained mass spectrometrist in accomplishing this task. We hope that this approach will be a useful tool in the development of quantitative approaches for comprehensive proteomics techniques. Graphical Abstract ᅟ.

Transitioning from Targeted to Comprehensive Mass Spectrometry Using Genetic Algorithms

NASA Astrophysics Data System (ADS)

Jaffe, Jacob D.; Feeney, Caitlin M.; Patel, Jinal; Lu, Xiaodong; Mani, D. R.

2016-11-01

Targeted proteomic assays are becoming increasingly popular because of their robust quantitative applications enabled by internal standardization, and they can be routinely executed on high performance mass spectrometry instrumentation. However, these assays are typically limited to 100s of analytes per experiment. Considerable time and effort are often expended in obtaining and preparing samples prior to targeted analyses. It would be highly desirable to detect and quantify 1000s of analytes in such samples using comprehensive mass spectrometry techniques (e.g., SWATH and DIA) while retaining a high degree of quantitative rigor for analytes with matched internal standards. Experimentally, it is facile to port a targeted assay to a comprehensive data acquisition technique. However, data analysis challenges arise from this strategy concerning agreement of results from the targeted and comprehensive approaches. Here, we present the use of genetic algorithms to overcome these challenges in order to configure hybrid targeted/comprehensive MS assays. The genetic algorithms are used to select precursor-to-fragment transitions that maximize the agreement in quantification between the targeted and the comprehensive methods. We find that the algorithm we used provided across-the-board improvement in the quantitative agreement between the targeted assay data and the hybrid comprehensive/targeted assay that we developed, as measured by parameters of linear models fitted to the results. We also found that the algorithm could perform at least as well as an independently-trained mass spectrometrist in accomplishing this task. We hope that this approach will be a useful tool in the development of quantitative approaches for comprehensive proteomics techniques.

Roster of Physics Departments with Enrollment and Degree Data, 2015: Results from the 2015 Survey of Enrollments and Degrees. Focus On

ERIC Educational Resources Information Center

Nicholson, Starr; Mulvey, Patrick J.

2016-01-01

Physics bachelor's degree production continues to increase, with the 8,122 bachelor's awarded representing yet another all-time high. Further increases in physics bachelor's degree production are anticipated as undergraduate junior- and senior-level enrollments continue to climb. The all-time high of 1,860 physics PhDs conferred in the class of…

Roster of Astronomy Departments with Enrollment and Degree Data, 2015: Results from the 2015 Survey of Enrollments and Degrees. Focus On

ERIC Educational Resources Information Center

Nicholson, Starr; Mulvey, Patrick J.

2016-01-01

Physics bachelor's degree production continues to increase, with the 8,122 bachelor's awarded representing yet another all-time high. Further increases in physics bachelor's degree production are anticipated as undergraduate junior- and senior-level enrollments continue to climb. The all-time high of 1,860 physics PhDs conferred in the class of…

Signalment, clinical signs, and prognostic indicators associated with high-grade second- or third-degree atrioventricular block in dogs: 124 cases (January 1, 1997-December 31, 1997).

PubMed

Schrope, Donald P; Kelch, William J

2006-06-01

To evaluate signalment, clinical signs, and prognosis associated with high-grade second- or third-degree atrioventricular block (AVB) in dogs. Retrospective case series. 124 dogs. Data were gathered from ECGs, veterinarian questionnaires, echocardiograms, and radiographs submitted for review; compared with data from a large control group; and examined for association between variables and duration of survival. A new classification system for AVB was evaluated. Afghan, Catahoula Leopard Dog, Chow Chow, Cocker Spaniel, German Wirehaired Pointer, and Labrador Retriever breeds were predisposed to high-grade second- or third-degree AVB. Heavier, older, and sexually intact female dogs were overrepresented in the study group. Weakness, lethargy, exercise intolerance, and syncope were the most common clinical signs. The presence of clinical signs was not associated with duration of survival. Dogs with high-grade second-degree AVB had a duration of survival similar to that of dogs with third-degree AVB. Dogs with high-grade second- or third-degree AVB were at high risk for sudden death in the first 6 months after diagnosis. High ventricular escape rhythm rate and narrow escape-complex QRS width were negatively associated with duration of survival. Pacemaker implantation had a significant positive association with survival. Pacemaker implantation should be strongly considered in all dogs with high-grade second- or third-degree AVB regardless of whether clinical signs are evident. If medical treatment is warranted, vagolytic medications may be the best choice. A new classification system for AVB may merit further investigation.

Differences in STEM degree attainment by region, ethnicity, and degree type

NASA Astrophysics Data System (ADS)

Koledoye, Kimberly A.

Purpose One purpose of this study was to determine the extent to which a difference was present in the STEM degree attainment of all students and particularly of URMs between the 2001 and the 2009 academic year. The second purpose of this study was to determine the extent to which a difference was present in the attainment of STEM associate degrees and bachelor degrees of all students and particularly of URMs awarded between the 2001 and the 2009 academic year. Another purpose of this study was to determine the extent to which a difference existed in STEM associate degree and STEM bachelor degree attainment among geographic regions between the 2001 and the 2009 academic years. The extent to which a difference existed in the STEM bachelor degree and associate degree attainment of URMs among geographic regions between the 2001 to the 2009 academic year was ascertained. The final purpose of this study was to determine the extent to which a difference was present in STEM associate degree and bachelor degree attainment of all students and particularly URMs as a function of degree type between the 2001 academic year and the 2009 academic year. Methodology Archival data from the Integrated Postsecondary Education Data System were utilized to compare STEM degree attainment for regions, regions for URMs, STEM degree attainment overall and for URMs, STEM degree attainment classified by associate degrees and bachelor degrees for all students and URMs, and STEM degree attainment of associate degrees and bachelor degrees for all students and URMs by specific degree type between 2001 and 2009. Findings In this non-experimental causal comparative investigation, statistically significant differences were revealed in 95 of the 165 comparisons. Declining associate degree attainment was concerning, particularly in the computer and information sciences and engineering and engineering technologies. Moderate increases were determined in bachelor degree attainment with statistically

All-reflective optical target illumination system with high numerical aperture

DOEpatents

Thomas, Carlton E.; Sigler, Robert D.; Hoeger, John G.

1979-01-01

An all-reflective optical system for providing illumination of a target focal region at high numerical aperture from a pair of confluent collimated light beams. The collimated beams are each incident upon an associated concave eccentric pupil paraboloidal reflective surface, and thereby each focused through an opening in an associated outer ellipsoidal reflective surface onto a plane reflector. Each beam is reflected by its associated plane reflector onto the opposing concave surface of the outer ellipsoids to be focused through an opening in the plane surface onto an opposing inner concave ellipsoidal reflective surface, and thence onto the target region.

Genome-scale measurement of off-target activity using Cas9 toxicity in high-throughput screens.

PubMed

Morgens, David W; Wainberg, Michael; Boyle, Evan A; Ursu, Oana; Araya, Carlos L; Tsui, C Kimberly; Haney, Michael S; Hess, Gaelen T; Han, Kyuho; Jeng, Edwin E; Li, Amy; Snyder, Michael P; Greenleaf, William J; Kundaje, Anshul; Bassik, Michael C

2017-05-05

CRISPR-Cas9 screens are powerful tools for high-throughput interrogation of genome function, but can be confounded by nuclease-induced toxicity at both on- and off-target sites, likely due to DNA damage. Here, to test potential solutions to this issue, we design and analyse a CRISPR-Cas9 library with 10 variable-length guides per gene and thousands of negative controls targeting non-functional, non-genic regions (termed safe-targeting guides), in addition to non-targeting controls. We find this library has excellent performance in identifying genes affecting growth and sensitivity to the ricin toxin. The safe-targeting guides allow for proper control of toxicity from on-target DNA damage. Using this toxicity as a proxy to measure off-target cutting, we demonstrate with tens of thousands of guides both the nucleotide position-dependent sensitivity to single mismatches and the reduction of off-target cutting using truncated guides. Our results demonstrate a simple strategy for high-throughput evaluation of target specificity and nuclease toxicity in Cas9 screens.

Genome-scale measurement of off-target activity using Cas9 toxicity in high-throughput screens

PubMed Central

Morgens, David W.; Wainberg, Michael; Boyle, Evan A.; Ursu, Oana; Araya, Carlos L.; Tsui, C. Kimberly; Haney, Michael S.; Hess, Gaelen T.; Han, Kyuho; Jeng, Edwin E.; Li, Amy; Snyder, Michael P.; Greenleaf, William J.; Kundaje, Anshul; Bassik, Michael C.

2017-01-01

CRISPR-Cas9 screens are powerful tools for high-throughput interrogation of genome function, but can be confounded by nuclease-induced toxicity at both on- and off-target sites, likely due to DNA damage. Here, to test potential solutions to this issue, we design and analyse a CRISPR-Cas9 library with 10 variable-length guides per gene and thousands of negative controls targeting non-functional, non-genic regions (termed safe-targeting guides), in addition to non-targeting controls. We find this library has excellent performance in identifying genes affecting growth and sensitivity to the ricin toxin. The safe-targeting guides allow for proper control of toxicity from on-target DNA damage. Using this toxicity as a proxy to measure off-target cutting, we demonstrate with tens of thousands of guides both the nucleotide position-dependent sensitivity to single mismatches and the reduction of off-target cutting using truncated guides. Our results demonstrate a simple strategy for high-throughput evaluation of target specificity and nuclease toxicity in Cas9 screens. PMID:28474669

Muscle metabolism, temperature, and function during prolonged, intermittent, high-intensity running in air temperatures of 33 degrees and 17 degrees C.

PubMed

Morris, J G; Nevill, M E; Boobis, L H; Macdonald, I A; Williams, C

2005-12-01

Nine unacclimatized university sportsmen performed a prolonged, intermittent, high-intensity shuttle running test in hot (HT) (33 degrees C, dry bulb temperature, approximately 28 %, relative humidity) and moderate (MT) (17 degrees C, 63 %) environmental conditions. Subjects performed 60 m of walking, a 15-m sprint, 60 m of cruising ( approximately 85 % V.O (2max)), and 60 m of jogging ( approximately 45 %V.O (2max)) for 14.8 +/- 0.1 min followed by a 3-min rest, repeated until volitional exhaustion. The hot trial was performed first followed, 14 days later, by the moderate trial. During exercise subjects drank water ad libitum. Subjects ran almost twice as far in the moderate as in the hot trial (HT 11216 +/- 1411, MT 21644 +/- 1629, m, p < 0.01), and the decline in average 15-m sprint performance was greater in the heat (HT, 0.17 +/- 0.05, MT, 0.09 +/- 0.03, s, p < 0.05). Average heart rates, blood lactate and glucose, and plasma adrenaline and noradrenaline concentrations were greater in the HT (main effect trial, p < 0.01), as were serum cortisol concentration (main effect trial p < 0.05, n = 5) and muscle temperature (HT exhaustion vs. same time point in MT, 40.2 +/- 0.3 vs. 39.3 +/- 0.2, degrees C, p < 0.01). Peak torque during knee flexion and extension was not different pre-and post-exercise in the HT. Muscle glycogen utilization tended to be greater in the heat (HT 193.2 +/- 19.5, MT 143.8 +/- 23.9, mmol . kg dry wt (-1), p = 0.055, n = 8). In 7 out of the 8 subjects the increase in utilization was between 19 and just over 200 % greater in the HT. Glycogen remaining in the muscle at exhaustion was greater in the hot than moderate trial (HT 207.4 +/- 34.3, MT 126.5 +/- 46.8, mmol . kg dry wt (-1), p < 0.01, n = 8). Rectal temperature (T (rec)) was higher in the HT at exhaustion than at the same point in time in the moderate trial (HT, 39.60 +/- 0.15 vs. MT 38.75 +/- 0.10, degrees C, interaction trial-time, p < 0.01). There was a very strong negative

Targeting 100! Advanced Energy Efficient Building Technologies for High Performance Hospitals: Executive Summary.

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

Burpee, Heather; Loveland, Joel; Helmers, Aaron

2015-09-02

This research, Targeting 100!, provides a conceptual framework and decision-making structure at a schematic design level of precision for hospital owners, architects and engineers to radically reduce energy use in hospitals. Following the goals of Architecture 2030 and The 2030 Challenge, it offers access to design strategies and the cost implications of those strategies for new hospitals to utilize 60% less energy. The name, Targeting 100!, comes from the 2030 Challenge energy reduction goal for hospitals; a 60% energy use reduction from typical acute care hospital targets approximately 100 KBtu/SF Year, thus the name “Targeting 100!”. Targeting 100! was developedmore » through funding partnerships with the US Department of Energy and the Northwest Energy Efficiency’s BetterBricks Initiative. The technical team was led by the University of Washington Integrated Design Lab supported by deep collaboration with Solarc Architecture and Engineering, TBD Cost Consultants, and NBBJ Architecture. Through extensive research and design development, Targeting 100! provides a framework for developing high performance healthcare projects today and into the future. An online tool houses a Targeting 100! knowlegebase and roadmap. It can be accessed at: www.idlseattle.com/t100. The webtool is structured from high-level overview materials to detailed library with modeling inputs and outputs, providing a comprehensive report of the background, data, and outcomes from the project.« less

[Preparation and preliminary evaluation of KGDS-targeted ultrasound contrast agent].

PubMed

Gao, Feng; Ding, Yanfei; Sheng, Xiaoxi; Wang, Wei; Liang, Qi; Luo, Zhuoqiong; Zhou, Ping; Li, Hui

2009-12-01

To prepare a thrombus-targeted ultrasonic contrast agent and to investigate its targeted ability to fresh blood clots. We first synthesized FITC-KGDS-Palm compound, and then prepared thrombus-targeted microbubbles using "ultrasound & high speed shearing method". Fluorescence labeling thrombus-specific peptides and KGDS, directed at the activated glycoprotein(GP)IIb/IIIa receptor of platelets were attached to the surface of lipid microbubbles. The concentration and size of TUCA were measured by Malvern Zeta Sizer Nano-ZS590 and Coulter counter. Immunofluorescence was applied to confirm the conjugation. The conjunct ratio was assessed by flow cytometer (FCM). The KGDS-TUCA was straw yellow turbid liquor, and the concentration was 1.5 x 10(9)/mL, and the average size was 1.5 microm. The targeted microbubbles conjugated with the thrombus-specific peptides showed bright green rings by fluorescence microscope. FCM demonstrated that the wavelength of shell of KGDS-TUCA changed greatly, and the conjunct ratio was 90.04%. In vitro study showed KGDS-TUCA remained stable for 48 h at 4 degree C and target-attached to blood clots and showed good stability. The ultrasound & high speed shearing method to prepare TUCA is easy and in favor of purification. KGDS-TUCA has high specific biological activity. The conjunct ratio and stability of KGDS-TUCA are excellent.

Liver as a target for oligonucleotide therapeutics.

PubMed

Sehgal, Alfica; Vaishnaw, Akshay; Fitzgerald, Kevin

2013-12-01

Oligonucleotide-based therapeutics are an emerging class of drugs that hold the promise for silencing "un-druggable" targets,thus creating unique opportunities for innovative medicines. As opposed to gene therapy, oligonucleotides are considered to be more akin to small molecule therapeutics because they are small,completely synthetic in origin, do not integrate into the host genome,and have a defined duration of therapeutic activity after which effects recover to baseline. They offer a high degree of specificity at the genetic level, thereby reducing off-target effects.At the same time, they provide a strategy for targeting any gene in the genome, including transcripts that produce mutated proteins.Oligonucleotide-based therapeutics include short interfering RNA (siRNA), that degrade target mRNA through RISC mediated RNAi; anti-miRs, that target miRNAs; miRNA mimics, that regulate target mRNA; antisense oligonucleotides, that may be working through RNAseH mediated mRNA decay; mRNA upregulation,by targeting long non-coding RNAs; and oligonucleotides induced alternative splicing [1]. All these approaches require some minimal degree of homology at the nucleic acid sequence level for them to be functional. The different mechanisms of action and their relevant activity are outlined in Fig. 1. Besides homology,RNA secondary structure has also been exploited in the case of ribozymes and aptamers, which act by binding to nucleic acids or proteins, respectively. While there have been many reports of gene knockdown and gene modulation in cell lines and mice with all these methods, very few have advanced to clinical stages.The main obstacle to date has been the safe and effective intracellular delivery of these compounds in higher species, including humans. Indeed, their action requires direct interaction with DNA/RNA within the target cell so even when one solves the issues of tissue and cellular access, intracellular/intranuclear location represents yet another barrier to

Targeting tumor highly-expressed LAT1 transporter with amino acid-modified nanoparticles: Toward a novel active targeting strategy in breast cancer therapy.

PubMed

Li, Lin; Di, Xingsheng; Wu, Mingrui; Sun, Zhisu; Zhong, Lu; Wang, Yongjun; Fu, Qiang; Kan, Qiming; Sun, Jin; He, Zhonggui

2017-04-01

Designing active targeting nanocarriers with increased cellular accumulation of chemotherapeutic agents is a promising strategy in cancer therapy. Herein, we report a novel active targeting strategy based on the large amino acid transporter 1 (LAT1) overexpressed in a variety of cancers. Glutamate was conjugated to polyoxyethylene stearate as a targeting ligand to achieve LAT1-targeting PLGA nanoparticles. The targeting efficiency of nanoparticles was investigated in HeLa and MCF-7 cells. Significant increase in cellular uptake and cytotoxicity was observed in LAT1-targeting nanoparticles compared to the unmodified ones. More interestingly, the internalized LAT1 together with targeting nanoparticles could recycle back to the cell membrane within 3 h, guaranteeing sufficient transporters on cell membrane for continuous cellular uptake. The LAT1 targeting nanoparticles exhibited better tumor accumulation and antitumor effects. These results suggested that the overexpressed LAT1 on cancer cells holds a great potential to be a high-efficiency target for the rational design of active-targeting nanosystems. Copyright © 2016 Elsevier Inc. All rights reserved.

Deciphering the genomic targets of alkylating polyamide conjugates using high-throughput sequencing

PubMed Central

Chandran, Anandhakumar; Syed, Junetha; Taylor, Rhys D.; Kashiwazaki, Gengo; Sato, Shinsuke; Hashiya, Kaori; Bando, Toshikazu; Sugiyama, Hiroshi

2016-01-01

Chemically engineered small molecules targeting specific genomic sequences play an important role in drug development research. Pyrrole-imidazole polyamides (PIPs) are a group of molecules that can bind to the DNA minor-groove and can be engineered to target specific sequences. Their biological effects rely primarily on their selective DNA binding. However, the binding mechanism of PIPs at the chromatinized genome level is poorly understood. Herein, we report a method using high-throughput sequencing to identify the DNA-alkylating sites of PIP-indole-seco-CBI conjugates. High-throughput sequencing analysis of conjugate 2 showed highly similar DNA-alkylating sites on synthetic oligos (histone-free DNA) and on human genomes (chromatinized DNA context). To our knowledge, this is the first report identifying alkylation sites across genomic DNA by alkylating PIP conjugates using high-throughput sequencing. PMID:27098039

Protograph LDPC Codes with Node Degrees at Least 3

NASA Technical Reports Server (NTRS)

Divsalar, Dariush; Jones, Christopher

2006-01-01

In this paper we present protograph codes with a small number of degree-3 nodes and one high degree node. The iterative decoding threshold for proposed rate 1/2 codes are lower, by about 0.2 dB, than the best known irregular LDPC codes with degree at least 3. The main motivation is to gain linear minimum distance to achieve low error floor. Also to construct rate-compatible protograph-based LDPC codes for fixed block length that simultaneously achieves low iterative decoding threshold and linear minimum distance. We start with a rate 1/2 protograph LDPC code with degree-3 nodes and one high degree node. Higher rate codes are obtained by connecting check nodes with degree-2 non-transmitted nodes. This is equivalent to constraint combining in the protograph. The condition where all constraints are combined corresponds to the highest rate code. This constraint must be connected to nodes of degree at least three for the graph to have linear minimum distance. Thus having node degree at least 3 for rate 1/2 guarantees linear minimum distance property to be preserved for higher rates. Through examples we show that the iterative decoding threshold as low as 0.544 dB can be achieved for small protographs with node degrees at least three. A family of low- to high-rate codes with minimum distance linearly increasing in block size and with capacity-approaching performance thresholds is presented. FPGA simulation results for a few example codes show that the proposed codes perform as predicted.

Impact of Degree Heterogeneity on Attack Vulnerability of Interdependent Networks

NASA Astrophysics Data System (ADS)

Sun, Shiwen; Wu, Yafang; Ma, Yilin; Wang, Li; Gao, Zhongke; Xia, Chengyi

2016-09-01

The study of interdependent networks has become a new research focus in recent years. We focus on one fundamental property of interdependent networks: vulnerability. Previous studies mainly focused on the impact of topological properties upon interdependent networks under random attacks, the effect of degree heterogeneity on structural vulnerability of interdependent networks under intentional attacks, however, is still unexplored. In order to deeply understand the role of degree distribution and in particular degree heterogeneity, we construct an interdependent system model which consists of two networks whose extent of degree heterogeneity can be controlled simultaneously by a tuning parameter. Meanwhile, a new quantity, which can better measure the performance of interdependent networks after attack, is proposed. Numerical simulation results demonstrate that degree heterogeneity can significantly increase the vulnerability of both single and interdependent networks. Moreover, it is found that interdependent links between two networks make the entire system much more fragile to attacks. Enhancing coupling strength between networks can greatly increase the fragility of both networks against targeted attacks, which is most evident under the case of max-max assortative coupling. Current results can help to deepen the understanding of structural complexity of complex real-world systems.

When Graduate Degrees Prostitute the Educational Process: Degrees Gone Wild

ERIC Educational Resources Information Center

Lumadue, Richard T.

2006-01-01

Graduate degrees prostitute the educational process when they are sold to consumers by unaccredited degree/diploma mills as being equivalent to legitimate, bona-fide degrees awarded by accredited graduate schools. This article carefully analyzes the serious problems of bogus degrees and their association with the religious higher education…

Microfabricated Ion Beam Drivers for Magnetized Target Fusion

NASA Astrophysics Data System (ADS)

Persaud, Arun; Seidl, Peter; Ji, Qing; Ardanuc, Serhan; Miller, Joseph; Lal, Amit; Schenkel, Thomas

2015-11-01

Efficient, low-cost drivers are important for Magnetized Target Fusion (MTF). Ion beams offer a high degree of control to deliver the required mega joules of driver energy for MTF and they can be matched to several types of magnetized fuel targets, including compact toroids and solid targets. We describe an ion beam driver approach based on the MEQALAC concept (Multiple Electrostatic Quadrupole Array Linear Accelerator) with many beamlets in an array of micro-fabricated channels. The channels consist of a lattice of electrostatic quadrupoles (ESQ) for focusing and of radio-frequency (RF) electrodes for ion acceleration. Simulations with particle-in-cell and beam envelope codes predict >10x higher current densities compared to state-of-the-art ion accelerators. This increase results from dividing the total ion beam current up into many beamlets to control space charge forces. Focusing elements can be biased taking advantage of high breakdown electric fields in sub-mm structures formed using MEMS techniques (Micro-Electro-Mechanical Systems). We will present results on ion beam transport and acceleration in MEMS based beamlets. Acknowledgments: This work is supported by the U.S. DOE under Contract No. DE-AC02-05CH11231.

Field precision machining technology of target chamber in ICF lasers

NASA Astrophysics Data System (ADS)

Xu, Yuanli; Wu, Wenkai; Shi, Sucun; Duan, Lin; Chen, Gang; Wang, Baoxu; Song, Yugang; Liu, Huilin; Zhu, Mingzhi

2016-10-01

In ICF lasers, many independent laser beams are required to be positioned on target with a very high degree of accuracy during a shot. The target chamber provides a precision platform and datum reference for final optics assembly and target collimation and location system. The target chamber consists of shell with welded flanges, reinforced concrete pedestal, and lateral support structure. The field precision machining technology of target chamber in ICF lasers have been developed based on ShenGuangIII (SGIII). The same center of the target chamber is adopted in the process of design, fabrication, and alignment. The technologies of beam collimation and datum reference transformation are developed for the fabrication, positioning and adjustment of target chamber. A supporting and rotating mechanism and a special drilling machine are developed to bore the holes of ports. An adjustment mechanism is designed to accurately position the target chamber. In order to ensure the collimation requirements of the beam leading and focusing and the target positioning, custom-machined spacers are used to accurately correct the alignment error of the ports. Finally, this paper describes the chamber center, orientation, and centering alignment error measurements of SGIII. The measurements show the field precision machining of SGIII target chamber meet its design requirement. These information can be used on similar systems.

Comparison of therapeutic lipid target achievements among high-risk patients in Oman.

PubMed

Al-Waili, Khalid; Al-Zakwani, Ibrahim; Al-Dughaishi, Tamima; Baneerje, Yajnavalka; Al-Sabti, Hilal; Al-Hashmi, Khamis; Farhan, Hatem; Habsi, Khadija Al; Al-Hinai, Ali T; Al-Rasadi, Khalid

2014-05-01

We compared therapeutic lipid target achievements among patients with diabetes or coronary heart disease (CHD) in Oman. A retrospective chart review of 94 patients was conducted at an outpatient clinic in Sultan Qaboos University Hospital, Muscat, Oman. The variables included low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and apolipoprotein B (apo B). The overall mean age of the cohort was 59 ± 12 years, 54% were male, 66% were diabetic, 48% hypertensive, 45% had CHD, 94% were on simvastatin, 4% were on fenofibrate, and 2% were on both simvastatin and fenofibrate. Lipid goal attainments of calculated LDL-C (<2.6 mmol/L), apo B (<0.9 g/L), and non-HDL-C (<3.36 mmol/L) were reached in 52%, 39%, and 53% of the patients, respectively. A significant proportion of high-risk patients treated with lipid-lowering agents reach LDL-C but not the apo B treatment targets, suggesting that the use of apo B target values should also be considered.

PMHT Approach for Multi-Target Multi-Sensor Sonar Tracking in Clutter.

PubMed

Li, Xiaohua; Li, Yaan; Yu, Jing; Chen, Xiao; Dai, Miao

2015-11-06

Multi-sensor sonar tracking has many advantages, such as the potential to reduce the overall measurement uncertainty and the possibility to hide the receiver. However, the use of multi-target multi-sensor sonar tracking is challenging because of the complexity of the underwater environment, especially the low target detection probability and extremely large number of false alarms caused by reverberation. In this work, to solve the problem of multi-target multi-sensor sonar tracking in the presence of clutter, a novel probabilistic multi-hypothesis tracker (PMHT) approach based on the extended Kalman filter (EKF) and unscented Kalman filter (UKF) is proposed. The PMHT can efficiently handle the unknown measurements-to-targets and measurements-to-transmitters data association ambiguity. The EKF and UKF are used to deal with the high degree of nonlinearity in the measurement model. The simulation results show that the proposed algorithm can improve the target tracking performance in a cluttered environment greatly, and its computational load is low.

Air Force Officer Accession Planning: Addressing Key Gaps in Meeting Career Field Academic Degree Requirements for Nonrated Officers

DTIC Science & Technology

2016-06-09

C O R P O R A T I O N Research Report Air Force Officer Accession Planning Addressing Key Gaps in Meeting Career Field Academic Degree Requirements...various Air Force missions in particular career fields. Key to this goal for nonrated officers is establishing and enforcing academic degree...35 Developing Accession Targets by Academic Degree Type

Target isolation system, high power laser and laser peening method and system using same

DOEpatents

Dane, C. Brent; Hackel, Lloyd A.; Harris, Fritz

2007-11-06

A system for applying a laser beam to work pieces, includes a laser system producing a high power output beam. Target delivery optics are arranged to deliver the output beam to a target work piece. A relay telescope having a telescope focal point is placed in the beam path between the laser system and the target delivery optics. The relay telescope relays an image between an image location near the output of the laser system and an image location near the target delivery optics. A baffle is placed at the telescope focal point between the target delivery optics and the laser system to block reflections from the target in the target delivery optics from returning to the laser system and causing damage.

High or Low Target Prevalence Increases the Dual-Target Cost in Visual Search

ERIC Educational Resources Information Center

Menneer, Tamaryn; Donnelly, Nick; Godwin, Hayward J.; Cave, Kyle R.

2010-01-01

Previous studies have demonstrated a dual-target cost in visual search. In the current study, the relationship between search for one and search for two targets was investigated to examine the effects of target prevalence and practice. Color-shape conjunction stimuli were used with response time, accuracy and signal detection measures. Performance…

Infrared maritime target detection using the high order statistic filtering in fractional Fourier domain

NASA Astrophysics Data System (ADS)

Zhou, Anran; Xie, Weixin; Pei, Jihong

2018-06-01

Accurate detection of maritime targets in infrared imagery under various sea clutter conditions is always a challenging task. The fractional Fourier transform (FRFT) is the extension of the Fourier transform in the fractional order, and has richer spatial-frequency information. By combining it with the high order statistic filtering, a new ship detection method is proposed. First, the proper range of angle parameter is determined to make it easier for the ship components and background to be separated. Second, a new high order statistic curve (HOSC) at each fractional frequency point is designed. It is proved that maximal peak interval in HOSC reflects the target information, while the points outside the interval reflect the background. And the value of HOSC relative to the ship is much bigger than that to the sea clutter. Then, search the curve's maximal target peak interval and extract the interval by bandpass filtering in fractional Fourier domain. The value outside the peak interval of HOSC decreases rapidly to 0, so the background is effectively suppressed. Finally, the detection result is obtained by the double threshold segmenting and the target region selection method. The results show the proposed method is excellent for maritime targets detection with high clutters.

Increased effect of target eccentricity on covert shifts of visual attention in patients with neglect.

PubMed

Hamilton, Roy H; Stark, Marianna; Coslett, H Branch

2010-01-01

Debate continues regarding the mechanisms underlying covert shifts of visual attention. We examined the relationship between target eccentricity and the speed of covert shifts of attention in normal subjects and patients with brain lesions using a cued-response task in which cues and targets were presented at 2 degrees or 8 degrees lateral to the fixation point. Normal subjects were slower on invalid trials in the 8 degrees as compared to 2 degrees condition. Patients with right-hemisphere stroke with neglect were slower in their responses to left-sided invalid targets compared to valid targets, and demonstrated a significant increase in the effect of target validity as a function of target eccentricity. Additional data from one neglect patient (JM) demonstrated an exaggerated validity x eccentricity x side interaction for contralesional targets on a cued reaction time task with a central (arrow) cue. We frame these results in the context of a continuous 'moving spotlight' model of attention, and also consider the potential role of spatial saliency maps. By either account, we argue that neglect is characterized by an eccentricity-dependent deficit in the allocation of attention.

PREFACE: 1st Tensor Polarized Solid Target Workshop

NASA Astrophysics Data System (ADS)

2014-10-01

These are the proceedings of the first Tensor Spin Observables Workshop that was held in March 2014 at the Thomas Jefferson National Accelerator Facility in Newport News, Virginia. The conference was convened to study the physics that can be done with the recently approved E12-13-011 polarized target. A tensor polarized target holds the potential of initiating a new generation of tensor spin physics at Jefferson Lab. Experiments which utilize tensor polarized targets can help clarify how nuclear properties arise from partonic degrees of freedom, provide unique insight into short-range correlations and quark angular momentum, and also help pin down the polarization of the quark sea with a future Electron Ion Collider. This three day workshop was focused on tensor spin observables and the associated tensor target development. The workshop goals were to stimulate progress in the theoretical treatment of polarized spin-1 systems, foster the development of new proposals, and to reach a consensus on the optimal polarized target configuration for the tensor spin program. The workshop was sponsored by the University of New Hampshire, the Jefferson Science Associates, Florida International University, and Jefferson Lab. It was organized by Karl Slifer (chair), Patricia Solvignon, and Elena Long of the University of New Hampshire, Douglas Higinbotham and Christopher Keith of Jefferson Lab, and Misak Sargsian of the Florida International University. These proceedings represent the effort put forth by the community to begin exploring the possibilities that a high-luminosity, high-tensor polarized solid target can offer.

Highly multiplexed targeted DNA sequencing from single nuclei.

PubMed

Leung, Marco L; Wang, Yong; Kim, Charissa; Gao, Ruli; Jiang, Jerry; Sei, Emi; Navin, Nicholas E

2016-02-01

Single-cell DNA sequencing methods are challenged by poor physical coverage, high technical error rates and low throughput. To address these issues, we developed a single-cell DNA sequencing protocol that combines flow-sorting of single nuclei, time-limited multiple-displacement amplification (MDA), low-input library preparation, DNA barcoding, targeted capture and next-generation sequencing (NGS). This approach represents a major improvement over our previous single nucleus sequencing (SNS) Nature Protocols paper in terms of generating higher-coverage data (>90%), thereby enabling the detection of genome-wide variants in single mammalian cells at base-pair resolution. Furthermore, by pooling 48-96 single-cell libraries together for targeted capture, this approach can be used to sequence many single-cell libraries in parallel in a single reaction. This protocol greatly reduces the cost of single-cell DNA sequencing, and it can be completed in 5-6 d by advanced users. This single-cell DNA sequencing protocol has broad applications for studying rare cells and complex populations in diverse fields of biological research and medicine.

Target-Oriented High-Resolution SAR Image Formation via Semantic Information Guided Regularizations

NASA Astrophysics Data System (ADS)

Hou, Biao; Wen, Zaidao; Jiao, Licheng; Wu, Qian

2018-04-01

Sparsity-regularized synthetic aperture radar (SAR) imaging framework has shown its remarkable performance to generate a feature enhanced high resolution image, in which a sparsity-inducing regularizer is involved by exploiting the sparsity priors of some visual features in the underlying image. However, since the simple prior of low level features are insufficient to describe different semantic contents in the image, this type of regularizer will be incapable of distinguishing between the target of interest and unconcerned background clutters. As a consequence, the features belonging to the target and clutters are simultaneously affected in the generated image without concerning their underlying semantic labels. To address this problem, we propose a novel semantic information guided framework for target oriented SAR image formation, which aims at enhancing the interested target scatters while suppressing the background clutters. Firstly, we develop a new semantics-specific regularizer for image formation by exploiting the statistical properties of different semantic categories in a target scene SAR image. In order to infer the semantic label for each pixel in an unsupervised way, we moreover induce a novel high-level prior-driven regularizer and some semantic causal rules from the prior knowledge. Finally, our regularized framework for image formation is further derived as a simple iteratively reweighted $\\ell_1$ minimization problem which can be conveniently solved by many off-the-shelf solvers. Experimental results demonstrate the effectiveness and superiority of our framework for SAR image formation in terms of target enhancement and clutters suppression, compared with the state of the arts. Additionally, the proposed framework opens a new direction of devoting some machine learning strategies to image formation, which can benefit the subsequent decision making tasks.

Dishonorary Degrees

ERIC Educational Resources Information Center

Romano, Carlin

2008-01-01

If an honorary degree lacks values to begin with, does withdrawing it deliver a rebuke to the recipient? Is whatever honor that comes with the distinction embedded in the fancy paper, or is it wholly in the eye of the degree holder? Are honorary degrees really such silly things that individuals should mock their bestowal or withdrawal? The case of…

Exact sampling of graphs with prescribed degree correlations

NASA Astrophysics Data System (ADS)

Bassler, Kevin E.; Del Genio, Charo I.; Erdős, Péter L.; Miklós, István; Toroczkai, Zoltán

2015-08-01

Many real-world networks exhibit correlations between the node degrees. For instance, in social networks nodes tend to connect to nodes of similar degree and conversely, in biological and technological networks, high-degree nodes tend to be linked with low-degree nodes. Degree correlations also affect the dynamics of processes supported by a network structure, such as the spread of opinions or epidemics. The proper modelling of these systems, i.e., without uncontrolled biases, requires the sampling of networks with a specified set of constraints. We present a solution to the sampling problem when the constraints imposed are the degree correlations. In particular, we develop an exact method to construct and sample graphs with a specified joint-degree matrix, which is a matrix providing the number of edges between all the sets of nodes of a given degree, for all degrees, thus completely specifying all pairwise degree correlations, and additionally, the degree sequence itself. Our algorithm always produces independent samples without backtracking. The complexity of the graph construction algorithm is {O}({NM}) where N is the number of nodes and M is the number of edges.

Identifying apicoplast-targeting antimalarials using high-throughput compatible approaches

PubMed Central

Ekland, Eric H.; Schneider, Jessica; Fidock, David A.

2011-01-01

Malarial parasites have evolved resistance to all previously used therapies, and recent evidence suggests emerging resistance to the first-line artemisinins. To identify antimalarials with novel mechanisms of action, we have developed a high-throughput screen targeting the apicoplast organelle of Plasmodium falciparum. Antibiotics known to interfere with this organelle, such as azithromycin, exhibit an unusual phenotype whereby the progeny of drug-treated parasites die. Our screen exploits this phenomenon by assaying for “delayed death” compounds that exhibit a higher potency after two cycles of intraerythrocytic development compared to one. We report a primary assay employing parasites with an integrated copy of a firefly luciferase reporter gene and a secondary flow cytometry-based assay using a nucleic acid stain paired with a mitochondrial vital dye. Screening of the U.S. National Institutes of Health Clinical Collection identified known and novel antimalarials including kitasamycin. This inexpensive macrolide, used for agricultural applications, exhibited an in vitro IC50 in the 50 nM range, comparable to the 30 nM activity of our control drug, azithromycin. Imaging and pharmacologic studies confirmed kitasamycin action against the apicoplast, and in vivo activity was observed in a murine malaria model. These assays provide the foundation for high-throughput campaigns to identify novel chemotypes for combination therapies to treat multidrug-resistant malaria.—Ekland, E. H., Schneider, J., Fidock, D. A. Identifying apicoplast-targeting antimalarials using high-throughput compatible approaches. PMID:21746861

Analysis of the infrared detection system operating range based on polarization degree

NASA Astrophysics Data System (ADS)

Jiang, Kai; Liu, Wen; Liu, Kai; Duan, Jing; Yan, Pei-pei; Shan, Qiu-sha

2018-02-01

Infrared polarization detection technology has unique advantages in the field of target detection and identification because of using the polarization information of radiation. The mechanism of infrared polarization is introduced. Comparing with traditional infrared detection distance model, infrared detection operating range and Signal to Noise Ratio (SNR) model is built according to the polarization degree and noise. The influence of polarization degree on the SNR of infrared system is analyzed. At last, the basic condition of polarization detection SNR better than traditional infrared detection SNR is obtained.

Target Discovery for Precision Medicine Using High-Throughput Genome Engineering.

PubMed

Guo, Xinyi; Chitale, Poonam; Sanjana, Neville E

2017-01-01

Over the past few years, programmable RNA-guided nucleases such as the CRISPR/Cas9 system have ushered in a new era of precision genome editing in diverse model systems and in human cells. Functional screens using large libraries of RNA guides can interrogate a large hypothesis space to pinpoint particular genes and genetic elements involved in fundamental biological processes and disease-relevant phenotypes. Here, we review recent high-throughput CRISPR screens (e.g. loss-of-function, gain-of-function, and targeting noncoding elements) and highlight their potential for uncovering novel therapeutic targets, such as those involved in cancer resistance to small molecular drugs and immunotherapies, tumor evolution, infectious disease, inborn genetic disorders, and other therapeutic challenges.

Lens positioner with five degrees of freedom

DOEpatents

Kobierecki, Marian W.; Rienecker, Jr., Frederick

1978-01-01

A device for positioning lenses precisely with five degrees of freedom (three translations and two angular rotations). The unique features of the device are its compact design, large clear aperture, and high degree of positioning accuracy combined with five degrees of freedom in axis motion. Thus, the device provides precision and flexibility in positioning of optical components. BACKGROUND OF THE INVENTION The invention described herein was made in the course of, or under, Contract No. AT(29-1)-1183, with the United States Energy Research and Development Administration.

Your College Degree: The External Degree Way.

ERIC Educational Resources Information Center

Haponski, William C.; And Others

Information on undertaking an external degree program to obtain a college education is presented. An external degree program is one that has no, or minimal requirements for residence (on-campus attendance). Most often it can be entered at any time of the year and usually grants credit for documented learning already acquired. An external degree…

Policy Statements for the Associate Degree, the Associate in Applied Science Degree, and the Associate Degree in Nursing.

ERIC Educational Resources Information Center

American Association of Community and Junior Colleges, Washington, DC.

The policy statements contained in this document present the position of the American Association of Community and Junior Colleges (AACJC) on the Associate Degree, the Associate in Applied Science Degree (AAS), and the Associate Degree in Nursing. In its statement on the Associate Degree, the AACJC: (1) stresses the responsibility of faculty and…

Cross Section Measurements Using the Zero Degree Detector

NASA Technical Reports Server (NTRS)

Christl, M. J.; Adams, J. H., Jr.; Heilbronn, L.; Kuznetsov, E. N.; Miller, J.; Zeitlin, C.

2007-01-01

The Zero Degree Detector (ZDD) is an instrument that has been used in accelerator exposures to measure the angular dependence of particles produced in heavy ion fragmentation experiments. The ZDD uses two identical layers of pixelated silicon detectors that make coincident measurements over the active area of the instrument. The angular distribution of secondary particle produced in nuclear interactions for several heavy ions: and target materials will be presented along with performance characteristic of the instrument.

Target Surface Area Effects on Hot Electron Dynamics from High Intensity Laser-Plasma Interactions

DTIC Science & Technology

2016-08-19

New J. Phys. 18 (2016) 063020 doi:10.1088/1367-2630/18/6/063020 PAPER Target surface area effects on hot electron dynamics from high intensity laser ...Science, University ofMichigan, AnnArbor,MI 48109-2099, USA E-mail: czulick@umich.edu Keywords: laser -plasma,mass-limited, fast electrons, sheath...field Abstract Reduced surface area targets were studied using an ultra-high intensity femtosecond laser in order to determine the effect of electron

Laser acceleration of protons using multi-ion plasma gaseous targets

DOE PAGES

Liu, Tung -Chang; Shao, Xi; Liu, Chuan -Sheng; ...

2015-02-01

We present a theoretical and numerical study of a novel acceleration scheme by applying a combination of laser radiation pressure and shielded Coulomb repulsion in laser acceleration of protons in multi-species gaseous targets. By using a circularly polarized CO₂ laser pulse with a wavelength of 10 μm—much greater than that of a Ti: Sapphire laser—the critical density is significantly reduced, and a high-pressure gaseous target can be used to achieve an overdense plasma. This gives us a larger degree of freedom in selecting the target compounds or mixtures, as well as their density and thickness profiles. By impinging such amore » laser beam on a carbon–hydrogen target, the gaseous target is first compressed and accelerated by radiation pressure until the electron layer disrupts, after which the protons are further accelerated by the electron-shielded carbon ion layer. An 80 MeV quasi-monoenergetic proton beam can be generated using a half-sine shaped laser beam with a peak power of 70 TW and a pulse duration of 150 wave periods.« less

High-capacity quantum key distribution via hyperentangled degrees of freedom

NASA Astrophysics Data System (ADS)

Simon, David S.; Sergienko, Alexander V.

2014-06-01

Quantum key distribution (QKD) has long been a promising area for the application of quantum effects in solving real-world problems. However, two major obstacles have stood in the way of its widespread application: low secure key generation rates and short achievable operating distances. In this paper, a new physical mechanism for dealing with the first of these problems is proposed: the interplay between different degrees of freedom in a hyperentangled system (parametric down-conversion) is used to increase the Hilbert space dimension available for key generation while maintaining security. Polarization-based Bell tests provide security checking, while orbital angular momentum (OAM) and total angular momentum (TAM) provide a higher key generation rate. Whether to measure TAM or OAM is decided randomly in each trial. The concurrent noncommutativity of TAM with OAM and polarization provides the physical basis for quantum security. TAM measurements link polarization to OAM, so that if the legitimate participants measure OAM while the eavesdropper measures TAM (or vice-versa), then polarization entanglement is lost, revealing the eavesdropper. In contrast to other OAM-based QKD methods, complex active switching between OAM bases is not required; instead, passive switching by beam splitters combined with much simpler active switching between polarization bases makes implementation at high OAM more practical.

Phase Decomposition in the Fe-rich Fe-Ni-S System from 900 Degrees C to 300 Degrees C--Application to Meteoritic Metal

NASA Astrophysics Data System (ADS)

Ma, L.; Williams, D. B.; Goldstein, J. I.

1995-09-01

It has been observed that metal particles in ordinary chondrites contain essentially no P and that the tetrataenite rim of the metal particles is much wider than that in other types of meteorites, especially when the taenite rim abuts troilites (FeS) [1]. It is possible that S plays an important role in the formation of the zoned tetrataenite at low cooling temperatures. Most of the studies of the Fe-Ni-S system have concentrated on high temperature and high Ni-high S part of the ternary diagram [2][3]. In this study we have systematically investigated the microstructure and microchemistry of the Fe-rich Fe-Ni-S system in regions where meteoritic metal forms from 900 degrees C down to 300 degrees C. High spatial resolution electron probe microanalysis (EPMA) and analytical electron microscopy (AEM) techniques were employed. The two and three phase boundaries at high temperatures (900 degrees C to 600 degrees C) are consistent with previous studies. However, at 500 degrees C, an Fe-Ni phase with 51.6 +/- 1.4 wt.% Ni was observed to form along some of the g/g and g/FeS boundaries. The size of this Fe-Ni phase is as large as 10 micrometers in width. AEM analysis indicates that this Fe-Ni phase may have even higher Ni content, 56 wt.%. In addition, the phase has a FCC structure and is disordered. Because the composition of this phase is very close to the stoichiometric composition of FeNi, it is very likely that the phase is tetrataenite. High Ni precipitates with similar morphology were also observed in the Fe-Ni-S alloy aged at 400 degrees C. However, the Ni content is 60.9 +/- 4.0 wt.% measured with EPMA, which is much higher than that in the corresponding 500 degree C sample. The fact that all the high Ni precipitates formed at boundaries of g/g or g/FeS indicates the boundaries are favorable energy nucleation sites. Such a high Ni phase with a Ni content over 60 wt.% has not been observed in the Fe-Ni and Fe-Ni (P) systems above 400 degrees C. The tetrataenite

Target surface area effects on hot electron dynamics from high intensity laser–plasma interactions

DOE PAGES

Zulick, C.; Raymond, A.; McKelvey, A.; ...

2016-06-15

Reduced surface area targets were studied using an ultra-high intensity femtosecond laser in order to determine the effect of electron sheath field confinement on electron dynamics. X-ray emission due to energetic electrons was imaged using a K α imaging crystal. Electrons were observed to travel along the surface of wire targets, and were slowed mainly by the induced fields. Targets with reduced surface areas were correlated with increased hot electron densities and proton energies. Furthermore, Hybrid Vlasov–Fokker–Planck simulations demonstrated increased electric sheath field strength in reduced surface area targets.

Targeted protein degradation by PROTACs.

PubMed

Neklesa, Taavi K; Winkler, James D; Crews, Craig M

2017-06-01

Targeted protein degradation using the PROTAC technology is emerging as a novel therapeutic method to address diseases driven by the aberrant expression of a disease-causing protein. PROTAC molecules are bifunctional small molecules that simultaneously bind a target protein and an E3-ubiquitin ligase, thus causing ubiquitination and degradation of the target protein by the proteasome. Like small molecules, PROTAC molecules possess good tissue distribution and the ability to target intracellular proteins. Herein, we highlight the advantages of protein degradation using PROTACs, and provide specific examples where degradation offers therapeutic benefit over classical enzyme inhibition. Foremost, PROTACs can degrade proteins regardless of their function. This includes the currently "undruggable" proteome, which comprises approximately 85% of all human proteins. Other beneficial aspects of protein degradation include the ability to target overexpressed and mutated proteins, as well as the potential to demonstrate prolonged pharmacodynamics effect beyond drug exposure. Lastly, due to their catalytic nature and the pre-requisite ubiquitination step, an exquisitely potent molecules with a high degree of degradation selectivity can be designed. Impressive preclinical in vitro and in vivo PROTAC data have been published, and these data have propelled the development of clinically viable PROTACs. With the molecular weight falling in the 700-1000Da range, the delivery and bioavailability of PROTACs remain the largest hurdles on the way to the clinic. Solving these issues and demonstrating proof of concept clinical data will be the focus of many labs over the next few years. Copyright © 2017 Elsevier Inc. All rights reserved.

A MATLAB-based graphical user interface program for computing functionals of the geopotential up to ultra-high degrees and orders

NASA Astrophysics Data System (ADS)

Bucha, Blažej; Janák, Juraj

2013-07-01

We present a novel graphical user interface program GrafLab (GRAvity Field LABoratory) for spherical harmonic synthesis (SHS) created in MATLAB®. This program allows to comfortably compute 38 various functionals of the geopotential up to ultra-high degrees and orders of spherical harmonic expansion. For the most difficult part of the SHS, namely the evaluation of the fully normalized associated Legendre functions (fnALFs), we used three different approaches according to required maximum degree: (i) the standard forward column method (up to maximum degree 1800, in some cases up to degree 2190); (ii) the modified forward column method combined with Horner's scheme (up to maximum degree 2700); (iii) the extended-range arithmetic (up to an arbitrary maximum degree). For the maximum degree 2190, the SHS with fnALFs evaluated using the extended-range arithmetic approach takes only approximately 2-3 times longer than its standard arithmetic counterpart, i.e. the standard forward column method. In the GrafLab, the functionals of the geopotential can be evaluated on a regular grid or point-wise, while the input coordinates can either be read from a data file or entered manually. For the computation on a regular grid we decided to apply the lumped coefficients approach due to significant time-efficiency of this method. Furthermore, if a full variance-covariances matrix of spherical harmonic coefficients is available, it is possible to compute the commission errors of the functionals. When computing on a regular grid, the output functionals or their commission errors may be depicted on a map using automatically selected cartographic projection.

A robust close-range photogrammetric target extraction algorithm for size and type variant targets

NASA Astrophysics Data System (ADS)

Nyarko, Kofi; Thomas, Clayton; Torres, Gilbert

2016-05-01

The Photo-G program conducted by Naval Air Systems Command at the Atlantic Test Range in Patuxent River, Maryland, uses photogrammetric analysis of large amounts of real-world imagery to characterize the motion of objects in a 3-D scene. Current approaches involve several independent processes including target acquisition, target identification, 2-D tracking of image features, and 3-D kinematic state estimation. Each process has its own inherent complications and corresponding degrees of both human intervention and computational complexity. One approach being explored for automated target acquisition relies on exploiting the pixel intensity distributions of photogrammetric targets, which tend to be patterns with bimodal intensity distributions. The bimodal distribution partitioning algorithm utilizes this distribution to automatically deconstruct a video frame into regions of interest (ROI) that are merged and expanded to target boundaries, from which ROI centroids are extracted to mark target acquisition points. This process has proved to be scale, position and orientation invariant, as well as fairly insensitive to global uniform intensity disparities.

A manifold learning approach to target detection in high-resolution hyperspectral imagery

NASA Astrophysics Data System (ADS)

Ziemann, Amanda K.

Imagery collected from airborne platforms and satellites provide an important medium for remotely analyzing the content in a scene. In particular, the ability to detect a specific material within a scene is of high importance to both civilian and defense applications. This may include identifying "targets" such as vehicles, buildings, or boats. Sensors that process hyperspectral images provide the high-dimensional spectral information necessary to perform such analyses. However, for a d-dimensional hyperspectral image, it is typical for the data to inherently occupy an m-dimensional space, with m << d. In the remote sensing community, this has led to a recent increase in the use of manifold learning, which aims to characterize the embedded lower-dimensional, non-linear manifold upon which the hyperspectral data inherently lie. Classic hyperspectral data models include statistical, linear subspace, and linear mixture models, but these can place restrictive assumptions on the distribution of the data; this is particularly true when implementing traditional target detection approaches, and the limitations of these models are well-documented. With manifold learning based approaches, the only assumption is that the data reside on an underlying manifold that can be discretely modeled by a graph. The research presented here focuses on the use of graph theory and manifold learning in hyperspectral imagery. Early work explored various graph-building techniques with application to the background model of the Topological Anomaly Detection (TAD) algorithm, which is a graph theory based approach to anomaly detection. This led towards a focus on target detection, and in the development of a specific graph-based model of the data and subsequent dimensionality reduction using manifold learning. An adaptive graph is built on the data, and then used to implement an adaptive version of locally linear embedding (LLE). We artificially induce a target manifold and incorporate it into

Health risks of space exploration: targeted and nontargeted oxidative injury by high-charge and high-energy particles.

PubMed

Li, Min; Gonon, Géraldine; Buonanno, Manuela; Autsavapromporn, Narongchai; de Toledo, Sonia M; Pain, Debkumar; Azzam, Edouard I

2014-03-20

During deep space travel, astronauts are often exposed to high atomic number (Z) and high-energy (E) (high charge and high energy [HZE]) particles. On interaction with cells, these particles cause severe oxidative injury and result in unique biological responses. When cell populations are exposed to low fluences of HZE particles, a significant fraction of the cells are not traversed by a primary radiation track, and yet, oxidative stress induced in the targeted cells may spread to nearby bystander cells. The long-term effects are more complex because the oxidative effects persist in progeny of the targeted and affected bystander cells, which promote genomic instability and may increase the risk of age-related cancer and degenerative diseases. Greater understanding of the spatial and temporal features of reactive oxygen species bursts along the tracks of HZE particles, and the availability of facilities that can simulate exposure to space radiations have supported the characterization of oxidative stress from targeted and nontargeted effects. The significance of secondary radiations generated from the interaction of the primary HZE particles with biological material and the mitigating effects of antioxidants on various cellular injuries are central to understanding nontargeted effects and alleviating tissue injury. Elucidation of the mechanisms underlying the cellular responses to HZE particles, particularly under reduced gravity and situations of exposure to additional radiations, such as protons, should be useful in reducing the uncertainty associated with current models for predicting long-term health risks of space radiation. These studies are also relevant to hadron therapy of cancer.

The Effects of Moderate- and High-Fidelity Patient Simulator Use on Critical Thinking in Associate Degree Nursing Students

ERIC Educational Resources Information Center

Vieck, Jana

2013-01-01

The purpose of this study was to examine the impact of moderate- and high-fidelity patient simulator use on the critical thinking skills of associate degree nursing students. This quantitative study used a quasi-experimental design and the Health Sciences Reasoning Test (HSRT) to evaluate the critical thinking skills of third semester nursing…

Design of a liquid membrane target for high repetition rate neutron generation

NASA Astrophysics Data System (ADS)

Poole, Patrick; Andereck, C. David; Storm, Mike; Schumacher, Douglass

2013-10-01

Ultra-bright, pulsed, spatially-small sources of energetic neutrons have applications in radiography and non-destructive remote sensing. Neutrons can be generated by a process wherein ions accelerated from a laser-irradiated primary target subsequently bombard a converter material, causing neutron-producing nuclear reactions, such as 7Li(d,n)8Be. Deuterons from this process are suppressed by contamination that builds up on the rear of the solid primary target. To eliminate this issue we propose a self-replenishing liquid membrane target consisting of heavy water and deuterated surfactant, formed in-vacuum within a moveable wire frame. In addition to removing issues associated with solid target positioning and collateral damage, this apparatus provides flow rate and target thickness control, and allows for the high repetition rates required to generate desired neutron fluxes with a portable laser-based system. The apparatus design will be presented, as well as a novel interferometric method that measures the membrane thickness using tightly-focused light. This work was performed with support from DARPA.

Effects of degree and configuration of hearing loss on the contribution of high- and low-frequency speech information to bilateral speech understanding

PubMed Central

Hornsby, Benjamin W. Y.; Johnson, Earl E.; Picou, Erin

2011-01-01

Objectives The purpose of this study was to examine the effects of degree and configuration of hearing loss on the use of, and benefit from, information in amplified high- and low-frequency speech presented in background noise. Design Sixty-two adults with a wide range of high- and low-frequency sensorineural hearing loss (5–115+ dB HL) participated. To examine the contribution of speech information in different frequency regions, speech understanding in noise was assessed in multiple low- and high-pass filter conditions, as well as a band-pass (713–3534 Hz) and wideband (143–8976 Hz) condition. To increase audibility over a wide frequency range, speech and noise were amplified based on each individual’s hearing loss. A stepwise multiple linear regression approach was used to examine the contribution of several factors to 1) absolute performance in each filter condition and 2) the change in performance with the addition of amplified high- and low-frequency speech components. Results Results from the regression analysis showed that degree of hearing loss was the strongest predictor of absolute performance for low- and high-pass filtered speech materials. In addition, configuration of hearing loss affected both absolute performance for severely low-pass filtered speech and benefit from extending high-frequency (3534–8976 Hz) bandwidth. Specifically, individuals with steeply sloping high-frequency losses made better use of low-pass filtered speech information than individuals with similar low-frequency thresholds but less high-frequency loss. In contrast, given similar high-frequency thresholds, individuals with flat hearing losses received more benefit from extending high-frequency bandwidth than individuals with more sloping losses. Conclusions Consistent with previous work, benefit from speech information in a given frequency region generally decreases as degree of hearing loss in that frequency region increases. However, given a similar degree of loss

Scale-up of high specific activity 186gRe production using graphite-encased thick 186W targets and demonstration of an efficient target recycling process

DOE PAGES

Balkin, Ethan R.; Gagnon, Katherine; Dorman, Eric; ...

2017-08-18

Production of high specific activity 186gRe is of interest for development of theranostic radiopharmaceuticals. Previous studies have shown that high specific activity 186gRe can be obtained by cyclotron irradiation of enriched 186W via the 186W(d,2n) 186gRe reaction, but most irradiations were conducted at low beam currents and for short durations. In this paper, enriched 186W metal targets were irradiated at high incident deuteron beam currents to demonstrate production rates and contaminants produced when using thick targets. Full-stopping thick targets, as determined using SRIM, were prepared by uniaxial pressing of powdered natural abundance W metal or 96.86% enriched 186W metal encasedmore » between two layers of graphite flakes for target material stabilization. An assessment of structural integrity was made on each target preparation. To assess the performance of graphite-encased thick 186W metal targets, along with the impact of encasing on the separation chemistry, targets were first irradiated using a 22 MeV deuteron beam for 10 min at 10, 20, and 27 μA, with an estimated nominal deuteron energy of 18.7 MeV on the 186W target material (after energy degradation correction from top graphite layer). Gamma-ray spectrometry was performed post EOB on all targets to assess production yields and radionuclidic byproducts. The investigation also evaluated a method to recover and recycle enriched target material from a column isolation procedure. Material composition analyses of target materials, pass-through/wash solutions and recycling process isolates were conducted with SEM, FTIR, XRD, EDS and ICP-MS spectrometry. Finally, to demonstrate scaled-up production, a graphite-encased 186W target made from recycled 186W was irradiated for ~2 h with 18.7 MeV deuterons at a beam current of 27 μA to provide 0.90 GBq (24.3 mCi) of 186gRe, decay-corrected to the end of bombardment. ICP-MS analysis of the isolated 186gRe solution provided data that indicated the

Scale-up of high specific activity 186gRe production using graphite-encased thick 186W targets and demonstration of an efficient target recycling process

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

Balkin, Ethan R.; Gagnon, Katherine; Dorman, Eric

Production of high specific activity 186gRe is of interest for development of theranostic radiopharmaceuticals. Previous studies have shown that high specific activity 186gRe can be obtained by cyclotron irradiation of enriched 186W via the 186W(d,2n) 186gRe reaction, but most irradiations were conducted at low beam currents and for short durations. In this paper, enriched 186W metal targets were irradiated at high incident deuteron beam currents to demonstrate production rates and contaminants produced when using thick targets. Full-stopping thick targets, as determined using SRIM, were prepared by uniaxial pressing of powdered natural abundance W metal or 96.86% enriched 186W metal encasedmore » between two layers of graphite flakes for target material stabilization. An assessment of structural integrity was made on each target preparation. To assess the performance of graphite-encased thick 186W metal targets, along with the impact of encasing on the separation chemistry, targets were first irradiated using a 22 MeV deuteron beam for 10 min at 10, 20, and 27 μA, with an estimated nominal deuteron energy of 18.7 MeV on the 186W target material (after energy degradation correction from top graphite layer). Gamma-ray spectrometry was performed post EOB on all targets to assess production yields and radionuclidic byproducts. The investigation also evaluated a method to recover and recycle enriched target material from a column isolation procedure. Material composition analyses of target materials, pass-through/wash solutions and recycling process isolates were conducted with SEM, FTIR, XRD, EDS and ICP-MS spectrometry. Finally, to demonstrate scaled-up production, a graphite-encased 186W target made from recycled 186W was irradiated for ~2 h with 18.7 MeV deuterons at a beam current of 27 μA to provide 0.90 GBq (24.3 mCi) of 186gRe, decay-corrected to the end of bombardment. ICP-MS analysis of the isolated 186gRe solution provided data that indicated the

Improvement in adenoviral gene transfer efficiency after preincubation at +37 degrees C in vitro and in vivo.

PubMed

Kossila, Maija; Jauhiainen, Suvi; Laukkanen, Mikko O; Lehtolainen, Pauliina; Jääskeläinen, Maiju; Turunen, Päivi; Loimas, Sami; Wahlfors, Jarmo; Ylä-Herttuala, Seppo

2002-01-01

Adenovirus is a widely used vector in gene transfer experiments because it produces high transduction efficiency in vitro and in vivo by means of the coxsackie-adenovirus receptor (CAR) and major histocompatibility complex (MHC) class I alpha-2 domain. Adenoviral gene transfer efficiency has been reported to correlate with cellular CAR expression. We report here a simple method to increase adenoviral gene transfer efficiency in cells that do not express high levels of CAR: preincubation of adenovirus for 30-40 minutes at +37 degrees C significantly increased the transduction efficiency in vitro in CHO and BALB/3T3 cells, in which CAR is expressed at very low levels. Increased transduction efficiency of preincubated adenovirus was also detected in vivo in rat brain tissue. In addition, we found that adenoviruses were rapidly inactivated in human serum in a complement-independent manner, whereas fetal bovine serum (FBS) had hardly any effects on the viral infectivity. We conclude that preincubation of adenoviral vectors at +37 degrees C may substantially increase gene transfer efficiency in applications in which target cells do not express high levels of CAR.

Effect of Dissolved Oxygen on the Filterability of Jet Fuels for Temperatures Between 300 Degrees and 400 Degrees F

NASA Technical Reports Server (NTRS)

Mckeown, Anderson B; Hibbard, Robert R

1955-01-01

The effect of dissolved oxygen in the filter-clogging characteristics of three JP-4 and two JP-5 fuels was studied at 300 degrees to 400 degrees F in a bench- scale rig, employing filter paper as the filter medium. The residence time of the fuel at the high temperature was approximately 6 seconds. For these conditions, the clogging characteristics of the fuels increased with both increasing temperature and increasing concentration of dissolved oxygen. The amount of insoluble material formed at high temperatures necessary to produce clogging of filters was very small, of the order of 1 milligram per gallon of fuel.

High-density convergent plasma sputtering device for a liquid metal target using an unheated glass plate

NASA Astrophysics Data System (ADS)

Motomura, T.; Tabaru, T.

2018-06-01

A high-density convergent plasma sputtering device has been developed for a liquid metal target, using an unheated glass plate. The convergent magnetic field lines, which are produced by an external solenoid coil and a permanent magnet positioned behind the liquid metal target, effectively transport high-density plasmas near the target. In this study, a liquid gallium target was sputtered with nitrogen plasmas, without additive gas required for depositing gallium nitride films on the unheated substrates. The deposition rate of the GaN film was estimated at ˜13 nm/min at a gas pressure of 0.2 Pa. A strong diffraction peak was observed along the GaN (002) axis, with the use of an unheated glass plate and a target-substrate distance of ˜45 mm.

Information sources used by high school students in the college degree choice.

PubMed

Areces, Débora; Rodríguez Muñiz, Luis J; Suárez Álvarez, Javier; de la Roca, Yolanda; Cueli, Marisol

2016-08-01

Searching for information is a necessary step for young people to decide what to study and prevent school drop-out. The aim of this study is to identify the main sources of information used by students in choosing a university career and to assess the degree of usefulness of these sources. A new measuring instrument to assess the use and usefulness of the information sources used in choosing university studies was developed. 2,005 high school students aged 17 to 24 (M = 17.56, SD = .77) participated in the study, representing 44.95 % of the total of school centers of the Principality of Asturias (Spain). The new instrument has adequate psychometric properties and shows that the information from parents and web pages by universities are the most used and most useful information sources for pre-university students. Obtaining this type of information is very important, as it encourages investing in those activities or resources that are important for pre-university students.

Roster of Astronomy Departments with Enrollment and Degree Data, 2016: Results from the 2016 Survey of Enrollments and Degrees. Roster

ERIC Educational Resources Information Center

Nicholson, Starr; Mulvey, Patrick J.

2017-01-01

The number of both astronomy bachelor's degrees and PhDs awarded in the class of 2016 represent all-time highs. Astronomy bachelors have been increasing steadily for the last 15 years, with 469 degrees awarded in the class of 2016. With undergraduate astronomy enrollments continuing to grow, the trend is expected to continue for at least the next…

Two Universities, Two Degrees: A Dual Degree Program for Pharmacists.

ERIC Educational Resources Information Center

Milio, Frank

2001-01-01

Describes a dual degree program between Towson University and the University of Maryland School of Pharmacy, which allows a student to receive both a B.S. degree in Medicinal Chemistry and a Doctor of Pharmacy degree in a combined 7-year program. It also allows flexibility in pursuing alternate career goals. (EV)

SWATHtoMRM: Development of High-Coverage Targeted Metabolomics Method Using SWATH Technology for Biomarker Discovery.

PubMed

Zha, Haihong; Cai, Yuping; Yin, Yandong; Wang, Zhuozhong; Li, Kang; Zhu, Zheng-Jiang

2018-03-20

The complexity of metabolome presents a great analytical challenge for quantitative metabolite profiling, and restricts the application of metabolomics in biomarker discovery. Targeted metabolomics using multiple-reaction monitoring (MRM) technique has excellent capability for quantitative analysis, but suffers from the limited metabolite coverage. To address this challenge, we developed a new strategy, namely, SWATHtoMRM, which utilizes the broad coverage of SWATH-MS technology to develop high-coverage targeted metabolomics method. Specifically, SWATH-MS technique was first utilized to untargeted profile one pooled biological sample and to acquire the MS 2 spectra for all metabolites. Then, SWATHtoMRM was used to extract the large-scale MRM transitions for targeted analysis with coverage as high as 1000-2000 metabolites. Then, we demonstrated the advantages of SWATHtoMRM method in quantitative analysis such as coverage, reproducibility, sensitivity, and dynamic range. Finally, we applied our SWATHtoMRM approach to discover potential metabolite biomarkers for colorectal cancer (CRC) diagnosis. A high-coverage targeted metabolomics method with 1303 metabolites in one injection was developed to profile colorectal cancer tissues from CRC patients. A total of 20 potential metabolite biomarkers were discovered and validated for CRC diagnosis. In plasma samples from CRC patients, 17 out of 20 potential biomarkers were further validated to be associated with tumor resection, which may have a great potential in assessing the prognosis of CRC patients after tumor resection. Together, the SWATHtoMRM strategy provides a new way to develop high-coverage targeted metabolomics method, and facilitates the application of targeted metabolomics in disease biomarker discovery. The SWATHtoMRM program is freely available on the Internet ( http://www.zhulab.cn/software.php ).

Projectile-charge-state dependence of 0[degree] binary-encounter electron production in 30-MeV O[sup [ital q]+]+O[sub 2] collisions

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

Zouros, T.J.M.; Richard, P.; Wong, K.L.

Double-differential cross sections (DDCS's) for the production of binary-encounter electrons (BEE's) are reported for 30-MeV O[sup [ital q]+]+O[sub 2] collisions. The BEE DDCS's were measured at [theta]=0[degree] with respect to the beam direction for projectile charge states [ital q]=4--8. The measured BEE DDCS's were found to increase with decreasing charge state in agreement with other recent BEE results employing simpler H[sub 2] and He targets. Impulse-approximation calculations of BEE production for [theta]=0[degree]--45[degree] are also presented, in which it is assumed that target electrons undergo elastic scattering in the screened Coulomb field of the projectile ion. These calculations are shown tomore » be in agreement with our data at [theta]=0[degree] where only 2[ital s] and 2[ital p] target electrons are considered.« less

Health Risks of Space Exploration: Targeted and Nontargeted Oxidative Injury by High-Charge and High-Energy Particles

PubMed Central

Li, Min; Gonon, Géraldine; Buonanno, Manuela; Autsavapromporn, Narongchai; de Toledo, Sonia M.; Pain, Debkumar

2014-01-01

Abstract Significance: During deep space travel, astronauts are often exposed to high atomic number (Z) and high-energy (E) (high charge and high energy [HZE]) particles. On interaction with cells, these particles cause severe oxidative injury and result in unique biological responses. When cell populations are exposed to low fluences of HZE particles, a significant fraction of the cells are not traversed by a primary radiation track, and yet, oxidative stress induced in the targeted cells may spread to nearby bystander cells. The long-term effects are more complex because the oxidative effects persist in progeny of the targeted and affected bystander cells, which promote genomic instability and may increase the risk of age-related cancer and degenerative diseases. Recent Advances: Greater understanding of the spatial and temporal features of reactive oxygen species bursts along the tracks of HZE particles, and the availability of facilities that can simulate exposure to space radiations have supported the characterization of oxidative stress from targeted and nontargeted effects. Critical Issues: The significance of secondary radiations generated from the interaction of the primary HZE particles with biological material and the mitigating effects of antioxidants on various cellular injuries are central to understanding nontargeted effects and alleviating tissue injury. Future Directions: Elucidation of the mechanisms underlying the cellular responses to HZE particles, particularly under reduced gravity and situations of exposure to additional radiations, such as protons, should be useful in reducing the uncertainty associated with current models for predicting long-term health risks of space radiation. These studies are also relevant to hadron therapy of cancer. Antioxid. Redox Signal. 20, 1501–1523. PMID:24111926

Significantly high polarization degree of the very low-albedo asteroid (152679) 1998 KU2

NASA Astrophysics Data System (ADS)

Kuroda, Daisuke; Ishiguro, Masateru; Watanabe, Makoto; Hasegawa, Sunao; Sekiguchi, Tomohiko; Naito, Hiroyuki; Usui, Fumihiko; Imai, Masataka; Sato, Mitsuteru; Kuramoto, Kiyoshi

2018-03-01

We present a unique and significant polarimetric result regarding the near-Earth asteroid (152679) 1998 KU2, which has a very low geometric albedo. From our observations, we find that the linear polarization degrees of 1998 KU2 are 44.6 ± 0.5% in the RC band and 44.0 ± 0.6% in the V band at a solar phase angle of 81.0°. These values are the highest of any known airless body in the solar system (i.e., high-polarization comets, asteroids, and planetary satellites) at similar phase angles. This polarimetric observation is not only the first for primitive asteroids at large phase angles, but also for low-albedo (<0.1) airless bodies. Based on spectroscopic similarities and polarimetric measurements of materials that have been sorted by size in previous studies, we conjecture that 1998 KU2 has a highly microporous regolith structure comprising nano-sized carbon grains on the surface.

Nano-targeted induction of dual ferroptotic mechanisms eradicates high-risk neuroblastoma.

PubMed

Hassannia, Behrouz; Wiernicki, Bartosz; Ingold, Irina; Qu, Feng; Van Herck, Simon; Tyurina, Yulia Y; Bayır, Hülya; Abhari, Behnaz A; Angeli, Jose Pedro Friedmann; Choi, Sze Men; Meul, Eline; Heyninck, Karen; Declerck, Ken; Chirumamilla, Chandra Sekhar; Lahtela-Kakkonen, Maija; Van Camp, Guy; Krysko, Dmitri V; Ekert, Paul G; Fulda, Simone; De Geest, Bruno G; Conrad, Marcus; Kagan, Valerian E; Berghe, Wim Vanden; Vandenabeele, Peter; Berghe, Tom Vanden

2018-06-25

High-risk neuroblastoma is a devastating malignancy with very limited therapeutic options. Here, we identify withaferin A (WA) as a natural ferroptosis-inducing agent in neuroblastoma, which acts through a novel double-edged mechanism. WA dose-dependently either activates the nuclear factor-like 2 pathway through targeting of Kelch-like ECH-associated protein 1 (noncanonical ferroptosis induction) or inactivates glutathione peroxidase 4 (canonical ferroptosis induction). Noncanonical ferroptosis induction is characterized by an increase in intracellular labile Fe(II) upon excessive activation of heme oxygenase-1, which is sufficient to induce ferroptosis. This double-edged mechanism might explain the superior efficacy of WA as compared with etoposide or cisplatin in killing a heterogeneous panel of high-risk neuroblastoma cells, and in suppressing the growth and relapse rate of neuroblastoma xenografts. Nano-targeting of WA allows systemic application and suppressed tumor growth due to an enhanced accumulation at the tumor site. Collectively, our data propose a novel therapeutic strategy to efficiently kill cancer cells by ferroptosis.

Heptameric Targeting Ligands against EGFR and HER2 with High Stability and Avidity

PubMed Central

Kim, Dongwook; Yan, Yitang; Valencia, C. Alexander; Liu, Rihe

2012-01-01

Multivalency of targeting ligands provides significantly increased binding strength towards their molecular targets. Here, we report the development of a novel heptameric targeting system, with general applications, constructed by fusing a target-binding domain with the heptamerization domain of the Archaeal RNA binding protein Sm1 through a flexible hinge peptide. The previously reported affibody molecules against EGFR and HER2, ZEGFR and ZHER2, were used as target binding moieties. The fusion molecules were highly expressed in E. coli as soluble proteins and efficiently self-assembled into multimeric targeting ligands with the heptamer as the predominant form. We demonstrated that the heptameric molecules were resistant to protease-mediated digestion or heat- and SDS-induced denaturation. Surface plasmon resonance (SPR) analysis showed that both heptameric ZEGFR and ZHER2 ligands have a significantly enhanced binding strength to their target receptors with a nearly 100 to 1000 fold increase relative to the monomeric ligands. Cellular binding assays showed that heptameric ligands maintained their target-binding specificities similar to the monomeric forms towards their respective receptor. The non-toxic property of each heptameric ligand was demonstrated by the cell proliferation assay. In general,, the heptamerization strategy we describe here could be applied to the facile and efficient engineering of other protein domain- or short peptide-based affinity molecules to acquire significantly improved target-binding strengths with potential applications in the targeted delivery of various imaging or therapeutic agents.. PMID:22912791

Glycyrrhizin-modified O-carboxymethyl chitosan nanoparticles as drug vehicles targeting hepatocellular carcinoma.

PubMed

Shi, Lili; Tang, Cui; Yin, Chunhua

2012-10-01

Here we describe the O-carboxymethyl chitosan nanoparticles (CMCNP) modified by glycyrrhizin (GL) with various substitution degrees as hepatocellular carcinoma (HCC)-targeted delivery vehicles, which could efficiently deliver paclitaxel (PTX) into HCC. The resultant CMCNP-GL exhibited spherical in shape and high stability in plasma with fixed negative charged (~-30 mV) and a size range of 100-205 nm. PTX was loaded into CMCNP-GL with a maximal encapsulation efficiency of 83.7% and performed a biphasic release. CMCNP-GL promoted liver cancer SMMC-7721 cell internalization by approximate 10.0-fold as compared to unmodified CMCNP. Within 72 h, the IC(50) of PTX/CMCNP-GL, PTX/CMCNP, and PTX injection was 2.7-3.2, 8.1, and 13.5 μg/mL, respectively. Biodistribution experiments revealed that PTX/CMCNP-GL exerted significantly superior targeting to tumor than PTX/CMCNP. The in vivo tumor inhibition ratio of PTX/CMCNP-GL was 87.5%, showing remarkably higher than that of PTX/CMCNP (64.0%) and PTX injection (34.5%). CMCNP-GL with different substitution degrees possessed similar targeting property and therapeutic efficacy. Furthermore, toxicity studies suggested that blank CMCNP-GL had no systemic or hepatic toxicity. Copyright © 2012 Elsevier Ltd. All rights reserved.

Combinatorial study of degree assortativity in networks.

PubMed

Estrada, Ernesto

2011-10-01

Why are some networks degree-degree correlated (assortative), while most of the real-world ones are anticorrelated (disassortative)? Here, we prove, by combinatorial methods, that the assortativity of a network depends only on three structural factors: transitivity (clustering coefficient), intermodular connectivity, and branching. Then, a network is assortative if the contributions of the first two factors are larger than that of the third. Highly branched networks are likely to be disassortative.

Investigation at Low Speeds of Deflectors and Spoilers as Gust Alleviators on a Model of the Bell X-5 Airplane with 35 Degree Swept Wings and on a High-aspect-ratio 35 Degree Swept-wing-fuselage Model

NASA Technical Reports Server (NTRS)

Croom, Delwin R; Huffman, Jarrett K

1957-01-01

Results of an investigation at low speeds to determine the gust-alleviation capabilities (reduction in lift-curve slope) of spoilers and deflectors on a 35 degree swept-wing model of high aspect ratio and on a 1/4-scale model of the X-5 airplane with 35 degree swept wings indicate that deflector and spoiler-deflector types of controls can be designed to provide considerable gust alleviation for a swept-wing airplane while still maintaining stability and control.

Survival of the impactor during hypervelocity collisions - II. An analogue for high-porosity targets

NASA Astrophysics Data System (ADS)

Avdellidou, C.; Price, M. C.; Delbo, M.; Cole, M. J.

2017-01-01

We investigated how a target's porosity affects the outcome of a collision, with respect to the impactor's fate. Laboratory impact experiments using peridot projectiles were performed at a speed range between 0.3 and 3.0 km s-1, on to high-porosity water-ice (40 per cent) and fine-grained calcium carbonate (70 per cent) targets. We report that the amount of implanted material in the target body increases with increasing target's porosity, while the size frequency distribution of the projectile's ejecta fragments becomes steeper. A supplementary Raman study showed no sign of change of the Raman spectra of the recovered olivine projectile fragments indicate minimal physical change.

Evaluating the damage process of dynamic target by high-energy laser in ocean environment

NASA Astrophysics Data System (ADS)

Wang, Jing; Ye, Demao

2013-12-01

The high-energy laser, as one of directed energy weapon, is famous for its unique advantage of speed-of-light response which was considered as an ideal weapon against anti-ship missile. This paper commits to evaluate the damage process of missile by high-energy laser weapon. We analyze the propagation properties which are susceptible to atmospheric attenuation effects, atmospheric turbulence effects, thermal blooming effects in sky-sea atmosphere firstly. Then because laser weapons attack one target at a time and it takes several seconds at a minimum for the target engaged, a model of calculating the required t ime for damaging the attack target was built . In the end effective evaluation methods of hot-ablated and high-energy laser weapon's damaging effectiveness are made, when the body or the optical elements of the missile is irradiated by the concatenation wave laser weapon. And one of the issues just as laser power, propagation distance is changed; the model can make different evaluation. The above model can provide the theoretical basis for the high-energy laser weapon intercept anti-ship missile and tactic deraign rationality for naval ship-borne laser weapons.

Graduate Physics Degrees: Largest Departments and Degree Distribution. Focus On

ERIC Educational Resources Information Center

Mulvey, Patrick J.; Nicholson, Starr

2014-01-01

In the 2011-12 academic year there were 751 degree-granting physics departments in the U.S. Of these, 195 offered a PhD and 62 departments offered a master's as the highest physics degree. The remaining 494 departments offered a bachelor's as their highest physics degree. There were six universities that had two doctoral-granting physics…

Novel target for high-risk neuroblastoma identified in pre-clinical research | Center for Cancer Research

Cancer.gov

Pre-clinical research by investigators at the Center for Cancer Research and their colleagues have identified a number of novel epigenetic targets for high-risk neuroblastoma and validated a promising new targeted inhibitor in pre-clinical models.  Read more...

Update On The Development, Testing, And Manufacture Of High Density LEU-Foil Targets For The Production Of Mo-99

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

Creasy, John T

2015-05-12

This project has the objective to reduce and/or eliminate the use of HEU in commerce. Steps in the process include developing a target testing methodology that is bounding for all Mo-99 target irradiators, establishing a maximum target LEU-foil mass, developing a LEU-foil target qualification document, developing a bounding target failure analysis methodology (failure in reactor containment), optimizing safety vs. economics (goal is to manufacture a safe, but relatively inexpensive target to offset the inherent economic disadvantage of using LEU in place of HEU), and developing target material specifications and manufacturing QC test criteria. The slide presentation is organized under themore » following topics: Objective, Process Overview, Background, Team Structure, Key Achievements, Experiment and Activity Descriptions, and Conclusions. The High Density Target project has demonstrated: approx. 50 targets irradiated through domestic and international partners; proof of concept for two front end processing methods; fabrication of uranium foils for target manufacture; quality control procedures and steps for manufacture; multiple target assembly techniques; multiple target disassembly devices; welding of targets; thermal, hydraulic, and mechanical modeling; robust target assembly parametric studies; and target qualification analysis for insertion into very high flux environment. The High Density Target project has tested and proven several technologies that will benefit current and future Mo-99 producers.« less

Ultra-High-Contrast Laser Acceleration of Relativistic Electrons in Solid Targets

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

Higginson, Drew Pitney

2013-01-01

The cone-guided fast ignition approach to Inertial Con nement Fusion requires laser-accelerated relativistic electrons to deposit kilojoules of energy within an imploded fuel core to initiate fusion burn. One obstacle to coupling electron energy into the core is the ablation of material, known as preplasma, by laser energy proceeding nanoseconds prior to the main pulse. This causes the laser-absorption surface to be pushed back hundreds of microns from the initial target surface; thus increasing the distance that electrons must travel to reach the imploded core. Previous experiments have shown an order of magnitude decrease in coupling into surrogate targets whenmore » intentionally increasing the amount of preplasma. Additionally, for electrons to deposit energy within the core, they should have kinetic energies on the order of a few MeV, as less energetic electrons will be stopped prior to the core and more energetic electrons will pass through the core without depositing much energy. Thus a quantitative understanding of the electron energy spectrum and how it responds to varied laser parameters is paramount for fast ignition. For the rst time, this dissertation quantitatively investigates the acceleration of electrons using an ultra-high-contrast laser. Ultra-high-contrast lasers reduce the laser energy that reaches the target prior to the main pulse; drastically reducing the amount of preplasma. Experiments were performed in a cone-wire geometry relevant to fast ignition. These experiments irradiated the inner-tip of a Au cone with the laser and observed electrons that passed through a Cu wire attached to the outer-tip of the cone. The total emission of K x-rays is used as a diagnostic to infer the electron energy coupled into the wire. Imaging the x-ray emission allowed an e ective path-length of electrons within the wire to be determined, which constrained the electron energy spectrum. Experiments were carried out on the ultra-high-contrast Trident laser at

Human-like characteristics for high degree of freedom robotic door-opening end-effector

NASA Astrophysics Data System (ADS)

Gray, Jeremy P.; Campagna, Frank

2011-05-01

In the field of military Unmanned Ground Vehicles (UGV's), military units are forced to sweep largely populated cities and towns in search of hostile enemies. These urban types of operations are referred to as MOUT (Military Operations on Urban Terrain). During urban operations, these UGV's encounter difficulties when opening doors. Current manipulator end effectors have these difficulties, because they are not designed to mimic human hand operations. This paper explains the mechanical nature of the Modular Universal Door Opening End-effector (MUDOE). MUDOE is a result of our development research to improve robotic manipulators ability to negotiate closed doors. The presented solution has the ability to mimic human hand characteristics when opening doors. The end-effector possesses an ability to maintain a high Degree of Freedom (DoF), and grasp the doorknob by applying equally distributed forces to all points of contact.

Target material dependence of positron generation from high intensity laser-matter interactions

DOE PAGES

Williams, G. J.; Barnak, D.; Fiksel, G.; ...

2016-12-06

Here, the effective scaling of positron-electron pair production by direct, ultraintense laser-matter interaction is investigated for a range of target materials and thicknesses. An axial magnetic field, acting as a focusing lens, was employed to measure positron signals for targets with atomic numbers as low as copper (Z – 29). The pair production yield was found to be consistent with the Bethe-Heitler mechanism, where the number of positrons emitted into a 1 steradian cone angle from the target rear was found to be proportional to Z 2. The unexpectedly low scaling results from Coulomb collisions that act to stop ormore » scatter positrons into high angles. Monte Carlo simulations support the experimental results, providing a comprehensive power-law scaling relationship for all elemental materials and densities.« less

Absolute Quantification of Middle- to High-Abundant Plasma Proteins via Targeted Proteomics.

PubMed

Dittrich, Julia; Ceglarek, Uta

2017-01-01

The increasing number of peptide and protein biomarker candidates requires expeditious and reliable quantification strategies. The utilization of liquid chromatography coupled to quadrupole tandem mass spectrometry (LC-MS/MS) for the absolute quantitation of plasma proteins and peptides facilitates the multiplexed verification of tens to hundreds of biomarkers from smallest sample quantities. Targeted proteomics assays derived from bottom-up proteomics principles rely on the identification and analysis of proteotypic peptides formed in an enzymatic digestion of the target protein. This protocol proposes a procedure for the establishment of a targeted absolute quantitation method for middle- to high-abundant plasma proteins waiving depletion or enrichment steps. Essential topics as proteotypic peptide identification and LC-MS/MS method development as well as sample preparation and calibration strategies are described in detail.

Evaluation of third-degree and fourth-degree laceration rates as quality indicators.

PubMed

Friedman, Alexander M; Ananth, Cande V; Prendergast, Eri; D'Alton, Mary E; Wright, Jason D

2015-04-01

To examine the patterns and predictors of third-degree and fourth-degree laceration in women undergoing vaginal delivery. We identified a population-based cohort of women in the United States who underwent a vaginal delivery between 1998 and 2010 using the Nationwide Inpatient Sample. Multivariable log-linear regression models were developed to account for patient, obstetric, and hospital factors related to lacerations. Between-hospital variability of laceration rates was calculated using generalized log-linear mixed models. Among 7,096,056 women who underwent vaginal delivery in 3,070 hospitals, 3.3% (n=232,762) had a third-degree laceration and 1.1% (n=76,347) had a fourth-degree laceration. In an adjusted model for fourth-degree lacerations, important risk factors included shoulder dystocia and forceps and vacuum deliveries with and without episiotomy. Other demographic, obstetric, medical, and hospital variables, although statistically significant, were not major determinants of lacerations. Risk factors in a multivariable model for third-degree lacerations were similar to those in the fourth-degree model. Regression analysis of hospital rates (n=3,070) of lacerations demonstrated limited between-hospital variation. Risk of third-degree and fourth-degree laceration was most strongly related to operative delivery and shoulder dystocia. Between-hospital variation was limited. Given these findings and that the most modifiable practice related to lacerations would be reduction in operative vaginal deliveries (and a possible increase in cesarean delivery), third-degree and fourth-degree laceration rates may be a quality metric of limited utility.

Potential high-frequency off-target mutagenesis induced by CRISPR/Cas9 in Arabidopsis and its prevention.

PubMed

Zhang, Qiang; Xing, Hui-Li; Wang, Zhi-Ping; Zhang, Hai-Yan; Yang, Fang; Wang, Xue-Chen; Chen, Qi-Jun

2018-03-01

We present novel observations of high-specificity SpCas9 variants, sgRNA expression strategies based on mutant sgRNA scaffold and tRNA processing system, and CRISPR/Cas9-mediated T-DNA integrations. Specificity of CRISPR/Cas9 tools has been a major concern along with the reports of their successful applications. We report unexpected observations of high frequency off-target mutagenesis induced by CRISPR/Cas9 in T1 Arabidopsis mutants although the sgRNA was predicted to have a high specificity score. We also present evidence that the off-target effects were further exacerbated in the T2 progeny. To prevent the off-target effects, we tested and optimized two strategies in Arabidopsis, including introduction of a mCherry cassette for a simple and reliable isolation of Cas9-free mutants and the use of highly specific mutant SpCas9 variants. Optimization of the mCherry vectors and subsequent validation found that fusion of tRNA with the mutant rather than the original sgRNA scaffold significantly improves editing efficiency. We then examined the editing efficiency of eight high-specificity SpCas9 variants in combination with the improved tRNA-sgRNA fusion strategy. Our results suggest that highly specific SpCas9 variants require a higher level of expression than their wild-type counterpart to maintain high editing efficiency. Additionally, we demonstrate that T-DNA can be inserted into the cleavage sites of CRISPR/Cas9 targets with high frequency. Altogether, our results suggest that in plants, continuous attention should be paid to off-target effects induced by CRISPR/Cas9 in current and subsequent generations, and that the tools optimized in this report will be useful in improving genome editing efficiency and specificity in plants and other organisms.

Preparation and Physical Properties of Starch Stearates of Low to High Degree of Substitution

USDA-ARS?s Scientific Manuscript database

Starch stearates of degree of substitution (DS) 0.07-2.40 were prepared by heating dry starch and vinyl stearate in the ionic liquid BMIM dca at 75 Degrees C. Starch stearate of low DS (0.07) was insoluble in water but formed a gel and absorbed over seven times its weight of water. Starch stearate...

Quality control for normal liquid-based cytology: Rescreening, high-risk HPV targeted reviewing and/or high-risk HPV detection?

PubMed Central

Depuydt, Christophe E; Arbyn, Marc; Benoy, Ina H; Vandepitte, Johan; Vereecken, Annie J; Bogers, Johannes J

2009-01-01

The objective of this prospective study was to compare the number of CIN2+cases detected in negative cytology by different quality control (QC) methods. Full rescreening, high-risk (HR) human papillomavirus (HPV)-targeted reviewing and HR HPV detection were compared. Randomly selected negative cytology detected by BD FocalPoint™ (NFR), by guided screening of the prescreened which needed further review (GS) and by manual screening (MS) was used. A 3-year follow-up period was available. Full rescreening of cytology only detected 23.5% of CIN2+ cases, whereas the cytological rescreening of oncogenic positive slides (high-risk HPV-targeted reviewing) detected 7 of 17 CIN2+ cases (41.2%). Quantitative real-time PCR for 15 oncogenic HPV types detected all CIN2+ cases. Relative sensitivity to detect histological CIN2+ was 0.24 for full rescreening, 0.41 for HR-targeted reviewing and 1.00 for HR HPV detection. In more than half of the reviewed negative cytological preparations associated with histological CIN2+cases no morphologically abnormal cells were detected despite a positive HPV test. The visual cut-off for the detection of abnormal cytology was established at 6.5 HR HPV copies/cell. High-risk HPV detection has a higher yield for detection of CIN2+ cases as compared to manual screening followed by 5% full review, or compared to targeted reviewing of smears positive for oncogenic HPV types, and show diagnostic properties that support its use as a QC procedure in cytologic laboratories. PMID:18544049

Increased efficacy of photodynamic therapy via sequential targeting

NASA Astrophysics Data System (ADS)

Kessel, David; Aggarwal, Neha; Sloane, Bonnie F.

2014-03-01

Photokilling depends on the generation of death signals after photosensitized cells are irradiated. A variety of intracellular organelles can be targeted for photodamage, often with a high degree of specificity. We have discovered that a low level of photodamage directed against lysosomes can sensitize both a murine hepatoma cell line (in 2D culture) and an inflammatory breast cancer line of human origin (in a 3D model) to subsequent photodamage directed at mitochondria. Additional studies were carried out with hepatoma cells to explore possible mechanisms. The phototoxic effect of the `sequential targeting' approach was associated with an increased apoptotic response. The low level of lysosomal photodamage did not lead to any detectable migration of Fe++ from lysosomes to mitochondria or increased reactive oxygen species (ROS) formation after subsequent mitochondrial photodamage. Instead, there appears to be a signal generated that can amplify the pro-apoptotic effect of subsequent mitochondrial photodamage.

Development of high-performance alkali-hybrid polarized 3He targets for electron scattering

NASA Astrophysics Data System (ADS)

Singh, Jaideep T.; Dolph, P. A. M.; Tobias, W. A.; Averett, T. D.; Kelleher, A.; Mooney, K. E.; Nelyubin, V. V.; Wang, Yunxiao; Zheng, Yuan; Cates, G. D.

2015-05-01

Background: Polarized 3He targets have been used as effective polarized neutron targets for electron scattering experiments for over twenty years. Over the last ten years, the effective luminosity of polarized 3He targets based on spin-exchange optical pumping has increased by over an order of magnitude. This has come about because of improvements in commercially-available lasers and an improved understanding of the physics behind the polarization process. Purpose: We present the development of high-performance polarized 3He targets for use in electron scattering experiments. Improvements in the performance of polarized 3He targets, target properties, and operating parameters are documented. Methods: We utilize the technique of alkali-hybrid spin-exchange optical pumping to polarize the 3He targets. Spectrally narrowed diode lasers used for the optical pumping greatly improved the performance. A simulation of the alkali-hybrid spin-exchange optical pumping process was developed to provide guidance in the design of the targets. Data was collected during the characterization of 24 separate glass target cells, each of which was constructed while preparing for one of four experiments at Jefferson Laboratory in Newport News, Virginia. Results: From the data obtained we made determinations of the so-called X -factors that quantify a temperature-dependent and as-yet poorly understood spin-relaxation mechanism that limits the maximum achievable 3He polarization to well under 100%. The presence of the X -factor spin-relaxation mechanism was clearly evident in our data. Good agreement between the simulation and the actual target performance was obtained by including details such as off-resonant optical pumping. Included in our results is a measurement of the K -3He spin-exchange rate coefficient kseK=(7.46 ±0.62 ) ×10-20cm3/s over the temperature range 503 K to 563 K. Conclusions: In order to achieve high performance under the operating conditions described in this paper

Development and validation of a 48-target analytical method for high-throughput monitoring of genetically modified organisms.

PubMed

Li, Xiaofei; Wu, Yuhua; Li, Jun; Li, Yunjing; Long, Likun; Li, Feiwu; Wu, Gang

2015-01-05

The rapid increase in the number of genetically modified (GM) varieties has led to a demand for high-throughput methods to detect genetically modified organisms (GMOs). We describe a new dynamic array-based high throughput method to simultaneously detect 48 targets in 48 samples on a Fludigm system. The test targets included species-specific genes, common screening elements, most of the Chinese-approved GM events, and several unapproved events. The 48 TaqMan assays successfully amplified products from both single-event samples and complex samples with a GMO DNA amount of 0.05 ng, and displayed high specificity. To improve the sensitivity of detection, a preamplification step for 48 pooled targets was added to enrich the amount of template before performing dynamic chip assays. This dynamic chip-based method allowed the synchronous high-throughput detection of multiple targets in multiple samples. Thus, it represents an efficient, qualitative method for GMO multi-detection.

Development and Validation of A 48-Target Analytical Method for High-throughput Monitoring of Genetically Modified Organisms

PubMed Central

Li, Xiaofei; Wu, Yuhua; Li, Jun; Li, Yunjing; Long, Likun; Li, Feiwu; Wu, Gang

2015-01-01

The rapid increase in the number of genetically modified (GM) varieties has led to a demand for high-throughput methods to detect genetically modified organisms (GMOs). We describe a new dynamic array-based high throughput method to simultaneously detect 48 targets in 48 samples on a Fludigm system. The test targets included species-specific genes, common screening elements, most of the Chinese-approved GM events, and several unapproved events. The 48 TaqMan assays successfully amplified products from both single-event samples and complex samples with a GMO DNA amount of 0.05 ng, and displayed high specificity. To improve the sensitivity of detection, a preamplification step for 48 pooled targets was added to enrich the amount of template before performing dynamic chip assays. This dynamic chip-based method allowed the synchronous high-throughput detection of multiple targets in multiple samples. Thus, it represents an efficient, qualitative method for GMO multi-detection. PMID:25556930

A high precision micropositioner with five degrees of freedom based on an electromagnetic driving principle

NASA Astrophysics Data System (ADS)

Wang, Wanjun; He, Tian

1996-01-01

A five degrees of freedom high precision micropositioner based on spring suspension and electromagnetic driving has been designed, constructed, and tested. The device consists of two parts: a moving part and a stationary part. The moving part, named as ``motor'', is formed with a rigid frame and three groups of coils fixed on it. The stationary part of the device, called ``stator'', includes a chassis and twelve U-shaped magnetic ``shoes''. The motor is attached to the stator with flat springs whose linear suspension allows it to move in all dimensions except the rotation around z axis. The coils have been laid out in such a way that fractions of them pass through the air gaps between the facing magnets in the magnetic shoes. When electrical currents are supplied to the coils, the resulting Lorenz forces drive the motor to move in the five degrees of freedom allowed by the spring suspension. Since the system is inherently stable and there is no mechanical friction, the open-loop resolutions of the device are found to be limited only by that of the 12-bit D/A board used. A closed-loop translation resolution of 0.3 μm has been achieved over a working space of 180 μm by 180 μm by 680 μm. A closed-loop rotation resolution of 2.73×10-6 rad has been achieved over a working space of 1.38×10-3 rad. Potentially the device can be used for high precision microprobing and testing, cellular biology, microsurgery, and testing of micromechanical devices in the fast developing MEMS area.

High-Target Versus Low-Target Blood Pressure Management During Cardiopulmonary Bypass to Prevent Cerebral Injury in Cardiac Surgery Patients: A Randomized Controlled Trial.

PubMed

Vedel, Anne G; Holmgaard, Frederik; Rasmussen, Lars S; Langkilde, Annika; Paulson, Olaf B; Lange, Theis; Thomsen, Carsten; Olsen, Peter Skov; Ravn, Hanne Berg; Nilsson, Jens C

2018-04-24

Cerebral injury is an important complication after cardiac surgery with the use of cardiopulmonary bypass. The rate of overt stroke after cardiac surgery is 1% to 2%, whereas silent strokes, detected by diffusion-weighted magnetic resonance imaging, are found in up to 50% of patients. It is unclear whether a higher versus a lower blood pressure during cardiopulmonary bypass reduces cerebral infarction in these patients. In a patient- and assessor-blinded randomized trial, we allocated patients to a higher (70-80 mm Hg) or lower (40-50 mm Hg) target for mean arterial pressure by the titration of norepinephrine during cardiopulmonary bypass. Pump flow was fixed at 2.4 L·min -1 ·m -2 . The primary outcome was the total volume of new ischemic cerebral lesions (summed in millimeters cubed), expressed as the difference between diffusion-weighted imaging conducted preoperatively and again postoperatively between days 3 and 6. Secondary outcomes included diffusion-weighted imaging-evaluated total number of new ischemic lesions. Among the 197 enrolled patients, mean (SD) age was 65.0 (10.7) years in the low-target group (n=99) and 69.4 (8.9) years in the high-target group (n=98). Procedural risk scores were comparable between groups. Overall, diffusion-weighted imaging revealed new cerebral lesions in 52.8% of patients in the low-target group versus 55.7% in the high-target group ( P =0.76). The primary outcome of volume of new cerebral lesions was comparable between groups, 25 mm 3 (interquartile range, 0-118 mm 3 ; range, 0-25 261 mm 3 ) in the low-target group versus 29 mm 3 (interquartile range, 0-143 mm 3 ; range, 0-22 116 mm 3 ) in the high-target group (median difference estimate, 0; 95% confidence interval, -25 to 0.028; P =0.99), as was the secondary outcome of number of new lesions (1 [interquartile range, 0-2; range, 0-24] versus 1 [interquartile range, 0-2; range, 0-29] respectively; median difference estimate, 0; 95% confidence interval, 0-0; P =0

Apparatus, Method and Program Storage Device for Determining High-Energy Neutron/Ion Transport to a Target of Interest

NASA Technical Reports Server (NTRS)

Wilson, John W. (Inventor); Tripathi, Ram K. (Inventor); Cucinotta, Francis A. (Inventor); Badavi, Francis F. (Inventor)

2012-01-01

An apparatus, method and program storage device for determining high-energy neutron/ion transport to a target of interest. Boundaries are defined for calculation of a high-energy neutron/ion transport to a target of interest; the high-energy neutron/ion transport to the target of interest is calculated using numerical procedures selected to reduce local truncation error by including higher order terms and to allow absolute control of propagated error by ensuring truncation error is third order in step size, and using scaling procedures for flux coupling terms modified to improve computed results by adding a scaling factor to terms describing production of j-particles from collisions of k-particles; and the calculated high-energy neutron/ion transport is provided to modeling modules to control an effective radiation dose at the target of interest.

Twin target self-amplification-based DNA machine for highly sensitive detection of cancer-related gene.

PubMed

Xu, Huo; Jiang, Yifan; Liu, Dengyou; Liu, Kai; Zhang, Yafeng; Yu, Suhong; Shen, Zhifa; Wu, Zai-Sheng

2018-06-29

The sensitive detection of cancer-related genes is of great significance for early diagnosis and treatment of human cancers, and previous isothermal amplification sensing systems were often based on the reuse of target DNA, the amplification of enzymatic products and the accumulation of reporting probes. However, no reporting probes are able to be transformed into target species and in turn initiate the signal of other probes. Herein we reported a simple, isothermal and highly sensitive homogeneous assay system for tumor suppressor p53 gene detection based on a new autonomous DNA machine, where the signaling probe, molecular beacon (MB), was able to execute the function similar to target DNA besides providing the common signal. In the presence of target p53 gene, the operation of DNA machine can be initiated, and cyclical nucleic acid strand-displacement polymerization (CNDP) and nicking/polymerization cyclical amplification (NPCA) occur, during which the MB was opened by target species and cleaved by restriction endonuclease. In turn, the cleaved fragments could activate the next signaling process as target DNA did. According to the functional similarity, the cleaved fragment was called twin target, and the corresponding fashion to amplify the signal was named twin target self-amplification. Utilizing this newly-proposed DNA machine, the target DNA could be detected down to 0.1 pM with a wide dynamic range (6 orders of magnitude) and single-base mismatched targets were discriminated, indicating a very high assay sensitivity and good specificity. In addition, the DNA machine was not only used to screen the p53 gene in complex biological matrix but also was capable of practically detecting genomic DNA p53 extracted from A549 cell line. This indicates that the proposed DNA machine holds the potential application in biomedical research and early clinical diagnosis. Copyright © 2018 Elsevier B.V. All rights reserved.

Persistence in STEM: An investigation of the relationship between high school experiences in science and mathematics and college degree completion in STEM fields

NASA Astrophysics Data System (ADS)

Maltese, Adam V.

While the number of Bachelor's degrees awarded annually has nearly tripled over the past 40 years (NSF, 2008), the same cannot be said for degrees in the STEM (science, technology, engineering and mathematics) fields. The Bureau of Labor Statistics projects that by the year 2014 the combination of new positions and retirements will lead to 2 million job openings in STEM (BLS, 2005). Thus, the research questions I sought to answer with this study were: (1)What are the most common enrollment patterns for students who enter into and exit from the STEM pipeline during high school and college? (2) Controlling for differences in student background and early interest in STEM careers, what are the high school science and mathematics classroom experiences that characterize student completion of a college major in STEM? Using data from NELS:88 I analyzed descriptive statistics and completed logistic regressions to gain an understanding of factors related to student persistence in STEM. Approximately 4700 students with transcript records and who participated in all survey rounds were included in the analyses. The results of the descriptive analysis demonstrated that most students who went on to complete majors in STEM completed at least three or four years of STEM courses during high school, and enrolled in advanced high school mathematics and science courses at higher rates. At almost every pipeline checkpoint indicators of the level of coursework and achievement were significant in predicting student completion of a STEM degree. The results also support previous research that showed demographic variables have little effect on persistence once the sample is limited to those who have the intrinsic ability and desire to complete a college degree. The most significant finding is that measures of student interest and engagement in science and mathematics were significant in predicting completion of a STEM degree, above and beyond the effects of course enrollment and performance

Spot-welding solid targets for high current cyclotron irradiation

PubMed Central

Ellison, Paul A.; Valdovinos, Hector F.; Graves, Stephen A.; Barnhart, Todd E.; Nickles, Robert J.

2016-01-01

Zirconium-89 finds broad application for use in positron emission tomography. Its cyclotron production has been limited by the heat transfer from yttrium targets at high beam currents. A spot welding technique allows a three-fold increase in beam current, without affecting 89Zr quality. An yttrium foil, welded to a jet-cooled tantalum support base accommodates a 50 μA proton beam degraded to 14 MeV. The resulting activity yield of 48 ± 4 MBq/(μA·hr) now extends the outreach of 89Zr for a broader distribution. PMID:27771445

Many Mobile Health Apps Target High-Need, High-Cost Populations, But Gaps Remain.

PubMed

Singh, Karandeep; Drouin, Kaitlin; Newmark, Lisa P; Lee, JaeHo; Faxvaag, Arild; Rozenblum, Ronen; Pabo, Erika A; Landman, Adam; Klinger, Elissa; Bates, David W

2016-12-01

With rising smartphone ownership, mobile health applications (mHealth apps) have the potential to support high-need, high-cost populations in managing their health. While the number of available mHealth apps has grown substantially, no clear strategy has emerged on how providers should evaluate and recommend such apps to patients. Key stakeholders, including medical professional societies, insurers, and policy makers, have largely avoided formally recommending apps, which forces patients to obtain recommendations from other sources. To help stakeholders overcome barriers to reviewing and recommending apps, we evaluated 137 patient-facing mHealth apps-those intended for use by patients to manage their health-that were highly rated by consumers and recommended by experts and that targeted high-need, high-cost populations. We found that there is a wide variety of apps in the marketplace but that few apps address the needs of the patients who could benefit the most. We also found that consumers' ratings were poor indications of apps' clinical utility or usability and that most apps did not respond appropriately when a user entered potentially dangerous health information. Going forward, data privacy and security will continue to be major concerns in the dissemination of mHealth apps. Project HOPE—The People-to-People Health Foundation, Inc.

Substantial difference in target surface chemistry between reactive dc and high power impulse magnetron sputtering

NASA Astrophysics Data System (ADS)

Greczynski, G.; Mráz, S.; Schneider, J. M.; Hultman, L.

2018-02-01

The nitride layer formed in the target race track during the deposition of stoichiometric TiN thin films is a factor 2.5 thicker for high power impulse magnetron sputtering (HIPIMS), compared to conventional dc processing (DCMS). The phenomenon is explained using x-ray photoelectron spectroscopy analysis of the as-operated Ti target surface chemistry supported by sputter depth profiles, dynamic Monte Carlo simulations employing the TRIDYN code, and plasma chemical investigations by ion mass spectrometry. The target chemistry and the thickness of the nitride layer are found to be determined by the implantation of nitrogen ions, predominantly N+ and N2+ for HIPIMS and DCMS, respectively. Knowledge of this method-inherent difference enables robust processing of high quality functional coatings.

Six-degree-of-freedom missile simulation using the ADI AD 100 digital computer and ADSIM simulation language

NASA Technical Reports Server (NTRS)

Zwaanenburg, Koos

1989-01-01

The use of an AD 100 computer and the ADSIM language in the six-degree-of-freedom digital simulation of an air-to-ground missile is illustrated. The missile is launched from a moving platform, typically a helicopter, and is capable of striking a mobile target up to 10 kilometers away. The missile could be any tactical missile. The performance numbers of the AD 100 show that it is possible to implement a high performance missile model in a real-time simulation without the problems associated with an implementation on a general purpose computer using FORTRAN.

Ultra-High-Contrast Laser Acceleration of Relativistic Electrons in Solid Targets

NASA Astrophysics Data System (ADS)

Higginson, Drew Pitney

The cone-guided fast ignition approach to Inertial Confinement Fusion requires laser-accelerated relativistic electrons to deposit kilojoules of energy within an imploded fuel core to initiate fusion burn. One obstacle to coupling electron energy into the core is the ablation of material, known as preplasma, by laser energy proceeding nanoseconds prior to the main pulse. This causes the laser-absorption surface to be pushed back hundreds of microns from the initial target surface; thus increasing the distance that electrons must travel to reach the imploded core. Previous experiments have shown an order of magnitude decrease in coupling into surrogate targets when intentionally increasing the amount of preplasma. Additionally, for electrons to deposit energy within the core, they should have kinetic energies on the order of a few MeV, as less energetic electrons will be stopped prior to the core and more energetic electrons will pass through the core without depositing much energy. Thus a quantitative understanding of the electron energy spectrum and how it responds to varied laser parameters is paramount for fast ignition. For the first time, this dissertation quantitatively investigates the acceleration of electrons using an ultra-high-contrast laser. Ultra-high-contrast lasers reduce the laser energy that reaches the target prior to the main pulse; drastically reducing the amount of preplasma. Experiments were performed in a cone-wire geometry relevant to fast ignition. These experiments irradiated the inner-tip of a Au cone with the laser and observed electrons that passed through a Cu wire attached to the outer-tip of the cone. The total emission of Kalpha x-rays is used as a diagnostic to infer the electron energy coupled into the wire. Imaging the x-ray emission allowed an effective path-length of electrons within the wire to be determined, which constrained the electron energy spectrum. Experiments were carried out on the ultra-high-contrast Trident laser

The Low-Degree Shape of Mercury

NASA Astrophysics Data System (ADS)

Perry, M. E.; Neumann, G. A.; Mazarico, E.; Hauck, S. A., II; Solomon, S. C.; Zuber, M. T.; Smith, D. E.; Phillips, R. J.; Margot, J. L.; Johnson, C. L.; Ernst, C. M.; Oberst, J.

2015-12-01

The shape of Mercury, particularly when combined with its geoid, provides clues to the planet's internal structure, thermal evolution, and rotational history. Twenty-five million elevation measurements of the northern hemisphere, acquired by the Mercury Laser Altimeter on the MErcury Surface, Space ENvironment, GEochemistry, and Ranging spacecraft, were combined with 378 occultation measurements of radio-frequency signals from the spacecraft in the planet's southern hemisphere to reveal the low-degree shape of Mercury. We solved for the spherical-harmonic coefficients through degree and order 128 and found that Mercury's mean radius is 2439.36±0.02 km. The offset between the planet's centers of mass and figure is negligible (40±40 m) along the polar axis and modest (140±50 m) in the equatorial plane. Mercury's spherical-harmonic shape spectrum is dominated by degree 2, and the planet's first-order shape is that of a triaxial ellipsoid with semimajor axes a, b, and c. The polar radius, c, is 1.65 km less than (a+b)/2, and the equatorial difference, a-b, is 1.25 km. The long axis is rotated 15° west of Mercury's dynamically defined principal axis. Mercury's geoid is similarly dominated by degree 2 and well described by a triaxial ellipsoid. The degree-2 geoid and shape are highly correlated, but the power spectral density of the geoid at degree 2 is only 1% of its shape counterpart, implying substantial compensation of elevation variations on a global scale and that Mercury is not in hydrostatic equilibrium.

Six degree of freedom sensor

DOEpatents

Vann, Charles S.

1999-01-01

This small, non-contact optical sensor increases the capability and flexibility of computer controlled machines by detecting its relative position to a workpiece in all six degrees of freedom (DOF). At a fraction of the cost, it is over 200 times faster and up to 25 times more accurate than competing 3-DOF sensors. Applications range from flexible manufacturing to a 6-DOF mouse for computers. Until now, highly agile and accurate machines have been limited by their inability to adjust to changes in their tasks. By enabling them to sense all six degrees of position, these machines can now adapt to new and complicated tasks without human intervention or delay--simplifying production, reducing costs, and enhancing the value and capability of flexible manufacturing.

Six degree of freedom sensor

DOEpatents

Vann, C.S.

1999-03-16

This small, non-contact optical sensor increases the capability and flexibility of computer controlled machines by detecting its relative position to a workpiece in all six degrees of freedom (DOF). At a fraction of the cost, it is over 200 times faster and up to 25 times more accurate than competing 3-DOF sensors. Applications range from flexible manufacturing to a 6-DOF mouse for computers. Until now, highly agile and accurate machines have been limited by their inability to adjust to changes in their tasks. By enabling them to sense all six degrees of position, these machines can now adapt to new and complicated tasks without human intervention or delay--simplifying production, reducing costs, and enhancing the value and capability of flexible manufacturing. 3 figs.

A pilot systematic genomic comparison of recurrence risks of hepatitis B virus-associated hepatocellular carcinoma with low- and high-degree liver fibrosis.

PubMed

Yoo, Seungyeul; Wang, Wenhui; Wang, Qin; Fiel, M Isabel; Lee, Eunjee; Hiotis, Spiros P; Zhu, Jun

2017-12-07

Chronic hepatitis B virus (HBV) infection leads to liver fibrosis, which is a major risk factor in hepatocellular carcinoma (HCC) and an independent risk factor of recurrence after HCC tumor resection. The HBV genome can be inserted into the human genome, and chronic inflammation may trigger somatic mutations. However, how HBV integration and other genomic changes contribute to the risk of tumor recurrence with regards to the different degree of liver fibrosis is not clearly understood. We sequenced mRNAs of 21 pairs of tumor and distant non-neoplastic liver tissues of HBV-HCC patients and performed comprehensive genomic analyses of our RNAseq data and public available HBV-HCC sequencing data. We developed a robust pipeline for sensitively identifying HBV integration sites based on sequencing data. Simulations showed that our method outperformed existing methods. Applying it to our data, 374 and 106 HBV host genes were identified in non-neoplastic liver and tumor tissues, respectively. When applying it to other RNA sequencing datasets, consistently more HBV integrations were identified in non-neoplastic liver than in tumor tissues. HBV host genes identified in non-neoplastic liver samples significantly overlapped with known tumor suppressor genes. More significant enrichment of tumor suppressor genes was observed among HBV host genes identified from patients with tumor recurrence, indicating the potential risk of tumor recurrence driven by HBV integration in non-neoplastic liver tissues. We also compared SNPs of each sample with SNPs in a cancer census database and inferred samples' pathogenic SNP loads. Pathogenic SNP loads in non-neoplastic liver tissues were consistently higher than those in normal liver tissues. Additionally, HBV host genes identified in non-neoplastic liver tissues significantly overlapped with pathogenic somatic mutations, suggesting that HBV integration and somatic mutations targeting the same set of genes are important to tumorigenesis. HBV

Data Mining FAERS to Analyze Molecular Targets of Drugs Highly Associated with Stevens-Johnson Syndrome.

PubMed

Burkhart, Keith K; Abernethy, Darrell; Jackson, David

2015-06-01

Drug features that are associated with Stevens-Johnson syndrome (SJS) have not been fully characterized. A molecular target analysis of the drugs associated with SJS in the FDA Adverse Event Reporting System (FAERS) may contribute to mechanistic insights into SJS pathophysiology. The publicly available version of FAERS was analyzed to identify disproportionality among the molecular targets, metabolizing enzymes, and transporters for drugs associated with SJS. The FAERS in-house version was also analyzed for an internal comparison of the drugs most highly associated with SJS. Cyclooxygenases 1 and 2, carbonic anhydrase 2, and sodium channel 2 alpha were identified as disproportionately associated with SJS. Cytochrome P450 (CYPs) 3A4 and 2C9 are disproportionately represented as metabolizing enzymes of the drugs associated with SJS adverse event reports. Multidrug resistance protein 1 (MRP-1), organic anion transporter 1 (OAT1), and PEPT2 were also identified and are highly associated with the transport of these drugs. A detailed review of the molecular targets identifies important roles for these targets in immune response. The association with CYP metabolizing enzymes suggests that reactive metabolites and oxidative stress may have a contributory role. Drug transporters may enhance intracellular tissue concentrations and also have vital physiologic roles that impact keratinocyte proliferation and survival. Data mining FAERS may be used to hypothesize mechanisms for adverse drug events by identifying molecular targets that are highly associated with drug-induced adverse events. The information gained may contribute to systems biology disease models.

Electrospun N-doped Hierarchical Porous Carbon Nanofiber with Improved Graphitization Degree for High Performance Lithium Ion Capacitor.

PubMed

Li, Baohua; Shi, Ruiying; Han, Cuiping; Xu, Xiaofu; Qing, Xianying; Xu, Lei; Li, Hongfei; Li, Junqin; Wong, Ching-Ping

2018-05-14

Lithium ion capacitor (LIC) has been regarded as a promising device to combine the merits of lithium ion batteries and supercapacitors, which can meet the requirements for both high energy and power density. The development of advanced electrode is the key. Herein, we demonstrate the bottom-up synthesis of activated carbon nanofiber (a-PANF) with hierarchical porous structure and high graphitization degree. Electrospinning is employed to prepare interconnected fiber network with macropores and ferric acetylacetonate is introduced as both mesopore creating agent and graphitic catalyst to increase the graphitization degree. Furthermore, chemical activation enlarges the specific surface area by producing rich micropores. Half cell evaluation of the as-prepared a-PANF displays a discharge capacity of 80 mAh g-1 at 0.1 A g-1 within 2~4.5 V and no capacity fading after 1000 cycles at 2 A g-1, which is significantly higher than conventional activated carbon. Furthermore, the as-assembled LIC with a-PANF cathode and Fe3O4 anode achieves a superior energy density of 124.6 Wh kg-1 at a specific power of 93.8 W kg-1, and remains 103.7 Wh kg-1 at 4687.5 W kg-1, demonstrating the promising application of a-PANF as potential electrode candidates for efficient energy storage systems. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Reasons for the Slow Completion of Masters and Doctoral Degrees by Adult Learners in a South African Township

ERIC Educational Resources Information Center

Motseke, Masilonyana

2016-01-01

The aim of the study was to investigate the reasons why adult learners took longer than required to complete their Master's and Doctoral degrees. A questionnaire and focus group interviews were used to collect data. Twenty adult learners who registered for the Master's and Doctoral degrees at one township campus of a university were targeted, and…

Highly Efficient Targeted Mutagenesis in Mice Using TALENs

PubMed Central

Panda, Sudeepta Kumar; Wefers, Benedikt; Ortiz, Oskar; Floss, Thomas; Schmid, Bettina; Haass, Christian; Wurst, Wolfgang; Kühn, Ralf

2013-01-01

Targeted mouse mutants are instrumental for the analysis of gene function in health and disease. We recently provided proof-of-principle for the fast-track mutagenesis of the mouse genome, using transcription activator-like effector nucleases (TALENs) in one-cell embryos. Here we report a routine procedure for the efficient production of disease-related knockin and knockout mutants, using improved TALEN mRNAs that include a plasmid-coded poly(A) tail (TALEN-95A), circumventing the problematic in vitro polyadenylation step. To knock out the C9orf72 gene as a model of frontotemporal lobar degeneration, TALEN-95A mutagenesis induced sequence deletions in 41% of pups derived from microinjected embryos. Using TALENs together with mutagenic oligodeoxynucleotides, we introduced amyotrophic lateral sclerosis patient-derived missense mutations in the fused in sarcoma (Fus) gene at a rate of 6.8%. For the simple identification of TALEN-induced mutants and their progeny we validate high-resolution melt analysis (HRMA) of PCR products as a sensitive and universal genotyping tool. Furthermore, HRMA of off-target sites in mutant founder mice revealed no evidence for undesired TALEN-mediated processing of related genomic sequences. The combination of TALEN-95A mRNAs for enhanced mutagenesis and of HRMA for simplified genotyping enables the accelerated, routine production of new mouse models for the study of genetic disease mechanisms. PMID:23979585

The Roots of Alzheimer's Disease: Are High-Expanding Cortical Areas Preferentially Targeted?†.

PubMed

Fjell, Anders M; Amlien, Inge K; Sneve, Markus H; Grydeland, Håkon; Tamnes, Christian K; Chaplin, Tristan A; Rosa, Marcello G P; Walhovd, Kristine B

2015-09-01

Alzheimer's disease (AD) is regarded a human-specific condition, and it has been suggested that brain regions highly expanded in humans compared with other primates are selectively targeted. We calculated shared and unique variance in the distribution of AD atrophy accounted for by cortical expansion between macaque and human, affiliation to the default mode network (DMN), ontogenetic development and normal aging. Cortical expansion was moderately related to atrophy, but a critical discrepancy was seen in the medial temporo-parietal episodic memory network. Identification of "hotspots" and "coldspots" of expansion across several primate species did not yield compelling evidence for the hypothesis that highly expanded regions are specifically targeted. Controlling for distribution of atrophy in aging substantially attenuated the expansion-AD relationship. A path model showed that all variables explained unique variance in AD atrophy but were generally mediated through aging. This supports a systems-vulnerability model, where critical networks are subject to various negative impacts, aging in particular, rather than being selectively targeted in AD. An alternative approach is suggested, focused on the interplay of the phylogenetically old and preserved medial temporal lobe areas with more highly expanded association cortices governed by different principles of plasticity and stability. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

The first clinical implementation of a real-time six degree of freedom target tracking system during radiation therapy based on Kilovoltage Intrafraction Monitoring (KIM).

PubMed

Nguyen, Doan Trang; O'Brien, Ricky; Kim, Jung-Ha; Huang, Chen-Yu; Wilton, Lee; Greer, Peter; Legge, Kimberley; Booth, Jeremy T; Poulsen, Per Rugaard; Martin, Jarad; Keall, Paul J

2017-04-01

We present the first clinical implementation of a real-time six-degree of freedom (6DoF) Kilovoltage Intrafraction Monitoring (KIM) system which tracks the cancer target translational and rotational motions during treatment. The method was applied to measure and correct for target motion during stereotactic body radiotherapy (SBRT) for prostate cancer. Patient: A patient with prostate adenocarcinoma undergoing SBRT with 36.25Gy, delivered in 5 fractions was enrolled in the study. 6DoF KIM technology: 2D positions of three implanted gold markers in each of the kV images (125kV, 10mA at 11Hz) were acquired continuously during treatment. The 2D→3D target position estimation was based on a probability distribution function. The 3D→6DoF target rotation was calculated using an iterative closest point algorithm. The accuracy and precision of the KIM method was measured by comparing the real-time results with kV-MV triangulation. Of the five treatment fractions, KIM was utilised successfully in four fractions. The intrafraction prostate motion resulted in three couch shifts in two fractions when the prostate motion exceeded the pre-set action threshold of 2mm for more than 5s. KIM translational accuracy and precision were 0.3±0.6mm, -0.2±0.3mm and 0.2±0.7mm in the Left-Right (LR), Superior-Inferior (SI) and Anterior-Posterior (AP) directions, respectively. The KIM rotational accuracy and precision were 0.8°±2.0°, -0.5°±3.3° and 0.3°±1.6° in the roll, pitch and yaw directions, respectively. This treatment represents, to the best of our knowledge, the first time a cancer patient's tumour position and rotation have been monitored in real-time during treatment. The 6 DoF KIM system has sub-millimetre accuracy and precision in all three translational axes, and less than 1° accuracy and 4° precision in all three rotational axes. Copyright © 2017 Elsevier B.V. All rights reserved.

Highly Complementary Target RNAs Promote Release of Guide RNAs from Human Argonaute2

PubMed Central

De, Nabanita; Young, Lisa; Lau, Pick-Wei; Meisner, Nicole-Claudia; Morrissey, David V.; MacRae, Ian J.

2013-01-01

SUMMARY Argonaute proteins use small RNAs to guide the silencing of complementary target RNAs in many eukaryotes. Although small RNA biogenesis pathways are well studied, mechanisms for removal of guide RNAs from Argonaute are poorly understood. Here we show that the Argonaute2 (Ago2) guide RNA complex is extremely stable, with a half-life on the order of days. However, highly complementary target RNAs destabilize the complex and significantly accelerate release of the guide RNA from Ago2. This “unloading” activity can be enhanced by mismatches between the target and the guide 5′ end and attenuated by mismatches to the guide 3′ end. The introduction of 3′ mismatches leads to more potent silencing of abundant mRNAs in mammalian cells. These findings help to explain why the 3′ ends of mammalian microRNAs (miRNAs) rarely match their targets, suggest a mechanism for sequence-specific small RNA turnover, and offer insights for controlling small RNAs in mammalian cells. PMID:23664376

Efficient Interruption of Infection Chains by Targeted Removal of Central Holdings in an Animal Trade Network

PubMed Central

Büttner, Kathrin; Krieter, Joachim; Traulsen, Arne; Traulsen, Imke

2013-01-01

Centrality parameters in animal trade networks typically have right-skewed distributions, implying that these networks are highly resistant against the random removal of holdings, but vulnerable to the targeted removal of the most central holdings. In the present study, we analysed the structural changes of an animal trade network topology based on the targeted removal of holdings using specific centrality parameters in comparison to the random removal of holdings. Three different time periods were analysed: the three-year network, the yearly and the monthly networks. The aim of this study was to identify appropriate measures for the targeted removal, which lead to a rapid fragmentation of the network. Furthermore, the optimal combination of the removal of three holdings regardless of their centrality was identified. The results showed that centrality parameters based on ingoing trade contacts, e.g. in-degree, ingoing infection chain and ingoing closeness, were not suitable for a rapid fragmentation in all three time periods. More efficient was the removal based on parameters considering the outgoing trade contacts. In all networks, a maximum percentage of 7.0% (on average 5.2%) of the holdings had to be removed to reduce the size of the largest component by more than 75%. The smallest difference from the optimal combination for all three time periods was obtained by the removal based on out-degree with on average 1.4% removed holdings, followed by outgoing infection chain and outgoing closeness. The targeted removal using the betweenness centrality differed the most from the optimal combination in comparison to the other parameters which consider the outgoing trade contacts. Due to the pyramidal structure and the directed nature of the pork supply chain the most efficient interruption of the infection chain for all three time periods was obtained by using the targeted removal based on out-degree. PMID:24069293

Accreditation Issues Related to Adult Degree Programs

ERIC Educational Resources Information Center

Simpson, Edward G., Jr.

2004-01-01

Understanding the fundamental tenets and structure of the accreditation process can assist institutions in the design of high-quality degree programs while affording adult students a reasonable level of consumer protection.

A Descriptive Look at College Enrollment and Degree Completion of Baltimore City Graduates

ERIC Educational Resources Information Center

Durham, Rachel E.; Westlund, Erik

2011-01-01

Earning a college degree increases a person's life outcomes in income, employment, health, and quality of life. The average person with a bachelor's degree earns almost twice as much as a high school graduate and nearly triple that of someone who did not finish high school. The unemployment rate for people with bachelor's degrees is about…

Identification of human microRNA targets from isolated argonaute protein complexes.

PubMed

Beitzinger, Michaela; Peters, Lasse; Zhu, Jia Yun; Kremmer, Elisabeth; Meister, Gunter

2007-06-01

MicroRNAs (miRNAs) constitute a class of small non-coding RNAs that regulate gene expression on the level of translation and/or mRNA stability. Mammalian miRNAs associate with members of the Argonaute (Ago) protein family and bind to partially complementary sequences in the 3' untranslated region (UTR) of specific target mRNAs. Computer algorithms based on factors such as free binding energy or sequence conservation have been used to predict miRNA target mRNAs. Based on such predictions, up to one third of all mammalian mRNAs seem to be under miRNA regulation. However, due to the low degree of complementarity between the miRNA and its target, such computer programs are often imprecise and therefore not very reliable. Here we report the first biochemical identification approach of miRNA targets from human cells. Using highly specific monoclonal antibodies against members of the Ago protein family, we co-immunoprecipitate Ago-bound mRNAs and identify them by cloning. Interestingly, most of the identified targets are also predicted by different computer programs. Moreover, we randomly analyzed six different target candidates and were able to experimentally validate five as miRNA targets. Our data clearly indicate that miRNA targets can be experimentally identified from Ago complexes and therefore provide a new tool to directly analyze miRNA function.

Spot-welding solid targets for high current cyclotron irradiation.

PubMed

Ellison, Paul A; Valdovinos, Hector F; Graves, Stephen A; Barnhart, Todd E; Nickles, Robert J

2016-12-01

Zirconium-89 finds broad application for use in positron emission tomography. Its cyclotron production has been limited by the heat transfer from yttrium targets at high beam currents. A spot welding technique allows a three-fold increase in beam current, without affecting 89 Zr quality. An yttrium foil, welded to a jet-cooled tantalum support base accommodates a 50µA proton beam degraded to 14MeV. The resulting activity yield of 48±4 MBq/(μA∙hr) now extends the outreach of 89 Zr for a broader distribution. Copyright © 2016 Elsevier Ltd. All rights reserved.

A targeted illumination optical fiber probe for high resolution fluorescence imaging and optical switching

NASA Astrophysics Data System (ADS)

Shinde, Anant; Perinchery, Sandeep Menon; Murukeshan, Vadakke Matham

2017-04-01

An optical imaging probe with targeted multispectral and spatiotemporal illumination features has applications in many diagnostic biomedical studies. However, these systems are mostly adapted in conventional microscopes, limiting their use for in vitro applications. We present a variable resolution imaging probe using a digital micromirror device (DMD) with an achievable maximum lateral resolution of 2.7 μm and an axial resolution of 5.5 μm, along with precise shape selective targeted illumination ability. We have demonstrated switching of different wavelengths to image multiple regions in the field of view. Moreover, the targeted illumination feature allows enhanced image contrast by time averaged imaging of selected regions with different optical exposure. The region specific multidirectional scanning feature of this probe has facilitated high speed targeted confocal imaging.

Acoustical imaging of high-frequency elastic responses of targets

NASA Astrophysics Data System (ADS)

Morse, Scot F.; Hefner, Brian T.; Marston, Philip L.

2002-05-01

Acoustical imaging was used to investigate high-frequency elastic responses to sound of two targets in water. The backscattering of broadband bipolar acoustic pulses by a truncated cylindrical shell was recorded over a wide range of tilt angles [S. F. Morse and P. L. Marston, ``Backscattering of transients by tilted truncated cylindrical shells: time-frequency identification of ray contributions from measurements,'' J. Acoust. Soc. Am. (in press)]. This data set was used to form synthetic aperture images of the target based on the data within different angular apertures. Over a range of viewing angles, the visibility of the cylinder's closest rear corner was significantly enhanced by the meridional flexural wave contribution to the backscattering. In another experiment, the time evolution of acoustic holographic images was used to explore the response of tilted elastic circular disks to tone bursts having frequencies of 250 and 300 kHz. For different tilt angles, specific responses that enhance the backscattering were identified from the time evolution of the images [B. T. Hefner and P. L. Marston, Acoust. Res. Lett. Online 2, 55-60 (2001)]. [Work supported by ONR.

Mass Spectrometry Based Ultrasensitive DNA Methylation Profiling Using Target Fragmentation Assay.

PubMed

Lin, Xiang-Cheng; Zhang, Ting; Liu, Lan; Tang, Hao; Yu, Ru-Qin; Jiang, Jian-Hui

2016-01-19

Efficient tools for profiling DNA methylation in specific genes are essential for epigenetics and clinical diagnostics. Current DNA methylation profiling techniques have been limited by inconvenient implementation, requirements of specific reagents, and inferior accuracy in quantifying methylation degree. We develop a novel mass spectrometry method, target fragmentation assay (TFA), which enable to profile methylation in specific sequences. This method combines selective capture of DNA target from restricted cleavage of genomic DNA using magnetic separation with MS detection of the nonenzymatic hydrolysates of target DNA. This method is shown to be highly sensitive with a detection limit as low as 0.056 amol, allowing direct profiling of methylation using genome DNA without preamplification. Moreover, this method offers a unique advantage in accurately determining DNA methylation level. The clinical applicability was demonstrated by DNA methylation analysis using prostate tissue samples, implying the potential of this method as a useful tool for DNA methylation profiling in early detection of related diseases.

High-Precision Pinpointing of Luminescent Targets in Encoder-Assisted Scanning Microscopy Allowing High-Speed Quantitative Analysis.

PubMed

Zheng, Xianlin; Lu, Yiqing; Zhao, Jiangbo; Zhang, Yuhai; Ren, Wei; Liu, Deming; Lu, Jie; Piper, James A; Leif, Robert C; Liu, Xiaogang; Jin, Dayong

2016-01-19

Compared with routine microscopy imaging of a few analytes at a time, rapid scanning through the whole sample area of a microscope slide to locate every single target object offers many advantages in terms of simplicity, speed, throughput, and potential for robust quantitative analysis. Existing techniques that accommodate solid-phase samples incorporating individual micrometer-sized targets generally rely on digital microscopy and image analysis, with intrinsically low throughput and reliability. Here, we report an advanced on-the-fly stage scanning method to achieve high-precision target location across the whole slide. By integrating X- and Y-axis linear encoders to a motorized stage as the virtual "grids" that provide real-time positional references, we demonstrate an orthogonal scanning automated microscopy (OSAM) technique which can search a coverslip area of 50 × 24 mm(2) in just 5.3 min and locate individual 15 μm lanthanide luminescent microspheres with standard deviations of 1.38 and 1.75 μm in X and Y directions. Alongside implementation of an autofocus unit that compensates the tilt of a slide in the Z-axis in real time, we increase the luminescence detection efficiency by 35% with an improved coefficient of variation. We demonstrate the capability of advanced OSAM for robust quantification of luminescence intensities and lifetimes for a variety of micrometer-scale luminescent targets, specifically single down-shifting and upconversion microspheres, crystalline microplates, and color-barcoded microrods, as well as quantitative suspension array assays of biotinylated-DNA functionalized upconversion nanoparticles.

Targets for producing high purity I-123

NASA Technical Reports Server (NTRS)

Blue, J. W. (Inventor)

1978-01-01

Tellurium powder in improved targets is bombarded with a cyclotron beam to produce Xe-123. Flowing gas streams carry the Xe-123 through one cold trap which removes Xe-123 that subsequently decays to I-123. During this bombardment energy is deposited in the target material causing its temperature to rise. Some of the tellurium vaporizes and subsequently condenses on surfaces that are cooler than the vaporization temperature. Provision is made for the repeated bombardment of this condensed tellurium.

Target effects in isobaric yield ratio differences between projectile fragmentation reactions

NASA Astrophysics Data System (ADS)

Ma, Chun-Wang; Zhang, Yan-Li; Qiao, Chun-Yuan; Wang, Shan-Shan

2015-01-01

Background: The isobaric yield ratio difference (IBD) between reactions is know to be sensitive to the density difference between projectiles in heavy-ion collisions around the Fermi energy. Purpose: The target effects in the isobaric yield ratio (IYR) and the IBD results have been studied. Methods: The amount of isotopes in the 140 A MeV 48 ,40Ca +181Ta /9Be and 58 ,64Ni +181Ta /9Be reactions have been previously measured with high accuracy. The IYR and IBD results have been obtained from these reactions to study the effects of the light 9Be and heavy 181Ta targets. A ratio (rΔ μ) between the IBD results for the reactions with Ta and Be targets is defined to quantitatively show the target dependence of the IBD results. Results The IYRs for reactions with symmetric projectiles are more easily affected than those for reactions with neutron-rich projectiles. The IBD results are suppressed by using the 181Ta target to different degrees. Conclusions: The IYR and IBD results are influenced by the target used. The IBD for the I =1 isobaric chain is suggested as a probe to study the difference between the neutron and proton densities of the reaction systems.

Numerical Modeling of Complex Targets for High-Energy- Density Experiments with Ion Beams and other Drivers

DOE PAGES

Koniges, Alice; Liu, Wangyi; Lidia, Steven; ...

2016-04-01

We explore the simulation challenges and requirements for experiments planned on facilities such as the NDCX-II ion accelerator at LBNL, currently undergoing commissioning. Hydrodynamic modeling of NDCX-II experiments include certain lower temperature effects, e.g., surface tension and target fragmentation, that are not generally present in extreme high-energy laser facility experiments, where targets are completely vaporized in an extremely short period of time. Target designs proposed for NDCX-II range from metal foils of order one micron thick (thin targets) to metallic foam targets several tens of microns thick (thick targets). These high-energy-density experiments allow for the study of fracture as wellmore » as the process of bubble and droplet formation. We incorporate these physics effects into a code called ALE-AMR that uses a combination of Arbitrary Lagrangian Eulerian hydrodynamics and Adaptive Mesh Refinement. Inclusion of certain effects becomes tricky as we must deal with non-orthogonal meshes of various levels of refinement in three dimensions. A surface tension model used for droplet dynamics is implemented in ALE-AMR using curvature calculated from volume fractions. Thick foam target experiments provide information on how ion beam induced shock waves couple into kinetic energy of fluid flow. Although NDCX-II is not fully commissioned, experiments are being conducted that explore material defect production and dynamics.« less

Using cost-effectiveness analysis to evaluate targeting strategies: the case of vitamin A supplementation.

PubMed

Loevinsohn, B P; Sutter, R W; Costales, M O

1997-03-01

Given the demonstrated efficacy of vitamin A supplements in reducing childhood mortality, health officials now have to decide whether it would be efficient to target the supplements to high risk children. Decisions about targeting are complex because they depend on a number of factors; the degree of clustering of preventable deaths, the cost of the intervention, the side-effects of the intervention, the cost of identifying the high risk group, and the accuracy of the 'diagnosis' of risk. A cost-effectiveness analysis was used in the Philippines to examine whether vitamin A supplements should be given universally to all children 6-59 months, targeted broadly to children suffering from mild, moderate, or severe malnutrition, or targeted narrowly to pre-schoolers with moderate and severe malnutrition. The first year average cost of the universal approach was US$67.21 per death averted compared to $144.12 and $257.20 for the broad and narrow targeting approaches respectively. When subjected to sensitivity analysis the conclusion about the most cost-effective strategy was robust to changes in underlying assumptions such as the efficacy of supplements, clustering of deaths, and toxicity. Targeting vitamin A supplements to high risk children is not an efficient use of resources. Based on the results of this cost-effectiveness analysis and a consideration of alternate strategies, it is apparent that vitamin A, like immunization, should be provided to all pre-schoolers in the developing world. Issues about targeting public health interventions can usefully be addressed by cost-effectiveness analysis.

Second-Degree Learners in Associate Degree Nursing Programs: Characteristics and Progression Success

ERIC Educational Resources Information Center

McGinley, Patricia M.

2013-01-01

Second degree learners are attending associate (ADN), accelerated baccalaureate (BSN), and entry level masters (ELM) degree nursing programs. There is limited data related to the socio-demographic characteristics and graduation success rates of students attending accelerated BSN or ELM programs and no data related to second-degree learners…

Fragment-Based Screening of a Natural Product Library against 62 Potential Malaria Drug Targets Employing Native Mass Spectrometry

PubMed Central

2018-01-01

Natural products are well known for their biological relevance, high degree of three-dimensionality, and access to areas of largely unexplored chemical space. To shape our understanding of the interaction between natural products and protein targets in the postgenomic era, we have used native mass spectrometry to investigate 62 potential protein targets for malaria using a natural-product-based fragment library. We reveal here 96 low-molecular-weight natural products identified as binding partners of 32 of the putative malarial targets. Seventy-nine (79) fragments have direct growth inhibition on Plasmodium falciparum at concentrations that are promising for the development of fragment hits against these protein targets. This adds a fragment library to the published HTS active libraries in the public domain. PMID:29436819

Fragment-Based Screening of a Natural Product Library against 62 Potential Malaria Drug Targets Employing Native Mass Spectrometry.

PubMed

Vu, Hoan; Pedro, Liliana; Mak, Tin; McCormick, Brendan; Rowley, Jessica; Liu, Miaomiao; Di Capua, Angela; Williams-Noonan, Billy; Pham, Ngoc B; Pouwer, Rebecca; Nguyen, Bao; Andrews, Katherine T; Skinner-Adams, Tina; Kim, Jessica; Hol, Wim G J; Hui, Raymond; Crowther, Gregory J; Van Voorhis, Wesley C; Quinn, Ronald J

2018-04-13

Natural products are well known for their biological relevance, high degree of three-dimensionality, and access to areas of largely unexplored chemical space. To shape our understanding of the interaction between natural products and protein targets in the postgenomic era, we have used native mass spectrometry to investigate 62 potential protein targets for malaria using a natural-product-based fragment library. We reveal here 96 low-molecular-weight natural products identified as binding partners of 32 of the putative malarial targets. Seventy-nine (79) fragments have direct growth inhibition on Plasmodium falciparum at concentrations that are promising for the development of fragment hits against these protein targets. This adds a fragment library to the published HTS active libraries in the public domain.

High-resolution imaging and target designation through clouds or smoke

DOEpatents

Perry, Michael D.

2003-01-01

A method and system of combining gated intensifiers and advances in solid-state, short-pulse laser technology, compact systems capable of producing high resolution (i.e., approximately less than 20 centimeters) optical images through a scattering medium such as dense clouds, fog, smoke, etc. may be achieved from air or ground based platforms. Laser target designation through a scattering medium is also enabled by utilizing a short pulse illumination laser and a relatively minor change to the detectors on laser guided munitions.

Identification of GPC2 as an Oncoprotein and Candidate Immunotherapeutic Target in High-Risk Neuroblastoma.

PubMed

Bosse, Kristopher R; Raman, Pichai; Zhu, Zhongyu; Lane, Maria; Martinez, Daniel; Heitzeneder, Sabine; Rathi, Komal S; Kendsersky, Nathan M; Randall, Michael; Donovan, Laura; Morrissy, Sorana; Sussman, Robyn T; Zhelev, Doncho V; Feng, Yang; Wang, Yanping; Hwang, Jennifer; Lopez, Gonzalo; Harenza, Jo Lynne; Wei, Jun S; Pawel, Bruce; Bhatti, Tricia; Santi, Mariarita; Ganguly, Arupa; Khan, Javed; Marra, Marco A; Taylor, Michael D; Dimitrov, Dimiter S; Mackall, Crystal L; Maris, John M

2017-09-11

We developed an RNA-sequencing-based pipeline to discover differentially expressed cell-surface molecules in neuroblastoma that meet criteria for optimal immunotherapeutic target safety and efficacy. Here, we show that GPC2 is a strong candidate immunotherapeutic target in this childhood cancer. We demonstrate high GPC2 expression in neuroblastoma due to MYCN transcriptional activation and/or somatic gain of the GPC2 locus. We confirm GPC2 to be highly expressed on most neuroblastomas, but not detectable at appreciable levels in normal childhood tissues. In addition, we demonstrate that GPC2 is required for neuroblastoma proliferation. Finally, we develop a GPC2-directed antibody-drug conjugate that is potently cytotoxic to GPC2-expressing neuroblastoma cells. Collectively, these findings validate GPC2 as a non-mutated neuroblastoma oncoprotein and candidate immunotherapeutic target. Copyright © 2017 Elsevier Inc. All rights reserved.

The timecourse of space- and object-based attentional prioritization with varying degrees of certainty

PubMed Central

Drummond, Leslie; Shomstein, Sarah

2013-01-01

The relative contributions of objects (i.e., object-based) and underlying spatial (i.e., space-based representations) to attentional prioritization and selection remain unclear. In most experimental circumstances, the two representations overlap thus their respective contributions cannot be evaluated. Here, a dynamic version of the two-rectangle paradigm allowed for a successful de-coupling of spatial and object representations. Space-based (cued spatial location), cued end of the object, and object-based (locations within the cued object) effects were sampled at several timepoints following the cue with high or low certainty as to target location. In the high uncertainty condition spatial benefits prevailed throughout most of the timecourse, as evidenced by facilitatory and inhibitory effects. Additionally, the cued end of the object, rather than a whole object, received the attentional benefit. When target location was predictable (low uncertainty manipulation), only probabilities guided selection (i.e., evidence by a benefit for the statistically biased location). These results suggest that with high spatial uncertainty, all available information present within the stimulus display is used for the purposes of attentional selection (e.g., spatial locations, cued end of the object) albeit to varying degrees and at different time points. However, as certainty increases, only spatial certainty guides selection (i.e., object ends and whole objects are filtered out). Taken together, these results further elucidate the contributing role of space- and object-representations to attentional guidance. PMID:24367302

The siRNA Non-seed Region and Its Target Sequences Are Auxiliary Determinants of Off-Target Effects.

PubMed

Kamola, Piotr J; Nakano, Yuko; Takahashi, Tomoko; Wilson, Paul A; Ui-Tei, Kumiko

2015-12-01

RNA interference (RNAi) is a powerful tool for post-transcriptional gene silencing. However, the siRNA guide strand may bind unintended off-target transcripts via partial sequence complementarity by a mechanism closely mirroring micro RNA (miRNA) silencing. To better understand these off-target effects, we investigated the correlation between sequence features within various subsections of siRNA guide strands, and its corresponding target sequences, with off-target activities. Our results confirm previous reports that strength of base-pairing in the siRNA seed region is the primary factor determining the efficiency of off-target silencing. However, the degree of downregulation of off-target transcripts with shared seed sequence is not necessarily similar, suggesting that there are additional auxiliary factors that influence the silencing potential. Here, we demonstrate that both the melting temperature (Tm) in a subsection of siRNA non-seed region, and the GC contents of its corresponding target sequences, are negatively correlated with the efficiency of off-target effect. Analysis of experimentally validated miRNA targets demonstrated a similar trend, indicating a putative conserved mechanistic feature of seed region-dependent targeting mechanism. These observations may prove useful as parameters for off-target prediction algorithms and improve siRNA 'specificity' design rules.

Micro-channel-based high specific power lithium target

NASA Astrophysics Data System (ADS)

Mastinu, P.; Martın-Hernández, G.; Praena, J.; Gramegna, F.; Prete, G.; Agostini, P.; Aiello, A.; Phoenix, B.

2016-11-01

A micro-channel-based heat sink has been produced and tested. The device has been developed to be used as a Lithium target for the LENOS (Legnaro Neutron Source) facility and for the production of radioisotope. Nevertheless, applications of such device can span on many areas: cooling of electronic devices, diode laser array, automotive applications etc. The target has been tested using a proton beam of 2.8MeV energy and delivering total power shots from 100W to 1500W with beam spots varying from 5mm2 to 19mm2. Since the target has been designed to be used with a thin deposit of lithium and since lithium is a low-melting-point material, we have measured that, for such application, a specific power of about 3kW/cm2 can be delivered to the target, keeping the maximum surface temperature not exceeding 150° C.

Infrared target simulation environment for pattern recognition applications

NASA Astrophysics Data System (ADS)

Savakis, Andreas E.; George, Nicholas

1994-07-01

The generation of complete databases of IR data is extremely useful for training human observers and testing automatic pattern recognition algorithms. Field data may be used for realism, but require expensive and time-consuming procedures. IR scene simulation methods have emerged as a more economical and efficient alternative for the generation of IR databases. A novel approach to IR target simulation is presented in this paper. Model vehicles at 1:24 scale are used for the simulation of real targets. The temperature profile of the model vehicles is controlled using resistive circuits which are embedded inside the models. The IR target is recorded using an Inframetrics dual channel IR camera system. Using computer processing we place the recorded IR target in a prerecorded background. The advantages of this approach are: (1) the range and 3D target aspect can be controlled by the relative position between the camera and model vehicle; (2) the temperature profile can be controlled by adjusting the power delivered to the resistive circuit; (3) the IR sensor effects are directly incorporated in the recording process, because the real sensor is used; (4) the recorded target can embedded in various types of backgrounds recorded under different weather conditions, times of day etc. The effectiveness of this approach is demonstrated by generating an IR database of three vehicles which is used to train a back propagation neural network. The neural network is capable of classifying vehicle type, vehicle aspect, and relative temperature with a high degree of accuracy.

Development and calibration of an accurate 6-degree-of-freedom measurement system with total station

NASA Astrophysics Data System (ADS)

Gao, Yang; Lin, Jiarui; Yang, Linghui; Zhu, Jigui

2016-12-01

To meet the demand of high-accuracy, long-range and portable use in large-scale metrology for pose measurement, this paper develops a 6-degree-of-freedom (6-DOF) measurement system based on total station by utilizing its advantages of long range and relative high accuracy. The cooperative target sensor, which is mainly composed of a pinhole prism, an industrial lens, a camera and a biaxial inclinometer, is designed to be portable in use. Subsequently, a precise mathematical model is proposed from the input variables observed by total station, imaging system and inclinometer to the output six pose variables. The model must be calibrated in two levels: the intrinsic parameters of imaging system, and the rotation matrix between coordinate systems of the camera and the inclinometer. Then corresponding approaches are presented. For the first level, we introduce a precise two-axis rotary table as a calibration reference. And for the second level, we propose a calibration method by varying the pose of a rigid body with the target sensor and a reference prism on it. Finally, through simulations and various experiments, the feasibilities of the measurement model and calibration methods are validated, and the measurement accuracy of the system is evaluated.

High Resolution Crystal Structure of Human β-Glucuronidase Reveals Structural Basis of Lysosome Targeting

PubMed Central

Hassan, Md. Imtaiyaz; Waheed, Abdul; Grubb, Jeffery H.; Klei, Herbert E.; Korolev, Sergey; Sly, William S.

2013-01-01

Human β-glucuronidase (GUS) cleaves β-D-glucuronic acid residues from the non-reducing termini of glycosaminoglycan and its deficiency leads to mucopolysaccharidosis type VII (MPSVII). Here we report a high resolution crystal structure of human GUS at 1.7 Å resolution and present an extensive analysis of the structural features, unifying recent findings in the field of lysosome targeting and glycosyl hydrolases. The structure revealed several new details including a new glycan chain at Asn272, in addition to that previously observed at Asn173, and coordination of the glycan chain at Asn173 with Lys197 of the lysosomal targeting motif which is essential for phosphotransferase recognition. Analysis of the high resolution structure not only provided new insights into the structural basis for lysosomal targeting but showed significant differences between human GUS, which is medically important in its own right, and E. coli GUS, which can be selectively inhibited in the human gut to prevent prodrug activation and is also widely used as a reporter gene by plant biologists. Despite these differences, both human and E. coli GUS share a high structure homology in all three domains with most of the glycosyl hydrolases, suggesting that they all evolved from a common ancestral gene. PMID:24260279

Texture metric that predicts target detection performance

NASA Astrophysics Data System (ADS)

Culpepper, Joanne B.

2015-12-01

Two texture metrics based on gray level co-occurrence error (GLCE) are used to predict probability of detection and mean search time. The two texture metrics are local clutter metrics and are based on the statistics of GLCE probability distributions. The degree of correlation between various clutter metrics and the target detection performance of the nine military vehicles in complex natural scenes found in the Search_2 dataset are presented. Comparison is also made between four other common clutter metrics found in the literature: root sum of squares, Doyle, statistical variance, and target structure similarity. The experimental results show that the GLCE energy metric is a better predictor of target detection performance when searching for targets in natural scenes than the other clutter metrics studied.

SECOND TARGET STATION MODERATOR PERFORMANCE WITH A ROTATING TARGET

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

Remec, Igor; Gallmeier, Franz X; Rennich, Mark J

2016-01-01

Oak Ridge National Laboratory manages and operates the Spallation Neutron Source and the High Flux Isotope Reactor, two of the world's most advanced neutron scattering facilities. Both facilities are funded by the U.S. Department of Energy, Office of Science, Office of Basic Energy Science, and are available to researchers from all over the world. Delivering cutting edge science requires continuous improvements and development of the facilities and instruments. The SNS was designed from the outset to accommodate an additional target station, or Second Target Station (STS), and an upgraded accelerator feeding proton beams to STS and the existing First Targetmore » Station (FTS). Upgrade of the accelerator and the design and construction of STS are being proposed. The presently considered STS configuration is driven with short (<1 s) proton pulses at 10 Hz repetition rate and 467 kW proton beam power, and is optimized for high intensity and high resolution long wavelength neutron applications. STS will allow installation of 22 beamlines and will expand and complement the current national neutron scattering capabilities. In 2015 the STS studies were performed for a compact tungsten target; first a stationary tungsten plate target was analyzed to considerable details and then dropped in favor of a rotating target. For both target options the proton beam footprint as small as acceptable from mechanical and heat removal aspects is required to arrive at a compact-volume neutron production zone in the target, which is essential for tight coupling of target and moderators and for achieving high-intensity peak neutron fluxes. This paper will present recent STS work with the emphasis on neutronics and moderator performance.« less

Targeted carbon conservation at national scales with high-resolution monitoring

PubMed Central

Asner, Gregory P.; Knapp, David E.; Martin, Roberta E.; Tupayachi, Raul; Anderson, Christopher B.; Mascaro, Joseph; Sinca, Felipe; Chadwick, K. Dana; Higgins, Mark; Farfan, William; Llactayo, William; Silman, Miles R.

2014-01-01

Terrestrial carbon conservation can provide critical environmental, social, and climate benefits. Yet, the geographically complex mosaic of threats to, and opportunities for, conserving carbon in landscapes remain largely unresolved at national scales. Using a new high-resolution carbon mapping approach applied to Perú, a megadiverse country undergoing rapid land use change, we found that at least 0.8 Pg of aboveground carbon stocks are at imminent risk of emission from land use activities. Map-based information on the natural controls over carbon density, as well as current ecosystem threats and protections, revealed three biogeographically explicit strategies that fully offset forthcoming land-use emissions. High-resolution carbon mapping affords targeted interventions to reduce greenhouse gas emissions in rapidly developing tropical nations. PMID:25385593

Targeted carbon conservation at national scales with high-resolution monitoring.

PubMed

Asner, Gregory P; Knapp, David E; Martin, Roberta E; Tupayachi, Raul; Anderson, Christopher B; Mascaro, Joseph; Sinca, Felipe; Chadwick, K Dana; Higgins, Mark; Farfan, William; Llactayo, William; Silman, Miles R

2014-11-25

Terrestrial carbon conservation can provide critical environmental, social, and climate benefits. Yet, the geographically complex mosaic of threats to, and opportunities for, conserving carbon in landscapes remain largely unresolved at national scales. Using a new high-resolution carbon mapping approach applied to Perú, a megadiverse country undergoing rapid land use change, we found that at least 0.8 Pg of aboveground carbon stocks are at imminent risk of emission from land use activities. Map-based information on the natural controls over carbon density, as well as current ecosystem threats and protections, revealed three biogeographically explicit strategies that fully offset forthcoming land-use emissions. High-resolution carbon mapping affords targeted interventions to reduce greenhouse gas emissions in rapidly developing tropical nations.

Micro-cone targets for producing high energy and low divergence particle beams

DOEpatents

Le Galloudec, Nathalie

2013-09-10

The present invention relates to micro-cone targets for producing high energy and low divergence particle beams. In one embodiment, the micro-cone target includes a substantially cone-shaped body including an outer surface, an inner surface, a generally flat and round, open-ended base, and a tip defining an apex. The cone-shaped body tapers along its length from the generally flat and round, open-ended base to the tip defining the apex. In addition, the outer surface and the inner surface connect the base to the tip, and the tip curves inwardly to define an outer surface that is concave, which is bounded by a rim formed at a juncture where the outer surface meets the tip.

Kinematics of a New High Precision Three Degree-of-Freedom Parallel Manipulator

NASA Technical Reports Server (NTRS)

Tahmasebi, Farhad

2005-01-01

Closed-form direct and inverse kinematics of a new three degree-of-freedom (DOF) parallel manipulator with inextensible limbs and base-mounted actuators are presented. The manipulator has higher resolution and precision than the existing three DOF mechanisms with extensible limbs. Since all of the manipulator actuators are base-mounted; higher payload capacity, smaller actuator sizes, and lower power dissipation can be obtained. The manipulator is suitable for alignment applications where only tip, tilt, and piston motions are significant. The direct kinematics of the manipulator is reduced to solving an eighth-degree polynomial in the square of tangent of half-angle between one of the limbs and the base plane. Hence, there are at most sixteen assembly configurations for the manipulator. In addition, it is shown that the sixteen solutions are eight pairs of reflected configurations with respect to the base plane. Numerical examples for the direct and inverse kinematics of the manipulator are also presented.

Dogs Identify Agents in Third-Party Interactions on the Basis of the Observed Degree of Contingency.

PubMed

Tauzin, Tibor; Kovács, Krisztina; Topál, József

2016-08-01

To investigate whether dogs could recognize contingent reactivity as a marker of agents' interaction, we performed an experiment in which dogs were presented with third-party contingent events. In the perfect-contingency condition, dogs were shown an unfamiliar self-propelled agent (SPA) that performed actions corresponding to audio clips of verbal commands played by a computer. In the high-but-imperfect-contingency condition, the SPA responded to the verbal commands on only two thirds of the trials; in the low-contingency condition, the SPA responded to the commands on only one third of the trials. In the test phase, the SPA approached one of two tennis balls, and then the dog was allowed to choose one of the balls. The proportion of trials on which a dog chose the object indicated by the SPA increased with the degree of contingency: Dogs chose the target object significantly above chance level only in the perfect-contingency condition. This finding suggests that dogs may use the degree of temporal contingency observed in third-party interactions as a cue to identify agents. © The Author(s) 2016.

Sensitivity of postplanning target and OAR coverage estimates to dosimetric margin distribution sampling parameters.

PubMed

Xu, Huijun; Gordon, J James; Siebers, Jeffrey V

2011-02-01

A dosimetric margin (DM) is the margin in a specified direction between a structure and a specified isodose surface, corresponding to a prescription or tolerance dose. The dosimetric margin distribution (DMD) is the distribution of DMs over all directions. Given a geometric uncertainty model, representing inter- or intrafraction setup uncertainties or internal organ motion, the DMD can be used to calculate coverage Q, which is the probability that a realized target or organ-at-risk (OAR) dose metric D, exceeds the corresponding prescription or tolerance dose. Postplanning coverage evaluation quantifies the percentage of uncertainties for which target and OAR structures meet their intended dose constraints. The goal of the present work is to evaluate coverage probabilities for 28 prostate treatment plans to determine DMD sampling parameters that ensure adequate accuracy for postplanning coverage estimates. Normally distributed interfraction setup uncertainties were applied to 28 plans for localized prostate cancer, with prescribed dose of 79.2 Gy and 10 mm clinical target volume to planning target volume (CTV-to-PTV) margins. Using angular or isotropic sampling techniques, dosimetric margins were determined for the CTV, bladder and rectum, assuming shift invariance of the dose distribution. For angular sampling, DMDs were sampled at fixed angular intervals w (e.g., w = 1 degree, 2 degrees, 5 degrees, 10 degrees, 20 degrees). Isotropic samples were uniformly distributed on the unit sphere resulting in variable angular increments, but were calculated for the same number of sampling directions as angular DMDs, and accordingly characterized by the effective angular increment omega eff. In each direction, the DM was calculated by moving the structure in radial steps of size delta (=0.1, 0.2, 0.5, 1 mm) until the specified isodose was crossed. Coverage estimation accuracy deltaQ was quantified as a function of the sampling parameters omega or omega eff and delta. The

A Miniaturized Chemical Proteomic Approach for Target Profiling of Clinical Kinase Inhibitors in Tumor Biopsies

PubMed Central

Chamrád, Ivo; Rix, Uwe; Stukalov, Alexey; Gridling, Manuela; Parapatics, Katja; Müller, André C.; Altiok, Soner; Colinge, Jacques; Superti-Furga, Giulio; Haura, Eric B.; Bennett, Keiryn L.

2014-01-01

While targeted therapy based on the idea of attenuating the activity of a preselected, therapeutically relevant protein has become one of the major trends in modern cancer therapy, no truly specific targeted drug has been developed and most clinical agents have displayed a degree of polypharmacology. Therefore, the specificity of anticancer therapeutics has emerged as a highly important but severely underestimated issue. Chemical proteomics is a powerful technique combining postgenomic drug-affinity chromatography with high-end mass spectrometry analysis and bioinformatic data processing to assemble a target profile of a desired therapeutic molecule. Due to high demands on the starting material, however, chemical proteomic studies have been mostly limited to cancer cell lines. Herein, we report a down-scaling of the technique to enable the analysis of very low abundance samples, as those obtained from needle biopsies. By a systematic investigation of several important parameters in pull-downs with the multikinase inhibitor bosutinib, the standard experimental protocol was optimized to 100 µg protein input. At this level, more than 30 well-known targets were detected per single pull-down replicate with high reproducibility. Moreover, as presented by the comprehensive target profile obtained from miniaturized pull-downs with another clinical drug, dasatinib, the optimized protocol seems to be extendable to other drugs of interest. Sixty distinct human and murine targets were finally identified for bosutinib and dasatinib in chemical proteomic experiments utilizing core needle biopsy samples from xenotransplants derived from patient tumor tissue. Altogether, the developed methodology proves robust and generic and holds many promises for the field of personalized health care. PMID:23901793

Population equations for degree-heterogenous neural networks

NASA Astrophysics Data System (ADS)

Kähne, M.; Sokolov, I. M.; Rüdiger, S.

2017-11-01

We develop a statistical framework for studying recurrent networks with broad distributions of the number of synaptic links per neuron. We treat each group of neurons with equal input degree as one population and derive a system of equations determining the population-averaged firing rates. The derivation rests on an assumption of a large number of neurons and, additionally, an assumption of a large number of synapses per neuron. For the case of binary neurons, analytical solutions can be constructed, which correspond to steps in the activity versus degree space. We apply this theory to networks with degree-correlated topology and show that complex, multi-stable regimes can result for increasing correlations. Our work is motivated by the recent finding of subnetworks of highly active neurons and the fact that these neurons tend to be connected to each other with higher probability.

β-Lactam Antibiotics with a High Affinity for PBP2 Act Synergistically with the FtsZ-Targeting Agent TXA707 against Methicillin-Resistant Staphylococcus aureus

PubMed Central

Ferrer-González, Edgar; Kaul, Malvika; Parhi, Ajit K.; LaVoie, Edmond J.

2017-01-01

ABSTRACT Methicillin-resistant Staphylococcus aureus (MRSA) is a multidrug-resistant pathogen that poses a significant risk to global health today. We have developed a promising new FtsZ-targeting agent (TXA707) with potent activity against MRSA isolates resistant to current standard-of-care antibiotics. We present here results that demonstrate differing extents of synergy between TXA707 and a broad range of β-lactam antibiotics (including six cephalosporins, two penicillins, and two carbapenems) against MRSA. To explore whether there is a correlation between the extent of synergy and the preferential antibacterial target of each β-lactam, we determined the binding affinities of the β-lactam antibiotics for each of the four native penicillin-binding proteins (PBPs) of S. aureus using a fluorescence anisotropy competition assay. A comparison of the resulting PBP binding affinities with our corresponding synergy results reveals that β-lactams with a high affinity for PBP2 afford the greatest degree of synergy with TXA707 against MRSA. In addition, we present fluorescence and electron microscopy studies that suggest a potential mechanism underlying the synergy between TXA707 and the β-lactam antibiotics. In this connection, our microscopy results show a disruption of septum formation in TXA707-treated MRSA cells, with a concomitant mislocalization of the PBPs from midcell to nonproductive peripheral sites. Viewed as a whole, our results indicate that PBP2-targeting β-lactam antibiotics are optimal synergistic partners with FtsZ-targeting agents for use in combination therapy of MRSA infections. PMID:28630190

Growing degree day calculator

USDA-ARS?s Scientific Manuscript database

Degree-day benchmarks indicate discrete biological events in the development of insect pests. For the Sparganothis fruitworm, we have isolated all key development events and linked them to degree-day accumulations. These degree-day accumulations can greatly improve treatment timings for cranberry IP...

The impact of high-risk drivers and benefits of limiting their driving degree of freedom.

PubMed

Habtemichael, Filmon G; de Picado-Santos, Luis

2013-11-01

The perception of drivers regarding risk-taking behaviour is widely varied. High-risk drivers are the segment of drivers who are disproportionately represented in the majority of crashes. This study examines the typologies of drivers in risk-taking behaviour, the common high-risk driving errors (speeding, close following, abrupt lane-changing and impaired driving), their safety consequences and the technological (ITS) devices for their detection and correction. Limiting the driving degree of freedom of high-risk drivers is proposed and its benefits on safety as well as traffic operations are quantified using VISSIM microscopic traffic simulation at various proportions of high-risk drivers; namely, 4%, 8% and 12%. Assessment of the safety benefits was carried out by using the technique of simulated vehicle conflicts which was validated against historic crashes, and reduction in travel time was used to quantify the operational benefits. The findings imply that limiting the freedom of high-risk drivers resulted in a reduction of crashes by 12%, 21% and 27% in congested traffic conditions; 9%, 13% and 18% in lightly congested traffic conditions as well as 9%, 10% and 17% in non-congested traffic conditions for high-risk drivers in proportions of 4%, 8% and 12% respectively. Moreover, the surrogate safety measures indicated that there was a reduction in crash severity levels. The operational benefits amounted to savings of nearly 1% in travel time for all the proportions of high-risk drivers considered. The study concluded that limiting the freedom of high-risk drivers has safety and operational benefits; though there could be social, legal and institutional concerns for its practical implementation. Copyright © 2013 Elsevier Ltd. All rights reserved.

Effect of reduction degree on the adsorption properties of graphene sponge for dyes

NASA Astrophysics Data System (ADS)

Yu, Baowei; Chen, Lingyun; Wu, Ruihan; Liu, Xiaoyang; Li, Hongliang; Yang, Hua; Ming, Zhu; Bai, Yitong; Yang, Sheng-Tao

2017-04-01

Graphene sponge (GS) is usually prepared by reducing graphene oxide for the adsorption of pollutants. Different reduction methods lead to different reduction degrees, but the relationship between reduction degree and adsorption performance is still unexplored. In this study, we prepared three GS samples of different reduction degrees and compared their adsorption properties for different dyes. Taking methylene blue (MB) as the model dye, the adsorption isotherms, kinetics and influencing factors were investigated. The adsorptions of different dyes on three GS samples were also compared. Our results indicated that the adsorption of MB on GS was inhibited at high reduction degree by reducing the electrostatic interaction between oxygen containing groups and MB molecules. The adsorption kinetics slowed down at lower reduction degree. The pH showed more significant influence for highly reduced GS, which should be assigned to the deprotonation of hydroxyl groups at high pH. Ionic strength had ignorable effect on the adsorption. Beyond that, the dye properties also regulated the adsorption. The implication to the design of better GS adsorbents based on reduction degree is discussed.

Targeted delivery of 5-fluorouracil to HT-29 cells using high efficient folic acid-conjugated nanoparticles.

PubMed

Wang, Yichao; Li, Puwang; Chen, Lijue; Gao, Weimin; Zeng, Fanbo; Kong, Ling Xue

2015-02-01

The incorporation of a high percentage of targeting molecules into drug delivery system is one of the important methods for improving efficacy of targeting therapeutic drugs to cancer cells. PLGA-based drug delivery carriers with folic acid (FA) as targeting molecule have a low targeting efficiency due to a low FA conjugation ratio. In this work, we fabricated a FA-conjugated PLGA system using a crosslinker 1, 3-diaminopropane and have achieved a high conjugation ratio of 46.7% (mol/mol). The as-prepared PLGA-based biomaterial was used to encapsulate therapeutic drug 5-fluorouracil (5-FU) into nanoparticles. In the in vitro experiments, an IC₅₀ of 5.69 µg/mL has been achieved for 5-FU loaded PLGA-1, 3-diaminopropane-folic acid nanoparticles on HT-29 cancer cells and is significantly lower than that of 5-FU and 5-FU loaded PLGA nanoparticles which only have an IC₅₀ of 22.9 and 14.17 µg/mL, respectively. The fluorescent microscopy images showed that nanoparticles with FA are largely taken up by HT-29 cancer cells and the targeting nanoparticles have more affinity to cancer cells than the pure drugs and untreated nanoparticles. Therefore, the 1, 3-diaminopropane can facilitate the conjugation of FA to PLGA to form a novel polymer and 5-FU loaded PLGA-1, 3-diaminopropane-folic acid nanoparticles can be a highly efficient system for specific delivery of drugs to cancer cells.

The Relationship between Perceptions of Premenstrual Syndrome and Degree Performance

ERIC Educational Resources Information Center

Earl-Novell, Sarah L.; Jessop, Donna C.

2005-01-01

This paper explores whether female undergraduates self-reported experiences of pre-menstrual syndrome (PMS) were associated with degree performance, operationalized as degree class outcome, in a sample of 'high achieving' students (N = 55). Students reported that PMS was disruptive to academic work (comprising lectures, seminars, writing essays,…

High Expression of EphA4 Predicted Lesser Degree of Tumor Regression after Neoadjuvant Chemoradiotherapy in Rectal Cancer.

PubMed

Lin, Ching-Yih; Lee, Ying-En; Tian, Yu-Feng; Sun, Ding-Ping; Sheu, Ming-Jen; Lin, Chen-Yi; Li, Chien-Feng; Lee, Sung-Wei; Lin, Li-Ching; Chang, I-Wei; Wang, Chieh-Tien; He, Hong-Lin

2017-01-01

Background: Numerous transmembrane receptor tyrosine kinase pathways have been found to play an important role in tumor progression in some cancers. This study was aimed to evaluate the clinical impact of Eph receptor A4 (EphA4) in patients with rectal cancer treated with neoadjuvant concurrent chemoradiotherapy (CCRT) combined with mesorectal excision, with special emphasis on tumor regression. Methods: Analysis of the publicly available expression profiling dataset of rectal cancer disclosed that EphA4 was the top-ranking, significantly upregulated, transmembrane receptor tyrosine kinase pathway-associated gene in the non-responders to CCRT, compared with the responders. Immunohistochemical study was conducted to assess the EphA4 expression in pre-treatment biopsy specimens from 172 rectal cancer patients without distant metastasis. The relationships between EphA4 expression and various clinicopathological factors or survival were statistically analyzed. Results: EphA4 expression was significantly associated with vascular invasion ( P =0.015), post-treatment depth of tumor invasion ( P =0.006), pre-treatment and post-treatment lymph node metastasis ( P =0.004 and P =0.011, respectively). More importantly, high EphA4 expression was significantly predictive for lesser degree of tumor regression after CCRT ( P =0.031). At univariate analysis, high EphA4 expression was a negative prognosticator for disease-specific survival ( P =0.0009) and metastasis-free survival ( P =0.0001). At multivariate analysis, high expression of EphA4 still served as an independent adverse prognostic factor for disease-specific survival (HR, 2.528; 95% CI, 1.131-5.651; P =0.024) and metastasis-free survival (HR, 3.908; 95% CI, 1.590-9.601; P =0.003). Conclusion: High expression of EphA4 predicted lesser degree of tumor regression after CCRT and served as an independent negative prognostic factor in patients with rectal cancer.

Voyager 2 Neptune targeting strategy

NASA Technical Reports Server (NTRS)

Potts, C. L.; Francis, K.; Matousek, S. E.; Cesarone, R. J.; Gray, D. L.

1989-01-01

The success of the Voyager 2 flybys of Neptune and Triton depends upon the ability to correct the spacecraft's trajectory. Accurate spacecraft delivery to the desired encounter conditions will promote the maximum science return. However, Neptune's great distance causes large a priori uncertainties in Neptune and Triton ephemerides and planetary system parameters. Consequently, the 'ideal' trajectory is unknown beforehand. The targeting challenge is to utilize the gradually improving knowledge as the spacecraft approaches Neptune to meet the science objectives, but with an overriding concern for spacecraft safety and a desire to limit propellant expenditure. A unique targeting strategy has been developed in response to this challenge. Through the use of a Monte Carlo simulation, candidate strategies are evaluated by the degree to which they meet these objectives and are compared against each other in determining the targeting strategy to be adopted.

Chasing a Moving Target: Perceptions of Work Readiness and Graduate Capabilities in Music Higher Research Degree Students

ERIC Educational Resources Information Center

Harrison, Scott; Grant, Catherine

2016-01-01

Recent efforts to increase workplace readiness in university students have largely centred on undergraduates, with comparatively few strategies or studies focusing on higher research degree candidates. In the discipline of music, a wide diversity of possible career paths combined with rapidly changing career opportunities makes workplace readiness…

Identification of highly effective target genes for RNAi-mediated control of emerald ash borer, Agrilus planipennis.

PubMed

Rodrigues, Thais B; Duan, Jian J; Palli, Subba R; Rieske, Lynne K

2018-03-22

Recent study has shown that RNA interference (RNAi) is efficient in emerald ash borer (EAB), Agrilus planipennis, and that ingestion of double-stranded RNA (dsRNA) targeting specific genes causes gene silencing and mortality in neonates. Here, we report on the identification of highly effective target genes for RNAi-mediated control of EAB. We screened 13 candidate genes in neonate larvae and selected the most effective target genes for further investigation, including their effect on EAB adults and on a non-target organism, Tribolium castaneum. The two most efficient target genes selected, hsp (heat shock 70-kDa protein cognate 3) and shi (shibire), caused up to 90% mortality of larvae and adults. In EAB eggs, larvae, and adults, the hsp is expressed at higher levels when compared to that of shi. Ingestion of dsHSP and dsSHI caused mortality in both neonate larvae and adults. Administration of a mixture of both dsRNAs worked better than either dsRNA by itself. In contrast, injection of EAB.dsHSP and EAB.dsSHI did not cause mortality in T. castaneum. Thus, the two genes identified cause high mortality in the EAB with no apparent phenotype effects in a non-target organism, the red flour beetle, and could be used in RNAi-mediated control of this invasive pest.

Currently available medical engineering degrees in the UK. Part 1: Undergraduate degrees.

PubMed

Joyce, T

2009-05-01

This paper reviews mechanical-engineering-based medical engineering degrees which are currently provided at undergraduate level in the UK. At present there are 14 undergraduate degree programmes in medical engineering, offered by the University of Bath, University of Birmingham, University of Bradford, Cardiff University, University of Hull, Imperial College London, University of Leeds, University of Nottingham, University of Oxford, Queen Mary University of London, University of Sheffield, University of Southampton, University of Surrey, and Swansea University. All these undergraduate courses are delivered on a full-time basis, both 3 year BEng and 4 year MEng degrees. Half of the 14 degree courses share a core first 2 years with a mechanical engineering stream. The other seven programmes include medical engineering modules earlier in their degrees. Within the courses, a very wide range of medical-engineering-related modules are offered, although more common modules include biomaterials, biomechanics, and anatomy and physiology.

Polo-like kinase 1 is a therapeutic target in high-risk neuroblastoma.

PubMed

Ackermann, Sandra; Goeser, Felix; Schulte, Johannes H; Schramm, Alexander; Ehemann, Volker; Hero, Barbara; Eggert, Angelika; Berthold, Frank; Fischer, Matthias

2011-02-15

High-risk neuroblastoma remains a therapeutic challenge for pediatric oncologists. The Polo-like kinase 1 (PLK1) is highly expressed in many human cancers and is a target of the novel small-molecule inhibitor BI 2536, which has shown promising anticancer activity in adult malignancies. Here, we investigated the effect of BI 2536 on neuroblastoma cells in vitro and in vivo to explore PLK1 as a potential target in high-risk neuroblastoma therapy. PLK1 transcript levels were analyzed by microarrays in 476 primary neuroblastoma specimens, and correlation with prognostic markers and patient outcome was examined. To explore the effect of PLK1 inhibition on neuroblastoma cells, 7 cell lines were treated with BI 2536 and changes in growth properties were determined. Furthermore, nude mice with IMR-32 and SK-N-AS xenografts were treated with BI 2536. PLK1 is highly expressed in unfavorable neuroblastoma and in neuroblastoma cell lines. Expression of PLK1 is associated with unfavorable prognostic markers such as stage 4, age >18 months, MYCN amplification, unfavorable gene expression-based classification, and adverse patient outcome (P < 0.001 each). On treatment with nanomolar doses of BI 2536, all neuroblastoma cell lines analyzed showed significantly reduced proliferation, cell cycle arrest, and cell death. Moreover, BI 2536 abrogated growth of neuroblastoma xenografts in nude mice. Elevated PLK1 expression is significantly associated with high-risk neuroblastoma and unfavorable patient outcome. Inhibition of PLK1 using BI 2536 exhibits strong antitumor activity on human neuroblastoma cells in vitro and in vivo, opening encouraging new perspectives for the treatment of high-risk neuroblastoma. ©2010 AACR.

Tooth enamel oxygen "isoscapes" show a high degree of human mobility in prehistoric Britain.

PubMed

Pellegrini, Maura; Pouncett, John; Jay, Mandy; Pearson, Mike Parker; Richards, Michael P

2016-10-07

A geostatistical model to predict human skeletal oxygen isotope values (δ 18 O p ) in Britain is presented here based on a new dataset of Chalcolithic and Early Bronze Age human teeth. The spatial statistics which underpin this model allow the identification of individuals interpreted as 'non-local' to the areas where they were buried (spatial outliers). A marked variation in δ 18 O p is observed in several areas, including the Stonehenge region, the Peak District, and the Yorkshire Wolds, suggesting a high degree of human mobility. These areas, rich in funerary and ceremonial monuments, may have formed focal points for people, some of whom would have travelled long distances, ultimately being buried there. The dataset and model represent a baseline for future archaeological studies, avoiding the complex conversions from skeletal to water δ 18 O values-a process known to be problematic.

Building high-quality assay libraries for targeted analysis of SWATH MS data.

PubMed

Schubert, Olga T; Gillet, Ludovic C; Collins, Ben C; Navarro, Pedro; Rosenberger, George; Wolski, Witold E; Lam, Henry; Amodei, Dario; Mallick, Parag; MacLean, Brendan; Aebersold, Ruedi

2015-03-01

Targeted proteomics by selected/multiple reaction monitoring (S/MRM) or, on a larger scale, by SWATH (sequential window acquisition of all theoretical spectra) MS (mass spectrometry) typically relies on spectral reference libraries for peptide identification. Quality and coverage of these libraries are therefore of crucial importance for the performance of the methods. Here we present a detailed protocol that has been successfully used to build high-quality, extensive reference libraries supporting targeted proteomics by SWATH MS. We describe each step of the process, including data acquisition by discovery proteomics, assertion of peptide-spectrum matches (PSMs), generation of consensus spectra and compilation of MS coordinates that uniquely define each targeted peptide. Crucial steps such as false discovery rate (FDR) control, retention time normalization and handling of post-translationally modified peptides are detailed. Finally, we show how to use the library to extract SWATH data with the open-source software Skyline. The protocol takes 2-3 d to complete, depending on the extent of the library and the computational resources available.

A flexible and economical barcoding approach for highly multiplexed amplicon sequencing of diverse target genes

PubMed Central

Herbold, Craig W.; Pelikan, Claus; Kuzyk, Orest; Hausmann, Bela; Angel, Roey; Berry, David; Loy, Alexander

2015-01-01

High throughput sequencing of phylogenetic and functional gene amplicons provides tremendous insight into the structure and functional potential of complex microbial communities. Here, we introduce a highly adaptable and economical PCR approach to barcoding and pooling libraries of numerous target genes. In this approach, we replace gene- and sequencing platform-specific fusion primers with general, interchangeable barcoding primers, enabling nearly limitless customized barcode-primer combinations. Compared to barcoding with long fusion primers, our multiple-target gene approach is more economical because it overall requires lower number of primers and is based on short primers with generally lower synthesis and purification costs. To highlight our approach, we pooled over 900 different small-subunit rRNA and functional gene amplicon libraries obtained from various environmental or host-associated microbial community samples into a single, paired-end Illumina MiSeq run. Although the amplicon regions ranged in size from approximately 290 to 720 bp, we found no significant systematic sequencing bias related to amplicon length or gene target. Our results indicate that this flexible multiplexing approach produces large, diverse, and high quality sets of amplicon sequence data for modern studies in microbial ecology. PMID:26236305

Intravascular optical imaging of high-risk plaques in vivo by targeting macrophage mannose receptors

NASA Astrophysics Data System (ADS)

Kim, Ji Bak; Park, Kyeongsoon; Ryu, Jiheun; Lee, Jae Joong; Lee, Min Woo; Cho, Han Saem; Nam, Hyeong Soo; Park, Ok Kyu; Song, Joon Woo; Kim, Tae Shik; Oh, Dong Joo; Gweon, Daegab; Oh, Wang-Yuhl; Yoo, Hongki; Kim, Jin Won

2016-03-01

Macrophages mediate atheroma expansion and disruption, and denote high-risk arterial plaques. Therefore, they are substantially gaining importance as a diagnostic imaging target for the detection of rupture-prone plaques. Here, we developed an injectable near-infrared fluorescence (NIRF) probe by chemically conjugating thiolated glycol chitosan with cholesteryl chloroformate, NIRF dye (cyanine 5.5 or 7), and maleimide-polyethylene glycol-mannose as mannose receptor binding ligands to specifically target a subset of macrophages abundant in high-risk plaques. This probe showed high affinity to mannose receptors, low toxicity, and allowed the direct visualization of plaque macrophages in murine carotid atheroma. After the scale-up of the MMR-NIRF probe, the administration of the probe facilitated in vivo intravascular imaging of plaque inflammation in coronary-sized vessels of atheromatous rabbits using a custom-built dual-modal optical coherence tomography (OCT)-NIRF catheter-based imaging system. This novel imaging approach represents a potential imaging strategy enabling the identification of high-risk plaques in vivo and holds promise for future clinical implications.

Intravascular optical imaging of high-risk plaques in vivo by targeting macrophage mannose receptors

PubMed Central

Kim, Ji Bak; Park, Kyeongsoon; Ryu, Jiheun; Lee, Jae Joong; Lee, Min Woo; Cho, Han Saem; Nam, Hyeong Soo; Park, Ok Kyu; Song, Joon Woo; Kim, Tae Shik; Oh, Dong Joo; Gweon, DaeGab; Oh, Wang-Yuhl; Yoo, Hongki; Kim, Jin Won

2016-01-01

Macrophages mediate atheroma expansion and disruption, and denote high-risk arterial plaques. Therefore, they are substantially gaining importance as a diagnostic imaging target for the detection of rupture-prone plaques. Here, we developed an injectable near-infrared fluorescence (NIRF) probe by chemically conjugating thiolated glycol chitosan with cholesteryl chloroformate, NIRF dye (cyanine 5.5 or 7), and maleimide-polyethylene glycol-mannose as mannose receptor binding ligands to specifically target a subset of macrophages abundant in high-risk plaques. This probe showed high affinity to mannose receptors, low toxicity, and allowed the direct visualization of plaque macrophages in murine carotid atheroma. After the scale-up of the MMR-NIRF probe, the administration of the probe facilitated in vivo intravascular imaging of plaque inflammation in coronary-sized vessels of atheromatous rabbits using a custom-built dual-modal optical coherence tomography (OCT)-NIRF catheter-based imaging system. This novel imaging approach represents a potential imaging strategy enabling the identification of high-risk plaques in vivo and holds promise for future clinical implications. PMID:26948523

The effect of visual context on manual localization of remembered targets

NASA Technical Reports Server (NTRS)

Barry, S. R.; Bloomberg, J. J.; Huebner, W. P.

1997-01-01

This paper examines the contribution of egocentric cues and visual context to manual localization of remembered targets. Subjects pointed in the dark to the remembered position of a target previously viewed without or within a structured visual scene. Without a remembered visual context, subjects pointed to within 2 degrees of the target. The presence of a visual context with cues of straight ahead enhanced pointing performance to the remembered location of central but not off-center targets. Thus, visual context provides strong visual cues of target position and the relationship of body position to target location. Without a visual context, egocentric cues provide sufficient input for accurate pointing to remembered targets.

Physics Careers: To the Bachelor's Degree and Beyond

NASA Astrophysics Data System (ADS)

Bailey, Crystal

2012-03-01

In our current era, society needs an increased representation of physicists in the workforce to help solve the growing number of societal and environment problems we collectively face. And even though a physics bachelor's degree opens the door to an incredible diversity of high-paying and rewarding careers, most undergraduates are only aware of academic career paths (having mostly encountered only physics professors during their lifetime). This talk will provide in-depth information about physics career paths outside of academia which available to those with a bachelor's degree in physics, and will discuss how these options change as one moves through an advanced degree in physics. The talk will include real-life examples of working physicists at all stages of the degree path, and salary and employment sector statistics for physics bachelors, masters, and PhD recipients. The talk will also include information on additional careers and professional development resources for students.

From drug to protein: using yeast genetics for high-throughput target discovery.

PubMed

Armour, Christopher D; Lum, Pek Yee

2005-02-01

The budding yeast Saccharomyces cerevisiae has long been an effective eukaryotic model system for understanding basic cellular processes. The genetic tractability and ease of manipulation in the laboratory make yeast well suited for large-scale chemical and genetic screens. Several recent studies describing the use of yeast genetics for high-throughput drug target identification are discussed in this review.

Can a print-based intervention increase screening for first degree relatives of people with colorectal cancer? A randomised controlled trial.

PubMed

Carey, Mariko; Sanson-Fisher, Robert; Macrae, Finlay; Cameron, Emilie; Hill, David; D'Este, Catherine; Simmons, Jody; Doran, Christopher

2016-12-01

To test the effectiveness of a targeted print-based intervention to improve screening adherence in first degree relatives of people with colorectal cancer (CRC). People with CRC and their adult first degree relatives were identified through a population-based cancer registry and randomly allocated as a family unit to the intervention or control condition. The control group received general information about CRC screening. The intervention group received printed advice regarding screening that was targeted to their risk level. Screening adherence was assessed at baseline and at 12 months via self report. 752 (25%) index cases and 574 (34%) eligible first degree relatives consented to take part in the trial and completed baseline interviews. At 12 months, 58% of first degree relatives in the control group and 61% in the intervention group were adherent to screening guidelines (mixed effects logistic regression group by time interaction effect =2.7; 95%CI=1.2-5.9; P=0.013). Subgroup analysis indicated that the intervention was only effective for those with the lowest risk. Provision of personalised risk information may have a modest effect on adherence to CRC screening recommendations among first degree relatives of people diagnosed with CRC. Improved strategies for identifying and engaging first degree relatives are needed to maximise the population impact of the intervention. © 2016 The Authors.

Comparison of two-stage thermophilic (68 degrees C/55 degrees C) anaerobic digestion with one-stage thermophilic (55 degrees C) digestion of cattle manure.

PubMed

Nielsen, H B; Mladenovska, Z; Westermann, P; Ahring, B K

2004-05-05

A two-stage 68 degrees C/55 degrees C anaerobic degradation process for treatment of cattle manure was studied. In batch experiments, an increase of the specific methane yield, ranging from 24% to 56%, was obtained when cattle manure and its fractions (fibers and liquid) were pretreated at 68 degrees C for periods of 36, 108, and 168 h, and subsequently digested at 55 degrees C. In a lab-scale experiment, the performance of a two-stage reactor system, consisting of a digester operating at 68 degrees C with a hydraulic retention time (HRT) of 3 days, connected to a 55 degrees C reactor with 12-day HRT, was compared with a conventional single-stage reactor running at 55 degrees C with 15-days HRT. When an organic loading of 3 g volatile solids (VS) per liter per day was applied, the two-stage setup had a 6% to 8% higher specific methane yield and a 9% more effective VS-removal than the conventional single-stage reactor. The 68 degrees C reactor generated 7% to 9% of the total amount of methane of the two-stage system and maintained a volatile fatty acids (VFA) concentration of 4.0 to 4.4 g acetate per liter. Population size and activity of aceticlastic methanogens, syntrophic bacteria, and hydrolytic/fermentative bacteria were significantly lower in the 68 degrees C reactor than in the 55 degrees C reactors. The density levels of methanogens utilizing H2/CO2 or formate were, however, in the same range for all reactors, although the degradation of these substrates was significantly lower in the 68 degrees C reactor than in the 55 degrees C reactors. Temporal temperature gradient electrophoresis profiles (TTGE) of the 68 degrees C reactor demonstrated a stable bacterial community along with a less divergent community of archaeal species. Copyright 2004 Wiley Periodicals, Inc.

Trends in College Degrees.

ERIC Educational Resources Information Center

Kelinson, Jonathan W.

1998-01-01

Charts depict trends in bachelor's, master's, and doctoral degrees awarded by subject between 1982-83 and 1994-95, with projections to 2006. The data show the total number of degrees earned by women increased 35%; women now earn more degrees than men. By 1994, 21% of college students were over age 35. (SK)

Using the CPTAC Assay Portal to identify and implement highly characterized targeted proteomics assays

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

Whiteaker, Jeffrey R.; Halusa, Goran; Hoofnagle, Andrew N.

2016-02-12

The Clinical Proteomic Tumor Analysis Consortium (CPTAC) of the National Cancer Institute (NCI) has launched an Assay Portal (http://assays.cancer.gov) to serve as an open-source repository of well-characterized targeted proteomic assays. The portal is designed to curate and disseminate highly characterized, targeted mass spectrometry (MS)-based assays by providing detailed assay performance characterization data, standard operating procedures, and access to reagents. Assay content is accessed via the portal through queries to find assays targeting proteins associated with specific cellular pathways, protein complexes, or specific chromosomal regions. The position of the peptide analytes for which there are available assays are mapped relative tomore » other features of interest in the protein, such as sequence domains, isoforms, single nucleotide polymorphisms, and post-translational modifications. The overarching goals are to enable robust quantification of all human proteins and to standardize the quantification of targeted MS-based assays to ultimately enable harmonization of results over time and across laboratories.« less

Using the CPTAC Assay Portal to Identify and Implement Highly Characterized Targeted Proteomics Assays.

PubMed

Whiteaker, Jeffrey R; Halusa, Goran N; Hoofnagle, Andrew N; Sharma, Vagisha; MacLean, Brendan; Yan, Ping; Wrobel, John A; Kennedy, Jacob; Mani, D R; Zimmerman, Lisa J; Meyer, Matthew R; Mesri, Mehdi; Boja, Emily; Carr, Steven A; Chan, Daniel W; Chen, Xian; Chen, Jing; Davies, Sherri R; Ellis, Matthew J C; Fenyö, David; Hiltke, Tara; Ketchum, Karen A; Kinsinger, Chris; Kuhn, Eric; Liebler, Daniel C; Liu, Tao; Loss, Michael; MacCoss, Michael J; Qian, Wei-Jun; Rivers, Robert; Rodland, Karin D; Ruggles, Kelly V; Scott, Mitchell G; Smith, Richard D; Thomas, Stefani; Townsend, R Reid; Whiteley, Gordon; Wu, Chaochao; Zhang, Hui; Zhang, Zhen; Rodriguez, Henry; Paulovich, Amanda G

2016-01-01

The Clinical Proteomic Tumor Analysis Consortium (CPTAC) of the National Cancer Institute (NCI) has launched an Assay Portal (http://assays.cancer.gov) to serve as an open-source repository of well-characterized targeted proteomic assays. The portal is designed to curate and disseminate highly characterized, targeted mass spectrometry (MS)-based assays by providing detailed assay performance characterization data, standard operating procedures, and access to reagents. Assay content is accessed via the portal through queries to find assays targeting proteins associated with specific cellular pathways, protein complexes, or specific chromosomal regions. The position of the peptide analytes for which there are available assays are mapped relative to other features of interest in the protein, such as sequence domains, isoforms, single nucleotide polymorphisms, and posttranslational modifications. The overarching goals are to enable robust quantification of all human proteins and to standardize the quantification of targeted MS-based assays to ultimately enable harmonization of results over time and across laboratories.

The role of edges in the selection of a jump target in Mantis religiosa.

PubMed

Hyden, Karin; Kral, Karl

2005-09-30

Before jumping to a landing object, praying mantids determine the distance, using information obtained from retinal image motion resulting from horizontal peering movements. The present study investigates the peering-jump behaviour of Mantis religiosa larvae with regard to jump targets differing in shape and size. The experimental animals were presented with square, triangular and round target objects with visual extensions of 20 degrees and 40 degrees. The cardboard objects, presented against a uniform white background, were solid black or shaded with a gradation from white to black. It was found that larger objects were preferred to smaller ones as jump targets, and that the square and triangle were preferred to the round disk. When two objects were presented, no preference was exhibited between square and triangular objects. However, when three objects were presented, the square was preferred. For targets with a visual angle of 40 degrees, the amplitude and velocity of the horizontal peering movements were greater for the round disk than for the square or triangle. This amplification of the peering movements suggests that weaker motion signals are generated in the case of curved edges. This may help to account for the preference for the square and triangle as jump targets.

Potential impact of spatially targeted adult tuberculosis vaccine in Gujarat, India

PubMed Central

Chatterjee, Susmita; Rao, Krishna D.; Dowdy, David W.

2016-01-01

Some of the most promising vaccines in the pipeline for tuberculosis (TB) target adolescents and adults. Unlike for childhood vaccines, high-coverage population-wide vaccination is significantly more challenging for adult vaccines. Here, we aimed to estimate the impact of vaccine delivery strategies that were targeted to high-incidence geographical ‘hotspots’ compared with randomly allocated vaccination. We developed a spatially explicit mathematical model of TB transmission that distinguished these hotspots from the general population. We evaluated the impact of targeted and untargeted vaccine delivery strategies in India—a country that bears more than 25% of global TB burden, and may be a potential early adopter of the vaccine. We collected TB notification data and conducted a demonstration study in the state of Gujarat to validate our estimates of heterogeneity in TB incidence. We then projected the impact of randomly vaccinating 8% of adults in a single mass campaign to a spatially targeted vaccination preferentially delivered to 80% of adults in the hotspots, with both strategies augmented by continuous adolescent vaccination. In consultation with vaccine developers, we considered a vaccine efficacy of 60%, and evaluated the population-level impact after 10 years of vaccination. Spatial heterogeneity in TB notification (per 100 000/year) was modest in Gujarat: 190 in the hotspots versus 125 in the remaining population. At this level of heterogeneity, the spatially targeted vaccination was projected to reduce TB incidence by 28% after 10 years, compared with a 24% reduction projected to achieve via untargeted vaccination—a 1.17-fold augmentation in the impact of vaccination by spatially targeting. The degree of the augmentation was robust to reasonable variation in natural history assumptions, but depended strongly on the extent of spatial heterogeneity and mixing between the hotspot and general population. Identifying high-incidence hotspots and

Predicting Long-Term College Success through Degree Completion Using ACT[R] Composite Score, ACT Benchmarks, and High School Grade Point Average. ACT Research Report Series, 2012 (5)

ERIC Educational Resources Information Center

Radunzel, Justine; Noble, Julie

2012-01-01

This study compared the effectiveness of ACT[R] Composite score and high school grade point average (HSGPA) for predicting long-term college success. Outcomes included annual progress towards a degree (based on cumulative credit-bearing hours earned), degree completion, and cumulative grade point average (GPA) at 150% of normal time to degree…

Simulation of target interpretation based on infrared image features and psychology principle

NASA Astrophysics Data System (ADS)

Lin, Wei; Chen, Yu-hua; Gao, Hong-sheng; Wang, Zhan-feng; Wang, Ji-jun; Su, Rong-hua; Huang, Yan-ping

2009-07-01

It's an important and complicated process in target interpretation that target features extraction and identification, which effect psychosensorial quantity of interpretation person to target infrared image directly, and decide target viability finally. Using statistical decision theory and psychology principle, designing four psychophysical experiment, the interpretation model of the infrared target is established. The model can get target detection probability by calculating four features similarity degree between target region and background region, which were plotted out on the infrared image. With the verification of a great deal target interpretation in practice, the model can simulate target interpretation and detection process effectively, get the result of target interpretation impersonality, which can provide technique support for target extraction, identification and decision-making.

A novel W1999S mutation and non-target site resistance impact on acetyl-CoA carboxylase inhibiting herbicides to varying degrees in a UK Lolium multiflorum population.

PubMed

Kaundun, Shiv Shankhar; Bailly, Geraldine C; Dale, Richard P; Hutchings, Sarah-Jane; McIndoe, Eddie

2013-01-01

Acetyl-CoA carboxylase (ACCase) inhibiting herbicides are important products for the post-emergence control of grass weed species in small grain cereal crops. However, the appearance of resistance to ACCase herbicides over time has resulted in limited options for effective weed control of key species such as Lolium spp. In this study, we have used an integrated biological and molecular biology approach to investigate the mechanism of resistance to ACCase herbicides in a Lolium multiflorum Lam. from the UK (UK21). The study revealed a novel tryptophan to serine mutation at ACCase codon position 1999 impacting on ACCase inhibiting herbicides to varying degrees. The W1999S mutation confers dominant resistance to pinoxaden and partially recessive resistance to cycloxydim and sethoxydim. On the other hand, plants containing the W1999S mutation were sensitive to clethodim and tepraloxydim. Additionally population UK21 is characterised by other resistance mechanisms, very likely non non-target site based, affecting several aryloxyphenoxyproprionate (FOP) herbicides but not the practical field rate of pinoxaden. The positive identification of wild type tryptophan and mutant serine alleles at ACCase position 1999 could be readily achieved with an original DNA based derived cleaved amplified polymorphic sequence (dCAPS) assay that uses the same PCR product but two different enzymes for positively identifying the wild type tryptophan and mutant serine alleles identified here. This paper highlights intrinsic differences between ACCase inhibiting herbicides that could be exploited for controlling ryegrass populations such as UK21 characterised by compound-specific target site and non-target site resistance.

Connective tissue growth factor as a novel therapeutic target in high grade serous ovarian cancer.

PubMed

Moran-Jones, Kim; Gloss, Brian S; Murali, Rajmohan; Chang, David K; Colvin, Emily K; Jones, Marc D; Yuen, Samuel; Howell, Viive M; Brown, Laura M; Wong, Carol W; Spong, Suzanne M; Scarlett, Christopher J; Hacker, Neville F; Ghosh, Sue; Mok, Samuel C; Birrer, Michael J; Samimi, Goli

2015-12-29

Ovarian cancer is the most common cause of death among women with gynecologic cancer. We examined molecular profiles of fibroblasts from normal ovary and high-grade serous ovarian tumors to identify novel therapeutic targets involved in tumor progression. We identified 2,300 genes that are significantly differentially expressed in tumor-associated fibroblasts. Fibroblast expression of one of these genes, connective tissue growth factor (CTGF), was confirmed by immunohistochemistry. CTGF protein expression in ovarian tumor fibroblasts significantly correlated with gene expression levels. CTGF is a secreted component of the tumor microenvironment and is being pursued as a therapeutic target in pancreatic cancer. We examined its effect in in vitro and ex vivo ovarian cancer models, and examined associations between CTGF expression and clinico-pathologic characteristics in patients. CTGF promotes migration and peritoneal adhesion of ovarian cancer cells. These effects are abrogated by FG-3019, a human monoclonal antibody against CTGF, currently under clinical investigation as a therapeutic agent. Immunohistochemical analyses of high-grade serous ovarian tumors reveal that the highest level of tumor stromal CTGF expression was correlated with the poorest prognosis. Our findings identify CTGF as a promoter of peritoneal adhesion, likely to mediate metastasis, and a potential therapeutic target in high-grade serous ovarian cancer. These results warrant further studies into the therapeutic efficacy of FG-3019 in high-grade serous ovarian cancer.

Connective tissue growth factor as a novel therapeutic target in high grade serous ovarian cancer

PubMed Central

Moran-Jones, Kim; Gloss, Brian S.; Murali, Rajmohan; Chang, David K.; Colvin, Emily K.; Jones, Marc D.; Yuen, Samuel; Howell, Viive M.; Brown, Laura M.; Wong, Carol W.; Spong, Suzanne M.; Scarlett, Christopher J.; Hacker, Neville F.; Ghosh, Sue; Mok, Samuel C.; Birrer, Michael J.; Samimi, Goli

2015-01-01

Ovarian cancer is the most common cause of death among women with gynecologic cancer. We examined molecular profiles of fibroblasts from normal ovary and high-grade serous ovarian tumors to identify novel therapeutic targets involved in tumor progression. We identified 2,300 genes that are significantly differentially expressed in tumor-associated fibroblasts. Fibroblast expression of one of these genes, connective tissue growth factor (CTGF), was confirmed by immunohistochemistry. CTGF protein expression in ovarian tumor fibroblasts significantly correlated with gene expression levels. CTGF is a secreted component of the tumor microenvironment and is being pursued as a therapeutic target in pancreatic cancer. We examined its effect in in vitro and ex vivo ovarian cancer models, and examined associations between CTGF expression and clinico-pathologic characteristics in patients. CTGF promotes migration and peritoneal adhesion of ovarian cancer cells. These effects are abrogated by FG-3019, a human monoclonal antibody against CTGF, currently under clinical investigation as a therapeutic agent. Immunohistochemical analyses of high-grade serous ovarian tumors reveal that the highest level of tumor stromal CTGF expression was correlated with the poorest prognosis. Our findings identify CTGF as a promoter of peritoneal adhesion, likely to mediate metastasis, and a potential therapeutic target in high-grade serous ovarian cancer. These results warrant further studies into the therapeutic efficacy of FG-3019 in high-grade serous ovarian cancer. PMID:26575166

Combining targeted and nontargeted data analysis for liquid chromatography/high-resolution mass spectrometric analyses.

PubMed

Croley, Timothy R; White, Kevin D; Wong, Jon; Callahan, John H; Musser, Steven M; Antler, Margaret; Lashin, Vitaly; McGibbon, Graham A

2013-03-01

Increasing importation of food and the diversity of potential contaminants have necessitated more analytical testing of these foods. Historically, mass spectrometric methods for testing foods were confined to monitoring selected ions (SIM or MRM), achieving sensitivity by focusing on targeted ion signals. A limiting factor in this approach is that any contaminants not included on the target list are not typically identified and retrospective data mining is limited. A potential solution is to utilize high-resolution MS to acquire accurate mass full-scan data. Based on the instrumental resolution, these data can be correlated to the actual mass of a contaminant, which would allow for identification of both target compounds and compounds that are not on a target list (nontargets). The focus of this research was to develop software algorithms to provide rapid and accurate data processing of LC/MS data to identify both targeted and nontargeted analytes. Software from a commercial vendor was developed to process LC/MS data and the results were compared to an alternate, vendor-supplied solution. The commercial software performed well and demonstrated the potential for a fully automated processing solution. © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

An X-ray absorption spectroscopy study of the inversion degree in zinc ferrite nanocrystals dispersed on a highly porous silica aerogel matrix.

PubMed

Carta, D; Marras, C; Loche, D; Mountjoy, G; Ahmed, S I; Corrias, A

2013-02-07

The structural properties of zinc ferrite nanoparticles with spinel structure dispersed in a highly porous SiO(2) aerogel matrix were compared with a bulk zinc ferrite sample. In particular, the details of the cation distribution between the octahedral (B) and tetrahedral (A) sites of the spinel structure were determined using X-ray absorption spectroscopy. The analysis of both the X-ray absorption near edge structure and the extended X-ray absorption fine structure indicates that the degree of inversion of the zinc ferrite spinel structures varies with particle size. In particular, in the bulk microcrystalline sample, Zn(2+) ions are at the tetrahedral sites and trivalent Fe(3+) ions occupy octahedral sites (normal spinel). When particle size decreases, Zn(2+) ions are transferred to octahedral sites and the degree of inversion is found to increase as the nanoparticle size decreases. This is the first time that a variation of the degree of inversion with particle size is observed in ferrite nanoparticles grown within an aerogel matrix.

Roster of Astronomy Departments with Enrollment and Degree Data, 2014: Results from the 2014 Survey of Enrollments and Degrees. Focus On

ERIC Educational Resources Information Center

Nicholson, Starr; Mulvey, Patrick J.

2015-01-01

Undergraduate astronomy enrollments in the US continue to rise with junior and senior level enrollments exceeding the previous year's all-time high. The increasing undergraduate enrollments have produced 428 bachelor's in the 2013-14 academic year, also an all-time high. Undergraduate astronomy degree production will continue to rise given the…

A high-throughput microparticle microarray platform for dendritic cell-targeting vaccines.

PubMed

Acharya, Abhinav P; Clare-Salzler, Michael J; Keselowsky, Benjamin G

2009-09-01

Immunogenomic approaches combined with advances in adjuvant immunology are guiding progress toward rational design of vaccines. Furthermore, drug delivery platforms (e.g., synthetic particles) are demonstrating promise for increasing vaccine efficacy. Currently there are scores of known antigenic epitopes and adjuvants, and numerous synthetic delivery systems accessible for formulation of vaccines for various applications. However, the lack of an efficient means to test immune cell responses to the abundant combinations available represents a significant blockade on the development of new vaccines. In order to overcome this barrier, we report fabrication of a new class of microarray consisting of antigen/adjuvant-loadable poly(D,L lactide-co-glycolide) microparticles (PLGA MPs), identified as a promising carrier for immunotherapeutics, which are co-localized with dendritic cells (DCs), key regulators of the immune system and prime targets for vaccines. The intention is to utilize this high-throughput platform to optimize particle-based vaccines designed to target DCs in vivo for immune system-related disorders, such as autoimmune diseases, cancer and infection. Fabrication of DC/MP arrays leverages the use of standard contact printing miniarraying equipment in conjunction with surface modification to achieve co-localization of particles/cells on isolated islands while providing background non-adhesive surfaces to prevent off-island cell migration. We optimized MP overspotting pin diameter, accounting for alignment error, to allow construction of large, high-fidelity arrays. Reproducible, quantitative delivery of as few as 16+/-2 MPs per spot was demonstrated and two-component MP dosing arrays were constructed, achieving MP delivery which was independent of formulation, with minimal cross-contamination. Furthermore, quantification of spotted, surface-adsorbed MP degradation was demonstrated, potentially useful for optimizing MP release properties. Finally, we

Optimal random search for a single hidden target.

PubMed

Snider, Joseph

2011-01-01

A single target is hidden at a location chosen from a predetermined probability distribution. Then, a searcher must find a second probability distribution from which random search points are sampled such that the target is found in the minimum number of trials. Here it will be shown that if the searcher must get very close to the target to find it, then the best search distribution is proportional to the square root of the target distribution regardless of dimension. For a Gaussian target distribution, the optimum search distribution is approximately a Gaussian with a standard deviation that varies inversely with how close the searcher must be to the target to find it. For a network where the searcher randomly samples nodes and looks for the fixed target along edges, the optimum is either to sample a node with probability proportional to the square root of the out-degree plus 1 or not to do so at all.

Highly charged ion beams and their applications

NASA Astrophysics Data System (ADS)

Marler, Joan

2018-01-01

While much previous work with highly charged ions has been performed with the ions in the plasma state in which they were formed, beams of highly charged ions hold promise for exciting new experiments. Specifically low energy beams with a high degree of charge state purity are a prerequisite for momentum resolved cross section measurements and for efficient loading of highly charged ions into UHV traps for spectroscopy. The Clemson University facility is optimized for the delivery of such beams of highly charged ions with low kinetic energies. Near term experiments include energy resolved charge exchange with neutral targets.

Ultra-high resolution computed tomography imaging

DOEpatents

Paulus, Michael J.; Sari-Sarraf, Hamed; Tobin, Jr., Kenneth William; Gleason, Shaun S.; Thomas, Jr., Clarence E.

2002-01-01

A method for ultra-high resolution computed tomography imaging, comprising the steps of: focusing a high energy particle beam, for example x-rays or gamma-rays, onto a target object; acquiring a 2-dimensional projection data set representative of the target object; generating a corrected projection data set by applying a deconvolution algorithm, having an experimentally determined a transfer function, to the 2-dimensional data set; storing the corrected projection data set; incrementally rotating the target object through an angle of approximately 180.degree., and after each the incremental rotation, repeating the radiating, acquiring, generating and storing steps; and, after the rotating step, applying a cone-beam algorithm, for example a modified tomographic reconstruction algorithm, to the corrected projection data sets to generate a 3-dimensional image. The size of the spot focus of the beam is reduced to not greater than approximately 1 micron, and even to not greater than approximately 0.5 microns.

Dazzle camouflage, target tracking, and the confusion effect.

PubMed

Hogan, Benedict G; Cuthill, Innes C; Scott-Samuel, Nicholas E

2016-01-01

The influence of coloration on the ecology and evolution of moving animals in groups is poorly understood. Animals in groups benefit from the "confusion effect," where predator attack success is reduced with increasing group size or density. This is thought to be due to a sensory bottleneck: an increase in the difficulty of tracking one object among many. Motion dazzle camouflage has been hypothesized to disrupt accurate perception of the trajectory or speed of an object or animal. The current study investigates the suggestion that dazzle camouflage may enhance the confusion effect. Utilizing a computer game style experiment with human predators, we found that when moving in groups, targets with stripes parallel to the targets' direction of motion interact with the confusion effect to a greater degree, and are harder to track, than those with more conventional background matching patterns. The findings represent empirical evidence that some high-contrast patterns may benefit animals in groups. The results also highlight the possibility that orientation and turning may be more relevant in the mechanisms of dazzle camouflage than previously recognized.

Natural healing-inspired collagen-targeting surgical protein glue for accelerated scarless skin regeneration.

PubMed

Jeon, Eun Young; Choi, Bong-Hyuk; Jung, Dooyup; Hwang, Byeong Hee; Cha, Hyung Joon

2017-07-01

Skin scarring after deep dermal injuries is a major clinical problem due to the current therapies limited to established scars with poor understanding of healing mechanisms. From investigation of aberrations within the extracellular matrix involved in pathophysiologic scarring, it was revealed that one of the main factors responsible for impaired healing is abnormal collagen reorganization. Here, inspired by the fundamental roles of decorin, a collagen-targeting proteoglycan, in collagen remodeling, we created a scar-preventive collagen-targeting glue consisting of a newly designed collagen-binding mussel adhesive protein and a specific glycosaminoglycan. The collagen-targeting glue specifically bound to type I collagen in a dose-dependent manner and regulated the rate and the degree of fibrillogenesis. In a rat skin excisional model, the collagen-targeting glue successfully accelerated initial wound regeneration as defined by effective reepithelialization, neovascularization, and rapid collagen synthesis. Moreover, the improved dermal collagen architecture was demonstrated by uniform size of collagen fibrils, their regular packing, and a restoration of healthy tissue component. Collectively, our natural healing-inspired collagen-targeting glue may be a promising therapeutic option for improving the healing rate with high-quality and effective scar inhibition. Copyright © 2017 Elsevier Ltd. All rights reserved.

Impact of high-risk conjunctions on Active Debris Removal target selection

NASA Astrophysics Data System (ADS)

Lidtke, Aleksander A.; Lewis, Hugh G.; Armellin, Roberto

2015-10-01

Space debris simulations show that if current space launches continue unchanged, spacecraft operations might become difficult in the congested space environment. It has been suggested that Active Debris Removal (ADR) might be necessary in order to prevent such a situation. Selection of objects to be targeted by ADR is considered important because removal of non-relevant objects will unnecessarily increase the cost of ADR. One of the factors to be used in this ADR target selection is the collision probability accumulated by every object. This paper shows the impact of high-probability conjunctions on the collision probability accumulated by individual objects as well as the probability of any collision occurring in orbit. Such conjunctions cannot be predicted far in advance and, consequently, not all the objects that will be involved in such dangerous conjunctions can be removed through ADR. Therefore, a debris remediation method that would address such events at short notice, and thus help prevent likely collisions, is suggested.

Switchable DNA interfaces for the highly sensitive detection of label-free DNA targets.

PubMed

Rant, Ulrich; Arinaga, Kenji; Scherer, Simon; Pringsheim, Erika; Fujita, Shozo; Yokoyama, Naoki; Tornow, Marc; Abstreiter, Gerhard

2007-10-30

We report a method to detect label-free oligonucleotide targets. The conformation of surface-tethered probe nucleic acids is modulated by alternating electric fields, which cause the molecules to extend away from or fold onto the biased surface. Binding (hybridization) of targets to the single-stranded probes results in a pronounced enhancement of the layer-height modulation amplitude, monitored optically in real time. The method features an exceptional detection limit of <3 x 10(8) bound targets per cm(2) sensor area. Single base-pair mismatches in the sequences of DNA complements may readily be identified; moreover, binding kinetics and binding affinities can be determined with high accuracy. When driving the DNA to oscillate at frequencies in the kHz regime, distinct switching kinetics are revealed for single- and double-stranded DNA. Molecular dynamics are used to identify the binding state of molecules according to their characteristic kinetic fingerprints by using a chip-compatible detection format.

Switchable DNA interfaces for the highly sensitive detection of label-free DNA targets

PubMed Central

Rant, Ulrich; Arinaga, Kenji; Scherer, Simon; Pringsheim, Erika; Fujita, Shozo; Yokoyama, Naoki; Tornow, Marc; Abstreiter, Gerhard

2007-01-01

We report a method to detect label-free oligonucleotide targets. The conformation of surface-tethered probe nucleic acids is modulated by alternating electric fields, which cause the molecules to extend away from or fold onto the biased surface. Binding (hybridization) of targets to the single-stranded probes results in a pronounced enhancement of the layer-height modulation amplitude, monitored optically in real time. The method features an exceptional detection limit of <3 × 108 bound targets per cm2 sensor area. Single base-pair mismatches in the sequences of DNA complements may readily be identified; moreover, binding kinetics and binding affinities can be determined with high accuracy. When driving the DNA to oscillate at frequencies in the kHz regime, distinct switching kinetics are revealed for single- and double-stranded DNA. Molecular dynamics are used to identify the binding state of molecules according to their characteristic kinetic fingerprints by using a chip-compatible detection format. PMID:17951434

Pair production by high intensity picosecond laser interacting with thick solid target at XingGuangIII

NASA Astrophysics Data System (ADS)

Wu, Yuchi; Dong, Kegong; Yan, Yonghong; Zhu, Bin; Zhang, Tiankui; Chen, Jia; Yu, Minghai; Tan, Fang; Wang, Shaoyi; Han, Dan; Lu, Feng; Gu, Yuqiu

2017-06-01

An experiment for pair production by high intensity laser irradiating thick solid targets is present. The experiment used picosecond beam of the XingGuangIII laser facility, with intensities up to several 1019 W/cm2, pulse durations about 0.8 ps and laser energies around 120 J. Pairs were generated from 1 mm-thick tantalum disk targets with different diameters from 1 mm to 10 mm. Energy spectra of hot electron from targetrear surface represent a Maxwellian distribution and obey a scaling of ∼(Iλ2)0.5. Large quantity of positrons were observed at the target rear normal direction with a yield up to 2.8 × 109 e+/sr. Owing to the target rear surface sheath field, the positrons behave as a quasi-monoenergetic beam with peak energy of several MeV. Our experiment shows that the peak energy of positron beam is inversely proportional to the target diameter.

Estimation of genomic prediction accuracy from reference populations with varying degrees of relationship.

PubMed

Lee, S Hong; Clark, Sam; van der Werf, Julius H J

2017-01-01

Genomic prediction is emerging in a wide range of fields including animal and plant breeding, risk prediction in human precision medicine and forensic. It is desirable to establish a theoretical framework for genomic prediction accuracy when the reference data consists of information sources with varying degrees of relationship to the target individuals. A reference set can contain both close and distant relatives as well as 'unrelated' individuals from the wider population in the genomic prediction. The various sources of information were modeled as different populations with different effective population sizes (Ne). Both the effective number of chromosome segments (Me) and Ne are considered to be a function of the data used for prediction. We validate our theory with analyses of simulated as well as real data, and illustrate that the variation in genomic relationships with the target is a predictor of the information content of the reference set. With a similar amount of data available for each source, we show that close relatives can have a substantially larger effect on genomic prediction accuracy than lesser related individuals. We also illustrate that when prediction relies on closer relatives, there is less improvement in prediction accuracy with an increase in training data or marker panel density. We release software that can estimate the expected prediction accuracy and power when combining different reference sources with various degrees of relationship to the target, which is useful when planning genomic prediction (before or after collecting data) in animal, plant and human genetics.

Importance of small-degree nodes in assortative networks with degree-weight correlations

NASA Astrophysics Data System (ADS)

Ma, Sijuan; Feng, Ling; Monterola, Christopher Pineda; Lai, Choy Heng

2017-10-01

It has been known that assortative network structure plays an important role in spreading dynamics for unweighted networks. Yet its influence on weighted networks is not clear, in particular when weight is strongly correlated with the degrees of the nodes as we empirically observed in Twitter. Here we use the self-consistent probability method and revised nonperturbative heterogenous mean-field theory method to investigate this influence on both susceptible-infective-recovered (SIR) and susceptible-infective-susceptible (SIS) spreading dynamics. Both our simulation and theoretical results show that while the critical threshold is not significantly influenced by the assortativity, the prevalence in the supercritical regime shows a crossover under different degree-weight correlations. In particular, unlike the case of random mixing networks, in assortative networks, the negative degree-weight correlation leads to higher prevalence in their spreading beyond the critical transmissivity than that of the positively correlated. In addition, the previously observed inhibition effect on spreading velocity by assortative structure is not apparent in negatively degree-weight correlated networks, while it is enhanced for that of the positively correlated. Detailed investigation into the degree distribution of the infected nodes reveals that small-degree nodes play essential roles in the supercritical phase of both SIR and SIS spreadings. Our results have direct implications in understanding viral information spreading over online social networks and epidemic spreading over contact networks.

Magnetized Target Fusion in Advanced Propulsion Research

NASA Technical Reports Server (NTRS)

Cylar, Rashad

2003-01-01

The Magnetized Target Fusion (MTF) Propulsion lab at NASA Marshall Space Flight Center in Huntsville, Alabama has a program in place that has adopted to attempt to create a faster, lower cost and more reliable deep space transportation system. In this deep space travel the physics and development of high velocity plasma jets must be understood. The MTF Propulsion lab is also in attempt to open up the solar system for human exploration and commercial use. Fusion, as compared to fission, is just the opposite. Fusion involves the light atomic nuclei combination to produce denser nuclei. In the process, the energy is created by destroying the mass according to the distinguished equation: E = mc2 . Fusion energy development is being pursued worldwide as a very sustainable form of energy that is environmentally friendly. For the purposes of space exploration fusion reactions considered include the isotopes of hydrogen-deuterium (D2) and tritium (T3). Nuclei have an electrostatic repulsion between them and in order for the nuclei to fuse this repulsion must be overcome. One technique to bypass repulsion is to heat the nuclei to very high temperatures. The temperatures vary according to the type of reactions. For D-D reactions, one billion degrees Celsius is required, and for D-T reactions, one hundred million degrees is sufficient. There has to be energy input for useful output to be obtained form the fusion To make fusion propulsion practical, the mass, the volume, and the cost of the equipment to produce the reactions (generally called the reactor) need to be reduced by an order of magnitude or two from the state-of-the-art fusion machines. Innovations in fusion schemes are therefore required, especially for obtaining thrust for propulsive applications. Magnetized target fusion (MTF) is one of the innovative fusion concepts that have emerged over the last several years. MSFC is working with Los Alamos National Laboratory and other research groups in studying the

Development of a targeted transgenesis strategy in highly differentiated cells: a powerful tool for functional genomic analysis.

PubMed

Puttini, Stefania; Ouvrard-Pascaud, Antoine; Palais, Gael; Beggah, Ahmed T; Gascard, Philippe; Cohen-Tannoudji, Michel; Babinet, Charles; Blot-Chabaud, Marcel; Jaisser, Frederic

2005-03-16

Functional genomic analysis is a challenging step in the so-called post-genomic field. Identification of potential targets using large-scale gene expression analysis requires functional validation to identify those that are physiologically relevant. Genetically modified cell models are often used for this purpose allowing up- or down-expression of selected targets in a well-defined and if possible highly differentiated cell type. However, the generation of such models remains time-consuming and expensive. In order to alleviate this step, we developed a strategy aimed at the rapid and efficient generation of genetically modified cell lines with conditional, inducible expression of various target genes. Efficient knock-in of various constructs, called targeted transgenesis, in a locus selected for its permissibility to the tet inducible system, was obtained through the stimulation of site-specific homologous recombination by the meganuclease I-SceI. Our results demonstrate that targeted transgenesis in a reference inducible locus greatly facilitated the functional analysis of the selected recombinant cells. The efficient screening strategy we have designed makes possible automation of the transfection and selection steps. Furthermore, this strategy could be applied to a variety of highly differentiated cells.

Fluidic conduits for highly efficient purification of target species in EWOD-driven droplet microfluidics.

PubMed

Shah, Gaurav J; Kim, Chang-Jin Cj

2009-08-21

Due to the lack of continuous flows that would wash unwanted specifies and impurities off from a target location, droplet microfluidics commonly employs a long serial dilution process to purify target species. In this work, we achieve high-purity separation for the case of electrowetting-on-dielectric (EWOD) based droplet microfluidics by introducing a "fluidic conduit" between a sample droplet and a buffer droplet. The long and slender fluidic path minimizes the diffusion and fluidic mixing between the two droplets (thus eliminating non-specific transport) but provides a conduit between them for actively transported particles (thus allowing the specific transport). The conduit is purely fluidic, stabilized chemically (e.g. using surfactants) and controlled by EWOD. The effectiveness of the technique is demonstrated by eliminating approximately 97% non-magnetic beads in just one purification step, while maintaining high collection efficiency (>99%) of magnetic beads.

Tooth enamel oxygen “isoscapes” show a high degree of human mobility in prehistoric Britain

NASA Astrophysics Data System (ADS)

Pellegrini, Maura; Pouncett, John; Jay, Mandy; Pearson, Mike Parker; Richards, Michael P.

2016-10-01

A geostatistical model to predict human skeletal oxygen isotope values (δ18Op) in Britain is presented here based on a new dataset of Chalcolithic and Early Bronze Age human teeth. The spatial statistics which underpin this model allow the identification of individuals interpreted as ‘non-local’ to the areas where they were buried (spatial outliers). A marked variation in δ18Op is observed in several areas, including the Stonehenge region, the Peak District, and the Yorkshire Wolds, suggesting a high degree of human mobility. These areas, rich in funerary and ceremonial monuments, may have formed focal points for people, some of whom would have travelled long distances, ultimately being buried there. The dataset and model represent a baseline for future archaeological studies, avoiding the complex conversions from skeletal to water δ18O values-a process known to be problematic.

Targeting protein-protein interactions with trimeric ligands: high affinity inhibitors of the MAGUK protein family.

PubMed

Nissen, Klaus B; Haugaard-Kedström, Linda M; Wilbek, Theis S; Nielsen, Line S; Åberg, Emma; Kristensen, Anders S; Bach, Anders; Jemth, Per; Strømgaard, Kristian

2015-01-01

PDZ domains in general, and those of PSD-95 in particular, are emerging as promising drug targets for diseases such as ischemic stroke. We have previously shown that dimeric ligands that simultaneously target PDZ1 and PDZ2 of PSD-95 are highly potent inhibitors of PSD-95. However, PSD-95 and the related MAGUK proteins contain three consecutive PDZ domains, hence we envisioned that targeting all three PDZ domains simultaneously would lead to more potent and potentially more specific interactions with the MAGUK proteins. Here we describe the design, synthesis and characterization of a series of trimeric ligands targeting all three PDZ domains of PSD-95 and the related MAGUK proteins, PSD-93, SAP-97 and SAP-102. Using our dimeric ligands targeting the PDZ1-2 tandem as starting point, we designed novel trimeric ligands by introducing a PDZ3-binding peptide moiety via a cysteine-derivatized NPEG linker. The trimeric ligands generally displayed increased affinities compared to the dimeric ligands in fluorescence polarization binding experiments and optimized trimeric ligands showed low nanomolar inhibition towards the four MAGUK proteins, thus being the most potent inhibitors described. Kinetic experiments using stopped-flow spectrometry showed that the increase in affinity is caused by a decrease in the dissociation rate of the trimeric ligand as compared to the dimeric ligands, likely reflecting the lower probability of simultaneous dissociation of all three PDZ ligands. Thus, we have provided novel inhibitors of the MAGUK proteins with exceptionally high affinity, which can be used to further elucidate the therapeutic potential of these proteins.

Study of composition of espresso coffee prepared from various roast degrees of Coffea arabica L. coffee beans.

PubMed

Kučera, Lukáš; Papoušek, Roman; Kurka, Ondřej; Barták, Petr; Bednář, Petr

2016-05-15

Espresso coffee samples prepared at various roasting degrees defined according to its basic conventional classification (light, medium, medium-dark and dark roasted) were analyzed by ultra-performance liquid chromatography/tandem mass spectrometry. Obtained raw data were processed using multivariate statistical analysis (Principal Component Analysis, PCA) to evaluate chemical differences between each roasting degrees (untargeted part of study). All four roasting degrees were resolved in appropriate Score plot. Orthogonal Projections to Latent Structures provided signals of significant markers describing the differences among particular roasting degrees. Detailed interpretation of those signals by targeted LC/MS(2) analysis revealed four groups of compounds. The first two groups involve chlorogenic acids and related lactones. The signals of other two sets of markers were ascribed to some specific atractylosides and particular melanoidins. Ratios of contents of selected representatives of each group to the sum of all identified markers were proposed as definite parameters for determination of roasting degree of Brazilian coffee Arabica. Copyright © 2015 Elsevier Ltd. All rights reserved.

Numerical studies of the use of thin high-Z layers for reducing laser imprint in direct-drive inertial-fusion targets

NASA Astrophysics Data System (ADS)

Bates, Jason; Schmitt, Andrew; Karasik, Max; Obenschain, Steve

2012-10-01

Using the FAST code, we present numerical studies of the effect of thin metallic layers with high atomic number (high-Z) on the hydrodynamics of directly-driven inertial-confinement-fusion (ICF) targets. Previous experimental work on the NIKE Laser Facility at the U.S. Naval Research Laboratory demonstrated that the use of high-Z layers may be efficacious in reducing laser non-uniformities imprinted on the target during the start-up phase of the implosion. Such a reduction is highly desirable in a direct-drive ICF scenario because laser non-uniformities seed hydrodynamic instabilities that can amplify during the implosion process, prevent uniform compression and spoil high gain. One of the main objectives of the present work is to assess the utility of high-Z layers for achieving greater laser uniformity in polar-drive target designs planned for the National Ignition Facility. To address this problem, new numerical routines have recently been incorporated in the FAST code, including an improved radiation-transfer package and a three-dimensional ray-tracing algorithm. We will discuss these topics, and present initial simulation results for high-Z planar-target experiments planned on the NIKE Laser Facility later this year.

Electrostatically assembled dendrimer complex with a high-affinity protein binder for targeted gene delivery.

PubMed

Kim, Jong-Won; Lee, Joong-Jae; Choi, Joon Sig; Kim, Hak-Sung

2018-06-10

Although a variety of non-viral gene delivery systems have been developed, they still suffer from low efficiency and specificity. Herein, we present the assembly of a dendrimer complex comprising a DNA cargo and a targeting moiety as a new format for targeted gene delivery. A PAMAM dendrimer modified with histidine and arginine (HR-dendrimer) was used to enhance the endosomal escape and transfection efficiency. An EGFR-specific repebody, composed of leucine-rich repeat (LRR) modules, was employed as a targeting moiety. A polyanionic peptide was genetically fused to the repebody, followed by incubation with an HR-dendrimer and a DNA cargo to assemble the dendrimer complex through an electrostatic interaction. The resulting dendrimer complex was shown to deliver a DNA cargo with high efficiency in a receptor-specific manner. An analysis using a confocal microscope confirmed the internalization of the dendrimer complex and subsequent dissociation of a DNA cargo from the complex. The present approach can be broadly used in a targeted gene delivery in many areas. Copyright © 2018 Elsevier B.V. All rights reserved.

A Fluorescent Protein Scaffold for Presenting Structurally Constrained Peptides Provides an Effective Screening System to Identify High Affinity Target-Binding Peptides

PubMed Central

Kadonosono, Tetsuya; Yabe, Etsuri; Furuta, Tadaomi; Yamano, Akihiro; Tsubaki, Takuya; Sekine, Takuya; Kuchimaru, Takahiro; Sakurai, Minoru; Kizaka-Kondoh, Shinae

2014-01-01

Peptides that have high affinity for target molecules on the surface of cancer cells are crucial for the development of targeted cancer therapies. However, unstructured peptides often fail to bind their target molecules with high affinity. To efficiently identify high-affinity target-binding peptides, we have constructed a fluorescent protein scaffold, designated gFPS, in which structurally constrained peptides are integrated at residues K131–L137 of superfolder green fluorescent protein. Molecular dynamics simulation supported the suitability of this site for presentation of exogenous peptides with a constrained structure. gFPS can present 4 to 12 exogenous amino acids without a loss of fluorescence. When gFPSs presenting human epidermal growth factor receptor type 2 (HER2)-targeting peptides were added to the culture medium of HER2-expressing cells, we could easily identify the peptides with high HER2-affinity and -specificity based on gFPS fluorescence. In addition, gFPS could be expressed on the yeast cell surface and applied for a high-throughput screening. These results demonstrate that gFPS has the potential to serve as a powerful tool to improve screening of structurally constrained peptides that have a high target affinity, and suggest that it could expedite the one-step identification of clinically applicable cancer cell-binding peptides. PMID:25084350

Observation of enhanced zero-degree binary encounter electron production with decreasing charge-state q in 30 MeV O{sup q+} + O{sub 2} collisions

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

Zouros, T.J.M.; Wong, K.L.; Hidmi, H.I.

We have measured binary encounter electron production in collisions of 30 MeV O{sup q+} projectiles (q=4-8) and O{sub 2} targets. Measured double differential BEe cross-sections are found to increase with decreasing charge-state q, in agreement with similar previously reported zero-degree investigations for H{sub 2} and He targets. However, measurements for the same system but at 25{degrees} shows the opposite trend, that BEe cross sections decrease slightly with decreasing charge state.

Chemical modification of projectile residues and target material in a MEMIN cratering experiment

NASA Astrophysics Data System (ADS)

Ebert, Matthias; Hecht, Lutz; Deutsch, Alexander; Kenkmann, Thomas

2013-01-01

In the context of the MEMIN project, a hypervelocity cratering experiment has been performed using a sphere of the iron meteorite Campo del Cielo as projectile accelerated to 4.56 km s-1, and a block of Seeberger sandstone as target material. The ejecta, collected in a newly designed catcher, are represented by (1) weakly deformed, (2) highly deformed, and (3) highly shocked material. The latter shows shock-metamorphic features such as planar deformation features (PDF) in quartz, formation of diaplectic quartz glass, partial melting of the sandstone, and partially molten projectile, mixed mechanically and chemically with target melt. During mixing of projectile and target melts, the Fe of the projectile is preferentially partitioned into target melt to a greater degree than Ni and Co yielding a Fe/Ni that is generally higher than Fe/Ni in the projectile. This fractionation results from the differing siderophile properties, specifically from differences in reactivity of Fe, Ni, and Co with oxygen during projectile-target interaction. Projectile matter was also detected in shocked quartz grains. The average Fe/Ni of quartz with PDF (about 20) and of silica glasses (about 24) are in contrast to the average sandstone ratio (about 422), but resembles the Fe/Ni-ratio of the projectile (about 14). We briefly discuss possible reasons of projectile melting and vaporization in the experiment, in which the calculated maximum shock pressure does not exceed 55 GPa.

Double degree master program: Optical Design

NASA Astrophysics Data System (ADS)

Bakholdin, Alexey; Kujawinska, Malgorzata; Livshits, Irina; Styk, Adam; Voznesenskaya, Anna; Ezhova, Kseniia; Ermolayeva, Elena; Ivanova, Tatiana; Romanova, Galina; Tolstoba, Nadezhda

2015-10-01

Modern tendencies of higher education require development of master programs providing achievement of learning outcomes corresponding to quickly variable job market needs. ITMO University represented by Applied and Computer Optics Department and Optical Design and Testing Laboratory jointly with Warsaw University of Technology represented by the Institute of Micromechanics and Photonics at The Faculty of Mechatronics have developed a novel international master double-degree program "Optical Design" accumulating the expertise of both universities including experienced teaching staff, educational technologies, and experimental resources. The program presents studies targeting research and professional activities in high-tech fields connected with optical and optoelectronics devices, optical engineering, numerical methods and computer technologies. This master program deals with the design of optical systems of various types, assemblies and layouts using computer modeling means; investigation of light distribution phenomena; image modeling and formation; development of optical methods for image analysis and optical metrology including optical testing, materials characterization, NDT and industrial control and monitoring. The goal of this program is training a graduate capable to solve a wide range of research and engineering tasks in optical design and metrology leading to modern manufacturing and innovation. Variability of the program structure provides its flexibility and adoption according to current job market demands and personal learning paths for each student. In addition considerable proportion of internship and research expands practical skills. Some special features of the "Optical Design" program which implements the best practices of both Universities, the challenges and lessons learnt during its realization are presented in the paper.

Multiplexed Elimination of Wild-Type DNA and High-Resolution Melting Prior to Targeted Resequencing of Liquid Biopsies.

PubMed

Ladas, Ioannis; Fitarelli-Kiehl, Mariana; Song, Chen; Adalsteinsson, Viktor A; Parsons, Heather A; Lin, Nancy U; Wagle, Nikhil; Makrigiorgos, G Mike

2017-10-01

The use of clinical samples and circulating cell-free DNA (cfDNA) collected from liquid biopsies for diagnostic and prognostic applications in cancer is burgeoning, and improved methods that reduce the influence of excess wild-type (WT) portion of the sample are desirable. Here we present enrichment of mutation-containing sequences using enzymatic degradation of WT DNA. Mutation enrichment is combined with high-resolution melting (HRM) performed in multiplexed closed-tube reactions as a rapid, cost-effective screening tool before targeted resequencing. We developed a homogeneous, closed-tube approach to use a double-stranded DNA-specific nuclease for degradation of WT DNA at multiple targets simultaneously. The No Denaturation Nuclease-assisted Minor Allele Enrichment with Probe Overlap (ND-NaME-PrO) uses WT oligonucleotides overlapping both strands on putative DNA targets. Under conditions of partial denaturation (DNA breathing), the oligonucleotide probes enhance double-stranded DNA-specific nuclease digestion at the selected targets, with high preference toward WT over mutant DNA. To validate ND-NaME-PrO, we used multiplexed HRM, digital PCR, and MiSeq targeted resequencing of mutated genomic DNA and cfDNA. Serial dilution of KRAS mutation-containing DNA shows mutation enrichment by 10- to 120-fold and detection of allelic fractions down to 0.01%. Multiplexed ND-NaME-PrO combined with multiplexed PCR-HRM showed mutation scanning of 10-20 DNA amplicons simultaneously. ND-NaME-PrO applied on cfDNA from clinical samples enables mutation enrichment and HRM scanning over 10 DNA targets. cfDNA mutations were enriched up to approximately 100-fold (average approximately 25-fold) and identified via targeted resequencing. Closed-tube homogeneous ND-NaME-PrO combined with multiplexed HRM is a convenient approach to efficiently enrich for mutations on multiple DNA targets and to enable prescreening before targeted resequencing. © 2017 American Association for Clinical

Studies of Ion Acceleration from Thin Solid-Density Targets on High-Intensity Lasers

NASA Astrophysics Data System (ADS)

Willis, Christopher R.

experiment utilized new liquid crystal film targets developed at OSU, which may be formed at variable thicknesses from tens of nanometers to several microns. On this experiment, an optimum ion energy and flux was reached for targets of 600-900 nm, providing a peak proton energy of 24 MeV, and total ion flux of > 109 protons over 3.4 MeV from 5.5 J of laser energy at an intensity of 1 x 1020 W cm -2. The primary ion diagnostics for these two experiments are described in detail, including the analysis techniques needed to extract absolutely calibrated spatial and spectral distributions of the accelerated ions. Additionally, a new technique for target alignment is presented, providing repeatable target alignment on the micron scale. This allows for a repeatable laser intensity on target, allowing improved shot to shot consistency on high intensity experiments. In addition to these two experiments, work on the upgrade and characterization of the 400 TW Scarlet laser is discussed, including several calculations critical to the design and upgrade of the laser system, as well as prepulse characterization needed for experiments on thin targets.

Tumor targeting efficiency of bare nanoparticles does not mean the efficacy of loaded anticancer drugs: importance of radionuclide imaging for optimization of highly selective tumor targeting polymeric nanoparticles with or without drug.

PubMed

Lee, Beom Suk; Park, Kyeongsoon; Park, Sangjin; Kim, Gui Chul; Kim, Hyo Jung; Lee, Sangjoo; Kil, Heeseup; Oh, Seung Jun; Chi, Daeyoon; Kim, Kwangmeyung; Choi, Kuiwon; Kwon, Ick Chan; Kim, Sang Yoon

2010-10-15

The better understanding of polymeric nanoparticles as a drug delivery carrier is a decisive factor to get more efficient therapeutic response in vivo. Here, we report the non-invasive imaging of bare polymeric nanoparticles and drug-loaded polymeric nanoparticles to evaluate biodistribution in tumor bearing mice. To make nano-sized drug delivery carrier, glycol chitosan was modified with different degrees of hydrophobic N-acetyl histidine (NAcHis-GC-1, -2, and -3). The biodistribution of polymeric nanoparticles and drug was confirmed by using gamma camera with (131)I-labeled NAcHis-GC and (131)I-labeled doxorubicin (DOX) and by using in vivo live animal imaging with near-infrared fluorescence Cy5.5-labeled NAcHis-GC. Among bare nanoparticles, NAcHis-GC3 (7.8% NAcHis content) showed much higher tumor targeting efficiency than NAcHis-GC1 (3.3% NAcHis content) and NAcHis-GC2 (6.8% NAcHis content). In contrast, for drug-loaded nanoparticles, DOX-NAcHis-GC1 displayed two-fold higher tumor targeting property than DOX-NAcHis-GC3. These data imply that the biodistribution and tumor targeting efficiency between bare and drug-loaded nanoparticles may be greatly different. Therapeutic responses for NAcHis-GC nanoparticles after drug loading were also evaluated. In xenograft animal model, we could find out that DOX-NAcHis-GC1 with higher tumor targeting of DOX has more excellent therapeutic effect than DOX-NAcHis-GC3 and free DOX. These results mean that the hydrophobic core stability might be a critical factor for tumor targeting efficiency of nanoparticles. The present study indicates that by using molecular imaging, we can select more appropriate nanoparticles with the highest tumor targeting properties, leading to exerting more excellent therapeutic results in cancer therapy. Copyright © 2010 Elsevier B.V. All rights reserved.

Start codon targeted (SCoT) and target region amplification polymorphism (TRAP) for evaluating the genetic relationship of Dendrobium species.

PubMed

Feng, Shangguo; He, Refeng; Yang, Sai; Chen, Zhe; Jiang, Mengying; Lu, Jiangjie; Wang, Huizhong

2015-08-10

Two molecular marker systems, start codon targeted (SCoT) and target region amplification polymorphism (TRAP), were used for genetic relationship analysis of 36 Dendrobium species collected from China. Twenty-two selected SCoT primers produced 337 loci, of which 324 (96%) were polymorphic, whereas 13 TRAP primer combinations produced a total of 510 loci, with 500 (97.8%) of them being polymorphic. An average polymorphism information content of 0.953 and 0.983 was detected using the SCoT and TRAP primers, respectively, showing that a high degree of genetic diversity exists among Chinese Dendrobium species. The partition of clusters in the unweighted pair group method with arithmetic mean dendrogram and principal coordinate analysis plot based on the SCoT and TRAP markers was similar and clustered the 36 Dendrobium species into four main groups. Our results will provide useful information for resource protection and will also be useful to improve the current Dendrobium breeding programs. Our results also demonstrate that SCoT and TRAP markers are informative and can be used to evaluate genetic relationships between Dendrobium species. Copyright © 2015 Elsevier B.V. All rights reserved.

Measurement of electromagnetic pulses generated during interactions of high power lasers with solid targets

NASA Astrophysics Data System (ADS)

De Marco, M.; Krása, J.; Cikhardt, J.; Pfeifer, M.; Krouský, E.; Margarone, D.; Ahmed, H.; Borghesi, M.; Kar, S.; Giuffrida, L.; Vrana, R.; Velyhan, A.; Limpouch, J.; Korn, G.; Weber, S.; Velardi, L.; Delle Side, D.; Nassisi, V.; Ullschmied, J.

2016-06-01

A target irradiated with a high power laser pulse, blows off a large amount of charge and as a consequence the target itself becomes a generator of electromagnetic pulses (EMP) owing to high return current flowing to the ground through the target holder. The first measurement of the magnetic field induced by the neutralizing current reaching a value of a few kA was performed with the use of an inductive target probe at the PALS Laser Facility (Cikhardt et al. Rev. Sci. Instrum. 85 (2014) 103507). A full description of EMP generation should contain information on the spatial distribution and temporal variation of the electromagnetic field inside and outside of the interaction chamber. For this reason, we consider the interaction chamber as a resonant cavity in which different modes of EMP oscillate for hundreds of nanoseconds, until the EMP is transmitted outside through the glass windows and EM waves are attenuated. Since the experimental determination of the electromagnetic field distribution is limited by the number of employed antennas, a mapping of the electromagnetic field has to be integrated with numerical simulations. Thus, this work reports on a detailed numerical mapping of the electromagnetic field inside the interaction chamber at the PALS Laser Facility (covering a frequency spectrum from 100 MHz to 3 GHz) using the commercial code COMSOL Multiphysics 5.2. Moreover we carried out a comparison of the EMP generated in the parallelepiped-like interaction chamber used in the Vulcan Petawatt Laser Facility at the Rutherford Appleton Laboratory, against that produced in the spherical interaction chamber of PALS.

The development of high-performance alkali-hybrid polarized He 3 targets for electron scattering

DOE PAGES

Singh, Jaideep T.; Dolph, Peter A.M.; Tobias, William Al; ...

2015-05-01

We present the development of high-performance polarized ³He targets for use in electron scattering experiments that utilize the technique of alkali-hybrid spin-exchange optical pumping. We include data obtained during the characterization of 24 separate target cells, each of which was constructed while preparing for one of four experiments at Jefferson Laboratory in Newport News, Virginia. The results presented here document dramatic improvement in the performance of polarized ³He targets, as well as the target properties and operating parameters that made those improvements possible. Included in our measurements were determinations of the so-called X-factors that quantify a temperature-dependent and as-yet poorly understood spin-relaxation mechanism that limits the maximum achievable ³He polarization to well under 100%. The presence of this spin-relaxation mechanism was clearly evident in our data. We also present results from a simulation of the alkali-hydrid spin-exchange optical pumping process that was developed to provide guidance in the design of these targets. Good agreement with actual performance was obtained by including details such as off-resonant optical pumping. Now benchmarked against experimental data, the simulation is useful for the design of future targets. Included in our results is a measurement of the K- ³He spin-exchange rate coefficientmore » $$k^\\mathrm{K}_\\mathrm{se} = \\left ( 7.46 \\pm 0.62 \\right )\\!\\times\\!10^{-20}\\ \\mathrm{cm^3/s}$$ over the temperature range 503 K to 563 K.« less

A Novel W1999S Mutation and Non-Target Site Resistance Impact on Acetyl-CoA Carboxylase Inhibiting Herbicides to Varying Degrees in a UK Lolium multiflorum Population

PubMed Central

Kaundun, Shiv Shankhar; Bailly, Geraldine C.; Dale, Richard P.; Hutchings, Sarah-Jane; McIndoe, Eddie

2013-01-01

Background Acetyl-CoA carboxylase (ACCase) inhibiting herbicides are important products for the post-emergence control of grass weed species in small grain cereal crops. However, the appearance of resistance to ACCase herbicides over time has resulted in limited options for effective weed control of key species such as Lolium spp. In this study, we have used an integrated biological and molecular biology approach to investigate the mechanism of resistance to ACCase herbicides in a Lolium multiflorum Lam. from the UK (UK21). Methodology/Principal Findings The study revealed a novel tryptophan to serine mutation at ACCase codon position 1999 impacting on ACCase inhibiting herbicides to varying degrees. The W1999S mutation confers dominant resistance to pinoxaden and partially recessive resistance to cycloxydim and sethoxydim. On the other hand, plants containing the W1999S mutation were sensitive to clethodim and tepraloxydim. Additionally population UK21 is characterised by other resistance mechanisms, very likely non non-target site based, affecting several aryloxyphenoxyproprionate (FOP) herbicides but not the practical field rate of pinoxaden. The positive identification of wild type tryptophan and mutant serine alleles at ACCase position 1999 could be readily achieved with an original DNA based derived cleaved amplified polymorphic sequence (dCAPS) assay that uses the same PCR product but two different enzymes for positively identifying the wild type tryptophan and mutant serine alleles identified here. Conclusion/Significance This paper highlights intrinsic differences between ACCase inhibiting herbicides that could be exploited for controlling ryegrass populations such as UK21 characterised by compound-specific target site and non-target site resistance. PMID:23469130

Full-scale-wind-tunnel Tests of a 35 Degree Sweptback Wing Airplane with High-velocity Blowing over the Training-edge Flaps

NASA Technical Reports Server (NTRS)

Kelley, Mark W; Tolhurst, William H JR

1955-01-01

A wind-tunnel investigation was made to determine the effects of ejecting high-velocity air near the leading edge of plain trailing-edge flaps on a 35 degree sweptback wing. The tests were made with flap deflections from 45 degrees to 85 degrees and with pressure ratios across the flap nozzles from sub-critical up to 2.9. A limited study of the effects of nozzle location and configuration on the efficiency of the flap was made. Measurements of the lift, drag, and pitching moment were made for Reynolds numbers from 5.8 to 10.1x10(6). Measurements were also made of the weight rate of flow, pressure, and temperature of the air supplied to the flap nozzles.The results show that blowing on the deflected flap produced large flap lift increments. The amount of air required to prevent flow separation on the flap was significantly less than that estimated from published two-dimensional data. When the amount of air ejected over the flap was just sufficient to prevent flow separation, the lift increment obtained agreed well with linear inviscid fluid theory up to flap deflections of 60 degrees. The flap lift increment at 85 degrees flap deflection was about 80 percent of that predicted theoretically.With larger amounts of air blown over the flap, these lift increments could be significantly increased. It was found that the performance of the flap was relatively insensitive to the location of the flap nozzle, to spacers in the nozzle, and to flow disturbances such as those caused by leading-edge slats or discontinuities on the wing or flap surfaces. Analysis of the results indicated that installation of this system on an F-86 airplane is feasible.

Compatibility of materials with liquid metal targets for SNS

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

DiStefano, J.R.; Pawel, S.J.; DeVan, J.H.

1996-06-01

Several heavy liquid metals are candidates as the target in a spallation neutron source: Hg, Pb, Bi, and Pb-Bi eutectic. Systems with these liquid metals have been used in the past and a data-base on compatibility already exists. Two major compatibility issues have been identified when selecting a container material for these liquid metals: temperature gradient mass transfer and liquid metal embrittlement or LME. Temperature gradient mass transfer refers to dissolution of material from the high temperature portions of a system and its deposition in the lower temperature areas. Solution and deposition rate constants along with temperature, {Delta}T, and velocitymore » are usually the most important parameters. For most candidate materials mass transfer corrosion has been found to be proportionately worse in Bi compared with Hg and Pb. For temperatures to {approx}550{degrees}C, ferritic/martensitic steels have been satisfactory in Pb or Hg systems and the maximum temperature can be extended to {approx}650{degrees}C with additions of inhibitors to the liquid metal, e.g. Mg, Ti, Zr. Above {approx}600{degrees}C, austenitic stainless steels have been reported to be unsatisfactory, largely because of the mass transfer of nickel. Blockage of flow from deposition of material is usually the life-limiting effect of this type of corrosion. However, mass transfer corrosion at lower temperatures has not been studied. At low temperatures (usually < 150{degrees}C), LME has been reported for some liquid metal/container alloy combinations. Liquid metal embrittlement, like hydrogen embrittlement, results in brittle fracture of a normally ductile material.« less

Synaptotagmin-mediated bending of the target membrane is a critical step in Ca2+-regulated fusion

PubMed Central

Hui, Enfu; Johnson, Colin P.; Yao, Jun; Dunning, F. Mark; Chapman, Edwin R.

2009-01-01

Summary Decades ago it was proposed that exocytosis involves invagination of the target membrane, resulting in a highly localized site of contact between the bilayers destined to fuse. The vesicle protein synaptotagmin-I (syt) bends membranes in response to Ca2+, but whether this drives localized invagination of the target membrane to accelerate fusion has not been determined; previous studies relied on reconstituted vesicles that were already highly curved and used mutations in syt that were not selective for membrane-bending activity. Here, we directly address this question by utilizing vesicles with different degrees of curvature. A tubulation-defective syt mutant was able to promote fusion between highly curved SNARE-bearing liposomes, but exhibited a marked loss of activity when the membranes were relatively flat. Moreover, bending of flat membranes by adding an N-BAR domain rescued the function of the tubulation-deficient syt mutant. Hence, syt-mediated membrane bending is a critical step in membrane fusion. PMID:19703397

The SDSS-IV extended baryon oscillation spectroscopic survey: Luminous red galaxy target selection

DOE PAGES

Prakash, Abhishek; Licquia, Timothy C.; Newman, Jeffrey A.; ...

2016-06-08

Here, we describe the algorithm used to select the luminous red galaxy (LRG) sample for the extended Baryon Oscillation Spectroscopic Survey (eBOSS) of the Sloan Digital Sky Survey IV (SDSS-IV) using photometric data from both the SDSS and the Wide-field Infrared Survey Explorer. LRG targets are required to meet a set of color selection criteria and have z-band and i-band MODEL magnitudes z < 19.95 and 19.9 < i < 21.8, respectively. Our algorithm selects roughly 50 LRG targets per square degree, the great majority of which lie in the redshift range 0.6 < z < 1.0 (median redshift 0.71).more » We also demonstrate that our methods are highly effective at eliminating stellar contamination and lower-redshift galaxies. We perform a number of tests using spectroscopic data from SDSS-III/BOSS ancillary programs to determine the redshift reliability of our target selection and its ability to meet the science requirements of eBOSS. The SDSS spectra are of high enough signal-to-noise ratio that at least ~89% of the target sample yields secure redshift measurements. Finally, we present tests of the uniformity and homogeneity of the sample, demonstrating that it should be clean enough for studies of the large-scale structure of the universe at higher redshifts than SDSS-III/BOSS LRGs reached.« less

THE SDSS-IV EXTENDED BARYON OSCILLATION SPECTROSCOPIC SURVEY: LUMINOUS RED GALAXY TARGET SELECTION

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

Prakash, Abhishek; Licquia, Timothy C.; Newman, Jeffrey A.

2016-06-01

We describe the algorithm used to select the luminous red galaxy (LRG) sample for the extended Baryon Oscillation Spectroscopic Survey (eBOSS) of the Sloan Digital Sky Survey IV (SDSS-IV) using photometric data from both the SDSS and the Wide-field Infrared Survey Explorer . LRG targets are required to meet a set of color selection criteria and have z -band and i -band MODEL magnitudes z < 19.95 and 19.9 < i < 21.8, respectively. Our algorithm selects roughly 50 LRG targets per square degree, the great majority of which lie in the redshift range 0.6 < z < 1.0 (medianmore » redshift 0.71). We demonstrate that our methods are highly effective at eliminating stellar contamination and lower-redshift galaxies. We perform a number of tests using spectroscopic data from SDSS-III/BOSS ancillary programs to determine the redshift reliability of our target selection and its ability to meet the science requirements of eBOSS. The SDSS spectra are of high enough signal-to-noise ratio that at least ∼89% of the target sample yields secure redshift measurements. We also present tests of the uniformity and homogeneity of the sample, demonstrating that it should be clean enough for studies of the large-scale structure of the universe at higher redshifts than SDSS-III/BOSS LRGs reached.« less

A physics-based solver to optimize the illumination of cylindrical targets in spherically distributed high power laser systems.

PubMed

Gourdain, P-A

2017-05-01

In recent years, our understanding of high energy density plasmas has played an important role in improving inertial fusion confinement and in emerging new fields of physics, such as laboratory astrophysics. Every new idea required developing innovative experimental platforms at high power laser facilities, such as OMEGA or NIF. These facilities, designed to focus all their beams onto spherical targets or hohlraum windows, are now required to shine them on more complex targets. While the pointing on planar geometries is relatively straightforward, it becomes problematic for cylindrical targets or target with more complex geometries. This publication describes how the distribution of laser beams on a cylindrical target can be done simply by using a set of physical laws as a pointing procedure. The advantage of the method is threefold. First, it is straightforward, requiring no mathematical enterprise besides solving ordinary differential equations. Second, it will converge if a local optimum exists. Finally, it is computationally inexpensive. Experimental results show that this approach produces a geometrical beam distribution that yields cylindrically symmetric implosions.

A physics-based solver to optimize the illumination of cylindrical targets in spherically distributed high power laser systems

NASA Astrophysics Data System (ADS)

Gourdain, P.-A.

2017-05-01

In recent years, our understanding of high energy density plasmas has played an important role in improving inertial fusion confinement and in emerging new fields of physics, such as laboratory astrophysics. Every new idea required developing innovative experimental platforms at high power laser facilities, such as OMEGA or NIF. These facilities, designed to focus all their beams onto spherical targets or hohlraum windows, are now required to shine them on more complex targets. While the pointing on planar geometries is relatively straightforward, it becomes problematic for cylindrical targets or target with more complex geometries. This publication describes how the distribution of laser beams on a cylindrical target can be done simply by using a set of physical laws as a pointing procedure. The advantage of the method is threefold. First, it is straightforward, requiring no mathematical enterprise besides solving ordinary differential equations. Second, it will converge if a local optimum exists. Finally, it is computationally inexpensive. Experimental results show that this approach produces a geometrical beam distribution that yields cylindrically symmetric implosions.

Scrutinizing data helps team target high-cost DRGs, improve costly tracheostomy care.

PubMed

1997-10-01

Targeting high-cost DRGs using data collection, analysis: A hospital team analyzed DRGs with the highest excess charges and found DRG 483 (tracheostomy) had astronomical charges. Here's the step-by-step story of how they analyzed individual physician resource utilization, care progression through the hospital, and admission source to identify areas for clinical improvement, plus their findings and how they're putting them to use to improve care and reduce costs.

High-speed and high-resolution UPLC separation at zero degrees Celsius

PubMed Central

Wales, Thomas E.; Fadgen, Keith E.; Gerhardt, Geoff C.; Engen, John R.

2008-01-01

The conformational properties of proteins can be probed with hydrogen/deuterium exchange mass spectrometry (HXMS). In order to maintain the deuterium label during LC/MS analyses, chromatographic separation must be done rapidly (usually in under 8–10 minutes) and at zero degrees Celsius. Traditional RP-HPLC with ~3 micron particles has shown generally poor chromatographic performance under these conditions and thereby has been prohibitive for HXMS analyses of larger proteins and many protein complexes. Ultra performance liquid chromatography (UPLC) employs particles smaller than 2 microns in diameter to achieve superior resolution, speed, and sensitivity as compared to HPLC. UPLC has previously been shown to be compatible with the fast separation and low temperature requirements of HXMS. Here we present construction and validation of a custom UPLC system for HXMS. The system is based on the Waters nanoACQUITY platform and contains a Peltier-cooled module that houses the injection and switching valves, online pepsin digestion column, and C-18 analytical separation column. Single proteins in excess of 95 kDa and a four-protein mixture in excess of 250 kDa have been used to validate the performance of this new system. Near baseline resolution was achieved in 6 minute separations at 0 °C and displayed a median chromatographic peak width of ~2.7 sec at half height. Deuterium recovery was similar to that obtained using a conventional HPLC and icebath. This new system represents a significant advancement in HXMS technology that is expected to make the technique more accessible and mainstream in the near future. PMID:18672890

Automation of the targeting and reflective alignment concept

NASA Technical Reports Server (NTRS)

Redfield, Robin C.

1992-01-01

The automated alignment system, described herein, employs a reflective, passive (requiring no power) target and includes a PC-based imaging system and one camera mounted on a six degree of freedom robot manipulator. The system detects and corrects for manipulator misalignment in three translational and three rotational directions by employing the Targeting and Reflective Alignment Concept (TRAC), which simplifies alignment by decoupling translational and rotational alignment control. The concept uses information on the camera and the target's relative position based on video feedback from the camera. These relative positions are converted into alignment errors and minimized by motions of the robot. The system is robust to exogenous lighting by virtue of a subtraction algorithm which enables the camera to only see the target. These capabilities are realized with relatively minimal complexity and expense.

Targeted inhibition of histone H3K27 demethylation is effective in high-risk neuroblastoma.

PubMed

Lochmann, Timothy L; Powell, Krista M; Ham, Jungoh; Floros, Konstantinos V; Heisey, Daniel A R; Kurupi, Richard I J; Calbert, Marissa L; Ghotra, Maninderjit S; Greninger, Patricia; Dozmorov, Mikhail; Gowda, Madhu; Souers, Andrew J; Reynolds, C Patrick; Benes, Cyril H; Faber, Anthony C

2018-05-16

High-risk neuroblastoma is often distinguished by amplification of MYCN and loss of differentiation potential. We performed high-throughput drug screening of epigenetic-targeted therapies across a large and diverse tumor cell line panel and uncovered the hypersensitivity of neuroblastoma cells to GSK-J4, a small-molecule dual inhibitor of lysine 27 of histone 3 (H3K27) demethylases ubiquitously transcribed tetratricopeptide repeat, X chromosome (UTX), and histone demethylase Jumonji D3 (JMJD3). Mechanistically, GSK-J4 induced neuroblastoma differentiation and endoplasmic reticulum (ER) stress, with accompanying up-regulation of p53 up-regulated modulator of apoptosis (PUMA) and induction of cell death. Retinoic acid (RA)-resistant neuroblastoma cells were sensitive to GSK-J4. In addition, GSK-J4 was effective at blocking the growth of chemorefractory and patient-derived xenograft models of high-risk neuroblastoma in vivo. Furthermore, GSK-J4 and RA combination increased differentiation and ER stress over GSK-J4 effects and limited the growth of neuroblastomas resistant to either drug alone. In MYCN -amplified neuroblastoma, PUMA induction by GSK-J4 sensitized tumors to the B cell lymphoma 2 (BCL-2) inhibitor venetoclax, demonstrating that epigenetic-targeted therapies and BCL-2 homology domain 3 mimetics can be rationally combined to treat this high-risk subset of neuroblastoma. Therefore, H3K27 demethylation inhibition is a promising therapeutic target to treat high-risk neuroblastoma, and H3K27 demethylation can be part of rational combination therapies to induce robust antineuroblastoma activity. Copyright © 2018 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.

Improving the Desulfurization Degree of High-Grade Nickel Matte via a Two-Step Oxidation Roasting Process

NASA Astrophysics Data System (ADS)

Xi, Zhao; Wang, Zhixing; Li, Xinhai; Guo, Huajun; Yan, Guochun; Wang, Jiexi

2018-05-01

Generally, sulfur elimination from nickel matte was incomplete in the one-step oxidation roasting process. In this work, X-ray diffraction, scanning electron microscopy/energy-dispersive X-ray spectroscopy, and chemical analysis of the roasted products were carried out to explain this phenomenon. The results indicated that the melting of heazlewoodite was the main limiting factor. Thereafter, the oxidation mechanism of high-grade nickel matte from room temperature to 1000 °C was studied. It was found that the transformation from heazlewoodite (Ni3S2) to nickel sulfide (NiS) took place from 400 °C to 520 °C. Considering that the melting temperature of NiS was much higher than that of Ni3S2, a low-temperature roasting step was suggested to suppress the melting of heazlewoodite. Under the optimum conditions (520 °C for 120 minutes followed by 800 °C for 80 minutes), the degree of desulfurization reached 99.52 pct. These results indicated that the two-step oxidation roasting method could be a promising process for producing low-sulfur calcine from high-grade nickel matte.

Trajectories of Black Men from Baccalaureate Degree Attainment through Career Transition

ERIC Educational Resources Information Center

Carty, Karenann

2010-01-01

College degree attainment is an important predictor of labor market outcomes. Earning a degree beyond high school has an impact on participation in the labor force, occupational status, and earnings. Black males in the United States are at risk of not pursuing or completing post-secondary education and are underrepresented in professional and…

The 2-degree Field Lensing Survey: design and clustering measurements

NASA Astrophysics Data System (ADS)

Blake, Chris; Amon, Alexandra; Childress, Michael; Erben, Thomas; Glazebrook, Karl; Harnois-Deraps, Joachim; Heymans, Catherine; Hildebrandt, Hendrik; Hinton, Samuel R.; Janssens, Steven; Johnson, Andrew; Joudaki, Shahab; Klaes, Dominik; Kuijken, Konrad; Lidman, Chris; Marin, Felipe A.; Parkinson, David; Poole, Gregory B.; Wolf, Christian

2016-11-01

We present the 2-degree Field Lensing Survey (2dFLenS), a new galaxy redshift survey performed at the Anglo-Australian Telescope. 2dFLenS is the first wide-area spectroscopic survey specifically targeting the area mapped by deep-imaging gravitational lensing fields, in this case the Kilo-Degree Survey. 2dFLenS obtained 70 079 redshifts in the range z < 0.9 over an area of 731 deg2, and is designed to extend the data sets available for testing gravitational physics and promote the development of relevant algorithms for joint imaging and spectroscopic analysis. The redshift sample consists first of 40 531 Luminous Red Galaxies (LRGs), which enable analyses of galaxy-galaxy lensing, redshift-space distortion, and the overlapping source redshift distribution by cross-correlation. An additional 28 269 redshifts form a magnitude-limited (r < 19.5) nearly complete subsample, allowing direct source classification and photometric-redshift calibration. In this paper, we describe the motivation, target selection, spectroscopic observations, and clustering analysis of 2dFLenS. We use power spectrum multipole measurements to fit the redshift-space distortion parameter of the LRG sample in two redshift ranges 0.15 < z < 0.43 and 0.43 < z < 0.7 as β = 0.49 ± 0.15 and β = 0.26 ± 0.09, respectively. These values are consistent with those obtained from LRGs in the Baryon Oscillation Spectroscopic Survey. 2dFLenS data products will be released via our website http://2dflens.swin.edu.au.

CRISPRscan: designing highly efficient sgRNAs for CRISPR/Cas9 targeting in vivo

PubMed Central

Moreno-Mateos, Miguel A.; Vejnar, Charles E.; Beaudoin, Jean-Denis; Fernandez, Juan P.; Mis, Emily K.; Khokha, Mustafa K.; Giraldez, Antonio J.

2015-01-01

CRISPR/Cas9 technology provides a powerful system for genome engineering. However, variable activity across different single guide RNAs (sgRNAs) remains a significant limitation. We have analyzed the molecular features that influence sgRNA stability, activity and loading into Cas9 in vivo. We observe that guanine enrichment and adenine depletion increase sgRNA stability and activity, while loading, nucleosome positioning and Cas9 off-target binding are not major determinants. We additionally identified truncated and 5′ mismatch-containing sgRNAs as efficient alternatives to canonical sgRNAs. Based on these results, we created a predictive sgRNA-scoring algorithm (CRISPRscan.org) that effectively captures the sequence features affecting Cas9/sgRNA activity in vivo. Finally, we show that targeting Cas9 to the germ line using a Cas9-nanos-3′-UTR fusion can generate maternal-zygotic mutants, increase viability and reduce somatic mutations. Together, these results provide novel insights into the determinants that influence Cas9 activity and a framework to identify highly efficient sgRNAs for genome targeting in vivo. PMID:26322839

Polarized Solid State Target

NASA Astrophysics Data System (ADS)

Dutz, Hartmut; Goertz, Stefan; Meyer, Werner

2017-01-01

The polarized solid state target is an indispensable experimental tool to study single and double polarization observables at low intensity particle beams like tagged photons. It was one of the major components of the Crystal-Barrel experiment at ELSA. Besides the operation of the 'CB frozen spin target' within the experimental program of the Crystal-Barrel collaboration both collaborative groups of the D1 project, the polarized target group of the Ruhr Universität Bochum and the Bonn polarized target group, have made significant developments in the field of polarized targets within the CRC16. The Bonn polarized target group has focused its work on the development of technically challenging polarized solid target systems towards the so called '4π continuous mode polarized target' to operate them in combination with 4π-particle detection systems. In parallel, the Bochum group has developed various highly polarized deuterated target materials and high precision NMR-systems, in the meantime used for polarization experiments at CERN, JLAB and MAMI, too.

Degree Attainment. Snapshot™ Report, Winter 2015

ERIC Educational Resources Information Center

National Student Clearinghouse, 2015

2015-01-01

This Snapshot Report presents information on student degree attainment in science and engineering disciplines for 2004 and 2014. It offers data on the following: (1) Science and Engineering Degrees as Percentage of All Degrees; (2) Gender Distribution of Science and Engineering Degrees by Level; (3) Gender Distribution of Bachelor's Degrees in…

HDice, Highly-Polarized Low-Background Frozen-Spin HD Targets for CLAS experiments at Jefferson Lab

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

Wei, Xiangdong; Bass, Christopher; D'Angelo, Annalisa

2012-12-01

Large, portable frozen-spin HD (Deuterium-Hydride) targets have been developed for studying nucleon spin properties with low backgrounds. Protons and Deuterons in HD are polarized at low temperatures (~10mK) inside a vertical dilution refrigerator (Oxford Kelvinox-1000) containing a high magnetic field (up to 17T). The targets reach a frozen-spin state within a few months, after which they can be cold transferred to an In-Beam Cryostat (IBC). The IBC, a thin-walled dilution refrigerator operating either horizontally or vertically, is use with quasi-4{pi} detector systems in open geometries with minimal energy loss for exiting reaction products in nucleon structure experiments. The first applicationmore » of this advanced target system has been used for Spin Sum Rule experiments at the LEGS facility in Brookhaven National Laboratory. An improved target production and handling system has been developed at Jefferson Lab for experiments with the CEBAF Large Acceptance Spectrometer, CLAS.« less

Tooth enamel oxygen “isoscapes” show a high degree of human mobility in prehistoric Britain

PubMed Central

Pellegrini, Maura; Pouncett, John; Jay, Mandy; Pearson, Mike Parker; Richards, Michael P.

2016-01-01

A geostatistical model to predict human skeletal oxygen isotope values (δ18Op) in Britain is presented here based on a new dataset of Chalcolithic and Early Bronze Age human teeth. The spatial statistics which underpin this model allow the identification of individuals interpreted as ‘non-local’ to the areas where they were buried (spatial outliers). A marked variation in δ18Op is observed in several areas, including the Stonehenge region, the Peak District, and the Yorkshire Wolds, suggesting a high degree of human mobility. These areas, rich in funerary and ceremonial monuments, may have formed focal points for people, some of whom would have travelled long distances, ultimately being buried there. The dataset and model represent a baseline for future archaeological studies, avoiding the complex conversions from skeletal to water δ18O values–a process known to be problematic. PMID:27713538

Perceptual load vs. dilution: the roles of attentional focus, stimulus category, and target predictability.

PubMed

Chen, Zhe; Cave, Kyle R

2013-01-01

Many studies have shown that increasing the number of neutral stimuli in a display decreases distractor interference. This result has been interpreted within two different frameworks; a perceptual load account, based on a reduction in spare resources, and a dilution account, based on a degradation in distractor representation and/or an increase in crosstalk between the distractor and the neutral stimuli that contain visually similar features. In four experiments, we systematically manipulated the extent of attentional focus, stimulus category, and preknowledge of the target to examine how these factors would interact with the display set size to influence the degree of distractor processing. Display set size did not affect the degree of distractor processing in all situations. Increasing the number of neutral items decreased distractor processing only when a task induced a broad attentional focus that included the neutral stimuli, when the neutral stimuli were in the same category as the target and distractor, and when the preknowledge of the target was insufficient to guide attention to the target efficiently. These results suggest that the effect of neutral stimuli on the degree of distractor processing is more complex than previously assumed. They provide new insight into the competitive interactions between bottom-up and top-down processes that govern the efficiency of visual selective attention.

Life in the fast lane: high-throughput chemistry for lead generation and optimisation.

PubMed

Hunter, D

2001-01-01

The pharmaceutical industry has come under increasing pressure due to regulatory restrictions on the marketing and pricing of drugs, competition, and the escalating costs of developing new drugs. These forces can be addressed by the identification of novel targets, reductions in the development time of new drugs, and increased productivity. Emphasis has been placed on identifying and validating new targets and on lead generation: the response from industry has been very evident in genomics and high throughput screening, where new technologies have been applied, usually coupled with a high degree of automation. The combination of numerous new potential biological targets and the ability to screen large numbers of compounds against many of these targets has generated the need for large diverse compound collections. To address this requirement, high-throughput chemistry has become an integral part of the drug discovery process. Copyright 2002 Wiley-Liss, Inc.

The Influence of Academic Momentum and Associate Degree Credit Requirements on Community College Student Degree Completion

ERIC Educational Resources Information Center

Knox, Daniel

2017-01-01

This study addresses gaps in the theoretical and policy literature by examining the relationship between associate degree program credit requirements and four student outcomes: associate degree attainment, time to degree, final associate degree grade point average, and persistence. Using student unit record data, a longitudinal quantitative study…

High-resolution wavefront control of high-power laser systems

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

Brase, J; Brown, C; Carrano, C

1999-07-08

Nearly every new large-scale laser system application at LLNL has requirements for beam control which exceed the current level of available technology. For applications such as inertial confinement fusion, laser isotope separation, laser machining, and laser the ability to transport significant power to a target while maintaining good beam quality is critical. There are many ways that laser wavefront quality can be degraded. Thermal effects due to the interaction of high-power laser or pump light with the internal optical components or with the ambient gas are common causes of wavefront degradation. For many years, adaptive optics based on thing deformablemore » glass mirrors with piezoelectric or electrostrictive actuators have be used to remove the low-order wavefront errors from high-power laser systems. These adaptive optics systems have successfully improved laser beam quality, but have also generally revealed additional high-spatial-frequency errors, both because the low-order errors have been reduced and because deformable mirrors have often introduced some high-spatial-frequency components due to manufacturing errors. Many current and emerging laser applications fall into the high-resolution category where there is an increased need for the correction of high spatial frequency aberrations which requires correctors with thousands of degrees of freedom. The largest Deformable Mirrors currently available have less than one thousand degrees of freedom at a cost of approximately $1M. A deformable mirror capable of meeting these high spatial resolution requirements would be cost prohibitive. Therefore a new approach using a different wavefront control technology is needed. One new wavefront control approach is the use of liquid-crystal (LC) spatial light modulator (SLM) technology for the controlling the phase of linearly polarized light. Current LC SLM technology provides high-spatial-resolution wavefront control, with hundreds of thousands of degrees of

Target for production of X-rays

NASA Astrophysics Data System (ADS)

Korenev, S. A.

2004-09-01

The patented new type of X-ray target is considered in this report. The main concept of the target consists in developing a sandwich structure depositing a coating of materials with high Z on the substrate with low Z, high thermal conductivity and high thermal stability. The target presents multiple layers system. The thermal conditions for X-ray target are discussed. The experimental results for Ta target on the Al and Cu substrates are presented.

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

NASA Astrophysics Data System (ADS)

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

2017-08-01

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

Creating Career Ladders in University Systems: The Accelerated Associate's Degree Program for Unemployed Licensed Nurses at the Inter-American University of Puerto Rico.

ERIC Educational Resources Information Center

Melendez, Edwin; Suarez, Carlos

This document describes the Accelerated Associate's Degree Program for Licensed Practical Nurses (LPN) at the Inter-American University of Puerto Rico. The program, targeting unemployed LPNs living in San Juan, Puerto Rico, allows students to complete an associate's degree in one year. Fifty-four students enrolled during the first year and 50% of…

TU-H-BRC-06: Temperature Simulation of Tungsten and W25Re Targets to Deliver High Dose Rate 10 MV Photons

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

Wang, J; Trovati, S; Loo, B

Purpose: To study the impact of electron beam size, target thickness, and target temperature on the ability of the flattening filter-free mode (FFF) treatment head to deliver high-dose-rate irradiations. Methods: The dose distribution and transient temperature of the X-ray target under 10 MeV electron beam with pulse length of 5 microseconds, and repetition rate of 1000 Hz was studied. A MCNP model was built to calculate the percentage depth dose (PPD) distribution in a water phantom at a distance of 100 cm. ANSYS software was used to run heat transfer simulations. The PPD and temperature for both tungsten and W25Remore » targets for different electron beam sizes (FHWM 0.2, 0.5, 1 and 2 mm) and target thickness (0.2 to 2 mm) were studied. Results: Decreasing the target thickness from 1 mm to 0.5 mm, caused a surface dose increase about 10 percent. For both target materials, the peak temperature was about 1.6 times higher for 0.5 mm electron beam compared to the 1 mm beam after reaching their equilibrium. For increasing target thicknesses, the temperature rise caused by the first pulse is similar for all thicknesses, however the temperature difference for subsequent pulses becomes larger until a constant ratio is reached. The target peak temperature after reaching equilibrium can be calculated by adding the steady state temperature and the amplitude of the temperature oscillation. Conclusion: This work indicates the potential to obtain high dose rate irradiation by selecting target material, geometry and electron beam parameters. W25Re may not outperformed tungsten when the target is thick due to its relatively low thermal conductivity. The electron beam size only affects the target temperature but not the PPD. Thin target is preferred to obtain high dose rate and low target temperature, however, the resulting high surface dose is a major concern. NIH funding:R21 EB015957-01; DOD funding:W81XWH-13-1-0165 BL, PM, PB, and RF are founders of TibaRay, Inc. BL is also

Predictive distractor context facilitates attentional selection of high, but not intermediate and low, salience targets.

PubMed

Töllner, Thomas; Conci, Markus; Müller, Hermann J

2015-03-01

It is well established that we can focally attend to a specific region in visual space without shifting our eyes, so as to extract action-relevant sensory information from covertly attended locations. The underlying mechanisms that determine how fast we engage our attentional spotlight in visual-search scenarios, however, remain controversial. One dominant view advocated by perceptual decision-making models holds that the times taken for focal-attentional selection are mediated by an internal template that biases perceptual coding and selection decisions exclusively through target-defining feature coding. This notion directly predicts that search times remain unaffected whether or not participants can anticipate the upcoming distractor context. Here we tested this hypothesis by employing an illusory-figure localization task that required participants to search for an invariant target amongst a variable distractor context, which gradually changed--either randomly or predictably--as a function of distractor-target similarity. We observed a graded decrease in internal focal-attentional selection times--correlated with external behavioral latencies--for distractor contexts of higher relative to lower similarity to the target. Critically, for low but not intermediate and high distractor-target similarity, these context-driven effects were cortically and behaviorally amplified when participants could reliably predict the type of distractors. This interactive pattern demonstrates that search guidance signals can integrate information about distractor, in addition to target, identities to optimize distractor-target competition for focal-attentional selection. © 2014 Wiley Periodicals, Inc.

Challenges with Deploying and Integrating Environmental Control and Life Support Functions in a Lunar Architecture with High Degrees of Mobility

NASA Technical Reports Server (NTRS)

Bagdigian, Robert M.

2009-01-01

Visions of lunar outposts often depict a collection of fixed elements such as pressurized habitats, in and around which human inhabitants spend the large majority of their surface stay time. In such an outpost, an efficient deployment of environmental control and life support equipment can be achieved by centralizing certain functions within one or a minimum number of habitable elements and relying on the exchange of gases and liquids between elements via atmosphere ventilation and plumbed interfaces. However, a rigidly fixed outpost can constrain the degree to which the total lunar landscape can be explored. The capability to enable widespread access across the landscape makes a lunar architecture with a high degree of surface mobility attractive. Such mobility presents unique challenges to the efficient deployment of environmental control and life support functions in multiple elements that may for long periods of time be operated independently. This paper describes some of those anticipated challenges.

Absorption degree analysis on biogas separation with ionic liquid systems.

PubMed

Zhang, Xin; Zhang, Suojiang; Bao, Di; Huang, Ying; Zhang, Xiangping

2015-01-01

For biogas upgrading, present work mainly focuses on either thermodynamics or mass transfer properties. A systematical study on these two aspects is important for developing a new biogas separation process. In this work, a new criterion "absorption degree", which combines both thermodynamics and mass transfer properties, was proposed for the first time to comprehensively evaluate the absorption performance. Henry's law constants of CO2 and CH4 in ionic liquids-polyethylene glycol dimethyl ethers mixtures were investigated. The liquid-side mass transfer coefficients (kL) were determined. The results indicate that IL-NHD mixtures exhibit not only a high CO2/CH4 selectivity, but also a fast kL for CO2 absorption. The [bmim][NO3]+NHD mixtures present a high absorption degree value for CO2 but a low value for CH4. For presenting a highest relative absorption degree value, the 50wt% [bmim][NO3]+50wt% NHD mixture is recommended for biogas upgrading. Copyright © 2014 Elsevier Ltd. All rights reserved.

Thin film growth of the 2122-phase of BCSCO superconductor with high degree of crystalline perfection

NASA Technical Reports Server (NTRS)

Raina, K. K.; Narayanan, S.; Pandey, R. K.

1992-01-01

Thin films of the 80 K-phase of BiCaSrCu-oxide superconductor having the composition of Bi2Ca1.05Sr2.1Cu2.19O(x) and high degree of crystalline perfection have been grown on c-axis oriented twin free single crystal substrates of NdGaO3. This has been achieved by carefully establishing the growth conditions of the LPE experiments. The temperature regime of 850 to 830 C and quenching of the specimens on the termination of the growth period are found to be pertinent for the growth of quasi-single crystalline superconducting BCSCO films on NdGaO3 substrates. The TEM analysis reveals a single crystalline nature of these films which exhibit 100 percent reflectivity in infrared regions at liquid nitrogen temperature.

KENNEDY SPACE CENTER, FLA. - Workers in KSC's Vertical Processing Facility inspect the Near Infrared Camera and Multi-Object Spectrometer (NICMOS) on its handling fixture. NICMOS is one of two new scientific instruments that will replace two outdated instruments on the Hubble Space Telescope (HST). NICMOS will provide HST with the capability for infrared imaging and spectroscopic observations of astronomical targets. The refrigerator-sized NICMOS also is HST's first cryogenic instrument — its sensitive infrared detectors must operate at very cold temperatures of minus 355 degrees Fahrenheit or 58 degrees Kelvin. NICMOS will be installed in Hubble during STS-82, the second Hubble Space Telescope servicing mission. Liftoff is targeted Feb. 11 aboard Discovery with a crew of seven.

NASA Image and Video Library

1997-01-18

KENNEDY SPACE CENTER, FLA. - Workers in KSC's Vertical Processing Facility inspect the Near Infrared Camera and Multi-Object Spectrometer (NICMOS) on its handling fixture. NICMOS is one of two new scientific instruments that will replace two outdated instruments on the Hubble Space Telescope (HST). NICMOS will provide HST with the capability for infrared imaging and spectroscopic observations of astronomical targets. The refrigerator-sized NICMOS also is HST's first cryogenic instrument — its sensitive infrared detectors must operate at very cold temperatures of minus 355 degrees Fahrenheit or 58 degrees Kelvin. NICMOS will be installed in Hubble during STS-82, the second Hubble Space Telescope servicing mission. Liftoff is targeted Feb. 11 aboard Discovery with a crew of seven.

KENNEDY SPACE CENTER, FLA. - Workers in KSC's Vertical Processing Facility lower the Near Infrared Camera and Multi-Object Spectrometer (NICMOS) into the Second Axial Carrier. NICMOS is one of two new scientific instruments that will replace two outdated instruments on the Hubble Space Telescope (HST). NICMOS will provide HST with the capability for infrared imaging and spectroscopic observations of astronomical targets. The refrigerator-sized NICMOS also is HST's first cryogenic instrument — its sensitive infrared detectors must operate at very cold temperatures of minus 355 degrees Fahrenheit or 58 degrees Kelvin. NICMOS will be installed in Hubble during STS-82, the second Hubble Space Telescope servicing mission. Liftoff is targeted Feb. 11 aboard Discovery with a crew of seven.

NASA Image and Video Library

1997-01-18

KENNEDY SPACE CENTER, FLA. - Workers in KSC's Vertical Processing Facility lower the Near Infrared Camera and Multi-Object Spectrometer (NICMOS) into the Second Axial Carrier. NICMOS is one of two new scientific instruments that will replace two outdated instruments on the Hubble Space Telescope (HST). NICMOS will provide HST with the capability for infrared imaging and spectroscopic observations of astronomical targets. The refrigerator-sized NICMOS also is HST's first cryogenic instrument — its sensitive infrared detectors must operate at very cold temperatures of minus 355 degrees Fahrenheit or 58 degrees Kelvin. NICMOS will be installed in Hubble during STS-82, the second Hubble Space Telescope servicing mission. Liftoff is targeted Feb. 11 aboard Discovery with a crew of seven.

HRD Degrees.

ERIC Educational Resources Information Center

Geber, Beverly

1987-01-01

The author describes the growing movement toward accreditation for human resources development professionals. She covers the issue of diversity, undergraduate versus graduate degrees, and future trends. (CH)

Radiation force on absorbing targets and power measurements of a high intensity focused ultrasound (HIFU) source

NASA Astrophysics Data System (ADS)

Qian, Zuwen; Zhu, Zhemin; Ye, Shigong; Jiang, Wenhua; Zhu, Houqing; Yu, Jinshen

2010-10-01

Based on the analytic expressions for the radiated field of a circular concave piston given by Hasegawa et al., an integral for calculation of the radiation force on a plane absorbing target in a spherically focused field is derived. A general relation between acoustic power P and normal radiation force F n is obtained under the condition of kr ≫ 1. Numerical computation is carried out by using the symbolic computation program for practically focused sources and absorbing circular targets. The results show that, for a given source, there is a range of target positions where the radiation force is independent of the target’s position under the assumption that the contribution of the acoustic field behind the target to the radiation force can be neglected. The experiments are carried out and confirm that there is a range of target positions where the measured radiation force is basically independent of the target’s position even at high acoustic power (up to 700 W). It is believed that when the radiation force method is used to measure the acoustic power radiated from a focused source, the size of the target must be selected in such a way that no observable sound can be found in the region behind the target.

High performance structural laminate composite material for use to 1000.degree. F. and above, apparatus for and method of manufacturing same, and articles made with same

NASA Technical Reports Server (NTRS)

Seal, Ellis C. (Inventor); Biggs, Jr., Robert William (Inventor); Bodepudi, Venu Prasad (Inventor); Cranston, John A. (Inventor)

2003-01-01

A novel materials technology has been developed and demonstrated for providing a high modulus composite material for use to 1000.degree. F. and above. This material can be produced at 5-20% of the cost of refractory materials, and has higher structural properties. This technology successfully resolves the problem of thermal shock or ply lift, which limits traditional high temperature laminates (such as graphite/polyimide and graphite/phenolic) to temperatures of 550-650.degree. F. in thicker (0.25 and above) laminates. The technology disclosed herein is an enabling technology for the nose for the External Tank (ET) of the Space Shuttle, and has been shown to be capable of withstanding the severe environments encountered by the nose cone through wind tunnel testing, high temperature subcomponent testing, and full scale structural, dynamic, acoustic, and damage tolerance testing.

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

USGS Publications Warehouse

Steiger, John W.; Webb, Robert H.

2000-01-01

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

Degree versus direction: a comparison of four handedness classification schemes through the investigation of lateralised semantic priming.

PubMed

Kaploun, Kristen A; Abeare, Christopher A

2010-09-01

Four classification systems were examined using lateralised semantic priming in order to investigate whether degree or direction of handedness better captures the pattern of lateralised semantic priming. A total of 85 participants completed a lateralised semantic priming task and three handedness questionnaires. The classification systems tested were: (1) the traditional right- vs left-handed (RHs vs LHs); (2) a four-factor model of strong and weak right- and left-handers (SRHs, WRHs, SLHs, WLHs); (3) strong- vs mixed-handed (SHs vs MHs); and (4) a three-factor model of consistent left- (CLHs), inconsistent left- (ILHs), and consistent right-handers (CRHs). Mixed-factorial ANOVAs demonstrated significant visual field (VF) by handedness interactions for all but the third model. Results show that LHs, SLHs, CLHs, and ILHs responded faster to LVF targets, whereas RHs, SRHs, and CRHs responded faster to RVF targets; no significant VF by handedness interaction was found between SHs and MHs. The three-factor model better captures handedness group divergence on lateralised semantic priming by incorporating the direction of handedness as well as the degree. These findings help explain some of the variance in language lateralisation, demonstrating that direction of handedness is as important as degree. The need for greater consideration of handedness subgroups in laterality research is highlighted.

Targeting adolescent risk-taking behaviors: the contributions of egocentrism and sensation-seeking.

PubMed

Greene, K; Krcmar, M; Walters, L H; Rubin, D L; Jerold; Hale, L

2000-08-01

Tremendous resources are spent each year developing programs and messages targeting adolescent risk behavior. Adolescents are often reasonably well educated about methods for health promotion such as preventing HIV infection, yet they fail to act accordingly. One widely used individual difference variable, sensation-seeking, has been incorporated in health message design to some extent, but it fails to take development into account. Research on adolescent egocentrism suggests adolescents experience personal fable which can lead to an exaggerated sense of invulnerability. The present study sampled adolescents and college students to examine relative contributions of egocentrism and sensation-seeking to risk-taking behavior. Results indicate a latent factor labeled risk-seeking (primarily indicated by disinhibition and risk-taking personality, and to a lesser degree by invulnerability, experience-seeking, boredom susceptibility, and thrill and adventure-seeking) indeed predicted a latent factor labeled delinquent behavior (primarily indicated by alcohol consumption and delinquency, and to a lesser degree by drug use, drinking and driving, and risky driving). Other results indicate consistently high personal fable combined with high sensation-seeking explained most risk-taking behavior. Implications and directions for future research are discussed. Copyright 2000 The Association for Professionals in Services for Adolescents.

Characterization of aldehyde dehydrogenase 1 high ovarian cancer cells: Towards targeted stem cell therapy.

PubMed

Sharrow, Allison C; Perkins, Brandy; Collector, Michael I; Yu, Wayne; Simons, Brian W; Jones, Richard J

2016-08-01

The cancer stem cell (CSC) paradigm hypothesizes that successful clinical eradication of CSCs may lead to durable remission for patients with ovarian cancer. Despite mounting evidence in support of ovarian CSCs, their phenotype and clinical relevance remain unclear. We and others have found high aldehyde dehydrogenase 1 (ALDH(high)) expression in a variety of normal and malignant stem cells, and sought to better characterize ALDH(high) cells in ovarian cancer. We compared ALDH(high) to ALDH(low) cells in two ovarian cancer models representing distinct subtypes: FNAR-C1 cells, derived from a spontaneous rat endometrioid carcinoma, and the human SKOV3 cell line (described as both serous and clear cell subtypes). We assessed these populations for stem cell features then analyzed expression by microarray and qPCR. ALDH(high) cells displayed CSC properties, including: smaller size, quiescence, regenerating the phenotypic diversity of the cell lines in vitro, lack of contact inhibition, nonadherent growth, multi-drug resistance, and in vivo tumorigenicity. Microarray and qPCR analysis of the expression of markers reported by others to enrich for ovarian CSCs revealed that ALDH(high) cells of both models showed downregulation of CD24, but inconsistent expression of CD44, KIT and CD133. However, the following druggable targets were consistently expressed in the ALDH(high) cells from both models: mTOR signaling, her-2/neu, CD47 and FGF18/FGFR3. Based on functional characterization, ALDH(high) ovarian cancer cells represent an ovarian CSC population. Differential gene expression identified druggable targets that have the potential for therapeutic efficacy against ovarian CSCs from multiple subtypes. Copyright © 2016 Elsevier Inc. All rights reserved.

HGG-22. TARGETING NEURONAL ACTIVITY-REGULATED NEUROLIGIN-3 DEPENDENCY FOR HIGH-GRADE GLIOMA THERAPY

PubMed Central

Venkatesh, Humsa S; Tam, Lydia T; Woo, Pamelyn J; Monje, Michelle

2017-01-01

Abstract Neuronal activity promotes high-grade glioma (HGG) growth. An important mechanism mediating this neural regulation of brain cancer is activity-dependent cleavage and secretion of the synaptic molecule and glioma mitogen neuroligin-3 (Nlgn3), but the therapeutic potential of targeting Nlgn3 in glioma remains to be defined. Here, we demonstrate a striking dependence of HGG growth on microenvironmental Nlgn3 and determine a targetable mechanism of secretion. Patient-derived orthotopic xenografts of pediatric glioblastoma (pGBM) and diffuse intrinsic pontine glioma (DIPG) fail to grow in Nlgn3 knockout mice. Using genetic mouse models, we illustrate that Nlgn3 is cleaved from both neurons and oligodendrocyte precursor cells via the ADAM10 sheddase. Administration of an ADAM10 inhibitor robustly blocks pGBM and DIPG xenograft growth via modulation of the tumor microenvironment. This work defines the therapeutic potential of and a promising strategy for targeting Nlgn3 secretion in the glioma microenvironment, which could prove transformative for treatment of HGG.

Addressing an Overlooked Science Outreach Audience: Development of a Science Mentorship Program Focusing on Critical Thinking Skills for Adults Working toward a High School Equivalency Degree

ERIC Educational Resources Information Center

Gagnon, Nicole L.; Komor, Anna J.

2017-01-01

Adult learners seeking a high school equivalency degree are a highly motivated group of students that almost universally meet outreach audience goals of serving minority, low-income, and other disadvantaged populations. Despite the demonstrated need of this population, these students are not commonly served by university-sponsored science outreach…

360-degree 3D transvaginal ultrasound system for high-dose-rate interstitial gynaecological brachytherapy needle guidance

NASA Astrophysics Data System (ADS)

Rodgers, Jessica R.; Surry, Kathleen; D'Souza, David; Leung, Eric; Fenster, Aaron

2017-03-01

Treatment for gynaecological cancers often includes brachytherapy; in particular, in high-dose-rate (HDR) interstitial brachytherapy, hollow needles are inserted into the tumour and surrounding area through a template in order to deliver the radiation dose. Currently, there is no standard modality for visualizing needles intra-operatively, despite the need for precise needle placement in order to deliver the optimal dose and avoid nearby organs, including the bladder and rectum. While three-dimensional (3D) transrectal ultrasound (TRUS) imaging has been proposed for 3D intra-operative needle guidance, anterior needles tend to be obscured by shadowing created by the template's vaginal cylinder. We have developed a 360-degree 3D transvaginal ultrasound (TVUS) system that uses a conventional two-dimensional side-fire TRUS probe rotated inside a hollow vaginal cylinder made from a sonolucent plastic (TPX). The system was validated using grid and sphere phantoms in order to test the geometric accuracy of the distance and volumetric measurements in the reconstructed image. To test the potential for visualizing needles, an agar phantom mimicking the geometry of the female pelvis was used. Needles were inserted into the phantom and then imaged using the 3D TVUS system. The needle trajectories and tip positions in the 3D TVUS scan were compared to their expected values and the needle tracks visualized in magnetic resonance images. Based on this initial study, 360-degree 3D TVUS imaging through a sonolucent vaginal cylinder is a feasible technique for intra-operatively visualizing needles during HDR interstitial gynaecological brachytherapy.

High affinity γPNA sandwich hybridization assay for rapid detection of short nucleic acid targets with single mismatch discrimination.

PubMed

Goldman, Johnathan M; Zhang, Li Ang; Manna, Arunava; Armitage, Bruce A; Ly, Danith H; Schneider, James W

2013-07-08

Hybridization analysis of short DNA and RNA targets presents many challenges for detection. The commonly employed sandwich hybridization approach cannot be implemented for these short targets due to insufficient probe-target binding strengths for unmodified DNA probes. Here, we present a method capable of rapid and stable sandwich hybridization detection for 22 nucleotide DNA and RNA targets. Stable hybridization is achieved using an n-alkylated, polyethylene glycol γ-carbon modified peptide nucleic acid (γPNA) amphiphile. The γPNA's exceptionally high affinity enables stable hybridization of a second DNA-based probe to the remaining bases of the short target. Upon hybridization of both probes, an electrophoretic mobility shift is measured via interaction of the n-alkane modification on the γPNA with capillary electrophoresis running buffer containing nonionic surfactant micelles. We find that sandwich hybridization of both probes is stable under multiple binding configurations and demonstrate single base mismatch discrimination. The binding strength of both probes is also stabilized via coaxial stacking on adjacent hybridization to targets. We conclude with a discussion on the implementation of the proposed sandwich hybridization assay as a high-throughput microRNA detection method.

Currently available medical engineering degrees in the UK. Part 2: Postgraduate degrees.

PubMed

Joyce, T

2009-05-01

This paper considers taught medical engineering MSc degrees, based on mechanical engineering, which are provided in the UK. Currently there are 19 institutions which provide such postgraduate degree programmes. These are the University of Aberdeen, University of Bath, University of Bradford, Brunel University, University of Dundee, University of Hull, Imperial College London, Keele University, King's College London, University of Leeds, University of Liverpool, University of Nottingham, University of Oxford, Queen Mary University of London, University of Southampton, University of Strathclyde, University of Surrey, University of Ulster, and University of Warwick. While most courses are delivered on a 1 year full-time basis, other delivery modes are also available. Relatively few modules are offered as distance learning or short courses. A wide range of modules are offered by the various universities for the different taught MSc degrees. Common modules include biomaterials and biomechanics. The medical-engineering-related modules offered by a number of universities are also made available to students on allied MSc programmes and undergraduate degrees in medical engineering.

Pathways to Science and Engineering Bachelor's Degrees for Men and Women.

PubMed