Modes of elastic plates and shells in water driven by modulated radiation pressure of focused ultrasound

NASA Astrophysics Data System (ADS)

Marston, Philip L.; Daniel, Timothy D.; Abawi, Ahmad T.; Kirsteins, Ivars

2015-11-01

The modulated radiation pressure (MRP) of ultrasound has been used for decades to selectively excite low frequency modes associated with surface tension of fluid objects in water. Much less is known about the excitation of low frequency modes of less compliant metallic objects. Here we use MRP of focused ultrasound to excite resonant flexural vibrations of a circular metal plate in water. The source transducer was driven with a double-sideband suppressed carrier voltage as in. The response of the target (detected with a hydrophone) was at twice the modulation frequency and proportional to the square of the drive voltage. Since the radiation pressure of focused beams is spatially localized, mode shapes could be identified by scanning the source along the target while measuring the target's response. Additional measurements were done with an open-ended water-filled copper circular cylindrical shell in which resonant frequencies and mode shapes were also identified. These experiments show how focused ultrasound can be used to identify low-frequency modes of elastic objects without direct contact. Supported by ONR.

Optical stereo video signal processor

NASA Technical Reports Server (NTRS)

Craig, G. D. (Inventor)

1985-01-01

An otpical video signal processor is described which produces a two-dimensional cross-correlation in real time of images received by a stereo camera system. The optical image of each camera is projected on respective liquid crystal light valves. The images on the liquid crystal valves modulate light produced by an extended light source. This modulated light output becomes the two-dimensional cross-correlation when focused onto a video detector and is a function of the range of a target with respect to the stereo camera. Alternate embodiments utilize the two-dimensional cross-correlation to determine target movement and target identification.

Angular dependence of source-target-detector in active mode standoff infrared detection

NASA Astrophysics Data System (ADS)

Pacheco-Londoño, Leonardo C.; Castro-Suarez, John R.; Aparicio-Bolaños, Joaquín. A.; Hernández-Rivera, Samuel P.

2013-06-01

Active mode standoff measurement using infrared spectroscopy were carried out in which the angle between target and the source was varied from 0-70° with respect to the surface normal of substrates containing traces of highly energetic materials (explosives). The experiments were made using three infrared sources: a modulated source (Mod-FTIR), an unmodulated source (UnMod-FTIR) and a scanning quantum cascade laser (QCL), part of a dispersive mid infrared (MIR) spectrometer. The targets consisted of PENT 200 μg/cm2 deposited on aluminum plates placed at 1 m from the sources. The evaluation of the three modalities was aimed at verifying the influence of the highly collimated laser beam in the detection in comparison with the other sources. The Mod-FTIR performed better than QCL source in terms of the MIR signal intensity decrease with increasing angle.

Behold the voice of wrath: cross-modal modulation of visual attention by anger prosody.

PubMed

Brosch, Tobias; Grandjean, Didier; Sander, David; Scherer, Klaus R

2008-03-01

Emotionally relevant stimuli are prioritized in human information processing. It has repeatedly been shown that selective spatial attention is modulated by the emotional content of a stimulus. Until now, studies investigating this phenomenon have only examined within-modality effects, most frequently using pictures of emotional stimuli to modulate visual attention. In this study, we used simultaneously presented utterances with emotional and neutral prosody as cues for a visually presented target in a cross-modal dot probe task. Response times towards targets were faster when they appeared at the location of the source of the emotional prosody. Our results show for the first time a cross-modal attentional modulation of visual attention by auditory affective prosody.

Programmable phase plate for tool modification in laser machining applications

DOEpatents

Thompson Jr., Charles A.; Kartz, Michael W.; Brase, James M.; Pennington, Deanna; Perry, Michael D.

2004-04-06

A system for laser machining includes a laser source for propagating a laser beam toward a target location, and a spatial light modulator having individual controllable elements capable of modifying a phase profile of the laser beam to produce a corresponding irradiance pattern on the target location. The system also includes a controller operably connected to the spatial light modulator for controlling the individual controllable elements. By controlling the individual controllable elements, the phase profile of the laser beam may be modified into a desired phase profile so as to produce a corresponding desired irradiance pattern on the target location capable of performing a machining operation on the target location.

Investigating effects of communications modulation technique on targeting performance

NASA Astrophysics Data System (ADS)

Blasch, Erik; Eusebio, Gerald; Huling, Edward

2006-05-01

One of the key challenges facing the global war on terrorism (GWOT) and urban operations is the increased need for rapid and diverse information from distributed sources. For users to get adequate information on target types and movements, they would need reliable data. In order to facilitate reliable computational intelligence, we seek to explore the communication modulation tradeoffs affecting information distribution and accumulation. In this analysis, we explore the modulation techniques of Orthogonal Frequency Division Multiplexing (OFDM), Direct Sequence Spread Spectrum (DSSS), and statistical time-division multiple access (TDMA) as a function of the bit error rate and jitter that affect targeting performance. In the analysis, we simulate a Link 16 with a simple bandpass frequency shift keying (PSK) technique using different Signal-to-Noise ratios. The communications transfer delay and accuracy tradeoffs are assessed as to the effects incurred in targeting performance.

Radiation source

DOEpatents

Thode, Lester E.

1981-01-01

A device and method for relativistic electron beam heating of a high-density plasma in a small localized region. A relativistic electron beam generator or accelerator produces a high-voltage electron beam which propagates along a vacuum drift tube and is modulated to initiate electron bunching within the beam. The beam is then directed through a low-density gas chamber which provides isolation between the vacuum modulator and the relativistic electron beam target. The relativistic beam is then applied to a high-density target plasma which typically comprises DT, DD, or similar thermonuclear gas at a density of 10.sup.17 to 10.sup.20 electrons per cubic centimeter. The target gas is ionized prior to application of the relativistic electron beam by means of a laser or other preionization source to form a plasma. Utilizing a relativistic electron beam with an individual particle energy exceeding 3 MeV, classical scattering by relativistic electrons passing through isolation foils is negligible. As a result, relativistic streaming instabilities are initiated within the high-density target plasma causing the relativistic electron beam to efficiently deposit its energy into a small localized region of the high-density plasma target.

FPGA Techniques Based New Hybrid Modulation Strategies for Voltage Source Inverters

PubMed Central

Sudha, L. U.; Baskaran, J.; Elankurisil, S. A.

2015-01-01

This paper corroborates three different hybrid modulation strategies suitable for single-phase voltage source inverter. The proposed method is formulated using fundamental switching and carrier based pulse width modulation methods. The main tale of this proposed method is to optimize a specific performance criterion, such as minimization of the total harmonic distortion (THD), lower order harmonics, switching losses, and heat losses. The proposed method is articulated using fundamental switching and carrier based pulse width modulation methods. Thus, the harmonic pollution in the power system will be reduced and the power quality will be augmented with better harmonic profile for a target fundamental output voltage. The proposed modulation strategies are simulated in MATLAB r2010a and implemented in a Xilinx spartan 3E-500 FG 320 FPGA processor. The feasibility of these modulation strategies is authenticated through simulation and experimental results. PMID:25821852

Multisource inverse-geometry CT. Part II. X-ray source design and prototype

PubMed Central

Neculaes, V. Bogdan; Caiafa, Antonio; Cao, Yang; De Man, Bruno; Edic, Peter M.; Frutschy, Kristopher; Gunturi, Satish; Inzinna, Lou; Reynolds, Joseph; Vermilyea, Mark; Wagner, David; Zhang, Xi; Zou, Yun; Pelc, Norbert J.; Lounsberry, Brian

2016-01-01

Purpose: This paper summarizes the development of a high-power distributed x-ray source, or “multisource,” designed for inverse-geometry computed tomography (CT) applications [see B. De Man et al., “Multisource inverse-geometry CT. Part I. System concept and development,” Med. Phys. 43, 4607–4616 (2016)]. The paper presents the evolution of the source architecture, component design (anode, emitter, beam optics, control electronics, high voltage insulator), and experimental validation. Methods: Dispenser cathode emitters were chosen as electron sources. A modular design was adopted, with eight electron emitters (two rows of four emitters) per module, wherein tungsten targets were brazed onto copper anode blocks—one anode block per module. A specialized ceramic connector provided high voltage standoff capability and cooling oil flow to the anode. A matrix topology and low-noise electronic controls provided switching of the emitters. Results: Four modules (32 x-ray sources in two rows of 16) have been successfully integrated into a single vacuum vessel and operated on an inverse-geometry computed tomography system. Dispenser cathodes provided high beam current (>1000 mA) in pulse mode, and the electrostatic lenses focused the current beam to a small optical focal spot size (0.5 × 1.4 mm). Controlled emitter grid voltage allowed the beam current to be varied for each source, providing the ability to modulate beam current across the fan of the x-ray beam, denoted as a virtual bowtie filter. The custom designed controls achieved x-ray source switching in <1 μs. The cathode-grounded source was operated successfully up to 120 kV. Conclusions: A high-power, distributed x-ray source for inverse-geometry CT applications was successfully designed, fabricated, and operated. Future embodiments may increase the number of spots and utilize fast read out detectors to increase the x-ray flux magnitude further, while still staying within the stationary target inherent thermal limitations. PMID:27487878

Multisource inverse-geometry CT. Part II. X-ray source design and prototype

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

Neculaes, V. Bogdan, E-mail: neculaes@ge.com; Caia

2016-08-15

Purpose: This paper summarizes the development of a high-power distributed x-ray source, or “multisource,” designed for inverse-geometry computed tomography (CT) applications [see B. De Man et al., “Multisource inverse-geometry CT. Part I. System concept and development,” Med. Phys. 43, 4607–4616 (2016)]. The paper presents the evolution of the source architecture, component design (anode, emitter, beam optics, control electronics, high voltage insulator), and experimental validation. Methods: Dispenser cathode emitters were chosen as electron sources. A modular design was adopted, with eight electron emitters (two rows of four emitters) per module, wherein tungsten targets were brazed onto copper anode blocks—one anode blockmore » per module. A specialized ceramic connector provided high voltage standoff capability and cooling oil flow to the anode. A matrix topology and low-noise electronic controls provided switching of the emitters. Results: Four modules (32 x-ray sources in two rows of 16) have been successfully integrated into a single vacuum vessel and operated on an inverse-geometry computed tomography system. Dispenser cathodes provided high beam current (>1000 mA) in pulse mode, and the electrostatic lenses focused the current beam to a small optical focal spot size (0.5 × 1.4 mm). Controlled emitter grid voltage allowed the beam current to be varied for each source, providing the ability to modulate beam current across the fan of the x-ray beam, denoted as a virtual bowtie filter. The custom designed controls achieved x-ray source switching in <1 μs. The cathode-grounded source was operated successfully up to 120 kV. Conclusions: A high-power, distributed x-ray source for inverse-geometry CT applications was successfully designed, fabricated, and operated. Future embodiments may increase the number of spots and utilize fast read out detectors to increase the x-ray flux magnitude further, while still staying within the stationary target inherent thermal limitations.« less

SU-F-T-336: A Quick Auto-Planning (QAP) Method for Patient Intensity Modulated Radiotherapy (IMRT)

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

Peng, J; Zhang, Z; Wang, J

2016-06-15

Purpose: The aim of this study is to develop a quick auto-planning system that permits fast patient IMRT planning with conformal dose to the target without manual field alignment and time-consuming dose distribution optimization. Methods: The planning target volume (PTV) of the source and the target patient were projected to the iso-center plane in certain beameye- view directions to derive the 2D projected shapes. Assuming the target interior was isotropic for each beam direction boundary analysis under polar coordinate was performed to map the source shape boundary to the target shape boundary to derive the source-to-target shape mapping function. Themore » derived shape mapping function was used to morph the source beam aperture to the target beam aperture over all segments in each beam direction. The target beam weights were re-calculated to deliver the same dose to the reference point (iso-center) as the source beam did in the source plan. The approach was tested on two rectum patients (one source patient and one target patient). Results: The IMRT planning time by QAP was 5 seconds on a laptop computer. The dose volume histograms and the dose distribution showed the target patient had the similar PTV dose coverage and OAR dose sparing with the source patient. Conclusion: The QAP system can instantly and automatically finish the IMRT planning without dose optimization.« less

Wide band stepped frequency ground penetrating radar

DOEpatents

Bashforth, M.B.; Gardner, D.; Patrick, D.; Lewallen, T.A.; Nammath, S.R.; Painter, K.D.; Vadnais, K.G.

1996-03-12

A wide band ground penetrating radar system is described embodying a method wherein a series of radio frequency signals is produced by a single radio frequency source and provided to a transmit antenna for transmission to a target and reflection therefrom to a receive antenna. A phase modulator modulates those portions of the radio frequency signals to be transmitted and the reflected modulated signal is combined in a mixer with the original radio frequency signal to produce a resultant signal which is demodulated to produce a series of direct current voltage signals, the envelope of which forms a cosine wave shaped plot which is processed by a Fast Fourier Transform Unit 44 into frequency domain data wherein the position of a preponderant frequency is indicative of distance to the target and magnitude is indicative of the signature of the target. 6 figs.

Nonsteroidal anti-inflammatory drug activated gene-1 (NAG-1) modulators from natural products as anti-cancer agents

USDA-ARS?s Scientific Manuscript database

Natural products are rich source of gene modulators for prevention and treatment of cancer. In recent days, nonsteroidal anti-inflammatory drug (NSAID) activated gene-1 (NAG-1) has been focused as a new target of diverse cancers like colorectal, pancreatic, prostate, and breast. A variety of natural...

The light ion pulsed power induction accelerator for ETF

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

Mazarakis, M.G.; Olson, R.E.; Olson, C.L.

1994-12-31

Our Engineering Test Facility (ETF) driver concept is based on HERMES III and RHEPP technologies. Actually, it is a scaled-down version of the LMF design incorporating repetition rate capabilities of up to 10 Hz CW. The preconceptual design presented here provides 200-TW peak power to the ETF target during 10 ns, equal to 2-MJ total ion beam energy. Linear inductive voltage addition driving a self-magnetically insulated transmission line (MITL) is utilized to generate the 36-MV peak voltage needed for lithium ion beams. The {approximately} 3-MA ion current is achieved by utilizing many accelerating modules in parallel. Since the current permore » module is relatively modest ({approximately}300 kA), two-stage or one-stage extraction diodes can be utilized for the generation of singly charged lithium ions. The accelerating modules are arranged symmetrically around the fusion chamber in order to provide uniform irradiation onto the ETF target. In addition, the modules are fired in a programmed sequence in order to generate the optimum power pulse shape onto the target. This design utilizes RHEPP accelerator modules as the principal power source.« less

Wide band stepped frequency ground penetrating radar

DOEpatents

Bashforth, Michael B.; Gardner, Duane; Patrick, Douglas; Lewallen, Tricia A.; Nammath, Sharyn R.; Painter, Kelly D.; Vadnais, Kenneth G.

1996-01-01

A wide band ground penetrating radar system (10) embodying a method wherein a series of radio frequency signals (60) is produced by a single radio frequency source (16) and provided to a transmit antenna (26) for transmission to a target (54) and reflection therefrom to a receive antenna (28). A phase modulator (18) modulates those portion of the radio frequency signals (62) to be transmitted and the reflected modulated signal (62) is combined in a mixer (34) with the original radio frequency signal (60) to produce a resultant signal (53) which is demodulated to produce a series of direct current voltage signals (66) the envelope of which forms a cosine wave shaped plot (68) which is processed by a Fast Fourier Transform unit 44 into frequency domain data (70) wherein the position of a preponderant frequency is indicative of distance to the target (54) and magnitude is indicative of the signature of the target (54).

Targeting Stable Rotors to Treat Atrial Fibrillation.

PubMed

Narayan, Sanjiv M; Krummen, David E

2012-09-01

Therapy for atrial fibrillation (AF) remains suboptimal, in large part because its mechanisms are unclear. While pulmonary vein ectopy may trigger AF, it remains uncertain how AF, once triggered, is actually sustained. Recent discoveries show that human AF is maintained by a small number of rotors or focal sources. AF sources are widely distributed in patient-specific locations, often remote from pulmonary veins and in the right atrium and stable for prolonged periods of time. In a multicentre experience, brief targeted ablation at sources (focal impulse and rotor modulation [FIRM]) terminated AF predominantly to sinus rhythm prior to pulmonary vein isolation and eliminated AF on rigorous followup. This review summarises the evidence for stable rotors and focal sources of human AF and their clinical role as ablation targets to eliminate paroxysmal, persistent and long-standing persistent AF.

Miniaturized High-Speed Modulated X-Ray Source

NASA Technical Reports Server (NTRS)

Gendreau, Keith C. (Inventor); Arzoumanian, Zaven (Inventor); Kenyon, Steven J. (Inventor); Spartana, Nick Salvatore (Inventor)

2015-01-01

A miniaturized high-speed modulated X-ray source (MXS) device and a method for rapidly and arbitrarily varying with time the output X-ray photon intensities and energies. The MXS device includes an ultraviolet emitter that emits ultraviolet light, a photocathode operably coupled to the ultraviolet light-emitting diode that emits electrons, an electron multiplier operably coupled to the photocathode that multiplies incident electrons, and an anode operably coupled to the electron multiplier that is configured to produce X-rays. The method for modulating MXS includes modulating an intensity of an ultraviolet emitter to emit ultraviolet light, generating electrons in response to the ultraviolet light, multiplying the electrons to become more electrons, and producing X-rays by an anode that includes a target material configured to produce X-rays in response to impact of the more electrons.

Scanning computed confocal imager

DOEpatents

George, John S.

2000-03-14

There is provided a confocal imager comprising a light source emitting a light, with a light modulator in optical communication with the light source for varying the spatial and temporal pattern of the light. A beam splitter receives the scanned light and direct the scanned light onto a target and pass light reflected from the target to a video capturing device for receiving the reflected light and transferring a digital image of the reflected light to a computer for creating a virtual aperture and outputting the digital image. In a transmissive mode of operation the invention omits the beam splitter means and captures light passed through the target.

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

Bieniosek, F.M.; Anders, A.; Barnard, J.J.

This effort contains two main components: The new induction-bunching module is expected to deliver higher fluence in the bunched beam, and the new target positioner will enable a significantly enhanced target physics repetition rate. The velocity ramp that bunches the K{sup +} beam in the neutralized drift compression section is established with a bipolar voltage ramp applied to an acceleration gap. An induction acceleration module creates this voltage waveform. The new bunching module (IBM) specially built for NDCX has approximately twice the capability (volt-seconds) as our original IBM. We reported on the beam line design for the best use ofmore » the bunching module in our FY08 Q2 report. Based on simulations and theoretical work, we chose to extend the drift compression section and use the additional volt-seconds to extend the pulse duration and keep the peak voltage swing (and velocity excursions) similar to the present module. Simulations showed that this approach, which extends the drift section, to be advantageous because it limits the chromatic aberrations in the beam spot on target. To this end, colleagues at PPPL have fabricated the meter-long extension to the ferroelectric plasma source and it was installed on the beam line with the new IBM in January 2009. Simulation results suggest a factor of two increase in energy deposition from the bunched beam. In the first WDM target run (August-November 2008) the target handling setup required opening the vacuum system to manually replace the target after each shot (which destroys the target). Because of the requirement for careful alignment of each individual target, the target shot repetition rate was no greater than 1 shot per day. Initial results of this run are reported in our FY08 4th Quarter Milestone Report. Based on the valuable experience gained in the initial run, we have designed and installed an improved target alignment and positioning system with the capability to reposition targets remotely. This capability allows us to significantly increase our shot repetition rate, and to take greater advantage of the pinhole/cone arrangement we have developed to localize the beam at final focus. In addition we have improved the capability of the optical diagnostic systems, and we have installed a new beam current transformer downstream of the target to monitor beam current transmitted through the target during an experiment. These improvements will allow us to better exploit the inherent capability of the NDCX facility for high repetition rate and thus to provide more detailed experimental data to assess WDM physics models of target behavior. This milestone has been met by demonstrating highly compressed beams with the new bunching module, which are neutralized in the longer drift compression section by the new ferro-electric plasma sources. The peak uncompressed beam intensity ({approx}600 kW/cm{sup 2}) is higher than in previous measurements, and the bunched beam current profiles are {approx}2ns. We have also demonstrated a large increase in the experimental data acquisition rate for target heating experiments. In the first test of the new remote-controlled target positioning system, we completed three successful target physics shots in less than two hours. Further improvements are expected.« less

Coherent hybrid electromagnetic field imaging

DOEpatents

Cooke, Bradly J [Jemez Springs, NM; Guenther, David C [Los Alamos, NM

2008-08-26

An apparatus and corresponding method for coherent hybrid electromagnetic field imaging of a target, where an energy source is used to generate a propagating electromagnetic beam, an electromagnetic beam splitting means to split the beam into two or more coherently matched beams of about equal amplitude, and where the spatial and temporal self-coherence between each two or more coherently matched beams is preserved. Two or more differential modulation means are employed to modulate each two or more coherently matched beams with a time-varying polarization, frequency, phase, and amplitude signal. An electromagnetic beam combining means is used to coherently combine said two or more coherently matched beams into a coherent electromagnetic beam. One or more electromagnetic beam controlling means are used for collimating, guiding, or focusing the coherent electromagnetic beam. One or more apertures are used for transmitting and receiving the coherent electromagnetic beam to and from the target. A receiver is used that is capable of square-law detection of the coherent electromagnetic beam. A waveform generator is used that is capable of generation and control of time-varying polarization, frequency, phase, or amplitude modulation waveforms and sequences. A means of synchronizing time varying waveform is used between the energy source and the receiver. Finally, a means of displaying the images created by the interaction of the coherent electromagnetic beam with target is employed.

Interaction of Object Binding Cues in Binaural Masking Pattern Experiments.

PubMed

Verhey, Jesko L; Lübken, Björn; van de Par, Steven

2016-01-01

Object binding cues such as binaural and across-frequency modulation cues are likely to be used by the auditory system to separate sounds from different sources in complex auditory scenes. The present study investigates the interaction of these cues in a binaural masking pattern paradigm where a sinusoidal target is masked by a narrowband noise. It was hypothesised that beating between signal and masker may contribute to signal detection when signal and masker do not spectrally overlap but that this cue could not be used in combination with interaural cues. To test this hypothesis an additional sinusoidal interferer was added to the noise masker with a lower frequency than the noise whereas the target had a higher frequency than the noise. Thresholds increase when the interferer is added. This effect is largest when the spectral interferer-masker and masker-target distances are equal. The result supports the hypothesis that modulation cues contribute to signal detection in the classical masking paradigm and that these are analysed with modulation bandpass filters. A monaural model including an across-frequency modulation process is presented that account for this effect. Interestingly, the interferer also affects dichotic thresholds indicating that modulation cues also play a role in binaural processing.

KIRMES: kernel-based identification of regulatory modules in euchromatic sequences.

PubMed

Schultheiss, Sebastian J; Busch, Wolfgang; Lohmann, Jan U; Kohlbacher, Oliver; Rätsch, Gunnar

2009-08-15

Understanding transcriptional regulation is one of the main challenges in computational biology. An important problem is the identification of transcription factor (TF) binding sites in promoter regions of potential TF target genes. It is typically approached by position weight matrix-based motif identification algorithms using Gibbs sampling, or heuristics to extend seed oligos. Such algorithms succeed in identifying single, relatively well-conserved binding sites, but tend to fail when it comes to the identification of combinations of several degenerate binding sites, as those often found in cis-regulatory modules. We propose a new algorithm that combines the benefits of existing motif finding with the ones of support vector machines (SVMs) to find degenerate motifs in order to improve the modeling of regulatory modules. In experiments on microarray data from Arabidopsis thaliana, we were able to show that the newly developed strategy significantly improves the recognition of TF targets. The python source code (open source-licensed under GPL), the data for the experiments and a Galaxy-based web service are available at http://www.fml.mpg.de/raetsch/suppl/kirmes/.

Anatomical Parameters of tDCS to Modulate the Motor System after Stroke: A Review

PubMed Central

Lefebvre, Stephanie; Liew, Sook-Lei

2017-01-01

Transcranial direct current stimulation (tDCS) is a non-invasive brain stimulation method to modulate the local field potential in neural tissue and consequently, cortical excitability. As tDCS is relatively portable, affordable, and accessible, the applications of tDCS to probe brain–behavior connections have rapidly increased in the last 10 years. One of the most promising applications is the use of tDCS to modulate excitability in the motor cortex after stroke and promote motor recovery. However, the results of clinical studies implementing tDCS to modulate motor excitability have been highly variable, with some studies demonstrating that as many as 50% or more of patients fail to show a response to stimulation. Much effort has therefore been dedicated to understand the sources of variability affecting tDCS efficacy. Possible suspects include the placement of the electrodes, task parameters during stimulation, dosing (current amplitude, duration of stimulation, frequency of stimulation), individual states (e.g., anxiety, motivation, attention), and more. In this review, we first briefly review potential sources of variability specific to stroke motor recovery following tDCS. We then examine how the anatomical variability in tDCS placement [e.g., neural target(s) and montages employed] may alter the neuromodulatory effects that tDCS exerts on the post-stroke motor system. PMID:28232816

Open innovation for phenotypic drug discovery: The PD2 assay panel.

PubMed

Lee, Jonathan A; Chu, Shaoyou; Willard, Francis S; Cox, Karen L; Sells Galvin, Rachelle J; Peery, Robert B; Oliver, Sarah E; Oler, Jennifer; Meredith, Tamika D; Heidler, Steven A; Gough, Wendy H; Husain, Saba; Palkowitz, Alan D; Moxham, Christopher M

2011-07-01

Phenotypic lead generation strategies seek to identify compounds that modulate complex, physiologically relevant systems, an approach that is complementary to traditional, target-directed strategies. Unlike gene-specific assays, phenotypic assays interrogate multiple molecular targets and signaling pathways in a target "agnostic" fashion, which may reveal novel functions for well-studied proteins and discover new pathways of therapeutic value. Significantly, existing compound libraries may not have sufficient chemical diversity to fully leverage a phenotypic strategy. To address this issue, Eli Lilly and Company launched the Phenotypic Drug Discovery Initiative (PD(2)), a model of open innovation whereby external research groups can submit compounds for testing in a panel of Lilly phenotypic assays. This communication describes the statistical validation, operations, and initial screening results from the first PD(2) assay panel. Analysis of PD(2) submissions indicates that chemical diversity from open source collaborations complements internal sources. Screening results for the first 4691 compounds submitted to PD(2) have confirmed hit rates from 1.6% to 10%, with the majority of active compounds exhibiting acceptable potency and selectivity. Phenotypic lead generation strategies, in conjunction with novel chemical diversity obtained via open-source initiatives such as PD(2), may provide a means to identify compounds that modulate biology by novel mechanisms and expand the innovation potential of drug discovery.

Are sigma modulators an effective opportunity for cancer treatment? A patent overview (1996-2016).

PubMed

Collina, Simona; Bignardi, Emanuele; Rui, Marta; Rossi, Daniela; Gaggeri, Raffaella; Zamagni, Alice; Cortesi, Michela; Tesei, Anna

2017-05-01

Although several molecular targets against cancer have been identified, there is a continuous need for new therapeutic strategies. Sigma Receptors (SRs) overexpression has been recently associated with different cancer conditions. Therefore, novel anticancer agents targeting SRs may increase the specificity of therapies, overcoming some of the common drawbacks of conventional chemotherapy. Areas covered: The present review focuses on patent documents disclosing SR modulators with possible application in cancer therapy and diagnosis. The analysis reviews patents of the last two decades (1996-2016); patents were grouped according to target subtypes (S1R, S2R, pan-SRs) and relevant Applicants. The literature was searched through Espacenet, ISI Web, PatentScope and PubMed databases. Expert opinion: The number of patents related to SRs and cancer has increased in the last twenty years, confirming the importance of this receptor family as valuable target against neoplasias. Despite their short history in the cancer scenario, many SR modulators are at pre-clinical stage and one is undergoing a phase II clinical trial. SRs ligands may represent a powerful source of innovative antitumor therapeutics. Further investigation is needed for validating SR modulators as anti-cancer drugs. We strongly hope that this review could stimulate the interest of both Academia and pharmaceutical companies.

Space Ultrareliable Modular Computer (SUMC) instruction simulator

NASA Technical Reports Server (NTRS)

Curran, R. T.

1972-01-01

The design principles, description, functional operation, and recommended expansion and enhancements are presented for the Space Ultrareliable Modular Computer interpretive simulator. Included as appendices are the user's manual, program module descriptions, target instruction descriptions, simulator source program listing, and a sample program printout. In discussing the design and operation of the simulator, the key problems involving host computer independence and target computer architectural scope are brought into focus.

High Precision Laser Range Sensor

NASA Technical Reports Server (NTRS)

Dubovitsky, Serge (Inventor); Lay, Oliver P. (Inventor)

2003-01-01

The present invention is an improved distance measuring interferometer that includes high speed phase modulators and additional phase meters to generate and analyze multiple heterodyne signal pairs with distinct frequencies. Modulation sidebands with large frequency separation are generated by the high speed electro-optic phase modulators, requiring only a single frequency stable laser source and eliminating the need for a fist laser to be tuned or stabilized relative to a second laser. The combination of signals produced by the modulated sidebands is separated and processed to give the target distance. The resulting metrology apparatus enables a sensor with submicron accuracy or better over a multi- kilometer ambiguity range.

Ion channel blockers for the treatment of neuropathic pain.

PubMed

Colombo, Elena; Francisconi, Simona; Faravelli, Laura; Izzo, Emanuela; Pevarello, Paolo

2010-05-01

Neuropathic pain, a severe chronic pain condition characterized by a complex pathophysiology, is a largely unmet medical need. Ion channels, which underlie cell excitability, are heavily implicated in the biological mechanisms that generate and sustain neuropathic pain. This review highlights the biological evidence supporting the involvement of voltage-, proton- and ligand-gated ion channels in the neuropathic pain setting. Ion channel modulators at different research or development stages are reviewed and referenced. Ion channel modulation is one of the main avenues to achieve novel, improved neuropathic pain treatments. Voltage-gated sodium and calcium channel and glutamate receptor modulators are likely to produce new, improved agents in the future. Rationally targeting subtypes of known ion channels, tackling recently discovered ion channel targets or combining drugs with different mechanism of action will be primary sources of new drugs in the longer term.

Audio Visual Integration with Competing Sources in the Framework of Audio Visual Speech Scene Analysis.

PubMed

Ganesh, Attigodu Chandrashekara; Berthommier, Frédéric; Schwartz, Jean-Luc

2016-01-01

We introduce "Audio-Visual Speech Scene Analysis" (AVSSA) as an extension of the two-stage Auditory Scene Analysis model towards audiovisual scenes made of mixtures of speakers. AVSSA assumes that a coherence index between the auditory and the visual input is computed prior to audiovisual fusion, enabling to determine whether the sensory inputs should be bound together. Previous experiments on the modulation of the McGurk effect by audiovisual coherent vs. incoherent contexts presented before the McGurk target have provided experimental evidence supporting AVSSA. Indeed, incoherent contexts appear to decrease the McGurk effect, suggesting that they produce lower audiovisual coherence hence less audiovisual fusion. The present experiments extend the AVSSA paradigm by creating contexts made of competing audiovisual sources and measuring their effect on McGurk targets. The competing audiovisual sources have respectively a high and a low audiovisual coherence (that is, large vs. small audiovisual comodulations in time). The first experiment involves contexts made of two auditory sources and one video source associated to either the first or the second audio source. It appears that the McGurk effect is smaller after the context made of the visual source associated to the auditory source with less audiovisual coherence. In the second experiment with the same stimuli, the participants are asked to attend to either one or the other source. The data show that the modulation of fusion depends on the attentional focus. Altogether, these two experiments shed light on audiovisual binding, the AVSSA process and the role of attention.

Intensity correlation imaging with sunlight-like source

NASA Astrophysics Data System (ADS)

Wang, Wentao; Tang, Zhiguo; Zheng, Huaibin; Chen, Hui; Yuan, Yuan; Liu, Jinbin; Liu, Yanyan; Xu, Zhuo

2018-05-01

We show a method of intensity correlation imaging of targets illuminated by a sunlight-like source both theoretically and experimentally. With a Faraday anomalous dispersion optical filter (FADOF), we have modulated the coherence time of a thermal source up to 0.167 ns. And we carried out measurements of temporal and spatial correlations, respectively, with an intensity interferometer setup. By skillfully using the even Fourier fitting on the very sparse sampling data, the images of targets are successfully reconstructed from the low signal-noise-ratio(SNR) interference pattern by applying an iterative phase retrieval algorithm. The resulting imaging quality is as well as the one obtained by the theoretical fitting. The realization of such a case will bring this technique closer to geostationary satellite imaging illuminated by sunlight.

Methods, systems and apparatus for controlling operation of two alternating current (AC) machines

DOEpatents

Gallegos-Lopez, Gabriel [Torrance, CA; Nagashima, James M [Cerritos, CA; Perisic, Milun [Torrance, CA; Hiti, Silva [Redondo Beach, CA

2012-02-14

A system is provided for controlling two AC machines. The system comprises a DC input voltage source that provides a DC input voltage, a voltage boost command control module (VBCCM), a five-phase PWM inverter module coupled to the two AC machines, and a boost converter coupled to the inverter module and the DC input voltage source. The boost converter is designed to supply a new DC input voltage to the inverter module having a value that is greater than or equal to a value of the DC input voltage. The VBCCM generates a boost command signal (BCS) based on modulation indexes from the two AC machines. The BCS controls the boost converter such that the boost converter generates the new DC input voltage in response to the BCS. When the two AC machines require additional voltage that exceeds the DC input voltage required to meet a combined target mechanical power required by the two AC machines, the BCS controls the boost converter to drive the new DC input voltage generated by the boost converter to a value greater than the DC input voltage.

Expediting analog design retargeting by design knowledge re-use and circuit synthesis: a practical example on a Delta-Sigma modulator

NASA Astrophysics Data System (ADS)

Webb, Matthew; Tang, Hua

2016-08-01

In the past decade or two, due to constant and rapid technology changes, analog design re-use or design retargeting to newer technologies has been brought to the table in order to expedite the design process and improve time-to-market. If properly conducted, analog design retargeting could significantly cut down design cycle compared to designs starting from the scratch. In this article, we present an empirical and general method for efficient analog design retargeting by design knowledge re-use and circuit synthesis (CS). The method first identifies circuit blocks that compose the source system and extracts the performance parameter specifications of each circuit block. Then, for each circuit block, it scales the values of design variables (DV) from the source design to derive an initial design in the target technology. Depending on the performance of this initial target design, a design space is defined for synthesis. Subsequently, each circuit block is automatically synthesised using state-of-art analog synthesis tools based on a combination of global and local optimisation techniques to achieve comparable performance specifications to those extracted from the source system. Finally, the overall system is composed of those synthesised circuit blocks in the target technology. We illustrate the method using a practical example of a complex Delta-Sigma modulator (DSM) circuit.

Recent advances in radiation cancer therapy

NASA Astrophysics Data System (ADS)

Ma, C.-M. Charlie

2007-03-01

This paper presents the recent advances in radiation therapy techniques for the treatment of cancer. Significant improvement has been made in imaging techniques such as CT, MRI, MRS, PET, ultrasound, etc. that have brought marked advances in tumor target and critical structure delineation for treatment planning and patient setup and target localization for accurate dose delivery in radiation therapy of cancer. Recent developments of novel treatment modalities including intensity-modulated x-ray therapy (IMXT), energy- and intensity modulated electron therapy (MERT) and intensity modulated proton therapy (IMPT) together with the use of advanced image guidance have enabled precise dose delivery for dose escalation and hypofractionation studies that may result in better local control and quality of life. Particle acceleration using laser-induced plasmas has great potential for new cost-effective radiation sources that may have a great impact on the management of cancer using radiation therapy.

The spatio-temporal dynamics of deviance and target detection in the passive and active auditory oddball paradigm: a sLORETA study.

PubMed

Justen, Christoph; Herbert, Cornelia

2018-04-19

Numerous studies have investigated the neural underpinnings of passive and active deviance and target detection in the well-known auditory oddball paradigm by means of event-related potentials (ERPs) or functional magnetic resonance imaging (fMRI). The present auditory oddball study investigates the spatio-temporal dynamics of passive versus active deviance and target detection by analyzing amplitude modulations of early and late ERPs while at the same time exploring the neural sources underling this modulation with standardized low-resolution brain electromagnetic tomography (sLORETA) . A 64-channel EEG was recorded from twelve healthy right-handed participants while listening to 'standards' and 'deviants' (500 vs. 1000 Hz pure tones) during a passive (block 1) and an active (block 2) listening condition. During passive listening, participants had to simply listen to the tones. During active listening they had to attend and press a key in response to the deviant tones. Passive and active listening elicited an N1 component, a mismatch negativity (MMN) as difference potential (whose amplitudes were temporally overlapping with the N1) and a P3 component. N1/MMN and P3 amplitudes were significantly more pronounced for deviants as compared to standards during both listening conditions. Active listening augmented P3 modulation to deviants significantly compared to passive listening, whereas deviance detection as indexed by N1/MMN modulation was unaffected by the task. During passive listening, sLORETA contrasts (deviants > standards) revealed significant activations in the right superior temporal gyrus (STG) and the lingual gyri bilaterally (N1/MMN) as well as in the left and right insulae (P3). During active listening, significant activations were found for the N1/MMN in the right inferior parietal lobule (IPL) and for the P3 in multiple cortical regions (e.g., precuneus). The results provide evidence for the hypothesis that passive as well as active deviance and target detection elicit cortical activations in spatially distributed brain regions and neural networks including the ventral attention network (VAN), dorsal attention network (DAN) and salience network (SN). Based on the temporal activation of the neural sources underlying ERP modulations, a neurophysiological model of passive and active deviance and target detection is proposed which can be tested in future studies.

Disentangling the attention network test: behavioral, event related potentials, and neural source analyses

PubMed Central

Galvao-Carmona, Alejandro; González-Rosa, Javier J.; Hidalgo-Muñoz, Antonio R.; Páramo, Dolores; Benítez, María L.; Izquierdo, Guillermo; Vázquez-Marrufo, Manuel

2014-01-01

Background: The study of the attentional system remains a challenge for current neuroscience. The “Attention Network Test” (ANT) was designed to study simultaneously three different attentional networks (alerting, orienting, and executive) based in subtraction of different experimental conditions. However, some studies recommend caution with these calculations due to the interactions between the attentional networks. In particular, it is highly relevant that several interpretations about attentional impairment have arisen from these calculations in diverse pathologies. Event related potentials (ERPs) and neural source analysis can be applied to disentangle the relationships between these attentional networks not specifically shown by behavioral measures. Results: This study shows that there is a basic level of alerting (tonic alerting) in the no cue (NC) condition, represented by a slow negative trend in the ERP trace prior to the onset of the target stimuli. A progressive increase in the CNV amplitude related to the amount of information provided by the cue conditions is also shown. Neural source analysis reveals specific modulations of the CNV related to a task-related expectancy presented in the NC condition; a late modulation triggered by the central cue (CC) condition and probably representing a generic motor preparation; and an early and late modulation for spatial cue (SC) condition suggesting specific motor and sensory preactivation. Finally, the first component in the information processing of the target stimuli modulated by the interaction between orienting network and the executive system can be represented by N1. Conclusions: The ANT is useful as a paradigm to study specific attentional mechanisms and their interactions. However, calculation of network effects is based in subtractions with non-comparable experimental conditions, as evidenced by the present data, which can induce misinterpretations in the study of the attentional capacity in human subjects. PMID:25352800

Chemical methodology as a source of small-molecule checkpoint inhibitors and heat shock protein 70 (Hsp70) modulators.

PubMed

Huryn, Donna M; Brodsky, Jeffrey L; Brummond, Kay M; Chambers, Peter G; Eyer, Benjamin; Ireland, Alex W; Kawasumi, Masaoki; Laporte, Matthew G; Lloyd, Kayla; Manteau, Baptiste; Nghiem, Paul; Quade, Bettina; Seguin, Sandlin P; Wipf, Peter

2011-04-26

Unique chemical methodology enables the synthesis of innovative and diverse scaffolds and chemotypes and allows access to previously unexplored "chemical space." Compound collections based on such new synthetic methods can provide small-molecule probes of proteins and/or pathways whose functions are not fully understood. We describe the identification, characterization, and evolution of two such probes. In one example, a pathway-based screen for DNA damage checkpoint inhibitors identified a compound, MARPIN (ATM and ATR pathway inhibitor) that sensitizes p53-deficient cells to DNA-damaging agents. Modification of the small molecule and generation of an immobilized probe were used to selectively bind putative protein target(s) responsible for the observed activity. The second example describes a focused library approach that relied on tandem multicomponent reaction methodologies to afford a series of modulators of the heat shock protein 70 (Hsp70) molecular chaperone. The synthesis of libraries based on the structure of MAL3-101 generated a collection of chemotypes, each modulating Hsp70 function, but exhibiting divergent pharmacological activities. For example, probes that compromise the replication of a disease-associated polyomavirus were identified. These projects highlight the importance of chemical methodology development as a source of small-molecule probes and as a drug discovery starting point.

Chemical methodology as a source of small-molecule checkpoint inhibitors and heat shock protein 70 (Hsp70) modulators

PubMed Central

Huryn, Donna M.; Brodsky, Jeffrey L.; Brummond, Kay M.; Chambers, Peter G.; Eyer, Benjamin; Ireland, Alex W.; Kawasumi, Masaoki; LaPorte, Matthew G.; Lloyd, Kayla; Manteau, Baptiste; Nghiem, Paul; Quade, Bettina; Seguin, Sandlin P.; Wipf, Peter

2011-01-01

Unique chemical methodology enables the synthesis of innovative and diverse scaffolds and chemotypes and allows access to previously unexplored “chemical space.” Compound collections based on such new synthetic methods can provide small-molecule probes of proteins and/or pathways whose functions are not fully understood. We describe the identification, characterization, and evolution of two such probes. In one example, a pathway-based screen for DNA damage checkpoint inhibitors identified a compound, MARPIN (ATM and ATR pathway inhibitor) that sensitizes p53-deficient cells to DNA-damaging agents. Modification of the small molecule and generation of an immobilized probe were used to selectively bind putative protein target(s) responsible for the observed activity. The second example describes a focused library approach that relied on tandem multicomponent reaction methodologies to afford a series of modulators of the heat shock protein 70 (Hsp70) molecular chaperone. The synthesis of libraries based on the structure of MAL3-101 generated a collection of chemotypes, each modulating Hsp70 function, but exhibiting divergent pharmacological activities. For example, probes that compromise the replication of a disease-associated polyomavirus were identified. These projects highlight the importance of chemical methodology development as a source of small-molecule probes and as a drug discovery starting point. PMID:21502524

Status of the ion sources developments for the Spiral2 project at GANILa)

NASA Astrophysics Data System (ADS)

Lehérissier, P.; Bajeat, O.; Barué, C.; Canet, C.; Dubois, M.; Dupuis, M.; Flambard, J. L.; Frigot, R.; Jardin, P.; Leboucher, C.; Lemagnen, F.; Maunoury, L.; Osmond, B.; Pacquet, J. Y.; Pichard, A.; Thuillier, T.; Peaucelle, C.

2012-02-01

The SPIRAL 2 facility is now under construction and will deliver either stable or radioactive ion beams. First tests of nickel beam production have been performed at GANIL with a new version of the large capacity oven, and a calcium beam has been produced on the heavy ion low energy beam transport line of SPIRAL 2, installed at LPSC Grenoble. For the production of radioactive beams, several target/ion-source systems (TISSs) are under development at GANIL as the 2.45 GHz electron cyclotron resonance ion source, the surface ionization source, and the oven prototype for heating the uranium carbide target up to 2000 °C. The existing test bench has been upgraded for these developments and a new one, dedicated for the validation of the TISS before mounting in the production module, is under design. Results and current status of these activities are presented.

Temporal Dynamics of Visual Attention Measured with Event-Related Potentials

PubMed Central

Kashiwase, Yoshiyuki; Matsumiya, Kazumichi; Kuriki, Ichiro; Shioiri, Satoshi

2013-01-01

How attentional modulation on brain activities determines behavioral performance has been one of the most important issues in cognitive neuroscience. This issue has been addressed by comparing the temporal relationship between attentional modulations on neural activities and behavior. Our previous study measured the time course of attention with amplitude and phase coherence of steady-state visual evoked potential (SSVEP) and found that the modulation latency of phase coherence rather than that of amplitude was consistent with the latency of behavioral performance. In this study, as a complementary report, we compared the time course of visual attention shift measured by event-related potentials (ERPs) with that by target detection task. We developed a novel technique to compare ERPs with behavioral results and analyzed the EEG data in our previous study. Two sets of flickering stimulus at different frequencies were presented in the left and right visual hemifields, and a target or distracter pattern was presented randomly at various moments after an attention-cue presentation. The observers were asked to detect targets on the attended stimulus after the cue. We found that two ERP components, P300 and N2pc, were elicited by the target presented at the attended location. Time-course analyses revealed that attentional modulation of the P300 and N2pc amplitudes increased gradually until reaching a maximum and lasted at least 1.5 s after the cue onset, which is similar to the temporal dynamics of behavioral performance. However, attentional modulation of these ERP components started later than that of behavioral performance. Rather, the time course of attentional modulation of behavioral performance was more closely associated with that of the concurrently recorded SSVEPs analyzed. These results suggest that neural activities reflected not by either the P300 or N2pc, but by the SSVEPs, are the source of attentional modulation of behavioral performance. PMID:23976966

Frequency-Modulated, Continuous-Wave Laser Ranging Using Photon-Counting Detectors

NASA Technical Reports Server (NTRS)

Erkmen, Baris I.; Barber, Zeb W.; Dahl, Jason

2014-01-01

Optical ranging is a problem of estimating the round-trip flight time of a phase- or amplitude-modulated optical beam that reflects off of a target. Frequency- modulated, continuous-wave (FMCW) ranging systems obtain this estimate by performing an interferometric measurement between a local frequency- modulated laser beam and a delayed copy returning from the target. The range estimate is formed by mixing the target-return field with the local reference field on a beamsplitter and detecting the resultant beat modulation. In conventional FMCW ranging, the source modulation is linear in instantaneous frequency, the reference-arm field has many more photons than the target-return field, and the time-of-flight estimate is generated by balanced difference- detection of the beamsplitter output, followed by a frequency-domain peak search. This work focused on determining the maximum-likelihood (ML) estimation algorithm when continuous-time photoncounting detectors are used. It is founded on a rigorous statistical characterization of the (random) photoelectron emission times as a function of the incident optical field, including the deleterious effects caused by dark current and dead time. These statistics enable derivation of the Cramér-Rao lower bound (CRB) on the accuracy of FMCW ranging, and derivation of the ML estimator, whose performance approaches this bound at high photon flux. The estimation algorithm was developed, and its optimality properties were shown in simulation. Experimental data show that it performs better than the conventional estimation algorithms used. The demonstrated improvement is a factor of 1.414 over frequency-domainbased estimation. If the target interrogating photons and the local reference field photons are costed equally, the optimal allocation of photons between these two arms is to have them equally distributed. This is different than the state of the art, in which the local field is stronger than the target return. The optimal processing of the photocurrent processes at the outputs of the two detectors is to perform log-matched filtering followed by a summation and peak detection. This implies that neither difference detection, nor Fourier-domain peak detection, which are the staples of the state-of-the-art systems, is optimal when a weak local oscillator is employed.

A beam optics study of a modular multi-source X-ray tube for novel computed tomography applications

NASA Astrophysics Data System (ADS)

Walker, Brandon J.; Radtke, Jeff; Chen, Guang-Hong; Eliceiri, Kevin W.; Mackie, Thomas R.

2017-10-01

A modular implementation of a scanning multi-source X-ray tube is designed for the increasing number of multi-source imaging applications in computed tomography (CT). An electron beam array coupled with an oscillating magnetic deflector is proposed as a means for producing an X-ray focal spot at any position along a line. The preliminary multi-source model includes three thermionic electron guns that are deflected in tandem by a slowly varying magnetic field and pulsed according to a scanning sequence that is dependent on the intended imaging application. Particle tracking simulations with particle dynamics analysis software demonstrate that three 100 keV electron beams are laterally swept a combined distance of 15 cm over a stationary target with an oscillating magnetic field of 102 G perpendicular to the beam axis. Beam modulation is accomplished using 25 μs pulse widths to a grid electrode with a reverse gate bias of -500 V and an extraction voltage of +1000 V. Projected focal spot diameters are approximately 1 mm for 138 mA electron beams and the stationary target stays within thermal limits for the 14 kW module. This concept could be used as a research platform for investigating high-speed stationary CT scanners, for lowering dose with virtual fan beam formation, for reducing scatter radiation in cone-beam CT, or for other industrial applications.

Emphasis of spatial cues in the temporal fine structure during the rising segments of amplitude-modulated sounds

PubMed Central

Dietz, Mathias; Marquardt, Torsten; Salminen, Nelli H.; McAlpine, David

2013-01-01

The ability to locate the direction of a target sound in a background of competing sources is critical to the survival of many species and important for human communication. Nevertheless, brain mechanisms that provide for such accurate localization abilities remain poorly understood. In particular, it remains unclear how the auditory brain is able to extract reliable spatial information directly from the source when competing sounds and reflections dominate all but the earliest moments of the sound wave reaching each ear. We developed a stimulus mimicking the mutual relationship of sound amplitude and binaural cues, characteristic to reverberant speech. This stimulus, named amplitude modulated binaural beat, allows for a parametric and isolated change of modulation frequency and phase relations. Employing magnetoencephalography and psychoacoustics it is demonstrated that the auditory brain uses binaural information in the stimulus fine structure only during the rising portion of each modulation cycle, rendering spatial information recoverable in an otherwise unlocalizable sound. The data suggest that amplitude modulation provides a means of “glimpsing” low-frequency spatial cues in a manner that benefits listening in noisy or reverberant environments. PMID:23980161

Detecting microRNAs of high influence on protein functional interaction networks: a prostate cancer case study

PubMed Central

2012-01-01

Background The use of biological molecular network information for diagnostic and prognostic purposes and elucidation of molecular disease mechanism is a key objective in systems biomedicine. The network of regulatory miRNA-target and functional protein interactions is a rich source of information to elucidate the function and the prognostic value of miRNAs in cancer. The objective of this study is to identify miRNAs that have high influence on target protein complexes in prostate cancer as a case study. This could provide biomarkers or therapeutic targets relevant for prostate cancer treatment. Results Our findings demonstrate that a miRNA’s functional role can be explained by its target protein connectivity within a physical and functional interaction network. To detect miRNAs with high influence on target protein modules, we integrated miRNA and mRNA expression profiles with a sequence based miRNA-target network and human functional and physical protein interactions (FPI). miRNAs with high influence on target protein complexes play a role in prostate cancer progression and are promising diagnostic or prognostic biomarkers. We uncovered several miRNA-regulated protein modules which were enriched in focal adhesion and prostate cancer genes. Several miRNAs such as miR-96, miR-182, and miR-143 demonstrated high influence on their target protein complexes and could explain most of the gene expression changes in our analyzed prostate cancer data set. Conclusions We describe a novel method to identify active miRNA-target modules relevant to prostate cancer progression and outcome. miRNAs with high influence on protein networks are valuable biomarkers that can be used in clinical investigations for prostate cancer treatment. PMID:22929553

Absolute Distance Measurement with the MSTAR Sensor

NASA Technical Reports Server (NTRS)

Lay, Oliver P.; Dubovitsky, Serge; Peters, Robert; Burger, Johan; Ahn, Seh-Won; Steier, William H.; Fetterman, Harrold R.; Chang, Yian

2003-01-01

The MSTAR sensor (Modulation Sideband Technology for Absolute Ranging) is a new system for measuring absolute distance, capable of resolving the integer cycle ambiguity of standard interferometers, and making it possible to measure distance with sub-nanometer accuracy. The sensor uses a single laser in conjunction with fast phase modulators and low frequency detectors. We describe the design of the system - the principle of operation, the metrology source, beamlaunching optics, and signal processing - and show results for target distances up to 1 meter. We then demonstrate how the system can be scaled to kilometer-scale distances.

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

Nalu is a Sierra ToolKit (STK) based application module, and it has provided a set of "lessons learned" for the STK transition effort through its early adoption of STK. It makes use of the open-sourced Trilinos/ Tpetra library. Through the investment of LORD and ASCR projects, the Nalu code module has been extended beyond prototype status. Physics capability includes low Mach, variable density turbulent flow. The ongoing objective for Nalu is to facilitate partnerships with external organizations in order to extend code capability and knowledge; however, it is not intended to support routine CFD analysis. The targeted usage of thismore » module is for non-NW applications that support work-for-others in the multiphysics energy sector.« less

Dual-modulation fiber Fabry-Perot interferometer with double reflection for slowly-varying displacements.

PubMed

Seat, H C; Chawah, P; Cattoen, M; Sourice, A; Plantier, G; Boudin, F; Chéry, J; Brunet, C; Bernard, P; Suleiman, M

2012-07-15

This Letter describes a dual-amplitude modulation technique incorporated into a double reflection extrinsic-type fiber Fabry-Perot interferometer to measure periodic, nonperiodic as well as quasi-static displacements. The modulation scheme simultaneously maintains the interference signal pair in quadrature and provides a reference signal for displacements inferior to a quarter of the source wavelength. The control and phase demodulation of the interferometer carried out via software enable quasi-real-time measurement and facilitates sensor alignment. The sensor system can be exploited in the low frequency range from 10(-3) to ∼500 Hz and has a resolution better than 2.2 nm, targeting applications in geophysics.

Cannabinoids Modulate Neuronal Activity and Cancer by CB1 and CB2 Receptor-Independent Mechanisms

PubMed Central

Soderstrom, Ken; Soliman, Eman; Van Dross, Rukiyah

2017-01-01

Cannabinoids include the active constituents of Cannabis or are molecules that mimic the structure and/or function of these Cannabis-derived molecules. Cannabinoids produce many of their cellular and organ system effects by interacting with the well-characterized CB1 and CB2 receptors. However, it has become clear that not all effects of cannabinoid drugs are attributable to their interaction with CB1 and CB2 receptors. Evidence now demonstrates that cannabinoid agents produce effects by modulating activity of the entire array of cellular macromolecules targeted by other drug classes, including: other receptor types; ion channels; transporters; enzymes, and protein- and non-protein cellular structures. This review summarizes evidence for these interactions in the CNS and in cancer, and is organized according to the cellular targets involved. The CNS represents a well-studied area and cancer is emerging in terms of understanding mechanisms by which cannabinoids modulate their activity. Considering the CNS and cancer together allow identification of non-cannabinoid receptor targets that are shared and divergent in both systems. This comparative approach allows the identified targets to be compared and contrasted, suggesting potential new areas of investigation. It also provides insight into the diverse sources of efficacy employed by this interesting class of drugs. Obtaining a comprehensive understanding of the diverse mechanisms of cannabinoid action may lead to the design and development of therapeutic agents with greater efficacy and specificity for their cellular targets. PMID:29066974

Device and method for electron beam heating of a high density plasma

DOEpatents

Thode, Lester E.

1981-01-01

A device and method for relativistic electron beam heating of a high density plasma in a small localized region. A relativistic electron beam generator produces a high voltage electron beam which propagates along a vacuum drift tube and is modulated to initiate electron bunching within the beam. The beam is then directed through a low density gas chamber which provides isolation between the vacuum modulator and the relativistic electron beam target. The relativistic beam is then applied to a high density target plasma which typically comprises DT, DD, hydrogen boron or similar thermonuclear gas at a density of 10.sup.17 to 10.sup.20 electrons per cubic centimeter. The target plasma is ionized prior to application of the electron beam by means of a laser or other preionization source. Utilizing a relativistic electron beam with an individual particle energy exceeding 3 MeV, classical scattering by relativistic electrons passing through isolation foils is negligible. As a result, relativistic streaming instabilities are initiated within the high density target plasma causing the relativistic electron beam to efficiently deposit its energy into a small localized region within the high density plasma target.

Target-in-the-loop phasing of a fiber laser array fed by a linewidth-broadened master oscillator

NASA Astrophysics Data System (ADS)

Hyde, Milo W.; Tyler, Glenn A.; Rosado Garcia, Carlos

2017-05-01

In a recent paper [J. Opt. Soc. Am. A 33, 1931-1937 (2016)], the target-in-the-loop (TIL) phasing of an RF-modulated or multi-phase-dithered fiber laser array, fed by a linewidth-broadened master oscillator (MO) source, was investigated. It was found that TIL phasing was possible even on a target with scattering features separated by more than the MO's coherence length as long as the received, backscattered irradiance changed with the array's modulation or phase dither. To simplify the problem and gain insight into how temporal coherence affects TIL phasing, speckle and atmospheric turbulence were omitted from the analysis. Here, the scenario analyzed in the prior work is generalized by including speckle and turbulence. First, the key analytical result from the prior paper is reviewed. Simulations, including speckle and turbulence, are then performed to test whether the conclusions derived from that result hold under more realistic conditions.

DIFFERENTIAL MODULATION OF CANCER-RELATED MOLECULAR NETWORKS IN HUMAN AND RAT URINARY BLADDER CELLS EXPOSED TO TRIVALENT ARSENICALS

EPA Science Inventory

Arsenic (As) is classified as a known human carcinogen with primary targets of urinary bladder (UB), skin and lung. The most prevalent source of As exposure in humans is drinking water contaminated with inorganic As (iAs), and millions of people worldwide are exposed to drinking ...

Dynamics of alpha control: Preparatory suppression of posterior alpha oscillations by frontal modulators revealed with combined EEG and event-related optical signal (EROS)

PubMed Central

Mathewson, Kyle E.; Beck, Diane M.; Ro, Tony; Maclin, Edward L.; Low, Kathy A.; Fabiani, Monica; Gratton, Gabriele

2015-01-01

We investigated the dynamics of brain processes facilitating conscious experience of external stimuli. Previously we proposed that alpha (8-12 Hz) oscillations, which fluctuate with both sustained and directed attention, represent a pulsed inhibition of ongoing sensory brain activity. Here we tested the prediction that inhibitory alpha oscillations in visual cortex are modulated by top-down signals from frontoparietal attention networks. We measured modulations in phase-coherent alpha oscillations from superficial frontal, parietal, and occipital cortices using the event-related optical signal (EROS), a measure of neuronal activity affording high spatiotemporal resolution, along with concurrently-recorded electroencephalogram (EEG), while subjects performed a visual target-detection task. The pre-target alpha oscillations measured with EEG and EROS from posterior areas were larger for subsequently undetected targets, supporting alpha's inhibitory role. Using EROS, we localized brain correlates of these awareness-related alpha oscillations measured at the scalp to the cuneus and precuneus. Crucially, EROS alpha suppression correlated with posterior EEG alpha power across subjects. Sorting the EROS data based on EEG alpha power quartiles to investigate alpha modulators revealed that suppression of posterior alpha was preceded by increased activity in regions of the dorsal attention network, and decreased activity in regions of the cingulo-opercular network. Cross-correlations revealed the temporal dynamics of activity within these preparatory networks prior to posterior alpha modulation. The novel combination of EEG and EROS afforded localization of the sources and correlates of alpha oscillations and their temporal relationships, supporting our proposal that top-down control from attention networks modulates both posterior alpha and awareness of visual stimuli. PMID:24702458

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

NASA Astrophysics Data System (ADS)

Kujala, Naresh Gandhi

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

Design a freeform microlens array module for any arbitrary-shape collimated beam shaping and color mixing

NASA Astrophysics Data System (ADS)

Chen, Enguo; Wu, Rengmao; Guo, Tailiang

2014-06-01

Collimated beam shaping with freeform surface usually employs a predefined mapping to tailor one or multiple freeform surfaces. Limitation on those designs is that the source, the freeform optics and the target are in fixed one-to-one correspondence with each other. To overcome this drawback, this paper presents a kind of freeform microlens array module integrated with an ultra-thin freeform microlens array and a condenser lens to reshape any arbitrary-shape collimated beam into a prescribed uniform rectangular illumination and achieve color mixing. The design theory is explicitly given, and some key issues are addressed. Several different application examples are given, and the target is obtained with high uniformity and energy efficiency. This freeform microlens array module, which shows better flexibility and practicality than the regular designs, can be used not only to reshape any arbitrary-shape collimated beam (or a collimated beam integrated with several sub-collimated beams), but also most importantly to achieve color mixing. With excellent optical performance and ultra-compact volume, this optical module together with the design theory can be further introduced into other applications and will have a huge market potential in the near future.

Practical experience and challenges in the operation of medical cyclotron.

PubMed

Kumar, Rajeev; Sonkawade, Rajendra G; Pandey, Anil K; Tripathi, Madhavi; Damle, Nishikant A; Kumar, Praveen; Bal, Chandra S

2017-01-01

The aim of this article was to share 10 years of operational experience of medical cyclotron and to provide working knowledge on the same. This experience has helped us gain working knowledge on cyclotron operation with practical points, which may help in improving F yield, minimizing the breakdown time, and help in the prevention of the occurrence of unusual events. Our facility has a self-shielded radioisotope delivery system eclipse 111 medical cyclotron with an 11 MeV proton beam in use for the past 10 years to produce positron emitters - namely, F, N, and F-2 gas - for PET imaging. During F production, we have followed a set protocol comprising the following: monitoring target pressure, rinsing the target with O water just immediately after bombardment, ion source feedback, radiofrequency (RF) feedback, and recording any unusual events that occurred during the operation. Besides this, enrichment of O water, target volume, target current, energy of the beam, variation in argon pressure on the target, bombardment duration, target status (new or old target or total number of previous bombardments on the same target), status of the delivery lines from target to the radiochemistry module (old or new) were also recorded. Rinsing with O water immediately after bombardment increases the life of the target and delivery line. The frequent problems encountered were with the ion source, RF, and target foil rupture. These problems were solved by rebuilding the ion source, changing the fuse of RF, and rebuilding the target. F yield can be increased by rinsing with O water immediately after bombardment. The effect of target leak - that is, rupture of vacuum window - can be avoided by immediate stoppage of bombardment.

Smart lighting using a liquid crystal modulator

NASA Astrophysics Data System (ADS)

Baril, Alexandre; Thibault, Simon; Galstian, Tigran

2017-08-01

Now that LEDs have massively invaded the illumination market, a clear trend has emerged for more efficient and targeted lighting. The project described here is at the leading edge of the trend and aims at developing an evaluation board to test smart lighting applications. This is made possible thanks to a new liquid crystal light modulator recently developed for broadening LED light beams. The modulator is controlled by electrical signals and is characterized by a linear working zone. This feature allows the implementation of a closed loop control with a sensor feedback. This project shows that the use of computer vision is a promising opportunity for cheap closed loop control. The developed evaluation board integrates the liquid crystal modulator, a webcam, a LED light source and all the required electronics to implement a closed loop control with a computer vision algorithm.

Accelerated Stress Testing of Multi-Source LED Products: Horticulture Lamps and Tunable-White Modules

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

Davis, Lynn; Rountree, Kelley; Mills, Karmann

This report discusses the use of accelerated stress testing (AST) to provide insights into the long-term behavior of commercial products utilizing different types of mid-power LEDs (MP-LEDs) integrated into the same LED module. Test results are presented from two commercial lamps intended for use in horticulture applications and one tunable-white LED module intended for use in educational and office lighting applications. Each of these products is designed to provide a custom spectrum for their targeted applications and each achieves this goal in different ways. Consequently, a comparison of the long-term stability of these devices will provide insights regarding approaches thatmore » could be used to possibly lengthen the lifetime of SSL products.« less

REACTIVE OXYGEN SPECIES: IMPACT ON SKELETAL MUSCLE

PubMed Central

Powers, Scott K.; Ji, Li Li; Kavazis, Andreas N.; Jackson, Malcolm J.

2014-01-01

It is well established that contracting muscles produce both reactive oxygen and nitrogen species. Although the sources of oxidant production during exercise continue to be debated, growing evidence suggests that mitochondria are not the dominant source. Regardless of the sources of oxidants in contracting muscles, intense and prolonged exercise can result in oxidative damage to both proteins and lipids in the contracting myocytes. Further, oxidants regulate numerous cell signaling pathways and modulate the expression of many genes. This oxidant-mediated change in gene expression involves changes at transcriptional, mRNA stability, and signal transduction levels. Furthermore, numerous products associated with oxidant-modulated genes have been identified and include antioxidant enzymes, stress proteins, and mitochondrial electron transport proteins. Interestingly, low and physiological levels of reactive oxygen species are required for normal force production in skeletal muscle, but high levels of reactive oxygen species result in contractile dysfunction and fatigue. Ongoing research continues to explore the redox-sensitive targets in muscle that are responsible for both redox-regulation of muscle adaptation and oxidant-mediated muscle fatigue. PMID:23737208

Separation negatives from Kodak film types SO-368 and SO-242

NASA Technical Reports Server (NTRS)

Weinstein, M. S.

1972-01-01

Two master resolution friskets were produced on Kodak film types SO-368 and SO-242. These target masters consisted of 21 density steps with three-bar resolution targets at five modulation levels within each step. The target masters were contact printed onto Kodak separation negative film, type 4131, using both a contact printing frame and enlarger as one method of exposure, and a Miller-Holzwarth contact printer as the other exposing device. Red, green, and blue Wratten filters were used to filter the exposing source. Tray processing was done with DK-50 developer diluted 1:2 at a temperature of 70 F. The resolution values were read for the SO-368 and SO-242 target masters, and the red, green, and blue separation negatives.

Studies of Properties of Pain Networks as Predictors of Targets of Stimulation for Treatment of Pain

DTIC Science & Technology

2011-12-05

H. (1999). Dissociation of sensory and affective dimensions of pain using hypnotic modulation. Pain 82, 159–171. Rasche, D., Rinaldi, P. C., Young, R...distribution, and reproduction in other forums, pro- vided the original authors and source are credited. Frontiers in Integrative Neuroscience www.frontiersin.org December 2011 | Volume 5 | Article 80 | 7

Spatial Probability Dynamically Modulates Visual Target Detection in Chickens

PubMed Central

Sridharan, Devarajan; Ramamurthy, Deepa L.; Knudsen, Eric I.

2013-01-01

The natural world contains a rich and ever-changing landscape of sensory information. To survive, an organism must be able to flexibly and rapidly locate the most relevant sources of information at any time. Humans and non-human primates exploit regularities in the spatial distribution of relevant stimuli (targets) to improve detection at locations of high target probability. Is the ability to flexibly modify behavior based on visual experience unique to primates? Chickens (Gallus domesticus) were trained on a multiple alternative Go/NoGo task to detect a small, briefly-flashed dot (target) in each of the quadrants of the visual field. When targets were presented with equal probability (25%) in each quadrant, chickens exhibited a distinct advantage for detecting targets at lower, relative to upper, hemifield locations. Increasing the probability of presentation in the upper hemifield locations (to 80%) dramatically improved detection performance at these locations to be on par with lower hemifield performance. Finally, detection performance in the upper hemifield changed on a rapid timescale, improving with successive target detections, and declining with successive detections at the diagonally opposite location in the lower hemifield. These data indicate the action of a process that in chickens, as in primates, flexibly and dynamically modulates detection performance based on the spatial probabilities of sensory stimuli as well as on recent performance history. PMID:23734188

Three-Dimensional Modeling of Low-Mode Asymmetries in OMEGA Cryogenic Implosions

NASA Astrophysics Data System (ADS)

Anderson, K. S.; McKenty, P. W.; Shvydky, A.; Collins, T. J. B.; Forrest, C. J.; Knauer, J. P.; Marozas, J. A.; Marshall, F. J.; Radha, P. B.; Sefkow, A. B.; Marinak, M. M.

2017-10-01

In direct-drive inertial confinement fusion implosions, long-wavelength asymmetries resulting from target offset, laser power imbalance, beam mispointing, etc. can be highly detrimental to target performance. Characterizing the effects of these asymmetry sources requires 3-D simulations performed in full-sphere geometry to accurately capture the evolution of shell perturbations and hot-spot flow. This paper will present 3-D HYDRA simulations characterizing the impact of these perturbation sources on yield and shell modulation. Various simulated observables are generated, and trends are analyzed and compared with experimental data. This material is based on work supported by the Department of Energy National Nuclear Security Administration under Award Numbers DE-NA0001944 and performed under the auspices of the LLNL under Contract No. DE-AC52-07NA27344.

The importance of explicitly mapping instructional analogies in science education

NASA Astrophysics Data System (ADS)

Asay, Loretta Johnson

Analogies are ubiquitous during instruction in science classrooms, yet research about the effectiveness of using analogies has produced mixed results. An aspect seldom studied is a model of instruction when using analogies. The few existing models for instruction with analogies have not often been examined quantitatively. The Teaching With Analogies (TWA) model (Glynn, 1991) is one of the models frequently cited in the variety of research about analogies. The TWA model outlines steps for instruction, including the step of explicitly mapping the features of the source to the target. An experimental study was conducted to examine the effects of explicitly mapping the features of the source and target in an analogy during computer-based instruction about electrical circuits. Explicit mapping was compared to no mapping and to a control with no analogy. Participants were ninth- and tenth-grade biology students who were each randomly assigned to one of three conditions (no analogy module, analogy module, or explicitly mapped analogy module) for computer-based instruction. Subjects took a pre-test before the instruction, which was used to assign them to a level of previous knowledge about electrical circuits for analysis of any differential effects. After the instruction modules, students took a post-test about electrical circuits. Two weeks later, they took a delayed post-test. No advantage was found for explicitly mapping the analogy. Learning patterns were the same, regardless of the type of instruction. Those who knew the least about electrical circuits, based on the pre-test, made the most gains. After the two-week delay, this group maintained the largest amount of their gain. Implications exist for science education classrooms, as analogy use should be based on research about effective practices. Further studies are suggested to foster the building of research-based models for classroom instruction with analogies.

The National Transport Code Collaboration Module Library

NASA Astrophysics Data System (ADS)

Kritz, A. H.; Bateman, G.; Kinsey, J.; Pankin, A.; Onjun, T.; Redd, A.; McCune, D.; Ludescher, C.; Pletzer, A.; Andre, R.; Zakharov, L.; Lodestro, L.; Pearlstein, L. D.; Jong, R.; Houlberg, W.; Strand, P.; Wiley, J.; Valanju, P.; John, H. St.; Waltz, R.; Mandrekas, J.; Mau, T. K.; Carlsson, J.; Braams, B.

2004-12-01

This paper reports on the progress in developing a library of code modules under the auspices of the National Transport Code Collaboration (NTCC). Code modules are high quality, fully documented software packages with a clearly defined interface. The modules provide a variety of functions, such as implementing numerical physics models; performing ancillary functions such as I/O or graphics; or providing tools for dealing with common issues in scientific programming such as portability of Fortran codes. Researchers in the plasma community submit code modules, and a review procedure is followed to insure adherence to programming and documentation standards. The review process is designed to provide added confidence with regard to the use of the modules and to allow users and independent reviews to validate the claims of the modules' authors. All modules include source code; clear instructions for compilation of binaries on a variety of target architectures; and test cases with well-documented input and output. All the NTCC modules and ancillary information, such as current standards and documentation, are available from the NTCC Module Library Website http://w3.pppl.gov/NTCC. The goal of the project is to develop a resource of value to builders of integrated modeling codes and to plasma physics researchers generally. Currently, there are more than 40 modules in the module library.

Combined hairpin-antisense compositions and methods for modulating expression

DOEpatents

Shanklin, John; Nguyen, Tam

2014-08-05

A nucleotide construct comprising a nucleotide sequence that forms a stem and a loop, wherein the loop comprises a nucleotide sequence that modulates expression of a target, wherein the stem comprises a nucleotide sequence that modulates expression of a target, and wherein the target modulated by the nucleotide sequence in the loop and the target modulated by the nucleotide sequence in the stem may be the same or different. Vectors, methods of regulating target expression, methods of providing a cell, and methods of treating conditions comprising the nucleotide sequence are also disclosed.

Combined hairpin-antisense compositions and methods for modulating expression

DOEpatents

Shanklin, John; Nguyen, Tam Huu

2015-11-24

A nucleotide construct comprising a nucleotide sequence that forms a stem and a loop, wherein the loop comprises a nucleotide sequence that modulates expression of a target, wherein the stem comprises a nucleotide sequence that modulates expression of a target, and wherein the target modulated by the nucleotide sequence in the loop and the target modulated by the nucleotide sequence in the stem may be the same or different. Vectors, methods of regulating target expression, methods of providing a cell, and methods of treating conditions comprising the nucleotide sequence are also disclosed.

The Comparison Study of Quadratic Infinite Beam Program on Optimization Instensity Modulated Radiation Therapy Treatment Planning (IMRTP) between Threshold and Exponential Scatter Method with CERR® In The Case of Lung Cancer

NASA Astrophysics Data System (ADS)

Hardiyanti, Y.; Haekal, M.; Waris, A.; Haryanto, F.

2016-08-01

This research compares the quadratic optimization program on Intensity Modulated Radiation Therapy Treatment Planning (IMRTP) with the Computational Environment for Radiotherapy Research (CERR) software. We assumed that the number of beams used for the treatment planner was about 9 and 13 beams. The case used the energy of 6 MV with Source Skin Distance (SSD) of 100 cm from target volume. Dose calculation used Quadratic Infinite beam (QIB) from CERR. CERR was used in the comparison study between Gauss Primary threshold method and Gauss Primary exponential method. In the case of lung cancer, the threshold variation of 0.01, and 0.004 was used. The output of the dose was distributed using an analysis in the form of DVH from CERR. The maximum dose distributions obtained were on the target volume (PTV) Planning Target Volume, (CTV) Clinical Target Volume, (GTV) Gross Tumor Volume, liver, and skin. It was obtained that if the dose calculation method used exponential and the number of beam 9. When the dose calculation method used the threshold and the number of beam 13, the maximum dose distributions obtained were on the target volume PTV, GTV, heart, and skin.

Development of a surgical navigation system based on 3D Slicer for intraoperative implant placement surgery

PubMed Central

Chen, Xiaojun; Xu, Lu; Wang, Huixiang; Wang, Fang; Wang, Qiugen; Kikinis, Ron

2017-01-01

Implant placement has been widely used in various kinds of surgery. However, accurate intraoperative drilling performance is essential to avoid injury to adjacent structures. Although some commercially-available surgical navigation systems have been approved for clinical applications, these systems are expensive and the source code is not available to researchers. 3D Slicer is a free, open source software platform for the research community of computer-aided surgery. In this study, a loadable module based on Slicer has been developed and validated to support surgical navigation. This research module allows reliable calibration of the surgical drill, point-based registration and surface matching registration, so that the position and orientation of the surgical drill can be tracked and displayed on the computer screen in real time, aiming at reducing risks. In accuracy verification experiments, the mean target registration error (TRE) for point-based and surface-based registration were 0.31±0.06mm and 1.01±0.06mm respectively, which should meet clinical requirements. Both phantom and cadaver experiments demonstrated the feasibility of our surgical navigation software module. PMID:28109564

Science yield modeling with the Exoplanet Open-Source Imaging Mission Simulator (EXOSIMS)

NASA Astrophysics Data System (ADS)

Delacroix, Christian; Savransky, Dmitry; Garrett, Daniel; Lowrance, Patrick; Morgan, Rhonda

2016-08-01

We report on our ongoing development of EXOSIMS and mission simulation results for WFIRST. We present the interface control and the modular structure of the software, along with corresponding prototypes and class definitions for some of the software modules. More specifically, we focus on describing the main steps of our high-fidelity mission simulator EXOSIMS, i.e., the completeness, optical system and zodiacal light modules definition, the target list module filtering, and the creation of a planet population within our simulated universe module. For the latter, we introduce the integration of a recent mass-radius model from the FORECASTER software. We also provide custom modules dedicated to WFIRST using both the Hybrid Lyot Coronagraph (HLC) and the Shaped Pupil Coronagraph (SPC) for detection and characterization, respectively. In that context, we show and discuss the results of some preliminary WFIRST simulations, focusing on comparing different methods of integration time calculation, through ensembles (large numbers) of survey simulations.

A continuous-wave ultrasound system for displacement amplitude and phase measurement.

PubMed

Finneran, James J; Hastings, Mardi C

2004-06-01

A noninvasive, continuous-wave ultrasonic technique was developed to measure the displacement amplitude and phase of mechanical structures. The measurement system was based on a method developed by Rogers and Hastings ["Noninvasive vibration measurement system and method for measuring amplitude of vibration of tissue in an object being investigated," U.S. Patent No. 4,819,643 (1989)] and expanded to include phase measurement. A low-frequency sound source was used to generate harmonic vibrations in a target of interest. The target was simultaneously insonified by a low-power, continuous-wave ultrasonic source. Reflected ultrasound was phase modulated by the target motion and detected with a separate ultrasonic transducer. The target displacement amplitude was obtained directly from the received ultrasound frequency spectrum by comparing the carrier and sideband amplitudes. Phase information was obtained by demodulating the received signal using a double-balanced mixer and low-pass filter. A theoretical model for the ultrasonic receiver field is also presented. This model coupled existing models for focused piston radiators and for pulse-echo ultrasonic fields. Experimental measurements of the resulting receiver fields compared favorably with theoretical predictions.

Analysis and measurement of the modulation transfer function of harmonic shear wave induced phase encoding imaging.

PubMed

McAleavey, Stephen A

2014-05-01

Shear wave induced phase encoding (SWIPE) imaging generates ultrasound backscatter images of tissue-like elastic materials by using traveling shear waves to encode the lateral position of the scatters in the phase of the received echo. In contrast to conventional ultrasound B-scan imaging, SWIPE offers the potential advantages of image formation without beam focusing or steering from a single transducer element, lateral resolution independent of aperture size, and the potential to achieve relatively high lateral resolution with low frequency ultrasound. Here a Fourier series description of the phase modulated echo signal is developed, demonstrating that echo harmonics at multiples of the shear wave frequency reveal target k-space data at identical multiples of the shear wavenumber. Modulation transfer functions of SWIPE imaging systems are calculated for maximum shear wave acceleration and maximum shear constraints, and compared with a conventionally focused aperture. The relative signal-to-noise ratio of the SWIPE method versus a conventionally focused aperture is found through these calculations. Reconstructions of wire targets in a gelatin phantom using 1 and 3.5 MHz ultrasound and a cylindrical shear wave source are presented, generated from the fundamental and second harmonic of the shear wave modulation frequency, demonstrating weak dependence of lateral resolution with ultrasound frequency.

Lithium ion beam divergence on SABRE extraction ion diode experiments

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

Hanson, D.L.; Cuneo, M.E.; Johnson, D.J.

Intense lithium beams are of particular interest for light ion inertial confinement fusion applications because lithium ions can be accelerated at high voltage in a single charge state (Li{sup +}) with a high mass-to-charge ratio and appropriate range for efficient focusing and heating of a hohlraum ICF target. Scaling to ion power densities adequate to drive high gain pellet implosions (600 TW at 30 MeV) will require a large number of beams transported, temporally bunched, and focused onto a target, with the necessary target standoff to ensure survival of the driver modules. For efficient long distance transport and focusing tomore » a small pellet, lithium beam divergence must be reduced to about 12 mrad or less (depending on the transport scheme). To support the eventual development of a light ion driver module for ICF applications, the authors are currently working to improve the composition, uniformity, and divergence of lithium ion beams produced by both passive LiF and active laser-generated lithium ion sources on extraction applied-B ion diodes on the SABRE accelerator (1 TW, 5 MV, 250 kA). While lithium beam divergence accounting and control are an essential goal of these experiments, divergence measurements for lithium beams present some unique problems not encountered to the same degree in divergence measurements on proton sources. To avoid these difficulties, the authors have developed a large aperture ion imaging diagnostic for time-resolved lithium divergence measurements. The authors will report on the operation of this lithium beam divergence diagnostic and on results of time-resolved divergence measurements in progress for passive LiF ion sources and laser-produced active lithium sources operated in diode configurations designed to control divergence growth. Comparisons will also be made with time-integrated divergence results obtained with small entrance aperture ultracompact pinhole cameras.« less

High-resolution three-dimensional imaging radar

NASA Technical Reports Server (NTRS)

Cooper, Ken B. (Inventor); Chattopadhyay, Goutam (Inventor); Siegel, Peter H. (Inventor); Dengler, Robert J. (Inventor); Schlecht, Erich T. (Inventor); Mehdi, Imran (Inventor); Skalare, Anders J. (Inventor)

2010-01-01

A three-dimensional imaging radar operating at high frequency e.g., 670 GHz, is disclosed. The active target illumination inherent in radar solves the problem of low signal power and narrow-band detection by using submillimeter heterodyne mixer receivers. A submillimeter imaging radar may use low phase-noise synthesizers and a fast chirper to generate a frequency-modulated continuous-wave (FMCW) waveform. Three-dimensional images are generated through range information derived for each pixel scanned over a target. A peak finding algorithm may be used in processing for each pixel to differentiate material layers of the target. Improved focusing is achieved through a compensation signal sampled from a point source calibration target and applied to received signals from active targets prior to FFT-based range compression to extract and display high-resolution target images. Such an imaging radar has particular application in detecting concealed weapons or contraband.

Comparison of gene expression responses to hypoxia in viviparous (Xiphophorus) and oviparous (Oryzias) fishes using a medaka microarray.

PubMed

Boswell, Mikki G; Wells, Melissa C; Kirk, Lyndsey M; Ju, Zhenlin; Zhang, Ziping; Booth, Rachell E; Walter, Ronald B

2009-03-01

Gene expression profiling using DNA microarray technology is a useful tool for assessing gene transcript level responses after an organism is exposed to environmental stress. Herein, we detail results from studies using an 8 k medaka (Oryzias latipes) microarray to assess modulated gene expression patterns upon hypoxia exposure of the live-bearing aquaria fish, Xiphophorus maculatus. To assess the reproducibility and reliability of using the medaka array in cross-genus hybridization, a two-factor ANOVA analysis of gene expression was employed. The data show the tissue source of the RNA used for array hybridization contributed more to the observed response of modulated gene targets than did the species source of the RNA. In addition, hierarchical clustering via heat map analyses of groupings of tissues and species (Xiphophorus and medaka) suggests that hypoxia induced similar responses in the same tissues from these two diverse aquatic model organisms. Our Xiphophorus results indicate 206 brain, 37 liver, and 925 gill gene targets exhibit hypoxia induced expression changes. Analysis of the Xiphophorus data to determine those features exhibiting a significant (p<0.05)+/-3 fold change produced only two gene targets within brain tissue and 80 features within gill tissue. Of these 82 characterized features, 39 were identified via homology searching (cut-off E-value of 1 x 10(-5)) and placed into one or more biological process gene ontology groups. Among these 39 genes, metabolic energy changes and manipulation was the most affected biological pathway (13 genes).

Leveraging 3D chemical similarity, target and phenotypic data in the identification of drug-protein and drug-adverse effect associations.

PubMed

Vilar, Santiago; Hripcsak, George

2016-01-01

Drug-target identification is crucial to discover novel applications for existing drugs and provide more insights about mechanisms of biological actions, such as adverse drug effects (ADEs). Computational methods along with the integration of current big data sources provide a useful framework for drug-target and drug-adverse effect discovery. In this article, we propose a method based on the integration of 3D chemical similarity, target and adverse effect data to generate a drug-target-adverse effect predictor along with a simple leveraging system to improve identification of drug-targets and drug-adverse effects. In the first step, we generated a system for multiple drug-target identification based on the application of 3D drug similarity into a large target dataset extracted from the ChEMBL. Next, we developed a target-adverse effect predictor combining targets from ChEMBL with phenotypic information provided by SIDER data source. Both modules were linked to generate a final predictor that establishes hypothesis about new drug-target-adverse effect candidates. Additionally, we showed that leveraging drug-target candidates with phenotypic data is very useful to improve the identification of drug-targets. The integration of phenotypic data into drug-target candidates yielded up to twofold precision improvement. In the opposite direction, leveraging drug-phenotype candidates with target data also yielded a significant enhancement in the performance. The modeling described in the current study is simple and efficient and has applications at large scale in drug repurposing and drug safety through the identification of mechanism of action of biological effects.

Dynamic modulated brachytherapy (DMBT) and intensity modulated brachytherapy (IMBT) for the treatment of rectal and breast carcinomas

NASA Astrophysics Data System (ADS)

Webster, Matthew Julian

The ultimate goal of any treatment of cancer is to maximize the likelihood of killing the tumor while minimizing the chance of damaging healthy tissues. One of the most effective ways to accomplish this is through radiation therapy, which must be able to target the tumor volume with a high accuracy while minimizing the dose delivered to healthy tissues. A successful method of accomplishing this is brachytherapy which works by placing the radiation source in very close proximity to the tumor. However, most current applications of brachytherapy rely mostly on the geometric manipulation of isotropic sources, which limits the ability to specifically target the tumor. The purpose of this work is to introduce several types of shielded brachytherapy applicators which are capable of targeting tumors with much greater accuracy than existing technologies. These applicators rely on the modulation of the dose profile through a high-density tungsten alloy shields to create anisotropic dose distributions. Two classes of applicators have been developed in this work. The first relies on the active motion of the shield, to aim a highly directional radiation profile. This allows for very precise control of the dose distribution for treatment, achieving unparalleled dose coverage to the tumor while sparing healthy tissues. This technique has been given the moniker of Dynamic Modulated Brachytherapy (DMBT). The second class of applicators, designed to reduce treatment complexity uses static applicators. These applicators retain the use of the tungsten shield, but the shield is motionless during treatment. By intelligently designing the shield, significant improvements over current methods have been demonstrated. Although these static applicators fail to match the dosimetric quality of DMBT applicators the simplified setup and treatment procedure gives them significant appeal. The focus of this work has been to optimize these shield designs, specifically for the treatment of rectal and breast carcinomas. The use of Monte Carlo methods and development of optimization algorithms have played a prominent role in accomplishing this. The use of shielded applicators, such as the ones described here, is the next logical step in the rapidly evolving field of brachytherapy.

Application of the first collision source method to CSNS target station shielding calculation

NASA Astrophysics Data System (ADS)

Zheng, Ying; Zhang, Bin; Chen, Meng-Teng; Zhang, Liang; Cao, Bo; Chen, Yi-Xue; Yin, Wen; Liang, Tian-Jiao

2016-04-01

Ray effects are an inherent problem of the discrete ordinates method. RAY3D, a functional module of ARES, which is a discrete ordinates code system, employs a semi-analytic first collision source method to mitigate ray effects. This method decomposes the flux into uncollided and collided components, and then calculates them with an analytical method and discrete ordinates method respectively. In this article, RAY3D is validated by the Kobayashi benchmarks and applied to the neutron beamline shielding problem of China Spallation Neutron Source (CSNS) target station. The numerical results of the Kobayashi benchmarks indicate that the solutions of DONTRAN3D with RAY3D agree well with the Monte Carlo solutions. The dose rate at the end of the neutron beamline is less than 10.83 μSv/h in the CSNS target station neutron beamline shutter model. RAY3D can effectively mitigate the ray effects and obtain relatively reasonable results. Supported by Major National S&T Specific Program of Large Advanced Pressurized Water Reactor Nuclear Power Plant (2011ZX06004-007), National Natural Science Foundation of China (11505059, 11575061), and the Fundamental Research Funds for the Central Universities (13QN34).

Spectro-temporal modulation masking patterns reveal frequency selectivity.

PubMed

Oetjen, Arne; Verhey, Jesko L

2015-02-01

The present study investigated the possibility that the human auditory system demonstrates frequency selectivity to spectro-temporal amplitude modulations. Threshold modulation depth for detecting sinusoidal spectro-temporal modulations was measured using a generalized masked threshold pattern paradigm with narrowband masker modulations. Four target spectro-temporal modulations were examined, differing in their temporal and spectral modulation frequencies: a temporal modulation of -8, 8, or 16 Hz combined with a spectral modulation of 1 cycle/octave and a temporal modulation of 4 Hz combined with a spectral modulation of 0.5 cycles/octave. The temporal center frequencies of the masker modulation ranged from 0.25 to 4 times the target temporal modulation. The spectral masker-modulation center-frequencies were 0, 0.5, 1, 1.5, and 2 times the target spectral modulation. For all target modulations, the pattern of average thresholds for the eight normal-hearing listeners was consistent with the hypothesis of a spectro-temporal modulation filter. Such a pattern of modulation-frequency sensitivity was predicted on the basis of psychoacoustical data for purely temporal amplitude modulations and purely spectral amplitude modulations. An analysis of separability indicates that, for the present data set, selectivity in the spectro-temporal modulation domain can be described by a combination of a purely spectral and a purely temporal modulation filter function.

Computational Ghost Imaging for Remote Sensing

NASA Technical Reports Server (NTRS)

Erkmen, Baris I.

2012-01-01

This work relates to the generic problem of remote active imaging; that is, a source illuminates a target of interest and a receiver collects the scattered light off the target to obtain an image. Conventional imaging systems consist of an imaging lens and a high-resolution detector array [e.g., a CCD (charge coupled device) array] to register the image. However, conventional imaging systems for remote sensing require high-quality optics and need to support large detector arrays and associated electronics. This results in suboptimal size, weight, and power consumption. Computational ghost imaging (CGI) is a computational alternative to this traditional imaging concept that has a very simple receiver structure. In CGI, the transmitter illuminates the target with a modulated light source. A single-pixel (bucket) detector collects the scattered light. Then, via computation (i.e., postprocessing), the receiver can reconstruct the image using the knowledge of the modulation that was projected onto the target by the transmitter. This way, one can construct a very simple receiver that, in principle, requires no lens to image a target. Ghost imaging is a transverse imaging modality that has been receiving much attention owing to a rich interconnection of novel physical characteristics and novel signal processing algorithms suitable for active computational imaging. The original ghost imaging experiments consisted of two correlated optical beams traversing distinct paths and impinging on two spatially-separated photodetectors: one beam interacts with the target and then illuminates on a single-pixel (bucket) detector that provides no spatial resolution, whereas the other beam traverses an independent path and impinges on a high-resolution camera without any interaction with the target. The term ghost imaging was coined soon after the initial experiments were reported, to emphasize the fact that by cross-correlating two photocurrents, one generates an image of the target. In CGI, the measurement obtained from the reference arm (with the high-resolution detector) is replaced by a computational derivation of the measurement-plane intensity profile of the reference-arm beam. The algorithms applied to computational ghost imaging have diversified beyond simple correlation measurements, and now include modern reconstruction algorithms based on compressive sensing.

Correlation between simulations and cavitation-induced erosion damage in Spallation Neutron Source target modules after operation

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

Riemer, Bernie; McClintock, David A; Kaminskas, Saulius

2014-01-01

An explicit finite element (FE) technique developed for estimating dynamic strain in the Spallation Neutron Source (SNS) mercury target module vessel is now providing insight into cavitation damage patterns observed in used targets. The technique uses an empirically developed material model for the mercury that describes liquid-like volumetric stiffness combined with a tensile pressure cut-off limit that approximates cavitation. The longest period each point in the mercury is at the tensile cut-off threshold is denoted its saturation time. Now, the pattern of saturation time can be obtained from these simulations and is being positively correlated with observed damage patterns andmore » is interpreted as a qualitative measure of damage potential. Saturation time has been advocated by collaborators at J-Parc as a factor in predicting bubble nuclei growth and collapse intensity. The larger the ratio of maximum bubble size to nucleus, the greater the bubble collapse intensity to be expected; longer saturation times result in greater ratios. With the recent development of a user subroutine for the FE solver saturation time is now provided over the entire mercury domain. Its pattern agrees with spots of damage seen above and below the beam axis on the SNS inner vessel beam window and elsewhere. The other simulation result being compared to observed damage patterns is mercury velocity at the wall. Related R&D has provided evidence for the damage mitigation that higher wall velocity provides. In comparison to observations in SNS targets, inverse correlation of high velocity to damage is seen. In effect, it is the combination of the patterns of saturation time and low velocity that seems to match actual damage patterns.« less

338-GHz Semiconductor Amplifier Module

NASA Technical Reports Server (NTRS)

Samoska, Lorene A.; Gaier, Todd C.; Soria, Mary M.; Fung, King Man; Rasisic, Vesna; Deal, William; Leong, Kevin; Mei, Xiao Bing; Yoshida, Wayne; Liu, Po-Hsin;

Feasibility Study of Compressive Sensing Underwater Imaging Lidar

DTIC Science & Technology

2014-03-28

Texas Instruments Digital Micromirror Devices development system. In addition, through these studies, the deficiencies and/or areas of lack...device, such as the Digital Micromirror Device (DMD), to spatially modulate the laser source that illuminates the target plane. The same binary patterns...Digital Micromirror Device (DMD) Applications," Proc. of SPIE, 2003, 4985, 14-25. [8] T. E. Giddings and J. J. Shirron, "Numerical Simulation of the

Programmable solid state atom sources for nanofabrication.

PubMed

Han, Han; Imboden, Matthias; Stark, Thomas; del Corro, Pablo G; Pardo, Flavio; Bolle, Cristian A; Lally, Richard W; Bishop, David J

2015-06-28

In this paper we discuss the development of a MEMS-based solid state atom source that can provide controllable atom deposition ranging over eight orders of magnitude, from ten atoms per square micron up to hundreds of atomic layers, on a target ∼1 mm away. Using a micron-scale silicon plate as a thermal evaporation source we demonstrate the deposition of indium, silver, gold, copper, iron, aluminum, lead and tin. Because of their small sizes and rapid thermal response times, pulse width modulation techniques are a powerful way to control the atomic flux. Pulsing the source with precise voltages and timing provides control in terms of when and how many atoms get deposited. By arranging many of these devices into an array, one has a multi-material, programmable solid state evaporation source. These micro atom sources are a complementary technology that can enhance the capability of a variety of nano-fabrication techniques.

Anticancer Natural Compounds as Epigenetic Modulators of Gene Expression

PubMed Central

Ratovitski, Edward A.

2017-01-01

Abstract: Accumulating evidence shows that hallmarks of cancer include: “genetic and epigenetic alterations leading to inactivation of cancer suppressors, overexpression of oncogenes, deregulation of intracellular signaling cascades, alterations of cancer cell metabolism, failure to undergo cancer cell death, induction of epithelial to mesenchymal transition, invasiveness, metastasis, deregulation of immune response and changes in cancer microenvironment, which underpin cancer development”. Natural compounds as bioactive ingredients isolated from natural sources (plants, fungi, marine life forms) have revolutionized the field of anticancer therapeutics and rapid developments in preclinical studies are encouraging. Natural compounds could affect the epigenetic molecular mechanisms that modulate gene expression, as well as DNA damage and repair mechanisms. The current review will describe the latest achievements in using naturally produced compounds targeting epigenetic regulators and modulators of gene transcription in vitro and in vivo to generate novel anticancer therapeutics. PMID:28367075

VizieR Online Data Catalog: IR-bright MSX sources in the SMC with Spitzer/IRS (Kraemer+, 2017)

NASA Astrophysics Data System (ADS)

Kraemer, K. E.; Sloan, G. C.; Wood, P. R.; Jones, O. C.; Egan, M. P.

2017-07-01

Our original set of infrared spectra of MSX SMC sources was obtained in Spitzer Cycle 1 (Program ID 3277, P.I. M. Egan). This program included 35 targets from the MSX SMC catalog. 24 targets were discussed in previous papers; this paper examines the remaining 11 sources in the sample. We also selected 4 objects in the MSX SMC catalog with similar photometric characteristics in an effort to uncover additional sources with crystalline dust. We observed these targets in Spitzer Cycle 3 (Program ID 30355, P.I. J. Houck). See tables 1 and 2 for observation data and basic properties of the targets. Table 3 lists 20 additional MSX SMC sources that were observed by other Spitzer IRS programs. Overall, 59 MSX SMC sources were observed with the IRS. The spectra were observed using the low-resolution modules of the IRS, Short-Low (SL) and Long-Low (LL), which provided spectra in the 5-14 and 14-37um ranges, respectively, at a resolution between ~60 and 120. For 10 evolved stars with oxygen-rich dust in our Cycle 1 program, we obtained spectra from 0.45 to 1.03um with the Double-Beam Spectrograph at the 2.3m telescope of the Australian National University at Siding Spring Observatory. A 0.45-0.89um spectrum for one of the stars in program 30355 was also observed. These spectra have a resolution of 10Å. Tables 5-7: catalog based on the 243 sources detected in the MSX survey of the SMC, updated with positions and photometry from more recent space-based missions and ground-based surveys. See the Appendix section for more details. The SMC catalog from MSX consists of the 243 sources in the main MSX catalog (Egan+ 2003, see V/114) that lie within the region 7°

Normal aging delays and compromises early multifocal visual attention during object tracking.

PubMed

Störmer, Viola S; Li, Shu-Chen; Heekeren, Hauke R; Lindenberger, Ulman

2013-02-01

Declines in selective attention are one of the sources contributing to age-related impairments in a broad range of cognitive functions. Most previous research on mechanisms underlying older adults' selection deficits has studied the deployment of visual attention to static objects and features. Here we investigate neural correlates of age-related differences in spatial attention to multiple objects as they move. We used a multiple object tracking task, in which younger and older adults were asked to keep track of moving target objects that moved randomly in the visual field among irrelevant distractor objects. By recording the brain's electrophysiological responses during the tracking period, we were able to delineate neural processing for targets and distractors at early stages of visual processing (~100-300 msec). Older adults showed less selective attentional modulation in the early phase of the visual P1 component (100-125 msec) than younger adults, indicating that early selection is compromised in old age. However, with a 25-msec delay relative to younger adults, older adults showed distinct processing of targets (125-150 msec), that is, a delayed yet intact attentional modulation. The magnitude of this delayed attentional modulation was related to tracking performance in older adults. The amplitude of the N1 component (175-210 msec) was smaller in older adults than in younger adults, and the target amplification effect of this component was also smaller in older relative to younger adults. Overall, these results indicate that normal aging affects the efficiency and timing of early visual processing during multiple object tracking.

Hispolon inhibits the growth of estrogen receptor positive human breast cancer cells through modulation of estrogen receptor alpha

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

Jang, Eun Hyang; Jang, Soon Young; Cho, In-Hye

Human estrogen receptor α (ERα) is a nuclear transcription factor that is a major therapeutic target in breast cancer. The transcriptional activity of ERα is regulated by certain estrogen-receptor modulators. Hispolon, isolated from Phellinus linteus, a traditional medicinal mushroom called Sanghwang in Korea, has been used to treat various pathologies, such as inflammation, gastroenteric disorders, lymphatic diseases, and cancers. In this latter context, Hispolon has been reported to exhibit therapeutic efficacy against various cancer cells, including melanoma, leukemia, hepatocarcinoma, bladder cancer, and gastric cancer cells. However, ERα regulation by Hispolon has not been reported. In this study, we investigated themore » effects of Hispolon on the growth of breast cancer cells. We found that Hispolon decreased expression of ERα at both mRNA and the protein levels in MCF7 and T47D human breast cancer cells. Luciferase reporter assays showed that Hispolon decreased the transcriptional activity of ERα. Hispolon treatment also inhibited expression of the ERα target gene pS2. We propose that Hispolon, an anticancer drug extracted from natural sources, inhibits cell growth through modulation of ERα in estrogen-positive breast cancer cells and is a candidate for use in human breast cancer chemotherapy. - Highlights: • Hispolon decreased ERα expression at both mRNA and protein levels. • Hispolon decreased ERα transcriptional activity. • Hispolon treatment inhibited expression of ERα target gene pS2. • Shikonin is a candidate chemotherapeutic target in the treatment of human breast cancer.« less

Extracting binaural information from simultaneous targets and distractors: Effects of amplitude modulation and asynchronous envelopes

PubMed Central

Stellmack, Mark A.; Byrne, Andrew J.; Viemeister, Neal F.

2010-01-01

When different components of a stimulus carry different binaural information, processing of binaural information in a target component is often affected. The present experiments examine whether such interference is affected by amplitude modulation and the relative phase of modulation of the target and distractors. In all experiments, listeners attempted to discriminate interaural time differences of a target stimulus in the presence of distractor stimuli with ITD=0. In Experiment 1, modulation of the distractors but not the target reduced interference between components. In Experiment 2, synthesized musical notes exhibited little binaural interference when there were slight asynchronies between different streams of notes (31 or 62 ms). The remaining experiments suggested that the reduction in binaural interference in the previous experiments was due neither to the complex spectra of the synthesized notes nor to greater detectability of the target in the presence of modulated distractors. These data suggest that this interference is reduced when components are modulated in ways that result in the target appearing briefly in isolation, not because of segregation cues. These data also suggest that modulation and asynchronies between modulators that might be encountered in real-world listening situations are adequate to reduce binaural interference to inconsequential levels. PMID:20815459

A new software on TUG-T60 autonomous telescope for astronomical transient events

NASA Astrophysics Data System (ADS)

Dindar, Murat; Helhel, Selçuk; Esenoğlu, Hasan; Parmaksızoğlu, Murat

2015-03-01

Robotic telescopes usually run under the control of a scheduler, which provides high-level control by selecting astronomical targets for observation. TÜBİTAK (Scientific and Technological Research Council of Turkey) National Observatory (TUG)-T60 Robotic Telescope is controlled by open-source OCAAS software, formally named Talon. This study introduces new software which was designed for Talon to catch GRB, GAIA and transient alerts. The new GRB software module (daemon process) alertd is running with all other modules of Talon such as telescoped; focus, dome; camerad and telrun. Maximum slew velocity and acceleration limits of the T60 telescope are enough fast for the GRB and transient observations.

The role of rotors in atrial fibrillation

PubMed Central

Swarup, Vijay; Narayan, Sanjiv M.

2015-01-01

Despite significant advances in our understanding of atrial fibrillation (AF) mechanisms in the last 15 years, ablation outcomes remain suboptimal. A potential reason is that many ablation techniques focus on anatomic, rather than patient-specific functional targets for ablation. Panoramic contact mapping, incorporating phase analysis, repolarization and conduction dynamics, and oscillations in AF rate, overcomes many prior difficulties with mapping AF. This approach provides evidence that the mechanisms sustaining human AF are deterministic, largely due to stable electrical rotors and focal sources in either atrium. Ablation of such sources (Focal Impulse and Rotor Modulation: FIRM ablation) has been shown to improve ablation outcome compared with conventional ablation alone; independent laboratories directly targeting stable rotors have shown similar results. Clinical trials examining the role of stand-alone FIRM ablation are in progress. Looking forward, translating insights from patient-specific mapping to evidence-based guidelines and clinical practice is the next challenge in improving patient outcomes in AF management. PMID:25713729

APT Blanket Thermal Analyses of Top Horizontal Row 1 Modules

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

Shadday, M.A.

1999-09-20

The Accelerator Production of Tritium (APT) cavity flood system (CFS) is designed to be the primary safeguard for the integrity of the blanket modules during loss of coolant accidents (LOCAs). For certain large break LOCAs the CFS also provides backup for the residual heat removal systems (RHRs) in cooling the target assemblies. In the unlikely event that the internal flow passages in a blanket module or target assembly dryout, decay heat in the metal structures will be dissipated to the CFS through the module or assembly walls (i.e., rung outer walls). The target assemblies consist of tungsten targets encased inmore » steel conduits, and they can safely sustain high metal temperatures. Under internally dry conditions, the cavity flood fluid will cool the target assemblies with vigorous nucleate boiling on the external surfaces. However, the metal structures in the blanket modules consist of lead cladded in aluminum, and they have a long-term exposure temperature limit currently set to 150 degrees C. Simultaneous LOCAs in both the target and blanket heat removal systems (HRS) could result in dryout of the target ladders, as well as the horizontal blanket modules above the target. The cavity flood coolant would boil on the outside surfaces of the target ladder rungs, and the resultant steam could reduce the effectiveness of convection heat transfer from the blanket modules to the cavity flood coolant. A two-part analysis was conducted to ascertain if the cavity flood system can adequately cool the blanket modules above the targets, even when boiling is occurring on the outer surfaces of the target ladder rungs. The first part of the analysis was to model transient thermal conduction in the front top horizontal row 1 module (i.e. top horizontal modules nearest the incoming beam), while varying parametrically the convection heat transfer coefficient (htc) for the external surfaces exposed to the cavity flood flow. This part of the analysis demonstrated that the module could adequately conduct heat to the outer module surfaces, given reasonable values for the convection heat transfer coefficients. The second part of the analysis consisted of two-phase flow modeling of the natural circulation of the cavity flood fluid past the top modules. Slots in the top shield allow the cavity flood fluid to circulate. The required width for these slots, to prevent steam from backing up and blanketing the outer surfaces of the top modules, was determined.« less

Sensing device and method for measuring emission time delay during irradiation of targeted samples

NASA Technical Reports Server (NTRS)

Danielson, J. D. Sheldon (Inventor)

2000-01-01

An apparatus for measuring emission time delay during irradiation of targeted samples by utilizing digital signal processing to determine the emission phase shift caused by the sample is disclosed. The apparatus includes a source of electromagnetic radiation adapted to irradiate a target sample. A mechanism generates first and second digital input signals of known frequencies with a known phase relationship, and a device then converts the first and second digital input signals to analog sinusoidal signals. An element is provided to direct the first input signal to the electromagnetic radiation source to modulate the source by the frequency thereof to irradiate the target sample and generate a target sample emission. A device detects the target sample emission and produces a corresponding first output signal having a phase shift relative to the phase of the first input signal, the phase shift being caused by the irradiation time delay in the sample. A member produces a known phase shift in the second input signal to create a second output signal. A mechanism is then provided for converting each of the first and second analog output signals to digital signals. A mixer receives the first and second digital output signals and compares the signal phase relationship therebetween to produce a signal indicative of the change in phase relationship between the first and second output signals caused by the target sample emission. Finally, a feedback arrangement alters the phase of the second input signal based on the mixer signal to ultimately place the first and second output signals in quadrature. Mechanisms for enhancing this phase comparison and adjustment technique are also disclosed.

Sensing device and method for measuring emission time delay during irradiation of targeted samples utilizing variable phase tracking

NASA Technical Reports Server (NTRS)

Danielson, J. D. Sheldon (Inventor)

2006-01-01

An apparatus for measuring emission time delay during irradiation of targeted samples by utilizing digital signal processing to determine the emission phase shift caused by the sample is disclosed. The apparatus includes a source of electromagnetic radiation adapted to irradiate a target sample. A mechanism generates first and second digital input signals of known frequencies with a known phase relationship, and a device then converts the first and second digital input signals to analog sinusoidal signals. An element is provided to direct the first input signal to the electromagnetic radiation source to modulate the source by the frequency thereof to irradiate the target sample and generate a target sample emission. A device detects the target sample emission and produces a corresponding first output signal having a phase shift relative to the phase of the first input signal, the phase shift being caused by the irradiation time delay in the sample. A member produces a known phase shift in the second input signal to create a second output signal. A mechanism is then provided for converting each of the first and second analog output signals to digital signals. A mixer receives the first and second digital output signals and compares the signal phase relationship therebetween to produce a signal indicative of the change in phase relationship between the first and second output signals caused by the target sample emission. Finally, a feedback arrangement alters the phase of the second input signal based on the mixer signal to ultimately place the first and second output signals in quadrature. Mechanisms for enhancing this phase comparison and adjustment technique are also disclosed.

Improvement in airborne position measurements based on an ultrasonic linear-period-modulated wave by 1-bit signal processing

NASA Astrophysics Data System (ADS)

Thong-un, Natee; Hirata, Shinnosuke; Kurosawa, Minoru K.

2015-07-01

In this paper, we describe an expansion of the airborne ultrasonic systems for object localization in the three-dimensional spaces of navigation. A system, which revises the microphone arrangement and algorithm, can expand the object-position measurement from +90° in a previous method up to +180° for both the elevation and azimuth angles. The proposed system consists of a sound source and four acoustical receivers. Moreover, the system is designed to utilize low-cost devices, and low-cost computation relying on 1-bit signal processing is used to support the real-time application on a field-programmable gate array (FPGA). An object location is identified using spherical coordinates. A spherical object, which has a curved surface, is considered a target for this system. The transmit pulse to the target is a linear-period-modulated ultrasonic wave with a chirp rate of 50-20 kHz. Statistical evaluation of this work is the experimental investigation under repeatability.

An optical fiber guided ultrasonic excitation and sensing system for online monitoring of nuclear power plants

NASA Astrophysics Data System (ADS)

Yang, J.; Lee, H.; Sohn, H.

2012-05-01

This study presents an embedded laser ultrasonic system for pipeline monitoring under high temperature environment. Recently, laser ultrasonics is becoming popular because of their advantageous characteristics such as (a) noncontact inspection, (b) immunity against electromagnetic interference (EMI), and (c) applicability under high temperature. However, the performance of conventional laser ultrasonic techniques for pipeline monitoring has been limited because many pipelines are covered by insulating materials and target surfaces are inaccessible. To overcome the problem, this study designs an embeddable optical fibers and fixing devices that deliver laser beams from laser sources to a target pipe using embedded optical fibers. For guided wave generation, an optical fiber is furnished with a beam collimator for irradiating a laser beam onto a target structure. The corresponding response is measured based on the principle of laser interferometry. Light from a monochromatic source is colliminated and delivered to a target surface by another optical with a focusing module, and reflected light is transmitted back to the interferometer through the same fiber. The feasibility of the proposed system for embedded ultrasonic measurement has been experimentally verified using a pipe specimen under high temperature.

Prospects for detection of target-dependent annual modulation in direct dark matter searches

DOE PAGES

Nobile, Eugenio Del; Gelmini, Graciela B.; Witte, Samuel J.

2016-02-03

Earth's rotation about the Sun produces an annual modulation in the expected scattering rate at direct dark matter detection experiments. The annual modulation as a function of the recoil energy E R imparted by the dark matter particle to a target nucleus is expected to vary depending on the detector material. However, for most interactions a change of variables from E R to v min, the minimum speed a dark matter particle must have to impart a fixed E R to a target nucleus, produces an annual modulation independent of the target element. We recently showed that if the darkmore » matter-nucleus cross section contains a non-factorizable target and dark matter velocity dependence, the annual modulation as a function of v min can be target dependent. Here we examine more extensively the necessary conditions for target-dependent modulation, its observability in present-day experiments, and the extent to which putative signals could identify a dark matter-nucleus differential cross section with a non-factorizable dependence on the dark matter velocity.« less

Mu2e transport solenoid prototype tests results

DOE PAGES

Lopes, Mauricio L.; G. Ambrosio; DiMarco, J.; ...

2016-02-08

The Fermilab Mu2e experiment has been developed to search for evidence of charged lepton flavor violation through the direct conversion of muons into electrons. The transport solenoid is an s-shaped magnet which guides the muons from the source to the stopping target. It consists of fifty-two superconducting coils arranged in twenty-seven coil modules. A full-size prototype coil module, with all the features of a typical module of the full assembly, was successfully manufactured by a collaboration between INFN-Genoa and Fermilab. The prototype contains two coils that can be powered independently. In order to validate the design, the magnet went throughmore » an extensive test campaign. Warm tests included magnetic measurements with a vibrating stretched wire, electrical and dimensional checks. As a result, the cold performance was evaluated by a series of power tests as well as temperature dependence and minimum quench energy studies.« less

Dietary Intervention by Phytochemicals and Their Role in Modulating Coding and Non-Coding Genes in Cancer

PubMed Central

Budisan, Liviuta; Gulei, Diana; Zanoaga, Oana Mihaela; Irimie, Alexandra Iulia; Chira, Sergiu; Braicu, Cornelia; Gherman, Claudia Diana; Berindan-Neagoe, Ioana

2017-01-01

Phytochemicals are natural compounds synthesized as secondary metabolites in plants, representing an important source of molecules with a wide range of therapeutic applications. These natural agents are important regulators of key pathological processes/conditions, including cancer, as they are able to modulate the expression of coding and non-coding transcripts with an oncogenic or tumour suppressor role. These natural agents are currently exploited for the development of therapeutic strategies alone or in tandem with conventional treatments for cancer. The aim of this paper is to review the recent studies regarding the role of these natural phytochemicals in different processes related to cancer inhibition, including apoptosis activation, angiogenesis and metastasis suppression. From the large palette of phytochemicals we selected epigallocatechin gallate (EGCG), caffeic acid phenethyl ester (CAPE), genistein, morin and kaempferol, due to their increased activity in modulating multiple coding and non-coding genes, targeting the main hallmarks of cancer. PMID:28587155

Dietary Intervention by Phytochemicals and Their Role in Modulating Coding and Non-Coding Genes in Cancer.

PubMed

Budisan, Liviuta; Gulei, Diana; Zanoaga, Oana Mihaela; Irimie, Alexandra Iulia; Sergiu, Chira; Braicu, Cornelia; Gherman, Claudia Diana; Berindan-Neagoe, Ioana

2017-06-01

Phytochemicals are natural compounds synthesized as secondary metabolites in plants, representing an important source of molecules with a wide range of therapeutic applications. These natural agents are important regulators of key pathological processes/conditions, including cancer, as they are able to modulate the expression of coding and non-coding transcripts with an oncogenic or tumour suppressor role. These natural agents are currently exploited for the development of therapeutic strategies alone or in tandem with conventional treatments for cancer. The aim of this paper is to review the recent studies regarding the role of these natural phytochemicals in different processes related to cancer inhibition, including apoptosis activation, angiogenesis and metastasis suppression. From the large palette of phytochemicals we selected epigallocatechin gallate (EGCG), caffeic acid phenethyl ester (CAPE), genistein, morin and kaempferol, due to their increased activity in modulating multiple coding and non-coding genes, targeting the main hallmarks of cancer.

Light-curve Modulation of Low-mass Stars in K2. I. Identification of 481 Fast Rotators in the Solar Neighborhood

NASA Astrophysics Data System (ADS)

Saylor, Dicy; Lepine, Sebastien; Crossfield, Ian; Petigura, Erik A.

2018-01-01

The K2 mission is targeting large numbers of nearby (d < 100 pc) GKM dwarfs selected from the SUPERBLINK proper motion survey (μ > 40 mas yr‑1, V < 20). Additionally, the mission is targeting low-mass, high proper motion stars associated with the local (d < 500 pc) Galactic halo population also selected from SUPERBLINK. K2 campaigns 0 through 8 monitored a total of 26,518 of these cool main-sequence stars. We used the auto-correlation function to search for fast rotators by identifying short-period photometric modulations in the K2 light curves. We identified 481 candidate fast rotators with rotation periods <4 days that show light-curve modulations consistent with starspots. Their kinematics show low average transverse velocities, suggesting that they are part of the young disk population. A subset (13) of the fast rotators is found among those targets with colors and kinematics consistent with the local Galactic halo population and may represent stars spun up by tidal interactions in close binary systems. We further demonstrate that the M dwarf fast rotators selected from the K2 light curves are significantly more likely to have UV excess and discuss the potential of the K2 mission to identify new nearby young GKM dwarfs on the basis of their fast rotation rates. Finally, we discuss the possible use of local halo stars as fiducial, non-variable sources in the Kepler fields.

Multi-pixel high-resolution three-dimensional imaging radar

NASA Technical Reports Server (NTRS)

Cooper, Ken B. (Inventor); Dengler, Robert J. (Inventor); Siegel, Peter H. (Inventor); Chattopadhyay, Goutam (Inventor); Ward, John S. (Inventor); Juan, Nuria Llombart (Inventor); Bryllert, Tomas E. (Inventor); Mehdi, Imran (Inventor); Tarsala, Jan A. (Inventor)

2012-01-01

A three-dimensional imaging radar operating at high frequency e.g., 670 GHz radar using low phase-noise synthesizers and a fast chirper to generate a frequency-modulated continuous-wave (FMCW) waveform, is disclosed that operates with a multiplexed beam to obtain range information simultaneously on multiple pixels of a target. A source transmit beam may be divided by a hybrid coupler into multiple transmit beams multiplexed together and directed to be reflected off a target and return as a single receive beam which is demultiplexed and processed to reveal range information of separate pixels of the target associated with each transmit beam simultaneously. The multiple transmit beams may be developed with appropriate optics to be temporally and spatially differentiated before being directed to the target. Temporal differentiation corresponds to a different intermediate frequencies separating the range information of the multiple pixels. Collinear transmit beams having differentiated polarizations may also be implemented.

Method and apparatus for laser-controlled proton beam radiology

DOEpatents

Johnstone, Carol J.

1998-01-01

A proton beam radiology system provides cancer treatment and proton radiography. The system includes an accelerator for producing an H.sup.- beam and a laser source for generating a laser beam. A photodetachment module is located proximate the periphery of the accelerator. The photodetachment module combines the H.sup.- beam and laser beam to produce a neutral beam therefrom within a subsection of the H.sup.- beam. The photodetachment module emits the neutral beam along a trajectory defined by the laser beam. The photodetachment module includes a stripping foil which forms a proton beam from the neutral beam. The proton beam is delivered to a conveyance segment which transports the proton beam to a patient treatment station. The photodetachment module further includes a laser scanner which moves the laser beam along a path transverse to the cross-section of the H.sup.- beam in order to form the neutral beam in subsections of the H.sup.- beam. As the scanning laser moves across the H.sup.- beam, it similarly varies the trajectory of the proton beam emitted from the photodetachment module and in turn varies the target location of the proton beam upon the patient. Intensity modulation of the proton beam can also be achieved by controlling the output of the laser.

Method and apparatus for laser-controlled proton beam radiology

DOEpatents

Johnstone, C.J.

1998-06-02

A proton beam radiology system provides cancer treatment and proton radiography. The system includes an accelerator for producing an H{sup {minus}} beam and a laser source for generating a laser beam. A photodetachment module is located proximate the periphery of the accelerator. The photodetachment module combines the H{sup {minus}} beam and laser beam to produce a neutral beam therefrom within a subsection of the H{sup {minus}} beam. The photodetachment module emits the neutral beam along a trajectory defined by the laser beam. The photodetachment module includes a stripping foil which forms a proton beam from the neutral beam. The proton beam is delivered to a conveyance segment which transports the proton beam to a patient treatment station. The photodetachment module further includes a laser scanner which moves the laser beam along a path transverse to the cross-section of the H{sup {minus}} beam in order to form the neutral beam in subsections of the H{sup {minus}} beam. As the scanning laser moves across the H{sup {minus}} beam, it similarly varies the trajectory of the proton beam emitted from the photodetachment module and in turn varies the target location of the proton beam upon the patient. Intensity modulation of the proton beam can also be achieved by controlling the output of the laser. 9 figs.

Controlling data transfers from an origin compute node to a target compute node

DOEpatents

Archer, Charles J [Rochester, MN; Blocksome, Michael A [Rochester, MN; Ratterman, Joseph D [Rochester, MN; Smith, Brian E [Rochester, MN

2011-06-21

Methods, apparatus, and products are disclosed for controlling data transfers from an origin compute node to a target compute node that include: receiving, by an application messaging module on the target compute node, an indication of a data transfer from an origin compute node to the target compute node; and administering, by the application messaging module on the target compute node, the data transfer using one or more messaging primitives of a system messaging module in dependence upon the indication.

Effects of Scene Modulation Image Blur and Noise Upon Human Target Acquisition Performance.

DTIC Science & Technology

1997-06-01

AFRL-HE-WP-TR-1998-0012 UNITED STATES AIR FORCE RESEARCH LABORATORY EFFECTS OF SCENE MODULATION IMAGE BLUR AND NOISE UPON HUMAN TARGET...COVERED INTERIM (July 1996 - August 1996) TITLE AND SUBTITLE Effects of Scene Modulation Image Blur and Noise Upon Human Target Acquisition...dilemma in image transmission and display is that we must compromise between die conflicting constraints of dynamic range and noise . Three target

A wavelet-based adaptive fusion algorithm of infrared polarization imaging

NASA Astrophysics Data System (ADS)

Yang, Wei; Gu, Guohua; Chen, Qian; Zeng, Haifang

2011-08-01

The purpose of infrared polarization image is to highlight man-made target from a complex natural background. For the infrared polarization images can significantly distinguish target from background with different features, this paper presents a wavelet-based infrared polarization image fusion algorithm. The method is mainly for image processing of high-frequency signal portion, as for the low frequency signal, the original weighted average method has been applied. High-frequency part is processed as follows: first, the source image of the high frequency information has been extracted by way of wavelet transform, then signal strength of 3*3 window area has been calculated, making the regional signal intensity ration of source image as a matching measurement. Extraction method and decision mode of the details are determined by the decision making module. Image fusion effect is closely related to the setting threshold of decision making module. Compared to the commonly used experiment way, quadratic interpolation optimization algorithm is proposed in this paper to obtain threshold. Set the endpoints and midpoint of the threshold searching interval as initial interpolation nodes, and compute the minimum quadratic interpolation function. The best threshold can be obtained by comparing the minimum quadratic interpolation function. A series of image quality evaluation results show this method has got improvement in fusion effect; moreover, it is not only effective for some individual image, but also for a large number of images.

Molecular targets for small-molecule modulators of circadian clocks

PubMed Central

He, Baokun; Chen, Zheng

2016-01-01

Background Circadian clocks are endogenous timing systems that regulate various aspects of mammalian metabolism, physiology and behavior. Traditional chronotherapy refers to the administration of drugs in a defined circadian time window to achieve optimal pharmacokinetic and therapeutic efficacies. In recent years, substantial efforts have been dedicated to developing novel small-molecule modulators of circadian clocks. Methods Here, we review the recent progress in the identification of molecular targets of small-molecule clock modulators and their efficacies in clock-related disorders. Specifically, we examine the clock components and regulatory factors as possible molecular targets of small molecules, and we review several key clock-related disorders as promising venues for testing the preventive/therapeutic efficacies of these small molecules. Finally, we also discuss circadian regulation of drug metabolism. Results Small molecules can modulate the period, phase and/or amplitude of the circadian cycle. Core clock proteins, nuclear hormone receptors, and clock-related kinases and other epigenetic regulators are promising molecular targets for small molecules. Through these targets small molecules exert protective effects against clock-related disorders including the metabolic syndrome, immune disorders, sleep disorders and cancer. Small molecules can also modulate circadian drug metabolism and response to existing therapeutics. Conclusion Small-molecule clock modulators target clock components or diverse cellular pathways that functionally impinge upon the clock. Target identification of new small-molecule modulators will deepen our understanding of key regulatory nodes in the circadian network. Studies of clock modulators will facilitate their therapeutic applications, alone or in combination, for clock-related diseases. PMID:26750111

Shizukaol D, a Dimeric Sesquiterpene Isolated from Chloranthus serratus, Represses the Growth of Human Liver Cancer Cells by Modulating Wnt Signalling Pathway.

PubMed

Tang, Lisha; Zhu, Hengrui; Yang, Xianmei; Xie, Fang; Peng, Jingtao; Jiang, Deke; Xie, Jun; Qi, Meiyan; Yu, Long

2016-01-01

Natural products have become sources of developing new drugs for the treatment of cancer. To seek candidate compounds that inhibit the growth of liver cancer, components of Chloranthus serratus were tested. Here, we report that shizukaol D, a dimeric sesquiterpene from Chloranthus serratus, exerted a growth inhibition effect on liver cancer cells in a dose- and time-dependent manner. We demonstrated that shizukaol D induced cells to undergo apoptosis. More importantly, shizukaol D attenuated Wnt signalling and reduced the expression of endogenous Wnt target genes, which resulted in decreased expression of β-catenin. Collectively, this study demonstrated that shizukaol D inhibited the growth of liver cancer cells by modulating Wnt pathway.

PeTMbase: A Database of Plant Endogenous Target Mimics (eTMs).

PubMed

Karakülah, Gökhan; Yücebilgili Kurtoğlu, Kuaybe; Unver, Turgay

2016-01-01

MicroRNAs (miRNA) are small endogenous RNA molecules, which regulate target gene expression at post-transcriptional level. Besides, miRNA activity can be controlled by a newly discovered regulatory mechanism called endogenous target mimicry (eTM). In target mimicry, eTMs bind to the corresponding miRNAs to block the binding of specific transcript leading to increase mRNA expression. Thus, miRNA-eTM-target-mRNA regulation modules involving a wide range of biological processes; an increasing need for a comprehensive eTM database arose. Except miRSponge with limited number of Arabidopsis eTM data no available database and/or repository was developed and released for plant eTMs yet. Here, we present an online plant eTM database, called PeTMbase (http://petmbase.org), with a highly efficient search tool. To establish the repository a number of identified eTMs was obtained utilizing from high-throughput RNA-sequencing data of 11 plant species. Each transcriptome libraries is first mapped to corresponding plant genome, then long non-coding RNA (lncRNA) transcripts are characterized. Furthermore, additional lncRNAs retrieved from GREENC and PNRD were incorporated into the lncRNA catalog. Then, utilizing the lncRNA and miRNA sources a total of 2,728 eTMs were successfully predicted. Our regularly updated database, PeTMbase, provides high quality information regarding miRNA:eTM modules and will aid functional genomics studies particularly, on miRNA regulatory networks.

Ribosomal S6 kinase (RSK) modulators: a patent review.

PubMed

Ludwik, Katarzyna A; Lannigan, Deborah A

2016-09-01

The p90 ribosomal S6 kinases (RSK) are a family of Ser/Thr protein kinases that are downstream effectors of MEK1/2-ERK1/2. Increased RSK activation is implicated in the etiology of multiple pathologies, including numerous types of cancers, cardiovascular disease, liver and lung fibrosis, and infections. The review summarizes the patent and scientific literature on small molecule modulators of RSK and their potential use as therapeutics. The patents were identified using World Intellectual Property Organization and United States Patent and Trademark Office databases. The compounds described are predominantly RSK inhibitors, but a RSK activator is also described. The majority of the inhibitors are not RSK-specific. Based on the overwhelming evidence that RSK is involved in a number of diseases that have high mortalities it seems surprising that there are no RSK modulators that have pharmacokinetic properties suitable for in vivo use. MEK1/2 inhibitors are in the clinic, but the efficacy of these compounds appears to be limited by their side effects. We hypothesize that targeting the downstream effectors of MEK1/2, like RSK, are an untapped source of drug targets and that they will generate less side effects than MEK1/2 inhibitors because they regulate fewer effectors.

Device and method for imploding a microsphere with a fast liner

DOEpatents

Thode, Lester E.

1981-01-01

A device and method for relativistic electron beam heating of a high-density plasma in a small localized region. A relativistic electron beam generator or accelerator produces a high-voltage electron beam which propagates along a vacuum drift tube and is modulated to initiate electron bunching within the beam. The beam is then directed through a low-density gas chamber which provides isolation between the vacuum modulator and the relativistic electron beam target. The relativistic beam is then applied to a high-density target plasma which typically comprises DT, DD, hydrogen boron or similar thermonuclear gas at a density of 10.sup.17 to 10.sup.20 electrons per cubic centimeter. The target gas is ionized prior to application of the electron beam by means of a laser or other preionization source to form a plasma. Utilizing a relativistic electron beam with an individual particle energy exceeding 3 MeV, classical scattering by relativistic electrons passing through isolation foils is negligible. As a result, relativistic streaming instabilities are initiated within the high-density target plasma causing the relativistic electron beam to efficiently deposit its energy and momentum into a small localized region of the high-density plasma target. Fast liners disposed in the high-density target plasma are explosively or ablatively driven to implosion by a heated annular plasma surrounding the fast liner generated by an annular relativistic electron beam. An azimuthal magnetic field produced by axial current flow in the annular plasma, causes the energy in the heated annular plasma to converge on the fast liner to drive the fast liner to implode a microsphere.

Device and method for relativistic electron beam heating of a high-density plasma to drive fast liners

DOEpatents

Thode, Lester E.

1981-01-01

A device and method for relativistic electron beam heating of a high-density plasma in a small localized region. A relativistic electron beam generator or accelerator produces a high-voltage electron beam which propagates along a vacuum drift tube and is modulated to initiate electron bunching within the beam. The beam is then directed through a low-density gas chamber which provides isolation between the vacuum modulator and the relativistic electron beam target. The relativistic beam is then applied to a high-density target plasma which typically comprises DT, DD, hydrogen boron or similar thermonuclear gas at a density of 10.sup.17 to 10.sup.20 electrons per cubic centimeter. The target gas is ionized prior to application of the electron beam by means of a laser or other preionization source to form a plasma. Utilizing a relativistic electron beam with an individual particle energy exceeding 3 MeV, classical scattering by relativistic electrons passing through isolation foils is negligible. As a result, relativistic streaming instabilities are initiated within the high-density target plasma causing the relativistic electron beam to efficiently deposit its energy and momentum into a small localized region of the high-density plasma target. Fast liners disposed in the high-density target plasma are explosively or ablatively driven to implosion by a heated annular plasma surrounding the fast liner which is generated by an annular relativistic electron beam. An azimuthal magnetic field produced by axial current flow in the annular plasma, causes the energy in the heated annular plasma to converge on the fast liner.

ACUTE TERMINATION OF HUMAN ATRIAL FIBRILLATION BY IDENTIFICATION AND CATHETER ABLATION OF LOCALIZED ROTORS AND SOURCES

PubMed Central

Shivkumar, Kalyanam; Ellenbogen, Kenneth A.; Hummel, John D.; Miller, John M.; Steinberg, Jonathan S.

2012-01-01

Catheter ablation of atrial fibrillation (AF) currently relies on eliminating triggers, and no reliable method exists to map the arrhythmia itself to identify ablation targets. The aim of this multicenter study was to define the use of Focal Impulse and Rotor Modulation (FIRM) for identifying ablation targets. METHODS We prospectively enrolled the first (n=14, 11 males) consecutive patients undergoing FIRM guided ablation for persistent (n=11) and paroxysmal AF at 5 centers. A 64 pole basket catheter was used for panoramic right and left atrial mapping during AF. AF electrograms were analyzed using a novel system to identify sustained rotors (spiral waves), or focal beats (centrifugal activation to surrounding atrium). Ablation was performed first at identified sources. The primary endpoints were acute AF termination or organization (>10 % cycle length prolongation). Conventional ablation was performed only after FIRM guided ablation. RESULTS 12/14 cases were mapped. AF sources were demonstrated in all patients (average of 1.9±0.8 per patient). Sources were left atrial in 18 cases, and right atrial in 5 cases, and 21/23 were rotors. FIRM guided ablation achieved the acute endpoint in all patients, consisting of AF termination in n=8 (4.9±3.9 min at the primary source), and organization in n=4. Total FIRM time for all patients was 12.3±8.6 min. CONCLUSIONS FIRM guided ablation revealed localized AF rotors/focal sources in patients with paroxysmal, persistent and longstanding persistent AF. Brief targeted FIRM guided ablation at a priori identified sites terminated or substantially organized AF in all cases prior to any other ablation. PMID:23130890

All-digital radar architecture

NASA Astrophysics Data System (ADS)

Molchanov, Pavlo A.

2014-10-01

All digital radar architecture requires exclude mechanical scan system. The phase antenna array is necessarily large because the array elements must be co-located with very precise dimensions and will need high accuracy phase processing system for aggregate and distribute T/R modules data to/from antenna elements. Even phase array cannot provide wide field of view. New nature inspired all digital radar architecture proposed. The fly's eye consists of multiple angularly spaced sensors giving the fly simultaneously thee wide-area visual coverage it needs to detect and avoid the threats around him. Fly eye radar antenna array consist multiple directional antennas loose distributed along perimeter of ground vehicle or aircraft and coupled with receiving/transmitting front end modules connected by digital interface to central processor. Non-steering antenna array allows creating all-digital radar with extreme flexible architecture. Fly eye radar architecture provides wide possibility of digital modulation and different waveform generation. Simultaneous correlation and integration of thousands signals per second from each point of surveillance area allows not only detecting of low level signals ((low profile targets), but help to recognize and classify signals (targets) by using diversity signals, polarization modulation and intelligent processing. Proposed all digital radar architecture with distributed directional antenna array can provide a 3D space vector to the jammer by verification direction of arrival for signals sources and as result jam/spoof protection not only for radar systems, but for communication systems and any navigation constellation system, for both encrypted or unencrypted signals, for not limited number or close positioned jammers.

Sound source localization identification accuracy: Envelope dependencies.

PubMed

Yost, William A

2017-07-01

Sound source localization accuracy as measured in an identification procedure in a front azimuth sound field was studied for click trains, modulated noises, and a modulated tonal carrier. Sound source localization accuracy was determined as a function of the number of clicks in a 64 Hz click train and click rate for a 500 ms duration click train. The clicks were either broadband or high-pass filtered. Sound source localization accuracy was also measured for a single broadband filtered click and compared to a similar broadband filtered, short-duration noise. Sound source localization accuracy was determined as a function of sinusoidal amplitude modulation and the "transposed" process of modulation of filtered noises and a 4 kHz tone. Different rates (16 to 512 Hz) of modulation (including unmodulated conditions) were used. Providing modulation for filtered click stimuli, filtered noises, and the 4 kHz tone had, at most, a very small effect on sound source localization accuracy. These data suggest that amplitude modulation, while providing information about interaural time differences in headphone studies, does not have much influence on sound source localization accuracy in a sound field.

Identification of polycystic ovary syndrome potential drug targets based on pathobiological similarity in the protein-protein interaction network

PubMed Central

Li, Wan; Wei, Wenqing; Li, Yiran; Xie, Ruiqiang; Guo, Shanshan; Wang, Yahui; Jiang, Jing; Chen, Binbin; Lv, Junjie; Zhang, Nana; Chen, Lina; He, Weiming

2016-01-01

Polycystic ovary syndrome (PCOS) is one of the most common endocrinological disorders in reproductive aged women. PCOS and Type 2 Diabetes (T2D) are closely linked in multiple levels and possess high pathobiological similarity. Here, we put forward a new computational approach based on the pathobiological similarity to identify PCOS potential drug target modules (PPDT-Modules) and PCOS potential drug targets in the protein-protein interaction network (PPIN). From the systems level and biological background, 1 PPDT-Module and 22 PCOS potential drug targets were identified, 21 of which were verified by literatures to be associated with the pathogenesis of PCOS. 42 drugs targeting to 13 PCOS potential drug targets were investigated experimentally or clinically for PCOS. Evaluated by independent datasets, the whole PPDT-Module and 22 PCOS potential drug targets could not only reveal the drug response, but also distinguish the statuses between normal and disease. Our identified PPDT-Module and PCOS potential drug targets would shed light on the treatment of PCOS. And our approach would provide valuable insights to research on the pathogenesis and drug response of other diseases. PMID:27191267

Biogem: an effective tool-based approach for scaling up open source software development in bioinformatics.

PubMed

Bonnal, Raoul J P; Aerts, Jan; Githinji, George; Goto, Naohisa; MacLean, Dan; Miller, Chase A; Mishima, Hiroyuki; Pagani, Massimiliano; Ramirez-Gonzalez, Ricardo; Smant, Geert; Strozzi, Francesco; Syme, Rob; Vos, Rutger; Wennblom, Trevor J; Woodcroft, Ben J; Katayama, Toshiaki; Prins, Pjotr

2012-04-01

Biogem provides a software development environment for the Ruby programming language, which encourages community-based software development for bioinformatics while lowering the barrier to entry and encouraging best practices. Biogem, with its targeted modular and decentralized approach, software generator, tools and tight web integration, is an improved general model for scaling up collaborative open source software development in bioinformatics. Biogem and modules are free and are OSS. Biogem runs on all systems that support recent versions of Ruby, including Linux, Mac OS X and Windows. Further information at http://www.biogems.info. A tutorial is available at http://www.biogems.info/howto.html bonnal@ingm.org.

Laser profilometer module based on a low-temperature cofired ceramic substrate

NASA Astrophysics Data System (ADS)

Heikkinen, Veli; Heikkinen, Mikko; Keranen, Kimmo; Mitikka, Risto S.; Putila, Veli-Pekka; Tukkiniemi, Kari

2005-09-01

We realized a laser profilometer module using low temperature cofired ceramics technology. The device consists of a vertical-cavity surface-emitting laser as the light source and a complementary metal oxide semiconductor image sensor as the detector. The laser transmitter produces a thin light stripe on the measurable object, and the receiver calculates the distance profile using triangulation. Because the design of optoelectronic modules, such as the laser profilometer, is usually carried out using specialized software, its electronic compatibility is very important. We developed a data transmission network using commercial optical, electrical, and mechanical design software, which enabled us to electronically transfer data between the designers. The module electronics were realized with multilayer ceramics technology that eases component assembly by providing precision alignment features in the substrate. The housing was manufactured from aluminum using electronic data transfer from the mechanical design software to the five-axis milling workstation. Target distance profiles were obtained from 100 points with an accuracy varying from 0.1 mm at a 5-cm distance to 2 cm at 1.5 m. The module has potential for distance measurement in portable devices where small size, light weight, and low power consumption are important.

Modulation Detection Interference for Asynchronous Presentation of Masker and Target in Listeners with Normal and Impaired Hearing

ERIC Educational Resources Information Center

Koopman, Jan; Houtgast, Tammo; Dreschler, Wouter A.

2008-01-01

Purpose: The sensitivity to sinusoidal amplitude modulations (SAMs) is reduced when other modulated maskers are presented simultaneously at a distant frequency (also referred to as "modulation detection interference" [MDI]). This article describes the results of onset differences between masker and target as a parameter. Method: Carrier…

Optically pre-amplified lidar-radar

NASA Astrophysics Data System (ADS)

Morvan, Loic; Dolfi, Daniel; Huignard, Jean-Pierre

2001-09-01

We present the concept of an optically pre-amplified intensity modulated lidar, where the modulation frequency is in the microwave domain (1-10 GHz). Such a system permits to combine directivity of laser beams with mature radar processing. As an intensity modulated or dual-frequency laser beam is directed on a target, the backscattered intensity is collected by an optical system, pass through an optical preamplifier, and is detected on a high speed photodiode in a direct detection scheme. A radar type processing permits then to extract range, speed and identification information. The association of spatially multimode amplifier and direct detection allows low sensitivity to atmospheric turbulence and large field of view. We demonstrated theoretically that optical pre-amplification can greatly enhance sensitivity, even in spatially multimode amplifiers, such as free-space amplifier or multimode doped fiber. Computed range estimates based on this concept are presented. Laboratory demonstrations using 1 to 3 GHz modulated laser sources and >20 dB gain in multimode amplifiers are detailed. Preliminary experimental results on range and speed measurements and possible use for large amplitude vibrometry will be presented.

Prefrontal cortex modulates posterior alpha oscillations during top-down guided visual perception

PubMed Central

Helfrich, Randolph F.; Huang, Melody; Wilson, Guy; Knight, Robert T.

2017-01-01

Conscious visual perception is proposed to arise from the selective synchronization of functionally specialized but widely distributed cortical areas. It has been suggested that different frequency bands index distinct canonical computations. Here, we probed visual perception on a fine-grained temporal scale to study the oscillatory dynamics supporting prefrontal-dependent sensory processing. We tested whether a predictive context that was embedded in a rapid visual stream modulated the perception of a subsequent near-threshold target. The rapid stream was presented either rhythmically at 10 Hz, to entrain parietooccipital alpha oscillations, or arrhythmically. We identified a 2- to 4-Hz delta signature that modulated posterior alpha activity and behavior during predictive trials. Importantly, delta-mediated top-down control diminished the behavioral effects of bottom-up alpha entrainment. Simultaneous source-reconstructed EEG and cross-frequency directionality analyses revealed that this delta activity originated from prefrontal areas and modulated posterior alpha power. Taken together, this study presents converging behavioral and electrophysiological evidence for frontal delta-mediated top-down control of posterior alpha activity, selectively facilitating visual perception. PMID:28808023

Domain-Adapted Convolutional Networks for Satellite Image Classification: A Large-Scale Interactive Learning Workflow

DOE PAGES

Lunga, Dalton D.; Yang, Hsiuhan Lexie; Reith, Andrew E.; ...

2018-02-06

Satellite imagery often exhibits large spatial extent areas that encompass object classes with considerable variability. This often limits large-scale model generalization with machine learning algorithms. Notably, acquisition conditions, including dates, sensor position, lighting condition, and sensor types, often translate into class distribution shifts introducing complex nonlinear factors and hamper the potential impact of machine learning classifiers. Here, this article investigates the challenge of exploiting satellite images using convolutional neural networks (CNN) for settlement classification where the class distribution shifts are significant. We present a large-scale human settlement mapping workflow based-off multiple modules to adapt a pretrained CNN to address themore » negative impact of distribution shift on classification performance. To extend a locally trained classifier onto large spatial extents areas we introduce several submodules: First, a human-in-the-loop element for relabeling of misclassified target domain samples to generate representative examples for model adaptation; second, an efficient hashing module to minimize redundancy and noisy samples from the mass-selected examples; and third, a novel relevance ranking module to minimize the dominance of source example on the target domain. The workflow presents a novel and practical approach to achieve large-scale domain adaptation with binary classifiers that are based-off CNN features. Experimental evaluations are conducted on areas of interest that encompass various image characteristics, including multisensors, multitemporal, and multiangular conditions. Domain adaptation is assessed on source–target pairs through the transfer loss and transfer ratio metrics to illustrate the utility of the workflow.« less

Domain-Adapted Convolutional Networks for Satellite Image Classification: A Large-Scale Interactive Learning Workflow

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

Lunga, Dalton D.; Yang, Hsiuhan Lexie; Reith, Andrew E.

Satellite imagery often exhibits large spatial extent areas that encompass object classes with considerable variability. This often limits large-scale model generalization with machine learning algorithms. Notably, acquisition conditions, including dates, sensor position, lighting condition, and sensor types, often translate into class distribution shifts introducing complex nonlinear factors and hamper the potential impact of machine learning classifiers. Here, this article investigates the challenge of exploiting satellite images using convolutional neural networks (CNN) for settlement classification where the class distribution shifts are significant. We present a large-scale human settlement mapping workflow based-off multiple modules to adapt a pretrained CNN to address themore » negative impact of distribution shift on classification performance. To extend a locally trained classifier onto large spatial extents areas we introduce several submodules: First, a human-in-the-loop element for relabeling of misclassified target domain samples to generate representative examples for model adaptation; second, an efficient hashing module to minimize redundancy and noisy samples from the mass-selected examples; and third, a novel relevance ranking module to minimize the dominance of source example on the target domain. The workflow presents a novel and practical approach to achieve large-scale domain adaptation with binary classifiers that are based-off CNN features. Experimental evaluations are conducted on areas of interest that encompass various image characteristics, including multisensors, multitemporal, and multiangular conditions. Domain adaptation is assessed on source–target pairs through the transfer loss and transfer ratio metrics to illustrate the utility of the workflow.« less

Seeking new anti-cancer agents from autophagy-regulating natural products.

PubMed

Hua, Fang; Shang, Shuang; Hu, Zhuo-Wei

2017-04-01

Natural products are an important original source of many widely used drugs, including anti-cancer drugs. Early research efforts for seeking anti-cancer therapy from the natural products are mainly focused on the compounds with cytotoxicity capability. The good examples include vinblastine, vincristine, the camptothecin derivatives; topotecan, irinotecan, epipodophyllotoxin derivatives and paclitaxel. In a recent decade, the fundamental progression has been made in the understanding of molecular and cellular mechanisms regarding tumor initiation, metastasis, therapeutic resistance, immune escape, and relapse, which provide a great opportunity for the development of new mechanism-based anticancer drugs, especially drugs against new molecular and cellular targets. Autophagy, a critical cell homeostasis mechanism and promising drug target involved in a verity of human diseases including cancer, can be modulated by many compounds derived from natural products. In this review, we'll give a short introduction of autophagy and discuss the roles of autophagy in the tumorigenesis and progression. And then, we summarize the accumulated evidences to show the anti-tumor effects of several compounds derived from natural products through modulation of autophagy activity.

Aquaporins as Targets of Dietary Bioactive Phytocompounds

PubMed Central

Tesse, Angela; Grossini, Elena; Tamma, Grazia; Brenner, Catherine; Portincasa, Piero; Marinelli, Raul A.; Calamita, Giuseppe

2018-01-01

Plant-derived bioactive compounds have protective role for plants but may also modulate several physiological processes of plant consumers. In the last years, a wide spectrum of phytochemicals have been found to be beneficial to health interacting with molecular signaling pathways underlying critical functions such as cell growth and differentiation, apoptosis, autophagy, inflammation, redox balance, cell volume regulation, metabolic homeostasis, and energy balance. Hence, a large number of biologically active phytocompounds of foods have been isolated, characterized, and eventually modified representing a natural source of novel molecules to prevent, delay or cure several human diseases. Aquaporins (AQPs), a family of membrane channel proteins involved in many body functions, are emerging among the targets of bioactive phytochemicals in imparting their beneficial actions. Here, we provide a comprehensive review of this fast growing topic focusing especially on what it is known on the modulatory effects played by several edible plant and herbal compounds on AQPs, both in health and disease. Phytochemical modulation of AQP expression may provide new medical treatment options to improve the prognosis of several diseases. PMID:29721498

Photonic Applications Using Electrooptic Optical Signal Processors

DTIC Science & Technology

2011-11-16

analog-to-digital conversion using a continuous wave multiwavelength source and phase modulation Author(s): Bortnik, B.J.; Fetterman, H.R. Source... multiwavelength source and phase modulation Bartosz J. Bortnik* and Harold R. Fetterman Department of Electrical Engineering, University of California Los...utilizing a cw multiwavelength source and phase modulation instead of a mode-locked laser is presented. The output of the cw multiwave- length source

Electrophysiological correlates of cocktail-party listening.

PubMed

Lewald, Jörg; Getzmann, Stephan

2015-10-01

Detecting, localizing, and selectively attending to a particular sound source of interest in complex auditory scenes composed of multiple competing sources is a remarkable capacity of the human auditory system. The neural basis of this so-called "cocktail-party effect" has remained largely unknown. Here, we studied the cortical network engaged in solving the "cocktail-party" problem, using event-related potentials (ERPs) in combination with two tasks demanding horizontal localization of a naturalistic target sound presented either in silence or in the presence of multiple competing sound sources. Presentation of multiple sound sources, as compared to single sources, induced an increased P1 amplitude, a reduction in N1, and a strong N2 component, resulting in a pronounced negativity in the ERP difference waveform (N2d) around 260 ms after stimulus onset. About 100 ms later, the anterior contralateral N2 subcomponent (N2ac) occurred in the multiple-sources condition, as computed from the amplitude difference for targets in the left minus right hemispaces. Cortical source analyses of the ERP modulation, resulting from the contrast of multiple vs. single sources, generally revealed an initial enhancement of electrical activity in right temporo-parietal areas, including auditory cortex, by multiple sources (at P1) that is followed by a reduction, with the primary sources shifting from right inferior parietal lobule (at N1) to left dorso-frontal cortex (at N2d). Thus, cocktail-party listening, as compared to single-source localization, appears to be based on a complex chronology of successive electrical activities within a specific cortical network involved in spatial hearing in complex situations. Copyright © 2015 Elsevier B.V. All rights reserved.

Characteristics of spectro-temporal modulation frequency selectivity in humans.

PubMed

Oetjen, Arne; Verhey, Jesko L

2017-03-01

There is increasing evidence that the auditory system shows frequency selectivity for spectro-temporal modulations. A recent study of the authors has shown spectro-temporal modulation masking patterns that were in agreement with the hypothesis of spectro-temporal modulation filters in the human auditory system [Oetjen and Verhey (2015). J. Acoust. Soc. Am. 137(2), 714-723]. In the present study, that experimental data and additional data were used to model this spectro-temporal frequency selectivity. The additional data were collected to investigate to what extent the spectro-temporal modulation-frequency selectivity results from a combination of a purely temporal amplitude-modulation filter and a purely spectral amplitude-modulation filter. In contrast to the previous study, thresholds were measured for masker and target modulations with opposite directions, i.e., an upward pointing target modulation and a downward pointing masker modulation. The comparison of this data set with previous corresponding data with the same direction from target and masker modulations indicate that a specific spectro-temporal modulation filter is required to simulate all aspects of spectro-temporal modulation frequency selectivity. A model using a modified Gabor filter with a purely temporal and a purely spectral filter predicts the spectro-temporal modulation masking data.

Minimally buffered data transfers between nodes in a data communications network

DOEpatents

Miller, Douglas R.

2015-06-23

Methods, apparatus, and products for minimally buffered data transfers between nodes in a data communications network are disclosed that include: receiving, by a messaging module on an origin node, a storage identifier, a origin data type, and a target data type, the storage identifier specifying application storage containing data, the origin data type describing a data subset contained in the origin application storage, the target data type describing an arrangement of the data subset in application storage on a target node; creating, by the messaging module, origin metadata describing the origin data type; selecting, by the messaging module from the origin application storage in dependence upon the origin metadata and the storage identifier, the data subset; and transmitting, by the messaging module to the target node, the selected data subset for storing in the target application storage in dependence upon the target data type without temporarily buffering the data subset.

Accurate and cost-effective MTF measurement system for lens modules of digital cameras

NASA Astrophysics Data System (ADS)

Chang, Gao-Wei; Liao, Chia-Cheng; Yeh, Zong-Mu

2007-01-01

For many years, the widening use of digital imaging products, e.g., digital cameras, has given rise to much attention in the market of consumer electronics. However, it is important to measure and enhance the imaging performance of the digital ones, compared to that of conventional cameras (with photographic films). For example, the effect of diffraction arising from the miniaturization of the optical modules tends to decrease the image resolution. As a figure of merit, modulation transfer function (MTF) has been broadly employed to estimate the image quality. Therefore, the objective of this paper is to design and implement an accurate and cost-effective MTF measurement system for the digital camera. Once the MTF of the sensor array is provided, that of the optical module can be then obtained. In this approach, a spatial light modulator (SLM) is employed to modulate the spatial frequency of light emitted from the light-source. The modulated light going through the camera under test is consecutively detected by the sensors. The corresponding images formed from the camera are acquired by a computer and then, they are processed by an algorithm for computing the MTF. Finally, through the investigation on the measurement accuracy from various methods, such as from bar-target and spread-function methods, it appears that our approach gives quite satisfactory results.

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

Fernandez-Gutierrez, Sulmer, E-mail: sulmer.a.fernandez.gutierrez@intel.com; Browning, Jim; Lin, Ming-Chieh

Phase-control of a magnetron is studied via simulation using a combination of a continuous current source and a modulated current source. The addressable, modulated current source is turned ON and OFF at the magnetron operating frequency in order to control the electron injection and the spoke phase. Prior simulation work using a 2D model of a Rising Sun magnetron showed that the use of 100% modulated current controlled the magnetron phase and allowed for dynamic phase control. In this work, the minimum fraction of modulated current source needed to achieve a phase control is studied. The current fractions (modulated versusmore » continuous) were varied from 10% modulated current to 100% modulated current to study the effects on phase control. Dynamic phase-control, stability, and start up time of the device were studied for all these cases showing that with 10% modulated current and 90% continuous current, a phase shift of 180° can be achieved demonstrating dynamic phase control.« less

Long-Term Memories Bias Sensitivity and Target Selection in Complex Scenes

PubMed Central

Patai, Eva Zita; Doallo, Sonia; Nobre, Anna Christina

2014-01-01

In everyday situations we often rely on our memories to find what we are looking for in our cluttered environment. Recently, we developed a new experimental paradigm to investigate how long-term memory (LTM) can guide attention, and showed how the pre-exposure to a complex scene in which a target location had been learned facilitated the detection of the transient appearance of the target at the remembered location (Summerfield, Lepsien, Gitelman, Mesulam, & Nobre, 2006; Summerfield, Rao, Garside, & Nobre, 2011). The present study extends these findings by investigating whether and how LTM can enhance perceptual sensitivity to identify targets occurring within their complex scene context. Behavioral measures showed superior perceptual sensitivity (d′) for targets located in remembered spatial contexts. We used the N2pc event-related potential to test whether LTM modulated the process of selecting the target from its scene context. Surprisingly, in contrast to effects of visual spatial cues or implicit contextual cueing, LTM for target locations significantly attenuated the N2pc potential. We propose that the mechanism by which these explicitly available LTMs facilitate perceptual identification of targets may differ from mechanisms triggered by other types of top-down sources of information. PMID:23016670

System and method for radiation dose calculation within sub-volumes of a monte carlo based particle transport grid

DOEpatents

Bergstrom, Paul M.; Daly, Thomas P.; Moses, Edward I.; Patterson, Jr., Ralph W.; Schach von Wittenau, Alexis E.; Garrett, Dewey N.; House, Ronald K.; Hartmann-Siantar, Christine L.; Cox, Lawrence J.; Fujino, Donald H.

2000-01-01

A system and method is disclosed for radiation dose calculation within sub-volumes of a particle transport grid. In a first step of the method voxel volumes enclosing a first portion of the target mass are received. A second step in the method defines dosel volumes which enclose a second portion of the target mass and overlap the first portion. A third step in the method calculates common volumes between the dosel volumes and the voxel volumes. A fourth step in the method identifies locations in the target mass of energy deposits. And, a fifth step in the method calculates radiation doses received by the target mass within the dosel volumes. A common volume calculation module inputs voxel volumes enclosing a first portion of the target mass, inputs voxel mass densities corresponding to a density of the target mass within each of the voxel volumes, defines dosel volumes which enclose a second portion of the target mass and overlap the first portion, and calculates common volumes between the dosel volumes and the voxel volumes. A dosel mass module, multiplies the common volumes by corresponding voxel mass densities to obtain incremental dosel masses, and adds the incremental dosel masses corresponding to the dosel volumes to obtain dosel masses. A radiation transport module identifies locations in the target mass of energy deposits. And, a dose calculation module, coupled to the common volume calculation module and the radiation transport module, for calculating radiation doses received by the target mass within the dosel volumes.

Object motion perception is shaped by the motor control mechanism of ocular pursuit.

PubMed

Schweigart, G; Mergner, T; Barnes, G R

2003-02-01

It is still a matter of debate whether the control of smooth pursuit eye movements involves an internal drive signal from object motion perception. We measured human target velocity and target position perceptions and compared them with the presumed pursuit control mechanism (model simulations). We presented normal subjects (Ns) and vestibular loss patients (Ps) with visual target motion in space. Concurrently, a visual background was presented, which was kept stationary or was moved with or against the target (five combinations). The motion stimuli consisted of smoothed ramp displacements with different dominant frequencies and peak velocities (0.05, 0.2, 0.8 Hz; 0.2-25.6 degrees /s). Subjects always pursued the target with their eyes. In a first experiment they gave verbal magnitude estimates of perceived target velocity in space and of self-motion in space. The target velocity estimates of both Ns and Ps tended to saturate at 0.8 Hz and with peak velocities >3 degrees /s. Below these ranges the velocity estimates showed a pronounced modulation in relation to the relative target-to-background motion ('background effect'; for example, 'background with'-motion decreased and 'against'-motion increased perceived target velocity). Pronounced only in Ps and not in Ns, there was an additional modulation in relation to the relative head-to-background motion, which co-varied with an illusion of self-motion in space (circular vection, CV) in Ps. In a second experiment, subjects performed retrospective reproduction of perceived target start and end positions with the same stimuli. Perceived end position was essentially veridical in both Ns and Ps (apart from a small constant offset). Reproduced start position showed an almost negligible background effect in Ns. In contrast, it showed a pronounced modulation in Ps, which again was related to CV. The results were compared with simulations of a model that we have recently presented for velocity control of eye pursuit. We found that the main features of target velocity perception (in terms of dynamics and modulation by background) closely correspond to those of the internal drive signal for target pursuit, compatible with the notion of a common source of both the perception and the drive signal. In contrast, the eye pursuit movement is almost free of the background effect. As an explanation, we postulate that the target-to-background component in the target pursuit drive signal largely neutralises the background-to-eye retinal slip signal (optokinetic reflex signal) that feeds into the eye premotor mechanism as a competitor of the target retinal slip signal. An extension of the model allowed us to simulate also the findings of the target position perception. It is assumed to be represented in a perceptual channel that is distinct from the velocity perception, building on an efference copy of the essentially accurate eye position. We hold that other visuomotor behaviour, such as target reaching with the hand, builds mainly on this target position percept and therefore is not contaminated by the background effect in the velocity percept. Generally, the coincidence of an erroneous velocity percept and an almost perfect eye pursuit movement during background motion is discussed as an instructive example of an action-perception dissociation. This dissociation cannot be taken to indicate that the two functions are internally represented in separate brain control systems, but rather reflects the intimate coupling between both functions.

Digital micromirror device-based laser-illumination Fourier ptychographic microscopy

PubMed Central

Kuang, Cuifang; Ma, Ye; Zhou, Renjie; Lee, Justin; Barbastathis, George; Dasari, Ramachandra R.; Yaqoob, Zahid; So, Peter T. C.

2015-01-01

We report a novel approach to Fourier ptychographic microscopy (FPM) by using a digital micromirror device (DMD) and a coherent laser source (532 nm) for generating spatially modulated sample illumination. Previously demonstrated FPM systems are all based on partially-coherent illumination, which offers limited throughput due to insufficient brightness. Our FPM employs a high power coherent laser source to enable shot-noise limited high-speed imaging. For the first time, a digital micromirror device (DMD), imaged onto the back focal plane of the illumination objective, is used to generate spatially modulated sample illumination field for ptychography. By coding the on/off states of the micromirrors, the illumination plane wave angle can be varied at speeds more than 4 kHz. A set of intensity images, resulting from different oblique illuminations, are used to numerically reconstruct one high-resolution image without obvious laser speckle. Experiments were conducted using a USAF resolution target and a fiber sample, demonstrating high-resolution imaging capability of our system. We envision that our approach, if combined with a coded-aperture compressive-sensing algorithm, will further improve the imaging speed in DMD-based FPM systems. PMID:26480361

Digital micromirror device-based laser-illumination Fourier ptychographic microscopy.

PubMed

Kuang, Cuifang; Ma, Ye; Zhou, Renjie; Lee, Justin; Barbastathis, George; Dasari, Ramachandra R; Yaqoob, Zahid; So, Peter T C

2015-10-19

We report a novel approach to Fourier ptychographic microscopy (FPM) by using a digital micromirror device (DMD) and a coherent laser source (532 nm) for generating spatially modulated sample illumination. Previously demonstrated FPM systems are all based on partially-coherent illumination, which offers limited throughput due to insufficient brightness. Our FPM employs a high power coherent laser source to enable shot-noise limited high-speed imaging. For the first time, a digital micromirror device (DMD), imaged onto the back focal plane of the illumination objective, is used to generate spatially modulated sample illumination field for ptychography. By coding the on/off states of the micromirrors, the illumination plane wave angle can be varied at speeds more than 4 kHz. A set of intensity images, resulting from different oblique illuminations, are used to numerically reconstruct one high-resolution image without obvious laser speckle. Experiments were conducted using a USAF resolution target and a fiber sample, demonstrating high-resolution imaging capability of our system. We envision that our approach, if combined with a coded-aperture compressive-sensing algorithm, will further improve the imaging speed in DMD-based FPM systems.

Modulation of neuronal responses during covert search for visual feature conjunctions

PubMed Central

Buracas, Giedrius T.; Albright, Thomas D.

2009-01-01

While searching for an object in a visual scene, an observer's attentional focus and eye movements are often guided by information about object features and spatial locations. Both spatial and feature-specific attention are known to modulate neuronal responses in visual cortex, but little is known of the dynamics and interplay of these mechanisms as visual search progresses. To address this issue, we recorded from directionally selective cells in visual area MT of monkeys trained to covertly search for targets defined by a unique conjunction of color and motion features and to signal target detection with an eye movement to the putative target. Two patterns of response modulation were observed. One pattern consisted of enhanced responses to targets presented in the receptive field (RF). These modulations occurred at the end-stage of search and were more potent during correct target identification than during erroneous saccades to a distractor in RF, thus suggesting that this modulation is not a mere presaccadic enhancement. A second pattern of modulation was observed when RF stimuli were nontargets that shared a feature with the target. The latter effect was observed during early stages of search and is consistent with a global feature-specific mechanism. This effect often terminated before target identification, thus suggesting that it interacts with spatial attention. This modulation was exhibited not only for motion but also for color cue, although MT neurons are known to be insensitive to color. Such cue-invariant attentional effects may contribute to a feature binding mechanism acting across visual dimensions. PMID:19805385

Modulation of neuronal responses during covert search for visual feature conjunctions.

PubMed

Buracas, Giedrius T; Albright, Thomas D

2009-09-29

While searching for an object in a visual scene, an observer's attentional focus and eye movements are often guided by information about object features and spatial locations. Both spatial and feature-specific attention are known to modulate neuronal responses in visual cortex, but little is known of the dynamics and interplay of these mechanisms as visual search progresses. To address this issue, we recorded from directionally selective cells in visual area MT of monkeys trained to covertly search for targets defined by a unique conjunction of color and motion features and to signal target detection with an eye movement to the putative target. Two patterns of response modulation were observed. One pattern consisted of enhanced responses to targets presented in the receptive field (RF). These modulations occurred at the end-stage of search and were more potent during correct target identification than during erroneous saccades to a distractor in RF, thus suggesting that this modulation is not a mere presaccadic enhancement. A second pattern of modulation was observed when RF stimuli were nontargets that shared a feature with the target. The latter effect was observed during early stages of search and is consistent with a global feature-specific mechanism. This effect often terminated before target identification, thus suggesting that it interacts with spatial attention. This modulation was exhibited not only for motion but also for color cue, although MT neurons are known to be insensitive to color. Such cue-invariant attentional effects may contribute to a feature binding mechanism acting across visual dimensions.

Empowering pharmacoinformatics by linked life science data

NASA Astrophysics Data System (ADS)

Goldmann, Daria; Zdrazil, Barbara; Digles, Daniela; Ecker, Gerhard F.

2017-03-01

With the public availability of large data sources such as ChEMBLdb and the Open PHACTS Discovery Platform, retrieval of data sets for certain protein targets of interest with consistent assay conditions is no longer a time consuming process. Especially the use of workflow engines such as KNIME or Pipeline Pilot allows complex queries and enables to simultaneously search for several targets. Data can then directly be used as input to various ligand- and structure-based studies. In this contribution, using in-house projects on P-gp inhibition, transporter selectivity, and TRPV1 modulation we outline how the incorporation of linked life science data in the daily execution of projects allowed to expand our approaches from conventional Hansch analysis to complex, integrated multilayer models.

A hybrid phase-space and histogram source model for GPU-based Monte Carlo radiotherapy dose calculation

NASA Astrophysics Data System (ADS)

Townson, Reid W.; Zavgorodni, Sergei

2014-12-01

In GPU-based Monte Carlo simulations for radiotherapy dose calculation, source modelling from a phase-space source can be an efficiency bottleneck. Previously, this has been addressed using phase-space-let (PSL) sources, which provided significant efficiency enhancement. We propose that additional speed-up can be achieved through the use of a hybrid primary photon point source model combined with a secondary PSL source. A novel phase-space derived and histogram-based implementation of this model has been integrated into gDPM v3.0. Additionally, a simple method for approximately deriving target photon source characteristics from a phase-space that does not contain inheritable particle history variables (LATCH) has been demonstrated to succeed in selecting over 99% of the true target photons with only ~0.3% contamination (for a Varian 21EX 18 MV machine). The hybrid source model was tested using an array of open fields for various Varian 21EX and TrueBeam energies, and all cases achieved greater than 97% chi-test agreement (the mean was 99%) above the 2% isodose with 1% / 1 mm criteria. The root mean square deviations (RMSDs) were less than 1%, with a mean of 0.5%, and the source generation time was 4-5 times faster. A seven-field intensity modulated radiation therapy patient treatment achieved 95% chi-test agreement above the 10% isodose with 1% / 1 mm criteria, 99.8% for 2% / 2 mm, a RMSD of 0.8%, and source generation speed-up factor of 2.5. Presented as part of the International Workshop on Monte Carlo Techniques in Medical Physics

Neural computations underpinning the strategic management of influence in advice giving.

PubMed

Hertz, Uri; Palminteri, Stefano; Brunetti, Silvia; Olesen, Cecilie; Frith, Chris D; Bahrami, Bahador

2017-12-19

Research on social influence has focused mainly on the target of influence (e.g., consumer and voter); thus, the cognitive and neurobiological underpinnings of the source of the influence (e.g., politicians and salesmen) remain unknown. Here, in a three-sided advice-giving game, two advisers competed to influence a client by modulating their own confidence in their advice about which lottery the client should choose. We report that advisers' strategy depends on their level of influence on the client and their merit relative to one another. Moreover, blood-oxygenation-level-dependent (BOLD) signal in the temporo-parietal junction is modulated by adviser's current level of influence on the client, and relative merit prediction error affects activity in medial-prefrontal cortex. Both types of social information modulate ventral striatum response. By demonstrating what happens in our mind and brain when we try to influence others, these results begin to explain the biological mechanisms that shape inter-individual differences in social conduct.

Non-canonical modulators of nuclear receptors.

PubMed

Tice, Colin M; Zheng, Ya-Jun

2016-09-01

Like G protein-coupled receptors (GPCRs) and protein kinases, nuclear receptors (NRs) are a rich source of pharmaceutical targets. Over 80 NR-targeting drugs have been approved for 18 NRs. The focus of drug discovery in NRs has hitherto been on identifying ligands that bind to the canonical ligand binding pockets of the C-terminal ligand binding domains (LBDs). Due to the development of drug resistance and selectivity concerns, there has been considerable interest in exploring other, non-canonical ligand binding sites. Unfortunately, the potencies of compounds binding at other sites have generally not been sufficient for clinical development. However, the situation has changed dramatically over the last 3years, as compounds with sufficient potency have been reported for several NR targets. Here we review recent developments in this area from a medicinal chemistry point of view in the hope of stimulating further interest in this area of research. Copyright © 2016 Elsevier Ltd. All rights reserved.

Metrology Camera System Using Two-Color Interferometry

NASA Technical Reports Server (NTRS)

Dubovitsky, Serge; Liebe, Carl Christian; Peters, Robert; Lay, Oliver

2007-01-01

A metrology system that contains no moving parts simultaneously measures the bearings and ranges of multiple reflective targets in its vicinity, enabling determination of the three-dimensional (3D) positions of the targets with submillimeter accuracy. The system combines a direction-measuring metrology camera and an interferometric range-finding subsystem. Because the system is based partly on a prior instrument denoted the Modulation Sideband Technology for Absolute Ranging (MSTAR) sensor and because of its 3D capability, the system is denoted the MSTAR3D. Developed for use in measuring the shape (for the purpose of compensating for distortion) of large structures like radar antennas, it can also be used to measure positions of multiple targets in the course of conventional terrestrial surveying. A diagram of the system is shown in the figure. One of the targets is a reference target having a known, constant distance with respect to the system. The system comprises a laser for generating local and target beams at a carrier frequency; a frequency shifting unit to introduce a frequency shift offset between the target and local beams; a pair of high-speed modulators that apply modulation to the carrier frequency in the local and target beams to produce a series of modulation sidebands, the highspeed modulators having modulation frequencies of FL and FM; a target beam launcher that illuminates the targets with the target beam; optics and a multipixel photodetector; a local beam launcher that launches the local beam towards the multi-pixel photodetector; a mirror for projecting to the optics a portion of the target beam reflected from the targets, the optics being configured to focus the portion of the target beam at the multi-pixel photodetector; and a signal-processing unit connected to the photodetector. The portion of the target beam reflected from the targets produces spots on the multi-pixel photodetector corresponding to the targets, respectively, and the signal-processing unit centroids the spots to determine bearings of the targets, respectively. As the spots oscillate in intensity because they are mixed with the local laser beam that is flood illuminating the focal plane, the phase of oscillation of each spot is measured, the phase of sidebands in the oscillation of each spot being proportional to a distance to the corresponding target relative to the reference target A.

Dissociated α-band modulations in the dorsal and ventral visual pathways in visuospatial attention and perception.

PubMed

Capilla, Almudena; Schoffelen, Jan-Mathijs; Paterson, Gavin; Thut, Gregor; Gross, Joachim

2014-02-01

Modulations of occipito-parietal α-band (8-14 Hz) power that are opposite in direction (α-enhancement vs. α-suppression) and origin of generation (ipsilateral vs. contralateral to the locus of attention) are a robust correlate of anticipatory visuospatial attention. Yet, the neural generators of these α-band modulations, their interdependence across homotopic areas, and their respective contribution to subsequent perception remain unclear. To shed light on these questions, we employed magnetoencephalography, while human volunteers performed a spatially cued detection task. Replicating previous findings, we found α-power enhancement ipsilateral to the attended hemifield and contralateral α-suppression over occipito-parietal sensors. Source localization (beamforming) analysis showed that α-enhancement and suppression were generated in 2 distinct brain regions, located in the dorsal and ventral visual streams, respectively. Moreover, α-enhancement and suppression showed different dynamics and contribution to perception. In contrast to the initial and transient dorsal α-enhancement, α-suppression in ventro-lateral occipital cortex was sustained and influenced subsequent target detection. This anticipatory biasing of ventro-lateral extrastriate α-activity probably reflects increased receptivity in the brain region specialized in processing upcoming target features. Our results add to current models on the role of α-oscillations in attention orienting by showing that α-enhancement and suppression can be dissociated in time, space, and perceptual relevance.

Recent Progress in the Design and Discovery of RXR Modulators Targeting Alternate Binding Sites of the Receptor.

PubMed

Su, Ying; Zeng, Zhiping; Chen, Ziwen; Xu, Dan; Zhang, Weidong; Zhang, Xiao-Kun

2017-01-01

Retinoid X receptors (RXRs) occupy a central position within the nuclear receptor superfamily. They not only function as important transcriptional factors but also exhibit diverse nongenomic biological activities. The pleiotropic actions of RXRs under both physiological and pathophysiological conditions confer RXRs important drug targets for the treatment of cancer, and metabolic and neurodegenerative diseases. RXR modulators have been studied for the purpose of developing both drug molecules and chemical tools for biological investigation of RXR. Development of RXR modulators has focused on small molecules targeting the canonical ligand-binding pocket. However, accumulating results have demonstrated that there are other binding mechanisms by which small molecules interact with RXR to act as RXR modulators. This review discusses the recent development in the design and discovery of RXR modulators with a focus on those targeting novel binding sites on RXR.

Modeling and Validation of Performance Limitations for the Optimal Design of Interferometric and Intensity-Modulated Fiber Optic Displacement Sensors

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

Moro, Erik A.

Optical fiber sensors offer advantages over traditional electromechanical sensors, making them particularly well-suited for certain measurement applications. Generally speaking, optical fiber sensors respond to a desired measurand through modulation of an optical signal's intensity, phase, or wavelength. Practically, non-contacting fiber optic displacement sensors are limited to intensity-modulated and interferometric (or phase-modulated) methodologies. Intensity-modulated fiber optic displacement sensors relate target displacement to a power measurement. The simplest intensity-modulated sensor architectures are not robust to environmental and hardware fluctuations, since such variability may cause changes in the measured power level that falsely indicate target displacement. Differential intensity-modulated sensors have been implemented, offeringmore » robustness to such intensity fluctuations, and the speed of these sensors is limited only by the combined speed of the photodetection hardware and the data acquisition system (kHz-MHz). The primary disadvantages of intensity-modulated sensing are the relatively low accuracy (?m-mm for low-power sensors) and the lack of robustness, which consequently must be designed, often with great difficulty, into the sensor's architecture. White light interferometric displacement sensors, on the other hand, offer increased accuracy and robustness. Unlike their monochromatic-interferometer counterparts, white light interferometric sensors offer absolute, unambiguous displacement measurements over large displacement ranges (cm for low-power, 5 mW, sources), necessitating no initial calibration, and requiring no environmental or feedback control. The primary disadvantage of white light interferometric displacement sensors is that their utility in dynamic testing scenarios is limited, both by hardware bandwidth and by their inherent high-sensitivity to Doppler-effects. The decision of whether to use either an intensity-modulated interferometric sensor depends on an appropriate performance function (e.g., desired displacement range, accuracy, robustness, etc.). In this dissertation, the performance limitations of a bundled differential intensity-modulated displacement sensor are analyzed, where the bundling configuration has been designed to optimize performance. The performance limitations of a white light Fabry-Perot displacement sensor are also analyzed. Both these sensors are non-contacting, but they have access to different regions of the performance-space. Further, both these sensors have different degrees of sensitivity to experimental uncertainty. Made in conjunction with careful analysis, the decision of which sensor to deploy need not be an uninformed one.« less

Method and apparatus for coherent burst ranging

DOEpatents

Wachter, Eric A.; Fisher, Walter G.

1998-01-01

A high resolution ranging method is described utilizing a novel modulated waveform, hereafter referred to as coherent burst modulation. In the coherent burst method, high frequency modulation of an acoustic or electromagnetic transmitter, such as a laser, is performed at a modulation frequency. This modulation frequency is transmitted quasi-continuously in the form of interrupted bursts of radiation. Energy from the transmitter is directed onto a target, interacts with the target, and the returning energy is collected. The encoded burst pattern contained in the collected return signal is detected coherently by a receiver that is tuned so as to be principally sensitive to the modulation frequency. The receiver signal is processed to determine target range using both time-of-flight of the burst envelope and phase shift of the high frequency modulation. This approach effectively decouples the maximum unambiguous range and range resolution relationship of earlier methods, thereby allowing high precision ranging to be conducted at arbitrarily long distances using at least one burst of encoded energy. The use of a receiver tuned to the high frequency modulation contained within the coherent burst vastly improves both sensitivity in the detection of the target return signal and rejection of background interferences, such as ambient acoustic or electromagnetic noise. Simultaneous transmission at several energies (or wavelengths) is possible by encoding each energy with a separate modulation frequency or pattern; electronic demodulation at the receiver allows the return pattern for each energy to be monitored independently. Radial velocity of a target can also be determined by monitoring change in phase shift of the return signal as a function of time.

Method and apparatus for coherent burst ranging

DOEpatents

Wachter, E.A.; Fisher, W.G.

1998-04-28

A high resolution ranging method is described utilizing a novel modulated waveform, hereafter referred to as coherent burst modulation. In the coherent burst method, high frequency modulation of an acoustic or electromagnetic transmitter, such as a laser, is performed at a modulation frequency. This modulation frequency is transmitted quasi-continuously in the form of interrupted bursts of radiation. Energy from the transmitter is directed onto a target, interacts with the target, and the returning energy is collected. The encoded burst pattern contained in the collected return signal is detected coherently by a receiver that is tuned so as to be principally sensitive to the modulation frequency. The receiver signal is processed to determine target range using both time-of-flight of the burst envelope and phase shift of the high frequency modulation. This approach effectively decouples the maximum unambiguous range and range resolution relationship of earlier methods, thereby allowing high precision ranging to be conducted at arbitrarily long distances using at least one burst of encoded energy. The use of a receiver tuned to the high frequency modulation contained within the coherent burst vastly improves both sensitivity in the detection of the target return signal and rejection of background interferences, such as ambient acoustic or electromagnetic noise. Simultaneous transmission at several energies (or wavelengths) is possible by encoding each energy with a separate modulation frequency or pattern; electronic demodulation at the receiver allows the return pattern for each energy to be monitored independently. Radial velocity of a target can also be determined by monitoring change in phase shift of the return signal as a function of time. 12 figs.

Thalamic modulation of cingulate seizure activity via the regulation of gap junctions in mice thalamocingulate slice.

PubMed

Chang, Wei-Pang; Wu, José Jiun-Shian; Shyu, Bai-Chuang

2013-01-01

The thalamus is an important target for deep brain stimulation in the treatment of seizures. However, whether the modulatory effect of thalamic inputs on cortical seizures occurs through the modulation of gap junctions has not been previously studied. Therefore, we tested the effects of different gap junction blockers and couplers in a drug-resistant seizure model and studied the role of gap junctions in the thalamic modulation on cortical seizures. Multielectrode array and calcium imaging were used to record the cortical seizures induced by 4-aminopyridine (250 µM) and bicuculline (5-50 µM) in a novel thalamocingulate slice preparation. Seizure-like activity was significantly attenuated by the pan-gap junction blockers carbenoxolone and octanol and specific neuronal gap junction blocker mefloquine. The gap junction coupler trimethylamine significantly enhanced seizure-like activity. Gap junction blockers did not influence the initial phase of seizure-like activity, but they significantly decreased the amplitude and duration of the maintenance phase. The development of seizures is regulated by extracellular potassium concentration. Carbenoxolone partially restored the amplitude and duration after removing the thalamic inputs. A two-dimensional current source density analysis showed that the sink and source signals shifted to deeper layers after removing the thalamic inputs during the clonic phase. These results indicate that the regulatory mechanism of deep brain stimulation in the thalamus occurs partially though gap junctions.

Thalamic Modulation of Cingulate Seizure Activity Via the Regulation of Gap Junctions in Mice Thalamocingulate Slice

PubMed Central

Chang, Wei-Pang; Wu, José Jiun-Shian; Shyu, Bai-Chuang

2013-01-01

The thalamus is an important target for deep brain stimulation in the treatment of seizures. However, whether the modulatory effect of thalamic inputs on cortical seizures occurs through the modulation of gap junctions has not been previously studied. Therefore, we tested the effects of different gap junction blockers and couplers in a drug-resistant seizure model and studied the role of gap junctions in the thalamic modulation on cortical seizures. Multielectrode array and calcium imaging were used to record the cortical seizures induced by 4-aminopyridine (250 µM) and bicuculline (5–50 µM) in a novel thalamocingulate slice preparation. Seizure-like activity was significantly attenuated by the pan-gap junction blockers carbenoxolone and octanol and specific neuronal gap junction blocker mefloquine. The gap junction coupler trimethylamine significantly enhanced seizure-like activity. Gap junction blockers did not influence the initial phase of seizure-like activity, but they significantly decreased the amplitude and duration of the maintenance phase. The development of seizures is regulated by extracellular potassium concentration. Carbenoxolone partially restored the amplitude and duration after removing the thalamic inputs. A two-dimensional current source density analysis showed that the sink and source signals shifted to deeper layers after removing the thalamic inputs during the clonic phase. These results indicate that the regulatory mechanism of deep brain stimulation in the thalamus occurs partially though gap junctions. PMID:23690968

Top-down knowledge modulates onset capture in a feedforward manner.

PubMed

Becker, Stefanie I; Lewis, Amanda J; Axtens, Jenna E

2017-04-01

How do we select behaviourally important information from cluttered visual environments? Previous research has shown that both top-down, goal-driven factors and bottom-up, stimulus-driven factors determine which stimuli are selected. However, it is still debated when top-down processes modulate visual selection. According to a feedforward account, top-down processes modulate visual processing even before the appearance of any stimuli, whereas others claim that top-down processes modulate visual selection only at a late stage, via feedback processing. In line with such a dual stage account, some studies found that eye movements to an irrelevant onset distractor are not modulated by its similarity to the target stimulus, especially when eye movements are launched early (within 150-ms post stimulus onset). However, in these studies the target transiently changed colour due to a colour after-effect that occurred during premasking, and the time course analyses were incomplete. The present study tested the feedforward account against the dual stage account in two eye tracking experiments, with and without colour after-effects (Exp. 1), as well when the target colour varied randomly and observers were informed of the target colour with a word cue (Exp. 2). The results showed that top-down processes modulated the earliest eye movements to the onset distractors (<150-ms latencies), without incurring any costs for selection of target matching distractors. These results unambiguously support a feedforward account of top-down modulation.

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

Clayton, James; Shedlock, Daniel; Langeveld, Willem G.J.

In the security and inspection market, there is a push towards highly mobile, reduced-dose active interrogation scanning and imaging systems to allow operation in urban environments. To achieve these goals, the accelerator system design needs to be smaller than existing systems. A smaller radiation exclusion zone may be accomplished through better beam collimation and an integrated, x-ray-source/detector-array assembly to allow feedback and control of an intensity-modulated x-ray source. A shaped low-Z target in the x-ray source can be used to generate a more forward peaked x-ray beam. Electron-beam steering can then be applied to direct the forward-peaked x rays towardmore » areas in the cargo with high attenuation. This paper presents an exploratory study to identify components and upgrades that would be required to meet the desired specifications, as well as the best technical approach to design and build a prototype.« less

Sensitivity of predicted bioaerosol exposure from open windrow composting facilities to ADMS dispersion model parameters.

PubMed

Douglas, P; Tyrrel, S F; Kinnersley, R P; Whelan, M; Longhurst, P J; Walsh, K; Pollard, S J T; Drew, G H

2016-12-15

Bioaerosols are released in elevated quantities from composting facilities and are associated with negative health effects, although dose-response relationships are not well understood, and require improved exposure classification. Dispersion modelling has great potential to improve exposure classification, but has not yet been extensively used or validated in this context. We present a sensitivity analysis of the ADMS dispersion model specific to input parameter ranges relevant to bioaerosol emissions from open windrow composting. This analysis provides an aid for model calibration by prioritising parameter adjustment and targeting independent parameter estimation. Results showed that predicted exposure was most sensitive to the wet and dry deposition modules and the majority of parameters relating to emission source characteristics, including pollutant emission velocity, source geometry and source height. This research improves understanding of the accuracy of model input data required to provide more reliable exposure predictions. Copyright © 2016. Published by Elsevier Ltd.

Bounded Empathy: Neural Responses to Outgroup Targets’ (Mis)fortunes

PubMed Central

Cikara, Mina; Fiske, Susan T.

2013-01-01

The current study investigates whether mere stereotypes are sufficient to modulate empathic responses to other people’s (mis)fortunes, how these modulations manifest in the brain, and whether affective and neural responses relate to endorsing harm against different outgroup targets. Participants feel least bad when misfortunes befall envied targets, and worst when misfortunes befall pitied targets, as compared to ingroup targets. Participants are also least willing to endorse harming pitied targets, despite pitied targets being outgroup members. However, those participants who exhibit increased activation in functionally-defined insula/MFG when viewing pity targets experience positive events not only report feeling worse about those events, but also more willing to harm pity targets in a tradeoff scenario. Similarly, increased activation in anatomically-defined bilateral anterior insula, in response to positive events, predicts increased willingness to harm envy targets, but decreased willingness to harm ingroup targets, above and beyond self-reported affect in response to the events. Stereotypes’ specific content, and not just outgroup membership, modulates empathic responses and related behavioral consequences including harm. PMID:21671744

Individual differences in spontaneous analogical transfer.

PubMed

Kubricht, James R; Lu, Hongjing; Holyoak, Keith J

2017-05-01

Research on analogical problem solving has shown that people often fail to spontaneously notice the relevance of a semantically remote source analog when solving a target problem, although they are able to form mappings and derive inferences when given a hint to recall the source. Relatively little work has investigated possible individual differences that predict spontaneous transfer, or how such differences may interact with interventions that facilitate transfer. In this study, fluid intelligence was measured for participants in an analogical problem-solving task, using an abridged version of the Raven's Progressive Matrices (RPM) test. In two experiments, we systematically compared the effect of augmenting verbal descriptions of the source with animations or static diagrams. Solution rates to Duncker's radiation problem were measured across varying source presentation conditions, and participants' understanding of the relevant source material was assessed. The pattern of transfer was best fit by a moderated mediation model: the positive impact of fluid intelligence on spontaneous transfer was mediated by its influence on source comprehension; however, this path was in turn modulated by provision of a supplemental animation via its influence on comprehension of the source. Animated source depictions were most beneficial in facilitating spontaneous transfer for those participants with low scores on the fluid intelligence measure.

Method and system using power modulation and velocity modulation producing sputtered thin films with sub-angstrom thickness uniformity or custom thickness gradients

DOEpatents

Montcalm, Claude [Livermore, CA; Folta, James Allen [Livermore, CA; Walton, Christopher Charles [Berkeley, CA

2003-12-23

A method and system for determining a source flux modulation recipe for achieving a selected thickness profile of a film to be deposited (e.g., with highly uniform or highly accurate custom graded thickness) over a flat or curved substrate (such as concave or convex optics) by exposing the substrate to a vapor deposition source operated with time-varying flux distribution as a function of time. Preferably, the source is operated with time-varying power applied thereto during each sweep of the substrate to achieve the time-varying flux distribution as a function of time. Preferably, the method includes the steps of measuring the source flux distribution (using a test piece held stationary while exposed to the source with the source operated at each of a number of different applied power levels), calculating a set of predicted film thickness profiles, each film thickness profile assuming the measured flux distribution and a different one of a set of source flux modulation recipes, and determining from the predicted film thickness profiles a source flux modulation recipe which is adequate to achieve a predetermined thickness profile. Aspects of the invention include a computer-implemented method employing a graphical user interface to facilitate convenient selection of an optimal or nearly optimal source flux modulation recipe to achieve a desired thickness profile on a substrate. The method enables precise modulation of the deposition flux to which a substrate is exposed to provide a desired coating thickness distribution.

Botanicals as Modulators of Neuroplasticity: Focus on BDNF

PubMed Central

Sangiovanni, Enrico; Brivio, Paola

2017-01-01

The involvement of brain-derived neurotrophic factor (BDNF) in different central nervous system (CNS) diseases suggests that this neurotrophin may represent an interesting and reliable therapeutic target. Accordingly, the search for new compounds, also from natural sources, able to modulate BDNF has been increasingly explored. The present review considers the literature on the effects of botanicals on BDNF. Botanicals considered were Bacopa monnieri (L.) Pennell, Coffea arabica L., Crocus sativus L., Eleutherococcus senticosus Maxim., Camellia sinensis (L.) Kuntze (green tea), Ginkgo biloba L., Hypericum perforatum L., Olea europaea L. (olive oil), Panax ginseng C.A. Meyer, Rhodiola rosea L., Salvia miltiorrhiza Bunge, Vitis vinifera L., Withania somnifera (L.) Dunal, and Perilla frutescens (L.) Britton. The effect of the active principles responsible for the efficacy of the extracts is reviewed and discussed as well. The high number of articles published (more than one hundred manuscripts for 14 botanicals) supports the growing interest in the use of natural products as BDNF modulators. The studies reported strengthen the hypothesis that botanicals may be considered useful modulators of BDNF in CNS diseases, without high side effects. Further clinical studies are mandatory to confirm botanicals as preventive agents or as useful adjuvant to the pharmacological treatment. PMID:29464125

Planning Framework for Mesolevel Optimization of Urban Runoff Control Schemes

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

Zhou, Qianqian; Blohm, Andrew; Liu, Bo

A planning framework is developed to optimize runoff control schemes at scales relevant for regional planning at an early stage. The framework employs less sophisticated modeling approaches to allow a practical application in developing regions with limited data sources and computing capability. The methodology contains three interrelated modules: (1)the geographic information system (GIS)-based hydrological module, which aims at assessing local hydrological constraints and potential for runoff control according to regional land-use descriptions; (2)the grading module, which is built upon the method of fuzzy comprehensive evaluation. It is used to establish a priority ranking system to assist the allocation of runoffmore » control targets at the subdivision level; and (3)the genetic algorithm-based optimization module, which is included to derive Pareto-based optimal solutions for mesolevel allocation with multiple competing objectives. The optimization approach describes the trade-off between different allocation plans and simultaneously ensures that all allocation schemes satisfy the minimum requirement on runoff control. Our results highlight the importance of considering the mesolevel allocation strategy in addition to measures at macrolevels and microlevels in urban runoff management. (C) 2016 American Society of Civil Engineers.« less

Achievements in the development of the Water Cooled Solid Breeder Test Blanket Module of Japan to the milestones for installation in ITER

NASA Astrophysics Data System (ADS)

Tsuru, Daigo; Tanigawa, Hisashi; Hirose, Takanori; Mohri, Kensuke; Seki, Yohji; Enoeda, Mikio; Ezato, Koichiro; Suzuki, Satoshi; Nishi, Hiroshi; Akiba, Masato

2009-06-01

As the primary candidate of ITER Test Blanket Module (TBM) to be tested under the leadership of Japan, a water cooled solid breeder (WCSB) TBM is being developed. This paper shows the recent achievements towards the milestones of ITER TBMs prior to the installation, which consist of design integration in ITER, module qualification and safety assessment. With respect to the design integration, targeting the detailed design final report in 2012, structure designs of the WCSB TBM and the interfacing components (common frame and backside shielding) that are placed in a test port of ITER and the layout of the cooling system are presented. As for the module qualification, a real-scale first wall mock-up fabricated by using the hot isostatic pressing method by structural material of reduced activation martensitic ferritic steel, F82H, and flow and irradiation test of the mock-up are presented. As for safety milestones, the contents of the preliminary safety report in 2008 consisting of source term identification, failure mode and effect analysis (FMEA) and identification of postulated initiating events (PIEs) and safety analyses are presented.

Testing the concept of a modulation filter bank: the audibility of component modulation and detection of phase change in three-component modulators.

PubMed

Sek, Aleksander; Moore, Brian C J

2003-05-01

Two experiments were performed to test the concept that the auditory system contains a "modulation filter bank" (MFB). Experiment 1 examined the ability to "hear out" the modulation frequency of the central component of a three-component modulator applied to a 4-kHz sinusoidal carrier. On each trial, three modulated stimuli were presented. The modulator of the first stimulus contained three components. Within a run the frequencies of the outer two components were fixed and the frequency of the central ("target") component was drawn randomly from one of five values. The modulators of second and third stimuli contained one component. One had a frequency equal to that of the target and the other had a frequency randomly selected from one of the other possible values. Subjects indicated whether the target corresponded to the second or third stimulus. Scores were around 80% correct when the components in the three-component modulator were widely spaced and when the frequencies of the target and comparison differed sufficiently. Experiment 2 examined the ability to hear a change in the relative phase of the components in a three-component modulator with harmonically spaced components, using a 31FC task. The frequency of the central component, f(c), was either 50 or 100 Hz. Scores were 80%-90% correct when the component spacing was < or = 0.5 f(c), but decreased markedly for greater spacings. Performance was only slightly impaired by randomizing the overall modulation depth from one stimulus to the next. The results of both experiments are broadly consistent with what would be expected from a MFB with a Q value of 1 or slightly less.

Non-invasive identification of stable rotors and focal sources for human atrial fibrillation: mechanistic classification of atrial fibrillation from the electrocardiogram.

PubMed

Jones, Aled R; Krummen, David E; Narayan, Sanjiv M

2013-09-01

To develop electrocardiogram (ECG) tools to quantify the number of sources for atrial fibrillation (AF), i.e. spatially stable rotors and focal impulses, and whether they lie in right or left atrium. Intracardiac mapping has recently shown that paroxysmal and persistent AF is sustained by rotors or focal sources that are stable in location and thus targets for limited ablation [focal impulse and rotor modulation (FIRM)] to eliminate AF. Importantly, the numbers and locations of concurrent sources determine both the complexity of AF and the approach for ablation. In 36 AF patients (n = 29 persistent, 63 ± 9 years) in the CONventional ablation with or without Focal Impulse and Rotor Modulation (CONFIRM) trial, we developed phase lock (PL) to quantify spatial repeatability of ECG 'F-waves' between leads over time. Phase lock spectrally quantifies the angle θ between F-wave voltages in planes formed by ECG leads I, aVF, and V1 at successive points in time. We compared PL with ECG spectral dominant frequency (DF) and organizational index (OI) to characterize stable rotors and focal sources validated by intracardiac FIRM mapping. Focal impulse and rotor modulation ablation alone at ≤3 sources acutely terminated and rendered AF non-inducible or substantially slowed AF in 31 of 36 patients. Receiver operating characteristics of PL for this endpoint had area under the curve (AUC) = 0.72, and the optimum cut-point (PL = 0.09) had 74% sensitivity, 92% positive predictive value (PPV). Receiver operating characteristics areas for OI and DF were 0.50 and 0.58, respectively. Left (n = 28) or right (n = 3) atrial sources were localized by PL with AUC = 0.85, sensitivity 100%, PPV 30%, and negative predictive value 100%. Spectral DF provided AUC = 0.79. Notably, PL did not comigrate with diagnosis of paroxysmal or persistent AF (P = NS), unlike ECG DF. The novel metric of ECG PL identifies patients with fewer (≤3) or greater numbers of stable rotors/focal sources for AF, validated by intracardiac FIRM mapping, and localized them to right or left atria. These data open the possibility of using 12-lead ECG analyses to classify AF mechanistically and plan procedures for right- or left-sided FIRM ablation.

Modulating the Neutron Flux from a Mirror Neutron Source

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

Ryutov, D D

2011-09-01

A 14-MeV neutron source based on a Gas-Dynamic Trap will provide a high flux of 14 MeV neutrons for fusion materials and sub-component testing. In addition to its main goal, the source has potential applications in condensed matter physics and biophysics. In this report, the author considers adding one more capability to the GDT-based neutron source, the modulation of the neutron flux with a desired frequency. The modulation may be an enabling tool for the assessment of the role of non-steady-state effects in fusion devices as well as for high-precision, low-signal basic science experiments favoring the use of the synchronousmore » detection technique. A conclusion is drawn that modulation frequency of up to 1 kHz and modulation amplitude of a few percent is achievable. Limitations on the amplitude of modulations at higher frequencies are discussed.« less

The stage of priming: are intertrial repetition effects attentional or decisional?

PubMed

Becker, Stefanie I

2008-02-01

In a visual search task, reaction times to a target are shorter when its features are repeated than when they switch. The present study investigated whether these priming effects affect the attentional stage of target selection, as proposed by the priming of pop-out account, or whether they modulate performance at a later, post-selectional stage, as claimed by the episodic retrieval view. Secondly, to test whether priming affects only the target-defining feature, or whether priming can apply to all target-features in a holistic fashion, two presentation conditions were invoked, that either promoted encoding of only the target-defining feature or holistic encoding of all target features. Results from four eye tracking experiments involving a size and colour singleton target showed that, first, priming modulates selectional processes concerned with guiding attention. Second, there were traces of holistic priming effects, which however were not modulated by the displays, but by expectation and task difficulty.

Modulated infrared radiant source

NASA Technical Reports Server (NTRS)

Stewart, W. F.; Edwards, S. F.; Vann, D. S.; Mccormick, R. F.

1981-01-01

A modulated, infrared radiant energy source was developed to calibrate an airborne nadir-viewing pressure modulated radiometer to be used to detect from Earth orbit trace gases in the troposphere. The technique used an 8 cm long, 0.005 cm diameter platinum-iridium wire as an isothermal, thin line radiant energy source maintained at 1200 K. A + or - 20 K signal, oscillating at controllable frequencies from dc to 20 Hz, was superimposed on it. This periodic variation of the line source energy was used to verify the pressure modulated radiometer's capability to distinguish between the signal variations caused by the Earth's background surface and the signal from the atmospheric gases of interest.

Optical fiber bundle displacement sensor using an ac-modulated light source with subnanometer resolution and low thermal drift

NASA Astrophysics Data System (ADS)

Shimamoto, Atsushi; Tanaka, Kohichi

1995-09-01

An optical fiber bundle displacement sensor with subnanometer order resolution and low thermal drift is proposed. The setup is based on a carrier amplifier system and involves techniques to eliminate fluctuation in the light power of the source. The achieved noise level of the sensor was 0.03 nm/ \\radical Hz \\end-radical . The stability was estimated by comparing the outputs of two different sensors from the same target for 4 ks (67 min). The relative displacements between the fiber bundle ends of the two sensors and the target surface varied in the area of 400 nm depending on the ambient temperature variation at 2 deg C. However, the difference in output between the two sensor systems is within 2 nm for more than 1 hour of measurement. It is expected that it would be reduced to within the area of 0.1 nm if the ambient temperature were controlled to within +/-0.1 deg C. It is concluded that the stability of the sensors is sufficiently good to be used with nanotechnological instruments.

Compressive sensing imaging through a drywall barrier at sub-THz and THz frequencies in transmission and reflection modes

NASA Astrophysics Data System (ADS)

Takan, Taylan; Özkan, Vedat A.; Idikut, Fırat; Yildirim, Ihsan Ozan; Şahin, Asaf B.; Altan, Hakan

2014-10-01

In this work sub-terahertz imaging using Compressive Sensing (CS) techniques for targets placed behind a visibly opaque barrier is demonstrated both experimentally and theoretically. Using a multiplied Schottky diode based millimeter wave source working at 118 GHz, metal cutout targets were illuminated in both reflection and transmission configurations with and without barriers which were made out of drywall. In both modes the image is spatially discretized using laser machined, 10 × 10 pixel metal apertures to demonstrate the technique of compressive sensing. The images were collected by modulating the source and measuring the transmitted flux through the apertures using a Golay cell. Experimental results were compared to simulations of the expected transmission through the metal apertures. Image quality decreases as expected when going from the non-obscured transmission case to the obscured transmission case and finally to the obscured reflection case. However, in all instances the image appears below the Nyquist rate which demonstrates that this technique is a viable option for Through the Wall Reflection Imaging (TWRI) applications.

A Novel Device for Total Acoustic Output Measurement of High Power Transducers

NASA Astrophysics Data System (ADS)

Howard, S.; Twomey, R.; Morris, H.; Zanelli, C. I.

2010-03-01

The objective of this work was to develop a device for ultrasound power measurement applicable over a broad range of medical transducer types, orientations and powers, and which supports automatic measurements to simplify use and minimize errors. Considering all the recommendations from standards such as IEC 61161, an accurate electromagnetic null-balance has been designed for ultrasound power measurements. The sensing element is placed in the water to eliminate errors due to surface tension and water evaporation, and the motion and detection of force is constrained to one axis, to increase immunity to vibration from the floor, water sloshing and water surface waves. A transparent tank was designed so it could easily be submerged in a larger tank to accommodate large transducers or side-firing geometries, and can also be turned upside-down for upward-firing transducers. A vacuum lid allows degassing the water and target in situ. An external control module was designed to operate the sensing/driving loop and to communicate to a local computer for data logging. The sensing algorithm, which incorporates temperature compensation, compares the feedback force needed to cancel the motion for sources in the "on" and "off" states. These two states can be controlled by the control unit or manually by the user, under guidance by a graphical user interface (the system presents measured power live during collection). Software allows calibration to standard weights, or to independently calibrated acoustic sources. The design accommodates a variety of targets, including cone, rubber, brush targets and an oil-filled target for power measurement via buoyancy changes. Measurement examples are presented, including HIFU sources operating at powers from 1 to 100.

Development of allosteric modulators of GPCRs for treatment of CNS disorders.

PubMed

Nickols, Hilary Highfield; Conn, P Jeffrey

2014-01-01

The discovery of allosteric modulators of G protein-coupled receptors (GPCRs) provides a promising new strategy with potential for developing novel treatments for a variety of central nervous system (CNS) disorders. Traditional drug discovery efforts targeting GPCRs have focused on developing ligands for orthosteric sites which bind endogenous ligands. Allosteric modulators target a site separate from the orthosteric site to modulate receptor function. These allosteric agents can either potentiate (positive allosteric modulator, PAM) or inhibit (negative allosteric modulator, NAM) the receptor response and often provide much greater subtype selectivity than orthosteric ligands for the same receptors. Experimental evidence has revealed more nuanced pharmacological modes of action of allosteric modulators, with some PAMs showing allosteric agonism in combination with positive allosteric modulation in response to endogenous ligand (ago-potentiators) as well as "bitopic" ligands that interact with both the allosteric and orthosteric sites. Drugs targeting the allosteric site allow for increased drug selectivity and potentially decreased adverse side effects. Promising evidence has demonstrated potential utility of a number of allosteric modulators of GPCRs in multiple CNS disorders, including neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease, and Huntington's disease, as well as psychiatric or neurobehavioral diseases such as anxiety, schizophrenia, and addiction. © 2013.

Dosimetric effects of weight loss or gain during volumetric modulated arc therapy and intensity-modulated radiation therapy for prostate cancer

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

Pair, Matthew L.; Du, Weiliang; Rojas, Hector D.

Weight loss or gain during the course of radiation therapy for prostate cancer can alter the planned dose to the target volumes and critical organs. Typically, source-to-surface distance (SSD) measurements are documented by therapists on a weekly basis to ensure that patients' exterior surface and isocenter-to-skin surface distances remain stable. The radiation oncology team then determines whether the patient has undergone a physical change sufficient to require a new treatment plan. The effect of weight change (SSD increase or decrease) on intensity-modulated radiation therapy (IMRT) or volumetric modulated arc therapy (VMAT) dosimetry is not well known, and it is unclearmore » when rescanning or replanning is needed. The purpose of this study was to determine the effects of weight change (SSD increase or decrease) on IMRT or VMAT dose delivery in patients with prostate cancer and to determine the SSD change threshold for replanning. Whether IMRT or VMAT provides better dose stability under weight change conditions was also determined. We generated clinical IMRT and VMAT prostate and seminal vesicle treatment plans for varying SSDs for 10 randomly selected patients with prostate cancer. The differences due to SSD change were quantified by a specific dose change for a specified volume of interest. The target mean dose, decreased or increased by 2.9% per 1-cm SSD decrease or increase in IMRT and by 3.6% in VMAT. If the SSD deviation is more than 1 cm, the radiation oncology team should determine whether to continue treatment without modifications, to adjust monitor units, or to resimulate and replan.« less

Modulated Source Interferometry with Combined Amplitude and Frequency Modulation

NASA Technical Reports Server (NTRS)

Gutierrez, Roman C. (Inventor)

1998-01-01

An improved interferometer is produced by modifying a conventional interferometer to include amplitude and/or frequency modulation of a coherent light source at radio or higher frequencies. The phase of the modulation signal can be detected in an interfering beam from an interferometer and can be used to determine the actual optical phase of the beam. As such, this improvement can be adapted to virtually any two-beam interferometer, including: Michelson, Mach-Zehnder, and Sagnac interferometers. The use of an amplitude modulated coherent tight source results in an interferometer that combines the wide range advantages of coherent interferometry with the precise distance measurement advantages of white light interferometry.

Effect of synthetic jet modulation schemes on the reduction of a laminar separation bubble

NASA Astrophysics Data System (ADS)

Seo, J. H.; Cadieux, F.; Mittal, R.; Deem, E.; Cattafesta, L.

2018-03-01

The response of a laminar separation bubble to synthetic jet forcing with various modulation schemes is investigated via direct numerical simulations. A simple sinusoidal waveform is considered as a reference case, and various amplitude modulation schemes, including the square-wave "burst" modulation, are employed in the simulations. The results indicate that burst modulation is less effective at reducing the length of the flow separation than the sinusoidal forcing primarily because burst modulation is associated with a broad spectrum of input frequencies that are higher than the target frequency for the flow control. It is found that such high-frequency forcing delays vortex roll-up and promotes vortex pairing and merging, which have an adverse effect on reducing the separation bubble length. A commonly used amplitude modulation scheme is also found to have reduced effectiveness due to its spectral content. A new amplitude modulation scheme which is tailored to impart more energy at the target frequency is proposed and shown to be more effective than the other modulation schemes. Experimental measurements confirm that modulation schemes can be preserved through the actuator and used to enhance the energy content at the target modulation frequency. The present study therefore suggests that the effectiveness of synthetic jet-based flow control could be improved by carefully designing the spectral content of the modulation scheme.

Laser-controlled optical transconductance varistor system

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

Nguyen, Hoang T.; Stuart, Brent C.

2017-07-11

An optical transconductance varistor system having a modulated radiation source configured to provide modulated stimulus, a wavelength converter operably connected to the modulated radiation source to produce a modulated stimulus having a predetermined wavelength, and a wide bandgap semiconductor photoconductive material in contact between two electrodes. The photoconductive material is operably coupled, such as by a beam transport module, to receive the modulated stimulus having the predetermined wavelength to control a current flowing through the photoconductive material when a voltage potential is present across the electrodes.

Occurrence of fibrates and their metabolites in source and drinking water in Shanghai and Zhejiang, China.

PubMed

Ido, Akiko; Hiromori, Youhei; Meng, Liping; Usuda, Haruki; Nagase, Hisamitsu; Yang, Min; Hu, Jianying; Nakanishi, Tsuyoshi

2017-04-12

Fibrates, which are widely used lipidaemic-modulating drugs, are emerging environmental pollutants. However, fibrate concentrations in the environment have not been thoroughly surveyed. Here, we determined concentrations of the most commonly used fibrates and their metabolites in source water and drinking water samples from ten drinking water treatment plants in Shanghai and Zhejiang, China, using solid-phase extraction and liquid chromatography-tandem mass spectrometry. All the target compounds were detected in at least some of the source water samples, at concentrations ranging from 0.04 ng/L (fenofibrate) to 1.53 ng/L (gemfibrozil). All the compounds except fenofibrate were also detected in at least some of the drinking water samples, at recoveries ranging from 35.5% to 91.7%, suggesting that these compounds are poorly removed by typical drinking water treatment processes. In a peroxisome proliferator-activated receptor α agonistic activity assay, the target compounds showed no significant activity at nanogram per litre concentrations; therefore, our results suggest that the fibrate concentrations in drinking water in Shanghai and Zhejiang, China do not significantly affect human health. However, because of the increasing westernization of the Chinese diet, fibrate use may increase, and thus monitoring fibrate concentrations in aquatic environments and drinking water in China will become increasingly important.

Occurrence of fibrates and their metabolites in source and drinking water in Shanghai and Zhejiang, China

PubMed Central

Ido, Akiko; Hiromori, Youhei; Meng, Liping; Usuda, Haruki; Nagase, Hisamitsu; Yang, Min; Hu, Jianying; Nakanishi, Tsuyoshi

2017-01-01

Fibrates, which are widely used lipidaemic-modulating drugs, are emerging environmental pollutants. However, fibrate concentrations in the environment have not been thoroughly surveyed. Here, we determined concentrations of the most commonly used fibrates and their metabolites in source water and drinking water samples from ten drinking water treatment plants in Shanghai and Zhejiang, China, using solid-phase extraction and liquid chromatography–tandem mass spectrometry. All the target compounds were detected in at least some of the source water samples, at concentrations ranging from 0.04 ng/L (fenofibrate) to 1.53 ng/L (gemfibrozil). All the compounds except fenofibrate were also detected in at least some of the drinking water samples, at recoveries ranging from 35.5% to 91.7%, suggesting that these compounds are poorly removed by typical drinking water treatment processes. In a peroxisome proliferator-activated receptor α agonistic activity assay, the target compounds showed no significant activity at nanogram per litre concentrations; therefore, our results suggest that the fibrate concentrations in drinking water in Shanghai and Zhejiang, China do not significantly affect human health. However, because of the increasing westernization of the Chinese diet, fibrate use may increase, and thus monitoring fibrate concentrations in aquatic environments and drinking water in China will become increasingly important. PMID:28401920

Occurrence of fibrates and their metabolites in source and drinking water in Shanghai and Zhejiang, China

NASA Astrophysics Data System (ADS)

Ido, Akiko; Hiromori, Youhei; Meng, Liping; Usuda, Haruki; Nagase, Hisamitsu; Yang, Min; Hu, Jianying; Nakanishi, Tsuyoshi

2017-04-01

Fibrates, which are widely used lipidaemic-modulating drugs, are emerging environmental pollutants. However, fibrate concentrations in the environment have not been thoroughly surveyed. Here, we determined concentrations of the most commonly used fibrates and their metabolites in source water and drinking water samples from ten drinking water treatment plants in Shanghai and Zhejiang, China, using solid-phase extraction and liquid chromatography-tandem mass spectrometry. All the target compounds were detected in at least some of the source water samples, at concentrations ranging from 0.04 ng/L (fenofibrate) to 1.53 ng/L (gemfibrozil). All the compounds except fenofibrate were also detected in at least some of the drinking water samples, at recoveries ranging from 35.5% to 91.7%, suggesting that these compounds are poorly removed by typical drinking water treatment processes. In a peroxisome proliferator-activated receptor α agonistic activity assay, the target compounds showed no significant activity at nanogram per litre concentrations; therefore, our results suggest that the fibrate concentrations in drinking water in Shanghai and Zhejiang, China do not significantly affect human health. However, because of the increasing westernization of the Chinese diet, fibrate use may increase, and thus monitoring fibrate concentrations in aquatic environments and drinking water in China will become increasingly important.

Apollo experience report: Development of guidance targeting techniques for the command module and launch vehicle

NASA Technical Reports Server (NTRS)

Yencharis, J. D.; Wiley, R. F.; Davis, R. S.; Holmes, Q. A.; Zeiler, K. T.

1972-01-01

The development of the guidance targeting techniques for the Apollo command module and launch vehicle is discussed for four types of maneuvers: (1) translunar injection, (2) translunar midcourse, (3) lunar orbit insertion, and (4) return to earth. The development of real-time targeting programs for these maneuvers and the targeting procedures represented are discussed. The material is intended to convey historically the development of the targeting techniques required to meet the defined target objectives and to illustrate the solutions to problems encountered during that development.

EEG neural oscillatory dynamics reveal semantic and response conflict at difference levels of conflict awareness

PubMed Central

Jiang, Jun; Zhang, Qinglin; Van Gaal, Simon

2015-01-01

Although previous work has shown that conflict can be detected in the absence of awareness, it is unknown how different sources of conflict (i.e., semantic, response) are processed in the human brain and whether these processes are differently modulated by conflict awareness. To explore this issue, we extracted oscillatory power dynamics from electroencephalographic (EEG) data recorded while human participants performed a modified version of the Stroop task. Crucially, in this task conflict awareness was manipulated by masking a conflict-inducing color word preceding a color patch target. We isolated semantic from response conflict by introducing four color words/patches, of which two were matched to the same response. We observed that both semantic as well as response conflict were associated with mid-frontal theta-band and parietal alpha-band power modulations, irrespective of the level of conflict awareness (high vs. low), although awareness of conflict increased these conflict-related power dynamics. These results show that both semantic and response conflict can be processed in the human brain and suggest that the neural oscillatory mechanisms in EEG reflect mainly “domain general” conflict processing mechanisms, instead of conflict source specific effects. PMID:26169473

EEG neural oscillatory dynamics reveal semantic and response conflict at difference levels of conflict awareness.

PubMed

Jiang, Jun; Zhang, Qinglin; Van Gaal, Simon

2015-07-14

Although previous work has shown that conflict can be detected in the absence of awareness, it is unknown how different sources of conflict (i.e., semantic, response) are processed in the human brain and whether these processes are differently modulated by conflict awareness. To explore this issue, we extracted oscillatory power dynamics from electroencephalographic (EEG) data recorded while human participants performed a modified version of the Stroop task. Crucially, in this task conflict awareness was manipulated by masking a conflict-inducing color word preceding a color patch target. We isolated semantic from response conflict by introducing four color words/patches, of which two were matched to the same response. We observed that both semantic as well as response conflict were associated with mid-frontal theta-band and parietal alpha-band power modulations, irrespective of the level of conflict awareness (high vs. low), although awareness of conflict increased these conflict-related power dynamics. These results show that both semantic and response conflict can be processed in the human brain and suggest that the neural oscillatory mechanisms in EEG reflect mainly "domain general" conflict processing mechanisms, instead of conflict source specific effects.

Aryl hydrocarbon receptor signaling modulates antiviral immune responses: ligand metabolism rather than chemical source is the stronger predictor of outcome.

PubMed

Boule, Lisbeth A; Burke, Catherine G; Jin, Guang-Bi; Lawrence, B Paige

2018-01-29

The aryl hydrocarbon receptor (AHR) offers a compelling target to modulate the immune system. AHR agonists alter adaptive immune responses, but the consequences differ across studies. We report here the comparison of four agents representing different sources of AHR ligands in mice infected with influenza A virus (IAV): TCDD, prototype exogenous AHR agonist; PCB126, pollutant with documented human exposure; ITE, novel pharmaceutical; and FICZ, degradation product of tryptophan. All four compounds diminished virus-specific IgM levels and increased the proportion of regulatory T cells. TCDD, PCB126 and ITE, but not FICZ, reduced virus-specific IgG levels and CD8 + T cell responses. Similarly, ITE, PCB126, and TCDD reduced Th1 and Tfh cells, whereas FICZ increased their frequency. In Cyp1a1-deficient mice, all compounds, including FICZ, reduced the response to IAV. Conditional Ahr knockout mice revealed that all four compounds require AHR within hematopoietic cells. Thus, differences in the immune response to IAV likely reflect variances in quality, magnitude, and duration of AHR signaling. This indicates that binding affinity and metabolism may be stronger predictors of immune effects than a compound's source of origin, and that harnessing AHR will require finding a balance between dampening immune-mediated pathologies and maintaining sufficient host defenses against infection.

Microbial Source Module (MSM): Documenting the Science and Software for Discovery, Evaluation, and Integration

EPA Science Inventory

The Microbial Source Module (MSM) estimates microbial loading rates to land surfaces from non-point sources, and to streams from point sources for each subwatershed within a watershed. A subwatershed, the smallest modeling unit, represents the common basis for information consume...

Target-object integration, attention distribution, and object orientation interactively modulate object-based selection.

PubMed

Al-Janabi, Shahd; Greenberg, Adam S

2016-10-01

The representational basis of attentional selection can be object-based. Various studies have suggested, however, that object-based selection is less robust than spatial selection across experimental paradigms. We sought to examine the manner by which the following factors might explain this variation: Target-Object Integration (targets 'on' vs. part 'of' an object), Attention Distribution (narrow vs. wide), and Object Orientation (horizontal vs. vertical). In Experiment 1, participants discriminated between two targets presented 'on' an object in one session, or presented as a change 'of' an object in another session. There was no spatial cue-thus, attention was initially focused widely-and the objects were horizontal or vertical. We found evidence of object-based selection only when targets constituted a change 'of' an object. Additionally, object orientation modulated the sign of object-based selection: We observed a same-object advantage for horizontal objects, but a same-object cost for vertical objects. In Experiment 2, an informative cue preceded a single target presented 'on' an object or as a change 'of' an object (thus, attention was initially focused narrowly). Unlike in Experiment 1, we found evidence of object-based selection independent of target-object integration. We again found that the sign of selection was modulated by the objects' orientation. This result may reflect a meridian effect, which emerged due to anisotropies in the cortical representations when attention is oriented endogenously. Experiment 3 revealed that object orientation did not modulate object-based selection when attention was oriented exogenously. Our findings suggest that target-object integration, attention distribution, and object orientation modulate object-based selection, but only in combination.

Feature-based attention to unconscious shapes and colors.

PubMed

Schmidt, Filipp; Schmidt, Thomas

2010-08-01

Two experiments employed feature-based attention to modulate the impact of completely masked primes on subsequent pointing responses. Participants processed a color cue to select a pair of possible pointing targets out of multiple targets on the basis of their color, and then pointed to the one of those two targets with a prespecified shape. All target pairs were preceded by prime pairs triggering either the correct or the opposite response. The time interval between cue and primes was varied to modulate the time course of feature-based attentional selection. In a second experiment, the roles of color and shape were switched. Pointing trajectories showed large priming effects that were amplified by feature-based attention, indicating that attention modulated the earliest phases of motor output. Priming effects as well as their attentional modulation occurred even though participants remained unable to identify the primes, indicating distinct processes underlying visual awareness, attention, and response control.

Circulating Magnetic Microbubbles for Localized Real-Time Control of Drug Delivery by Ultrasonography-Guided Magnetic Targeting and Ultrasound

PubMed Central

Chertok, Beata; Langer, Robert

2018-01-01

Image-guided and target-selective modulation of drug delivery by external physical triggers at the site of pathology has the potential to enable tailored control of drug targeting. Magnetic microbubbles that are responsive to magnetic and acoustic modulation and visible to ultrasonography have been proposed as a means to realize this drug targeting strategy. To comply with this strategy in vivo, magnetic microbubbles must circulate systemically and evade deposition in pulmonary capillaries, while also preserving magnetic and acoustic activities in circulation over time. Unfortunately, challenges in fabricating magnetic microbubbles with such characteristics have limited progress in this field. In this report, we develop magnetic microbubbles (MagMB) that display strong magnetic and acoustic activities, while also preserving the ability to circulate systemically and evade pulmonary entrapment. Methods: We systematically evaluated the characteristics of MagMB including their pharmacokinetics, biodistribution, visibility to ultrasonography and amenability to magneto-acoustic modulation in tumor-bearing mice. We further assessed the applicability of MagMB for ultrasonography-guided control of drug targeting. Results: Following intravenous injection, MagMB exhibited a 17- to 90-fold lower pulmonary entrapment compared to previously reported magnetic microbubbles and mimicked circulation persistence of the clinically utilized Definity microbubbles (>10 min). In addition, MagMB could be accumulated in tumor vasculature by magnetic targeting, monitored by ultrasonography and collapsed by focused ultrasound on demand to activate drug deposition at the target. Furthermore, drug delivery to target tumors could be enhanced by adjusting the magneto-acoustic modulation based on ultrasonographic monitoring of MagMB in real-time. Conclusions: Circulating MagMB in conjunction with ultrasonography-guided magneto-acoustic modulation may provide a strategy for tailored minimally-invasive control over drug delivery to target tissues. PMID:29290812

Modulation of Toll-like receptor signaling in innate immunity by natural products.

PubMed

Chen, Luxi; Yu, Jianhua

2016-08-01

For centuries, natural products and their derivatives have provided a rich source of compounds for the development of new immunotherapies in the treatment of human disease. Many of these compounds are currently undergoing clinical trials, particularly as anti-oxidative, anti-microbial, and anti-cancer agents. However, the function and mechanism of natural products in how they interact with our immune system has yet to be extensively explored. Natural immune modulators may provide the key to control and ultimately defeat disorders affecting the immune system. They can either up- or down-regulate the immune response with few undesired adverse effects. In this review, we summarize the recent advancements made in utilizing natural products for immunomodulation and their important molecular targets, members of the Toll-like receptor (TLR) family, in the innate immune system. Copyright © 2016 Elsevier B.V. All rights reserved.

Marine and Semi-Synthetic Hydroxysteroids as New Scaffolds for Pregnane X Receptor Modulation

PubMed Central

Sepe, Valentina; Di Leva, Francesco Saverio; D’Amore, Claudio; Festa, Carmen; De Marino, Simona; Renga, Barbara; D’Auria, Maria Valeria; Novellino, Ettore; Limongelli, Vittorio; D’Souza, Lisette; Majik, Mahesh; Zampella, Angela; Fiorucci, Stefano

2014-01-01

In recent years many sterols with unusual structures and promising biological profiles have been identified from marine sources. Here we report the isolation of a series of 24-alkylated-hydroxysteroids from the soft coral Sinularia kavarattiensis, acting as pregnane X receptor (PXR) modulators. Starting from this scaffold a number of derivatives were prepared and evaluated for their ability to activate the PXR by assessing transactivation and quantifying gene expression. Our study reveals that ergost-5-en-3β-ol (4) induces PXR transactivation in HepG2 cells and stimulates the expression of the PXR target gene CYP3A4. To shed light on the molecular basis of the interaction between these ligands and PXR, we investigated, through docking simulations, the binding mechanism of the most potent compound of the series, 4, to the PXR. Our findings provide useful functional and structural information to guide further investigations and drug design. PMID:24871460

Marine and semi-synthetic hydroxysteroids as new scaffolds for pregnane X receptor modulation.

PubMed

Sepe, Valentina; Di Leva, Francesco Saverio; D'Amore, Claudio; Festa, Carmen; De Marino, Simona; Renga, Barbara; D'Auria, Maria Valeria; Novellino, Ettore; Limongelli, Vittorio; D'Souza, Lisette; Majik, Mahesh; Zampella, Angela; Fiorucci, Stefano

2014-05-27

In recent years many sterols with unusual structures and promising biological profiles have been identified from marine sources. Here we report the isolation of a series of 24-alkylated-hydroxysteroids from the soft coral Sinularia kavarattiensis, acting as pregnane X receptor (PXR) modulators. Starting from this scaffold a number of derivatives were prepared and evaluated for their ability to activate the PXR by assessing transactivation and quantifying gene expression. Our study reveals that ergost-5-en-3β-ol (4) induces PXR transactivation in HepG2 cells and stimulates the expression of the PXR target gene CYP3A4. To shed light on the molecular basis of the interaction between these ligands and PXR, we investigated, through docking simulations, the binding mechanism of the most potent compound of the series, 4, to the PXR. Our findings provide useful functional and structural information to guide further investigations and drug design.

Arthropod toxins and their antinociceptive properties: From venoms to painkillers.

PubMed

Monge-Fuentes, Victoria; Arenas, Claudia; Galante, Priscilla; Gonçalves, Jacqueline Coimbra; Mortari, Márcia Renata; Schwartz, Elisabeth Ferroni

2018-03-29

The complex process of pain control commonly involves the use of systemic analgesics; however, in many cases, a more potent and effective polypharmacological approach is needed to promote clinically significant improvement. Additionally, considering side effects caused by current painkillers, drug discovery is once more turning to nature as a source of more efficient therapeutic alternatives. In this context, arthropod venoms contain a vast array of bioactive substances that have evolved to selectively bind to specific pharmacological targets involved in the pain signaling pathway, playing an important role as pain activators or modulators, the latter serving as promising analgesic agents. The current review explores how the pain pathway works and surveys neuroactive compounds obtained from arthropods' toxins, which function as pain modulators through their interaction with specific ion channels and membrane receptors, emerging as promising candidates for drug design and development. Copyright © 2018 Elsevier Inc. All rights reserved.

Establishment of A431 cell membrane chromatography-RPLC method for screening target components from Radix Caulophylli.

PubMed

Hou, Xiaofang; Wang, Sicen; Hou, Jingjing; He, Langchong

2011-03-01

We describe here an analytical method of A431 cell membrane chromatography (A431/CMC) (CMC, cell membrane chromatography) combined with RPLC for recognition, separation, and identification of target components from traditional Chinese medicines (TCMs) Radix Caulophylli. The A431 cells with high expressed epidermal growth factor receptor (EGFR) were used to prepare the stationary phase in the CMC model. Retention fractions on the A431-CMC model were collected using an automated fraction collection and injection module (FC/I). Each fraction was analyzed by RPLC under the optimized conditions. Gefitinib and erlotinib were used as standard compounds to investigate the suitability and reliability of the A431 cell membrane chromatography-RPLC method prior to screening target component from Radix Caulophylli total alkaloids. The results indicated that caulophine and taspine were the target component acting on the epidermal growth factor receptor. This method could be an efficient way in drug discovery using natural medicinal herbs as a source of novel compounds. Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Neural Dynamics Underlying Target Detection in the Human Brain

PubMed Central

Bansal, Arjun K.; Madhavan, Radhika; Agam, Yigal; Golby, Alexandra; Madsen, Joseph R.

2014-01-01

Sensory signals must be interpreted in the context of goals and tasks. To detect a target in an image, the brain compares input signals and goals to elicit the correct behavior. We examined how target detection modulates visual recognition signals by recording intracranial field potential responses from 776 electrodes in 10 epileptic human subjects. We observed reliable differences in the physiological responses to stimuli when a cued target was present versus absent. Goal-related modulation was particularly strong in the inferior temporal and fusiform gyri, two areas important for object recognition. Target modulation started after 250 ms post stimulus, considerably after the onset of visual recognition signals. While broadband signals exhibited increased or decreased power, gamma frequency power showed predominantly increases during target presence. These observations support models where task goals interact with sensory inputs via top-down signals that influence the highest echelons of visual processing after the onset of selective responses. PMID:24553944

High-order UWB pulses scheme to generate multilevel modulation formats based on incoherent optical sources.

PubMed

Bolea, Mario; Mora, José; Ortega, Beatriz; Capmany, José

2013-11-18

We present a high-order UWB pulses generator based on a microwave photonic filter which provides a set of positive and negative samples by using the slicing of an incoherent optical source and the phase inversion in a Mach-Zehnder modulator. The simple scalability and high reconfigurability of the system permit a better accomplishment of the FCC requirements. Moreover, the proposed scheme permits an easy adaptation to pulse amplitude modulation, bi phase modulation, pulse shape modulation and pulse position modulation. The flexibility of the scheme for being adaptable to multilevel modulation formats permits to increase the transmission bit rate by using hybrid modulation formats.

Directly Phase-Modulated Light Source

NASA Astrophysics Data System (ADS)

Yuan, Z. L.; Fröhlich, B.; Lucamarini, M.; Roberts, G. L.; Dynes, J. F.; Shields, A. J.

2016-07-01

The art of imparting information onto a light wave by optical signal modulation is fundamental to all forms of optical communication. Among many schemes, direct modulation of laser diodes stands out as a simple, robust, and cost-effective method. However, the simultaneous changes in intensity, frequency, and phase have prevented its application in the field of secure quantum communication. Here, we propose and experimentally demonstrate a directly phase-modulated light source which overcomes the main disadvantages associated with direct modulation and is suitable for diverse applications such as coherent communications and quantum cryptography. The source separates the tasks of phase preparation and pulse generation between a pair of semiconductor lasers leading to very pure phase states. Moreover, the cavity-enhanced electro-optic effect enables the first example of subvolt half-wave phase modulation at high signal rates. The source is compact, stable, and versatile, and we show its potential to become the standard transmitter for future quantum communication networks based on attenuated laser pulses.

Muscle Expression of SOD1(G93A) Modulates microRNA and mRNA Transcription Pattern Associated with the Myelination Process in the Spinal Cord of Transgenic Mice.

PubMed

Dobrowolny, Gabriella; Bernardini, Camilla; Martini, Martina; Baranzini, Mirko; Barba, Marta; Musarò, Antonio

2015-01-01

A crucial system severely affected in several neuromuscular diseases is the loss of effective connection between muscle and nerve, leading to a pathological non-communication between the two tissues. One of the best examples of impaired interplay between muscle and nerve is Amyotrophic Lateral Sclerosis, a neurodegenerative disease characterized by degeneration of motor neurons and muscle atrophy. Increasing evidences suggest that damage to motor neurons is enhanced by alterations in the neighboring non-neuronal cells and indicate that altered skeletal muscle might be the source of signals that impinge motor neuron activity and survival. Here we investigated whether muscle selective expression of SOD1(G93A) mutant gene modulates mRNAs and miRNAs expression at the level of spinal cord of MLC/SOD1(G93A) mice. Using a Taqman array, the Affymetrix Mouse Gene 2.0 ST approach and the MiRwalk 2.0 database, which provides information on miRNA and their predicted target genes, we revealed that muscle specific expression of SOD1(G93A) modulates relevant molecules of the genetic and epigenetic circuitry of myelin homeostasis in spinal cord of transgenic mice. Our study provides insights into the pathophysiological interplay between muscle and nerve and supports the hypothesis that muscle is a source of signals that can either positively or negatively affect the nervous system.

Covert enaction at work: Recording the continuous movements of visuospatial attention to visible or imagined targets by means of Steady-State Visual Evoked Potentials (SSVEPs).

PubMed

Gregori Grgič, Regina; Calore, Enrico; de'Sperati, Claudio

2016-01-01

Whereas overt visuospatial attention is customarily measured with eye tracking, covert attention is assessed by various methods. Here we exploited Steady-State Visual Evoked Potentials (SSVEPs) - the oscillatory responses of the visual cortex to incoming flickering stimuli - to record the movements of covert visuospatial attention in a way operatively similar to eye tracking (attention tracking), which allowed us to compare motion observation and motion extrapolation with and without eye movements. Observers fixated a central dot and covertly tracked a target oscillating horizontally and sinusoidally. In the background, the left and the right halves of the screen flickered at two different frequencies, generating two SSVEPs in occipital regions whose size varied reciprocally as observers attended to the moving target. The two signals were combined into a single quantity that was modulated at the target frequency in a quasi-sinusoidal way, often clearly visible in single trials. The modulation continued almost unchanged when the target was switched off and observers mentally extrapolated its motion in imagery, and also when observers pointed their finger at the moving target during covert tracking, or imagined doing so. The amplitude of modulation during covert tracking was ∼25-30% of that measured when observers followed the target with their eyes. We used 4 electrodes in parieto-occipital areas, but similar results were achieved with a single electrode in Oz. In a second experiment we tested ramp and step motion. During overt tracking, SSVEPs were remarkably accurate, showing both saccadic-like and smooth pursuit-like modulations of cortical responsiveness, although during covert tracking the modulation deteriorated. Covert tracking was better with sinusoidal motion than ramp motion, and better with moving targets than stationary ones. The clear modulation of cortical responsiveness recorded during both overt and covert tracking, identical for motion observation and motion extrapolation, suggests to include covert attention movements in enactive theories of mental imagery. Copyright © 2015 Elsevier Ltd. All rights reserved.

The Galway astronomical Stokes polarimeter: an all-Stokes optical polarimeter with ultra-high time resolution

NASA Astrophysics Data System (ADS)

Collins, Patrick; Kyne, Gillian; Lara, David; Redfern, Michael; Shearer, Andy; Sheehan, Brendan

2013-12-01

Many astronomical objects emit polarised light, which can give information both about their source mechanisms, and about (scattering) geometry in their source regions. To date (mostly) only the linearly polarised components of the emission have been observed in stellar sources. Observations have been constrained because of instrumental considerations to periods of excellent observing conditions, and to steady, slowly or periodically-varying sources. This leaves a whole range of interesting objects beyond the range of observation at present. The Galway Astronomical Stokes Polarimeter (GASP) has been developed to enable us to make observations on these very sources. GASP measures the four components of the Stokes Vector simultaneously over a broad wavelength range 400-800 nm., with a time resolution of order microseconds given suitable detectors and a bright source - this is possible because the optical design contains no moving or modulating components. The initial design of GASP is presented and we include some preliminary observational results demonstrating that components of the Stokes vector can be measured to % in conditions of poor atmospheric stability. Issues of efficiency and stability are addressed. An analysis of suitable astronomical targets, demanding the unique properties of GASP, is also presented.

Three dimensional intensity modulated brachytherapy (IMBT): dosimetry algorithm and inverse treatment planning.

PubMed

Shi, Chengyu; Guo, Bingqi; Cheng, Chih-Yao; Esquivel, Carlos; Eng, Tony; Papanikolaou, Niko

2010-07-01

The feasibility of intensity modulated brachytherapy (IMBT) to improve dose conformity for irregularly shaped targets has been previously investigated by researchers by means of using partially shielded sources. However, partial shielding does not fully explore the potential of IMBT. The goal of this study is to introduce the concept of three dimensional (3D) intensity modulated brachytherapy and solve two fundamental issues regarding the application of 3D IMBT treatment planning: The dose calculation algorithm and the inverse treatment planning method. A 3D IMBT treatment planning system prototype was developed using the MATLAB platform. This system consists of three major components: (1) A comprehensive IMBT source calibration method with dosimetric inputs from Monte Carlo (EGSnrc) simulations; (2) a "modified TG-43" (mTG-43) dose calculation formalism for IMBT dosimetry; and (3) a physical constraint based inverse IMBT treatment planning platform utilizing a simulated annealing optimization algorithm. The model S700 Axxent electronic brachytherapy source developed by Xoft, Inc. (Fremont, CA), was simulated in this application. Ten intracavitary accelerated partial breast irradiation (APBI) cases were studied. For each case, an "isotropic plan" with only optimized source dwell time and a fully optimized IMBT plan were generated and compared to the original plan in various dosimetric aspects, such as the plan quality, planning, and delivery time. The issue of the mechanical complexity of the IMBT applicator is not addressed in this study. IMBT approaches showed superior plan quality compared to the original plans and tht isotropic plans to different extents in all studied cases. An extremely difficult case with a small breast and a small distance to the ribs and skin, the IMBT plan minimized the high dose volume V200 by 16.1% and 4.8%, respectively, compared to the original and the isotropic plans. The conformity index for the target was increased by 0.13 and 0.04, respectively. The maximum dose to the skin was reduced by 56 and 28 cGy, respectively, per fraction. Also, the maximum dose to the ribs was reduced by 104 and 96 cGy, respectively, per fraction. The mean dose to the ipsilateral and contralateral breasts and lungs were also slightly reduced by the IMBT plan. The limitations of IMBT are the longer planning and delivery time. The IMBT plan took around 2 h to optimize, while the isotropic plan optimization could reach the global minimum within 5 min. The delivery time for the IMBT plan is typically four to six times longer than the corresponding isotropic plan. In this study, a dosimetry method for IMBT sources was proposed and an inverse treatment planning system prototype for IMBT was developed. The improvement of plan quality by 3D IMBT was demonstrated using ten APBI case studies. Faster computers and higher output of the source can further reduce plan optimization and delivery time, respectively.

Status of the Neutron Imaging and Diffraction Instrument IMAT

NASA Astrophysics Data System (ADS)

Kockelmann, Winfried; Burca, Genoveva; Kelleher, Joe F.; Kabra, Saurabh; Zhang, Shu-Yan; Rhodes, Nigel J.; Schooneveld, Erik M.; Sykora, Jeff; Pooley, Daniel E.; Nightingale, Jim B.; Aliotta, Francesco; Ponterio, Rosa C.; Salvato, Gabriele; Tresoldi, Dario; Vasi, Cirino; McPhate, Jason B.; Tremsin, Anton S.

A cold neutron imaging and diffraction instrument, IMAT, is currently being constructed at the ISIS second target station. IMAT will capitalize on time-of-flight transmission and diffraction techniques available at a pulsed neutron source. Analytical techniques will include neutron radiography, neutron tomography, energy-selective neutron imaging, and spatially resolved diffraction scans for residual strain and texture determination. Commissioning of the instrument will start in 2015, with time-resolving imaging detectors and two diffraction detector prototype modules. IMAT will be operated as a user facility for material science applications and will be open for developments of time-of-flight imaging methods.

Calculations vs. Measurements for Remnant Dose Rates from SNS Spent Structures

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

Popova, Irina I.; Gallmeier, Franz X.; Trotter, Steven M.

The Spallation Neutron Source (SNS) in Oak Ridge, Tennessee, is an accelerator driven neutron scattering facility for materials research. Presently SNS is capable to operate at 1.4 MW proton beam power incident on a mercury target with a proton beam energy of 1 GeV and 60 Hz repetition rate. SNS target system components are periodically replaced because they reach their end-of-life due to radiation induced material damage. Target vessel, which houses mercury target, is exchanged about two-three times per year and the proton beam window (PBW) is exchanged every two – three years.Each spent structure that leaves the SNS sitemore » requires supporting documentation with radionuclide inventory and dose rate prediction for the time of the transportation. Neutronics analyses are performed, assuming realistic irradiation history and decay case to ensure that the container/package, housing the structure, is compliant with the waste management regulations. Analyses are complex due to geometry, multi-code usage and following data treatment.To validate analyses, measurements of dose rates from the spent target vessel # 13 and PBW module #5 were performed. Neutronics analyses were performed to calculate residual dose rates from both structures for the time of measurements.« less

Real-time multi-target ranging based on chaotic polarization laser radars in the drive-response VCSELs.

PubMed

Zhong, Dongzhou; Xu, Geliang; Luo, Wei; Xiao, Zhenzhen

2017-09-04

According to the principle of complete chaos synchronization and the theory of Hilbert phase transformation, we propose a novel real-time multi-target ranging scheme by using chaotic polarization laser radar in the drive-response vertical-cavity surface-emitting lasers (VCSELs). In the scheme, to ensure each polarization component (PC) of the master VCSEL (MVCSEL) to be synchronized steadily with that of the slave VCSEL, the output x-PC and y-PC from the MVCSEL in the drive system and those in the response system are modulated by the linear electro-optic effect simultaneously. Under this condition, by simulating the influences of some key parameters of the system on the synchronization quality and the relative errors of the two-target ranging, related operating parameters can be optimized. The x-PC and the y-PC, as two chaotic radar sources, are used to implement the real-time ranging for two targets. It is found that the measured distances of the two targets at arbitrary position exhibit strong real-time stability and only slight jitter. Their resolutions are up to millimeters, and their relative errors are very small and less than 2.7%.

Development of allosteric modulators of GPCRs for treatment of CNS disorders

PubMed Central

Nickols, Hilary Highfield; Conn, P. Jeffrey

2013-01-01

The discovery of allosteric modulators of G protein-coupled receptors (GPCRs) provides a promising new strategy with potential for developing novel treatments for a variety of central nervous system (CNS) disorders. Traditional drug discovery efforts targeting GPCRs have focused on developing ligands for orthosteric sites which bind endogenous ligands. Allosteric modulators target a site separate from the orthosteric site to modulate receptor function. These allosteric agents can either potentiate (positive allosteric modulator, PAM) or inhibit (negative allosteric modulator, NAM) the receptor response and often provide much greater subtype selectivity than do orthosteric ligands for the same receptors. Experimental evidence has revealed more nuanced pharmacological modes of action of allosteric modulators, with some PAMs showing allosteric agonism in combination with positive allosteric modulation in response to endogenous ligand (ago-potentiators) as well as “bitopic” ligands that interact with both the allosteric and orthosteric sites. Drugs targeting the allosteric site allow for increased drug selectivity and potentially decreased adverse side effects. Promising evidence has demonstrated potential utility of a number of allosteric modulators of GPCRs in multiple CNS disorders, including neurodegenerative diseases such as Alzheimer’s disease, Parkinson’s disease, and Huntington’s disease, as well as psychiatric or neurobehavioral diseases such as anxiety, schizophrenia, and addiction. PMID:24076101

Dissociation in decision bias mechanism between probabilistic information and previous decision

PubMed Central

Kaneko, Yoshiyuki; Sakai, Katsuyuki

2015-01-01

Target detection performance is known to be influenced by events in the previous trials. It has not been clear, however, whether this bias effect is due to the previous sensory stimulus, motor response, or decision. Also it remains open whether or not the previous trial effect emerges via the same mechanism as the effect of knowledge about the target probability. In the present study, we asked normal human subjects to make a decision about the presence or absence of a visual target. We presented a pre-cue indicating the target probability before the stimulus, and also a decision-response mapping cue after the stimulus so as to tease apart the effect of decision from that of motor response. We found that the target detection performance was significantly affected by the probability cue in the current trial and also by the decision in the previous trial. While the information about the target probability modulated the decision criteria, the previous decision modulated the sensitivity to target-relevant sensory signals (d-prime). Using functional magnetic resonance imaging (fMRI), we also found that activation in the left intraparietal sulcus (IPS) was decreased when the probability cue indicated a high probability of the target. By contrast, activation in the right inferior frontal gyrus (IFG) was increased when the subjects made a target-present decision in the previous trial, but this change was observed specifically when the target was present in the current trial. Activation in these regions was associated with individual-difference in the decision computation parameters. We argue that the previous decision biases the target detection performance by modulating the processing of target-selective information, and this mechanism is distinct from modulation of decision criteria due to expectation of a target. PMID:25999844

Postdictive modulation of visual orientation.

PubMed

Kawabe, Takahiro

2012-01-01

The present study investigated how visual orientation is modulated by subsequent orientation inputs. Observers were presented a near-vertical Gabor patch as a target, followed by a left- or right-tilted second Gabor patch as a distracter in the spatial vicinity of the target. The task of the observers was to judge whether the target was right- or left-tilted (Experiment 1) or whether the target was vertical or not (Supplementary experiment). The judgment was biased toward the orientation of the distracter (the postdictive modulation of visual orientation). The judgment bias peaked when the target and distracter were temporally separated by 100 ms, indicating a specific temporal mechanism for this phenomenon. However, when the visibility of the distracter was reduced via backward masking, the judgment bias disappeared. On the other hand, the low-visibility distracter could still cause a simultaneous orientation contrast, indicating that the distracter orientation is still processed in the visual system (Experiment 2). Our results suggest that the postdictive modulation of visual orientation stems from spatiotemporal integration of visual orientation on the basis of a slow feature matching process.

Efficient “Communication through Coherence” Requires Oscillations Structured to Minimize Interference between Signals

PubMed Central

Akam, Thomas E.; Kullmann, Dimitri M.

2012-01-01

The ‘communication through coherence’ (CTC) hypothesis proposes that selective communication among neural networks is achieved by coherence between firing rate oscillation in a sending region and gain modulation in a receiving region. Although this hypothesis has stimulated extensive work, it remains unclear whether the mechanism can in principle allow reliable and selective information transfer. Here we use a simple mathematical model to investigate how accurately coherent gain modulation can filter a population-coded target signal from task-irrelevant distracting inputs. We show that selective communication can indeed be achieved, although the structure of oscillatory activity in the target and distracting networks must satisfy certain previously unrecognized constraints. Firstly, the target input must be differentiated from distractors by the amplitude, phase or frequency of its oscillatory modulation. When distracting inputs oscillate incoherently in the same frequency band as the target, communication accuracy is severely degraded because of varying overlap between the firing rate oscillations of distracting inputs and the gain modulation in the receiving region. Secondly, the oscillatory modulation of the target input must be strong in order to achieve a high signal-to-noise ratio relative to stochastic spiking of individual neurons. Thus, whilst providing a quantitative demonstration of the power of coherent oscillatory gain modulation to flexibly control information flow, our results identify constraints imposed by the need to avoid interference between signals, and reveal a likely organizing principle for the structure of neural oscillations in the brain. PMID:23144603

Hierarchical cortical transcriptome disorganization in autism.

PubMed

Lombardo, Michael V; Courchesne, Eric; Lewis, Nathan E; Pramparo, Tiziano

2017-01-01

Autism spectrum disorders (ASD) are etiologically heterogeneous and complex. Functional genomics work has begun to identify a diverse array of dysregulated transcriptomic programs (e.g., synaptic, immune, cell cycle, DNA damage, WNT signaling, cortical patterning and differentiation) potentially involved in ASD brain abnormalities during childhood and adulthood. However, it remains unclear whether such diverse dysregulated pathways are independent of each other or instead reflect coordinated hierarchical systems-level pathology. Two ASD cortical transcriptome datasets were re-analyzed using consensus weighted gene co-expression network analysis (WGCNA) to identify common co-expression modules across datasets. Linear mixed-effect models and Bayesian replication statistics were used to identify replicable differentially expressed modules. Eigengene network analysis was then utilized to identify between-group differences in how co-expression modules interact and cluster into hierarchical meta-modular organization. Protein-protein interaction analyses were also used to determine whether dysregulated co-expression modules show enhanced interactions. We find replicable evidence for 10 gene co-expression modules that are differentially expressed in ASD cortex. Rather than being independent non-interacting sources of pathology, these dysregulated co-expression modules work in synergy and physically interact at the protein level. These systems-level transcriptional signals are characterized by downregulation of synaptic processes coordinated with upregulation of immune/inflammation, response to other organism, catabolism, viral processes, translation, protein targeting and localization, cell proliferation, and vasculature development. Hierarchical organization of meta-modules (clusters of highly correlated modules) is also highly affected in ASD. These findings highlight that dysregulation of the ASD cortical transcriptome is characterized by the dysregulation of multiple coordinated transcriptional programs producing synergistic systems-level effects that cannot be fully appreciated by studying the individual component biological processes in isolation.

No apparent influence of psychometrically-defined schizotypy on orientation-dependent contextual modulation of visual contrast detection.

PubMed

Mannion, Damien J; Donkin, Chris; Whitford, Thomas J

2017-01-01

We investigated the relationship between psychometrically-defined schizotypy and the ability to detect a visual target pattern. Target detection is typically impaired by a surrounding pattern (context) with an orientation that is parallel to the target, relative to a surrounding pattern with an orientation that is orthogonal to the target (orientation-dependent contextual modulation). Based on reports that this effect is reduced in those with schizophrenia, we hypothesised that there would be a negative relationship between the relative score on psychometrically-defined schizotypy and the relative effect of orientation-dependent contextual modulation. We measured visual contrast detection thresholds and scores on the Oxford-Liverpool Inventory of Feelings and Experiences (O-LIFE) from a non-clinical sample ( N = 100). Contrary to our hypothesis, we find an absence of a monotonic relationship between the relative magnitude of orientation-dependent contextual modulation of visual contrast detection and the relative score on any of the subscales of the O-LIFE. The apparent difference of this result with previous reports on those with schizophrenia suggests that orientation-dependent contextual modulation may be an informative condition in which schizophrenia and psychometrically-defined schizotypy are dissociated. However, further research is also required to clarify the strength of orientation-dependent contextual modulation in those with schizophrenia.

Changes in predictive cuing modulate the hemispheric distribution of the P1 inhibitory response to attentional targets.

PubMed

Lasaponara, Stefano; D' Onofrio, Marianna; Dragone, Alessio; Pinto, Mario; Caratelli, Ludovica; Doricchi, Fabrizio

2017-05-01

Brain activity related to orienting of attention with spatial cues and brain responses to attentional targets are influenced the probabilistic contingency between cues and targets. Compared to predictive cues, cues predicting at chance the location of targets reduce the filtering out of uncued locations and the costs in reorienting attention to targets presented at these locations. Slagter et al. (2016) have recently suggested that the larger target related P1 component that is found in the hemisphere ipsilateral to validly cued targets reflects stimulus-driven inhibition in the processing of the unstimulated side of space contralateral to the same hemisphere. Here we verified whether the strength of this inhibition and the amplitude of the corresponding P1 wave are modulated by the probabilistic link between cues and targets. Healthy participants performed a task of endogenous orienting once with predictive and once with non-predictive directional cues. In the non-predictive condition we observed a drop in the amplitude of the P1 ipsilateral to the target and in the costs of reorienting. No change in the inter-hemispheric latencies of the P1 was found between the two predictive conditions. The N1 facilitatory component was unaffected by predictive cuing. These results show that the predictive context modulates the strength of the inhibitory P1 response and that this modulation is not matched with changes in the inter-hemispheric interaction between the P1 generators of the two hemispheres. Copyright © 2017. Published by Elsevier Ltd.

Predictability and context determine differences in conflict monitoring between adolescence and adulthood.

PubMed

Chmielewski, Witold X; Roessner, Veit; Beste, Christian

2015-10-01

The ability to link contextual information to actions is an important aspect of conflict monitoring and response selection. These mechanisms depend on medial prefrontal networks. Although these areas undergo a protracted development from adolescence to adulthood, it has remained elusive how the influence of contextual information on conflict monitoring is modulated between adolescence and adulthood. Using event-related potentials (ERPs) and source localization techniques we show that the ability to link contextual information to actions is altered and that the predictability of upcoming events is an important factor to consider in this context. In adolescents, conflict monitoring functions are not as much modulated by predictability factors as in adults. It seems that adults exhibit a stronger anticipation of upcoming events than adolescents. This results in disadvantages for adults when the upcoming context is not predictable. In adolescents, problems to predict upcoming events therefore turn out to be beneficial. Two cognitive-neurophysiological factors are important for this: The first factor is related to altered conflict monitoring functions associated with modulations of neural activity in the medial frontal cortex. The second factor is related to altered perceptual processing of target stimuli associated with modulations of neural activity in parieto-occipital areas. Copyright © 2015 Elsevier B.V. All rights reserved.

Building Better Planet Populations for EXOSIMS

NASA Astrophysics Data System (ADS)

Garrett, Daniel; Savransky, Dmitry

2018-01-01

The Exoplanet Open-Source Imaging Mission Simulator (EXOSIMS) software package simulates ensembles of space-based direct imaging surveys to provide a variety of science and engineering yield distributions for proposed mission designs. These mission simulations rely heavily on assumed distributions of planetary population parameters including semi-major axis, planetary radius, eccentricity, albedo, and orbital orientation to provide heuristics for target selection and to simulate planetary systems for detection and characterization. The distributions are encoded in PlanetPopulation modules within EXOSIMS which are selected by the user in the input JSON script when a simulation is run. The earliest written PlanetPopulation modules available in EXOSIMS are based on planet population models where the planetary parameters are considered to be independent from one another. While independent parameters allow for quick computation of heuristics and sampling for simulated planetary systems, results from planet-finding surveys have shown that many parameters (e.g., semi-major axis/orbital period and planetary radius) are not independent. We present new PlanetPopulation modules for EXOSIMS which are built on models based on planet-finding survey results where semi-major axis and planetary radius are not independent and provide methods for sampling their joint distribution. These new modules enhance the ability of EXOSIMS to simulate realistic planetary systems and give more realistic science yield distributions.

Method and infrastructure for cycle-reproducible simulation on large scale digital circuits on a coordinated set of field-programmable gate arrays (FPGAs)

DOEpatents

Asaad, Sameh W; Bellofatto, Ralph E; Brezzo, Bernard; Haymes, Charles L; Kapur, Mohit; Parker, Benjamin D; Roewer, Thomas; Tierno, Jose A

2014-01-28

A plurality of target field programmable gate arrays are interconnected in accordance with a connection topology and map portions of a target system. A control module is coupled to the plurality of target field programmable gate arrays. A balanced clock distribution network is configured to distribute a reference clock signal, and a balanced reset distribution network is coupled to the control module and configured to distribute a reset signal to the plurality of target field programmable gate arrays. The control module and the balanced reset distribution network are cooperatively configured to initiate and control a simulation of the target system with the plurality of target field programmable gate arrays. A plurality of local clock control state machines reside in the target field programmable gate arrays. The local clock state machines are configured to generate a set of synchronized free-running and stoppable clocks to maintain cycle-accurate and cycle-reproducible execution of the simulation of the target system. A method is also provided.

A feature-weighting account of priming in conjunction search.

PubMed

Becker, Stefanie I; Horstmann, Gernot

2009-02-01

Previous research on the priming effect in conjunction search has shown that repeating the target and distractor features across displays speeds mean response times but does not improve search efficiency: Repetitions do not reduce the set size effect-that is, the effect of the number of distractor items-but only modulate the intercept of the search function. In the present study, we investigated whether priming modulates search efficiency when a conjunctively defined target randomly changes between red and green. The results from an eyetracking experiment show that repeating the target across trials reduced the set size effect and, thus, did enhance search efficiency. Moreover, the probability of selecting the target as the first item in the display was higher when the target-distractor displays were repeated across trials than when they changed. Finally, red distractors were selected more frequently than green distractors when the previous target had been red (and vice versa). Taken together, these results indicate that priming in conjunction search modulates processes concerned with guiding attention to the target, by assigning more attentional weight to features sharing the previous target's color.

Ignition in tokamaks with modulated source of auxiliary heating

NASA Astrophysics Data System (ADS)

Morozov, D. Kh

2017-12-01

It is shown that the ignition may be achieved in tokamaks with the modulated power source. The time-averaged source power may be smaller than the steady-state source power, which is sufficient for the ignition. Nevertheless, the maximal power must be large enough, because the ignition must be achieved within a finite time interval.

Design of a nuclear isotope heat source assembly for a spaceborne mini-Brayton power module.

NASA Technical Reports Server (NTRS)

Wein, D.; Gorland, S. H.

1973-01-01

Results of a study to develop a feasible design definition of a heat source assembly (HSA) for use in nominal 500-, 1200-, or 2000-W(e) mini-Brayton spacecraft power systems. The HSA is a modular design which is used either as a single unit to provide thermal energy to the 500-W(e) mini-Brayton power module or in parallel with one or two additional HSAs for the 1200- or 2000-W(e) power module systems. Principal components consist of a multihundred watt RTG isotope heat source, a heat source heat exchanger which transfers the thermal energy from the heat source to the mini-Brayton power conversion system, an auxiliary cooling system which provides requisite cooling during nonoperation of the power conversion module and an emergency cooling system which precludes accidental release of isotope fuel in the event of system failure.

Impedance modulation and feedback corrections in tracking targets of variable size and frequency.

PubMed

Selen, Luc P J; van Dieën, Jaap H; Beek, Peter J

2006-11-01

Humans are able to adjust the accuracy of their movements to the demands posed by the task at hand. The variability in task execution caused by the inherent noisiness of the neuromuscular system can be tuned to task demands by both feedforward (e.g., impedance modulation) and feedback mechanisms. In this experiment, we studied both mechanisms, using mechanical perturbations to estimate stiffness and damping as indices of impedance modulation and submovement scaling as an index of feedback driven corrections. Eight subjects tracked three differently sized targets (0.0135, 0.0270, and 0.0405 rad) moving at three different frequencies (0.20, 0.25, and 0.33 Hz). Movement variability decreased with both decreasing target size and movement frequency, whereas stiffness and damping increased with decreasing target size, independent of movement frequency. These results are consistent with the theory that mechanical impedance acts as a filter of noisy neuromuscular signals but challenge stochastic theories of motor control that do not account for impedance modulation and only partially for feedback control. Submovements during unperturbed cycles were quantified in terms of their gain, i.e., the slope between their duration and amplitude in the speed profile. Submovement gain decreased with decreasing movement frequency and increasing target size. The results were interpreted to imply that submovement gain is related to observed tracking errors and that those tracking errors are expressed in units of target size. We conclude that impedance and submovement gain modulation contribute additively to tracking accuracy.

An all-silicon optical PC-to-PC link utilizing USB

NASA Astrophysics Data System (ADS)

Goosen, Marius E.; Alberts, Antonie C.; Venter, Petrus J.; du Plessis, Monuko; Rademeyer, Pieter

2013-02-01

An integrated silicon light source still remains the Holy Grail for integrated optical communication systems. Hot carrier luminescent light sources provide a way to create light in a standard CMOS process, potentially enabling cost effective optical communication between CMOS integrated circuits. In this paper we present a 1 Mb/s integrated silicon optical link for information transfer, targeting a real-world integrated solution by connecting two PCs via a USB port while transferring data optically between the devices. This realization represents the first optical communication product prototype utilizing a CMOS light emitter. The silicon light sources which are implemented in a standard 0.35 μm CMOS technology are electrically modulated and detected using a commercial silicon avalanche photodiode. Data rates exceeding 10 Mb/s using silicon light sources have previously been demonstrated using raw bit streams. In this work data is sent in two half duplex streams accompanied with the separate transmission of a clock. Such an optical communication system could find application in high noise environments where data fidelity, range and cost are a determining factor.

Reward-timing-dependent bidirectional modulation of cortical microcircuits during optical single-neuron operant conditioning.

PubMed

Hira, Riichiro; Ohkubo, Fuki; Masamizu, Yoshito; Ohkura, Masamichi; Nakai, Junichi; Okada, Takashi; Matsuzaki, Masanori

2014-11-24

Animals rapidly adapt to environmental change. To reveal how cortical microcircuits are rapidly reorganized when an animal recognizes novel reward contingency, we conduct two-photon calcium imaging of layer 2/3 motor cortex neurons in mice and simultaneously reinforce the activity of a single cortical neuron with water delivery. Here we show that when the target neuron is not relevant to a pre-trained forelimb movement, the mouse increases the target neuron activity and the number of rewards delivered during 15-min operant conditioning without changing forelimb movement behaviour. The reinforcement bidirectionally modulates the activity of subsets of non-target neurons, independent of distance from the target neuron. The bidirectional modulation depends on the relative timing between the reward delivery and the neuronal activity, and is recreated by pairing reward delivery and photoactivation of a subset of neurons. Reward-timing-dependent bidirectional modulation may be one of the fundamental processes in microcircuit reorganization for rapid adaptation.

Selection of specific protein binders for pre-defined targets from an optimized library of artificial helicoidal repeat proteins (alphaRep).

PubMed

Guellouz, Asma; Valerio-Lepiniec, Marie; Urvoas, Agathe; Chevrel, Anne; Graille, Marc; Fourati-Kammoun, Zaineb; Desmadril, Michel; van Tilbeurgh, Herman; Minard, Philippe

2013-01-01

We previously designed a new family of artificial proteins named αRep based on a subgroup of thermostable helicoidal HEAT-like repeats. We have now assembled a large optimized αRep library. In this library, the side chains at each variable position are not fully randomized but instead encoded by a distribution of codons based on the natural frequency of side chains of the natural repeats family. The library construction is based on a polymerization of micro-genes and therefore results in a distribution of proteins with a variable number of repeats. We improved the library construction process using a "filtration" procedure to retain only fully coding modules that were recombined to recreate sequence diversity. The final library named Lib2.1 contains 1.7×10(9) independent clones. Here, we used phage display to select, from the previously described library or from the new library, new specific αRep proteins binding to four different non-related predefined protein targets. Specific binders were selected in each case. The results show that binders with various sizes are selected including relatively long sequences, with up to 7 repeats. ITC-measured affinities vary with Kd values ranging from micromolar to nanomolar ranges. The formation of complexes is associated with a significant thermal stabilization of the bound target protein. The crystal structures of two complexes between αRep and their cognate targets were solved and show that the new interfaces are established by the variable surfaces of the repeated modules, as well by the variable N-cap residues. These results suggest that αRep library is a new and versatile source of tight and specific binding proteins with favorable biophysical properties.

Selection of Specific Protein Binders for Pre-Defined Targets from an Optimized Library of Artificial Helicoidal Repeat Proteins (alphaRep)

PubMed Central

Chevrel, Anne; Graille, Marc; Fourati-Kammoun, Zaineb; Desmadril, Michel; van Tilbeurgh, Herman; Minard, Philippe

2013-01-01

We previously designed a new family of artificial proteins named αRep based on a subgroup of thermostable helicoidal HEAT-like repeats. We have now assembled a large optimized αRep library. In this library, the side chains at each variable position are not fully randomized but instead encoded by a distribution of codons based on the natural frequency of side chains of the natural repeats family. The library construction is based on a polymerization of micro-genes and therefore results in a distribution of proteins with a variable number of repeats. We improved the library construction process using a “filtration” procedure to retain only fully coding modules that were recombined to recreate sequence diversity. The final library named Lib2.1 contains 1.7×109 independent clones. Here, we used phage display to select, from the previously described library or from the new library, new specific αRep proteins binding to four different non-related predefined protein targets. Specific binders were selected in each case. The results show that binders with various sizes are selected including relatively long sequences, with up to 7 repeats. ITC-measured affinities vary with Kd values ranging from micromolar to nanomolar ranges. The formation of complexes is associated with a significant thermal stabilization of the bound target protein. The crystal structures of two complexes between αRep and their cognate targets were solved and show that the new interfaces are established by the variable surfaces of the repeated modules, as well by the variable N-cap residues. These results suggest that αRep library is a new and versatile source of tight and specific binding proteins with favorable biophysical properties. PMID:24014183

Mismatch and G-Stack Modulated Probe Signals on SNP Microarrays

PubMed Central

Binder, Hans; Fasold, Mario; Glomb, Torsten

2009-01-01

Background Single nucleotide polymorphism (SNP) arrays are important tools widely used for genotyping and copy number estimation. This technology utilizes the specific affinity of fragmented DNA for binding to surface-attached oligonucleotide DNA probes. We analyze the variability of the probe signals of Affymetrix GeneChip SNP arrays as a function of the probe sequence to identify relevant sequence motifs which potentially cause systematic biases of genotyping and copy number estimates. Methodology/Principal Findings The probe design of GeneChip SNP arrays enables us to disentangle different sources of intensity modulations such as the number of mismatches per duplex, matched and mismatched base pairings including nearest and next-nearest neighbors and their position along the probe sequence. The effect of probe sequence was estimated in terms of triple-motifs with central matches and mismatches which include all 256 combinations of possible base pairings. The probe/target interactions on the chip can be decomposed into nearest neighbor contributions which correlate well with free energy terms of DNA/DNA-interactions in solution. The effect of mismatches is about twice as large as that of canonical pairings. Runs of guanines (G) and the particular type of mismatched pairings formed in cross-allelic probe/target duplexes constitute sources of systematic biases of the probe signals with consequences for genotyping and copy number estimates. The poly-G effect seems to be related to the crowded arrangement of probes which facilitates complex formation of neighboring probes with at minimum three adjacent G's in their sequence. Conclusions The applied method of “triple-averaging” represents a model-free approach to estimate the mean intensity contributions of different sequence motifs which can be applied in calibration algorithms to correct signal values for sequence effects. Rules for appropriate sequence corrections are suggested. PMID:19924253

Modifying Ventricular Fibrillation by Targeted Rotor Substrate Ablation: Proof-of-Concept from Experimental Studies to Clinical VF

PubMed Central

KRUMMEN, DAVID E.; HAYASE, JUSTIN; VAMPOLA, STEPHEN P.; HO, GORDON; SCHRICKER, AMIR A.; LALANI, GAUTAM G.; BAYKANER, TINA; COE, TAYLOR M.; CLOPTON, PAUL; RAPPEL, WOUTER-JAN; OMENS, JEFFREY H.; NARAYAN, SANJIV M.

2016-01-01

Introduction Recent work has suggested a role for organized sources in sustaining ventricular fibrillation (VF). We assessed whether ablation of rotor substrate could modulate VF inducibility in canines, and used this proof-of-concept as a foundation to suppress antiarrhythmic drug-refractory clinical VF in a patient with structural heart disease. Methods and Results In 9 dogs, we introduced 64-electrode basket catheters into one or both ventricles, used rapid pacing at a recorded induction threshold to initiate VF, and then defibrillated after 18±8 seconds. Endocardial rotor sites were identified from basket recordings using phase mapping, and ablation was performed at nonrotor (sham) locations (7 ± 2 minutes) and then at rotor sites (8 ± 2 minutes, P = 0.10 vs. sham); the induction threshold was remeasured after each. Sham ablation did not alter canine VF induction threshold (preablation 150 ± 16 milliseconds, postablation 144 ± 16 milliseconds, P = 0.54). However, rotor site ablation rendered VF noninducible in 6/9 animals (P = 0.041), and increased VF induction threshold in the remaining 3. Clinical proof-of-concept was performed in a patient with repetitive ICD shocks due to VF refractory to antiarrhythmic drugs. Following biventricular basket insertion, VF was induced and then defibrillated. Mapping identified 4 rotors localized at borderzone tissue, and rotor site ablation (6.3 ± 1.5 minutes/site) rendered VF noninducible. The VF burden fell from 7 ICD shocks in 8 months preablation to zero ICD therapies at 1 year, without antiarrhythmic medications. Conclusions Targeted rotor substrate ablation suppressed VF in an experimental model and a patient with refractory VF. Further studies are warranted on the efficacy of VF source modulation. PMID:26179310

Anti-dynamic-crosstalk method for single photon LIDAR detection

NASA Astrophysics Data System (ADS)

Zhang, Fan; Liu, Qiang; Gong, Mali; Fu, Xing

2017-11-01

With increasing number of vehicles equipped with light detection and ranging (LIDAR), crosstalk is identified as a critical and urgent issue in the range detection for active collision avoidance. Chaotic pulse position modulation (CPPM) applied in the transmitting pulse train has been shown to prevent crosstalk as well as range ambiguity. However, static and unified strategy on discrimination threshold and the number of accumulated pulse is not valid against crosstalk with varying number of sources and varying intensity of each source. This paper presents an adaptive algorithm to distinguish the target echo from crosstalk with dynamic and unknown level of intensity in the context of intelligent vehicles. New strategy is given based on receiver operating characteristics (ROC) curves that consider the detection requirements of the probability of detection and false alarm for the scenario with varying crosstalk. In the adaptive algorithm, the detected results are compared by the new strategy with both the number of accumulated pulses and the threshold being raised step by step, so that the target echo can be exactly identified from crosstalk with the dynamic and unknown level of intensity. The validity of the algorithm has been verified through the experiments with a single photon detector and the time correlated single photo counting (TCSPC) technique, demonstrating a marked drop in required shots for identifying the target compared with static and unified strategy

Temporal characteristic analysis of laser-modulated pulsed X-ray source for space X-ray communication

NASA Astrophysics Data System (ADS)

Hang, Shuang; Liu, Yunpeng; Li, Huan; Tang, Xiaobin; Chen, Da

2018-04-01

X-ray communication (XCOM) is a new communication type and is expected to realize high-speed data transmission in some special communication scenarios, such as deep space communication and blackout communication. This study proposes a high-speed modulated X-ray source scheme based on the laser-to-X-ray conversion. The temporal characteristics of the essential components of the proposed laser-modulated pulsed X-ray source (LMPXS) were analyzed to evaluate its pulse emission performance. Results show that the LMPXS can provide a maximum modulation rate up to 100 Mbps which is expected to significantly improve the data rate of XCOM.

Emerging Paradigm of Intracellular Targeting of G Protein-Coupled Receptors.

PubMed

Chaturvedi, Madhu; Schilling, Justin; Beautrait, Alexandre; Bouvier, Michel; Benovic, Jeffrey L; Shukla, Arun K

2018-05-04

G protein-coupled receptors (GPCRs) recognize a diverse array of extracellular stimuli, and they mediate a broad repertoire of signaling events involved in human physiology. Although the major effort on targeting GPCRs has typically been focused on their extracellular surface, a series of recent developments now unfold the possibility of targeting them from the intracellular side as well. Allosteric modulators binding to the cytoplasmic surface of GPCRs have now been described, and their structural mechanisms are elucidated by high-resolution crystal structures. Furthermore, pepducins, aptamers, and intrabodies targeting the intracellular face of GPCRs have also been successfully utilized to modulate receptor signaling. Moreover, small molecule compounds, aptamers, and synthetic intrabodies targeting β-arrestins have also been discovered to modulate GPCR endocytosis and signaling. Here, we discuss the emerging paradigm of intracellular targeting of GPCRs, and outline the current challenges, potential opportunities, and future outlook in this particular area of GPCR biology. Copyright © 2018 Elsevier Ltd. All rights reserved.

Emerging potential of natural products for targeting mucins for therapy against inflammation and cancer.

PubMed

Macha, Muzafar A; Krishn, Shiv Ram; Jahan, Rahat; Banerjee, Kasturi; Batra, Surinder K; Jain, Maneesh

2015-03-01

Deregulated mucin expression is a hallmark of several inflammatory and malignant pathologies. Emerging evidence suggests that, apart from biomarkers, these deregulated mucins are functional contributors to the pathogenesis in inflammation and cancer. Both overexpression and downregulation of mucins in various organ systems is associated with pathobiology of inflammation and cancer. Restoration of mucin homeostasis has become an important goal for therapy and management of such disorders has fueled the quest for selective mucomodulators. With improved understanding of mucin regulation and mechanistic insights into their pathobiological roles, there is optimism to find selective non-toxic agents capable of modulating mucin expression and function. Recently, natural compounds derived from dietary sources have drawn attention due to their anti-inflammatory and anti-oxidant properties and low toxicity. Considerable efforts have been directed towards evaluating dietary natural products as chemopreventive and therapeutic agents; identification, characterization and synthesis of their active compounds; and improving their delivery and bioavailability. We describe the current understanding of mucin regulation, rationale for targeting mucins with natural products and discuss some natural products that modulate mucin expression and functions. We further discuss the approaches and parameters that should guide future research to identify and evaluate selective natural mucomodulators for therapy. Copyright © 2015 Elsevier Ltd. All rights reserved.

Emerging Potential of Natural Products for Targeting Mucins for Therapy Against Inflammation and Cancer

PubMed Central

Macha, Muzafar A.; Krishn, Shiv Ram; Jahan, Rahat; Banerjee, Kasturi; Batra, Surinder K.; Jain, Maneesh

2015-01-01

Deregulated mucin expression is a hallmark of several inflammatory and malignant pathologies. Emerging evidence suggests that, apart from biomarkers, these deregulated mucins are functional contributors to pathogenesis in inflammation and cancer. Both overexpression and downregulation of mucins in various organ systems is associated with pathobiology of inflammation and cancer. Restoration of mucin homeostasis has become an important goal for therapy and management of such disorders and has fueled the quest for selective mucomodulators. With improved understanding of mucin regulation and mechanistic insights into their pathobiological roles, there is optimism to find selective non-toxic agents capable of modulating mucin expression and function. Recently, natural compounds derived from dietary sources have drawn attention due to their anti-inflammatory and anti-oxidant properties and low toxicity. Considerable efforts have been directed towards evaluating dietary natural products as chemopreventive and therapeutic agents; identification, characterization and synthesis of their active compounds; and improving their delivery and bioavailability. We describe the current understanding of mucin regulation, rationale for targeting mucins with natural products and discuss some natural products that modulate mucin expression and functions. We further discuss the approaches and parameters that should guide future research to identify and evaluate selective natural mucomodulators for therapy. PMID:25624117

SEQUOIA: significance enhanced network querying through context-sensitive random walk and minimization of network conductance.

PubMed

Jeong, Hyundoo; Yoon, Byung-Jun

2017-03-14

Network querying algorithms provide computational means to identify conserved network modules in large-scale biological networks that are similar to known functional modules, such as pathways or molecular complexes. Two main challenges for network querying algorithms are the high computational complexity of detecting potential isomorphism between the query and the target graphs and ensuring the biological significance of the query results. In this paper, we propose SEQUOIA, a novel network querying algorithm that effectively addresses these issues by utilizing a context-sensitive random walk (CSRW) model for network comparison and minimizing the network conductance of potential matches in the target network. The CSRW model, inspired by the pair hidden Markov model (pair-HMM) that has been widely used for sequence comparison and alignment, can accurately assess the node-to-node correspondence between different graphs by accounting for node insertions and deletions. The proposed algorithm identifies high-scoring network regions based on the CSRW scores, which are subsequently extended by maximally reducing the network conductance of the identified subnetworks. Performance assessment based on real PPI networks and known molecular complexes show that SEQUOIA outperforms existing methods and clearly enhances the biological significance of the query results. The source code and datasets can be downloaded from http://www.ece.tamu.edu/~bjyoon/SEQUOIA .

Thermally multiplexed polymerase chain reaction.

PubMed

Phaneuf, Christopher R; Pak, Nikita; Saunders, D Curtis; Holst, Gregory L; Birjiniuk, Joav; Nagpal, Nikita; Culpepper, Stephen; Popler, Emily; Shane, Andi L; Jerris, Robert; Forest, Craig R

2015-07-01

Amplification of multiple unique genetic targets using the polymerase chain reaction (PCR) is commonly required in molecular biology laboratories. Such reactions are typically performed either serially or by multiplex PCR. Serial reactions are time consuming, and multiplex PCR, while powerful and widely used, can be prone to amplification bias, PCR drift, and primer-primer interactions. We present a new thermocycling method, termed thermal multiplexing, in which a single heat source is uniformly distributed and selectively modulated for independent temperature control of an array of PCR reactions. Thermal multiplexing allows amplification of multiple targets simultaneously-each reaction segregated and performed at optimal conditions. We demonstrate the method using a microfluidic system consisting of an infrared laser thermocycler, a polymer microchip featuring 1 μl, oil-encapsulated reactions, and closed-loop pulse-width modulation control. Heat transfer modeling is used to characterize thermal performance limitations of the system. We validate the model and perform two reactions simultaneously with widely varying annealing temperatures (48 °C and 68 °C), demonstrating excellent amplification. In addition, to demonstrate microfluidic infrared PCR using clinical specimens, we successfully amplified and detected both influenza A and B from human nasopharyngeal swabs. Thermal multiplexing is scalable and applicable to challenges such as pathogen detection where patients presenting non-specific symptoms need to be efficiently screened across a viral or bacterial panel.

Modular radiochemistry synthesis system

DOEpatents

Satyamurthy, Nagichettiar; Barrio, Jorge R.; Amarasekera, Bernard; Van Dam, Michael R.; Olma, Sebastian; Williams, Dirk; Eddings, Mark; Shen, Clifton Kwang-Fu

2016-11-01

A modular chemical production system includes multiple modules for performing a chemical reaction, particularly of radiochemical compounds, from a remote location. One embodiment comprises a reaction vessel including a moveable heat source with the position thereof relative to the reaction vessel being controllable from a remote position. Alternatively the heat source may be fixed in location and the reaction vial is moveable into and out of the heat source. The reaction vessel has one or more sealing plugs, the positioning of which in relationship to the reaction vessel is controllable from a remote position. Also the one or more reaction vessel sealing plugs can include one or more conduits there through for delivery of reactants, gases at atmospheric or an elevated pressure, inert gases, drawing a vacuum and removal of reaction end products to and from the reaction vial, the reaction vial with sealing plug in position being operable at elevated pressures. The modular chemical production system is assembled from modules which can each include operating condition sensors and controllers configured for monitoring and controlling the individual modules and the assembled system from a remote position. Other modules include, but are not limited to a Reagent Storage and Delivery Module, a Cartridge Purification Module, a Microwave Reaction Module, an External QC/Analysis/Purification Interface Module, an Aliquotting Module, an F-18 Drying Module, a Concentration Module, a Radiation Counting Module, and a Capillary Reactor Module.

Modular radiochemistry synthesis system

DOEpatents

Satyamurthy, Nagichettiar; Barrio, Jorge R.; Amarasekera, Bernard; Van Dam, R. Michael; Olma, Sebastian; Williams, Dirk; Eddings, Mark; Shen, Clifton Kwang-Fu

2015-12-15

A modular chemical production system includes multiple modules for performing a chemical reaction, particularly of radiochemical compounds, from a remote location. One embodiment comprises a reaction vessel including a moveable heat source with the position thereof relative to the reaction vessel being controllable from a remote position. Alternatively the heat source may be fixed in location and the reaction vial is moveable into and out of the heat source. The reaction vessel has one or more sealing plugs, the positioning of which in relationship to the reaction vessel is controllable from a remote position. Also the one or more reaction vessel sealing plugs can include one or more conduits there through for delivery of reactants, gases at atmospheric or an elevated pressure, inert gases, drawing a vacuum and removal of reaction end products to and from the reaction vial, the reaction vial with sealing plug in position being operable at elevated pressures. The modular chemical production system is assembled from modules which can each include operating condition sensors and controllers configured for monitoring and controlling the individual modules and the assembled system from a remote position. Other modules include, but are not limited to a Reagent Storage and Delivery Module, a Cartridge Purification Module, a Microwave Reaction Module, an External QC/Analysis/Purification Interface Module, an Aliquotting Module, an F-18 Drying Module, a Concentration Module, a Radiation Counting Module, and a Capillary Reactor Module.

Modular radiochemistry synthesis system

DOEpatents

Satyamurthy, Nagichettiar; Barrio, Jorge R; Amarasekera, Bernard; Van Dam, R. Michael; Olma, Sebastian; Williams, Dirk; Eddings, Mark A; Shen, Clifton Kwang-Fu

2015-02-10

A modular chemical production system includes multiple modules for performing a chemical reaction, particularly of radiochemical compounds, from a remote location. One embodiment comprises a reaction vessel including a moveable heat source with the position thereof relative to the reaction vessel being controllable from a remote position. Alternatively the heat source may be fixed in location and the reaction vial is moveable into and out of the heat source. The reaction vessel has one or more sealing plugs, the positioning of which in relationship to the reaction vessel is controllable from a remote position. Also the one or more reaction vessel sealing plugs can include one or more conduits there through for delivery of reactants, gases at atmospheric or an elevated pressure, inert gases, drawing a vacuum and removal of reaction end products to and from the reaction vial, the reaction vial with sealing plug in position being operable at elevated pressures. The modular chemical production system is assembled from modules which can each include operating condition sensors and controllers configured for monitoring and controlling the individual modules and the assembled system from a remote position. Other modules include, but are not limited to a Reagent Storage and Delivery Module, a Cartridge Purification Module, a Microwave Reaction Module, an External QC/Analysis/Purification Interface Module, an Aliquotting Module, an F-18 Drying Module, a Concentration Module, a Radiation Counting Module, and a Capillary Reactor Module.

35-GHz radar sensor for automotive collision avoidance

NASA Astrophysics Data System (ADS)

Zhang, Jun

1999-07-01

This paper describes the development of a radar sensor system used for automotive collision avoidance. Because the heavy truck may have great larger radar cross section than a motorcyclist has, the radar receiver may have a large dynamic range. And multi-targets at different speed may confuse the echo spectrum causing the ambiguity between range and speed of target. To get more information about target and background and to adapt to the large dynamic range and multi-targets, a frequency modulated and pseudo- random binary sequences phase modulated continuous wave radar system is described. The analysis of this double- modulation system is given. A high-speed signal processing and data processing component are used to process and combine the data and information from echo at different direction and at every moment.

Angle-dependent modulated spectral peaks of proton beams generated in ultrashort intense laser-solid interactions

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

Su, L. N.; Hu, Z. D.; Zheng, Y.

2014-09-15

Proton acceleration from 4 μm thick aluminum foils irradiated by 30-TW Ti:sapphire laser pulses is investigated using an angle-resolved proton energy spectrometer. We find that a modulated spectral peak at ∼0.82 MeV is presented at 2.5° off the target normal direction. The divergence angle of the modulated zone is 3.8°. Two-dimensional particle-in-cell simulations reveal that self-generated toroidal magnetic field at the rear surface of the target foil is responsible for the modulated spectral feature. The field deflects the low energy protons, resulting in the modulated energy spectrum with certain peaks.

Attentional awakening: gradual modulation of temporal attention in rapid serial visual presentation.

PubMed

Ariga, Atsunori; Yokosawa, Kazuhiko

2008-03-01

Orienting attention to a point in time facilitates processing of an item within rapidly changing surroundings. We used a one-target RSVP task to look for differences in accuracy in reporting a target related to when the target temporally appeared in the sequence. The results show that observers correctly report a target early in the sequence less frequently than later in the sequence. Previous RSVP studies predicted equivalently accurate performances for one target wherever it appeared in the sequence. We named this new phenomenon attentional awakening, which reflects a gradual modulation of temporal attention in a rapid sequence.

Effect of eye position on saccades and neuronal responses to acoustic stimuli in the superior colliculus of the behaving cat.

PubMed

Populin, Luis C; Tollin, Daniel J; Yin, Tom C T

2004-10-01

We examined the motor error hypothesis of visual and auditory interaction in the superior colliculus (SC), first tested by Jay and Sparks in the monkey. We trained cats to direct their eyes to the location of acoustic sources and studied the effects of eye position on both the ability of cats to localize sounds and the auditory responses of SC neurons with the head restrained. Sound localization accuracy was generally not affected by initial eye position, i.e., accuracy was not proportionally affected by the deviation of the eyes from the primary position at the time of stimulus presentation, showing that eye position is taken into account when orienting to acoustic targets. The responses of most single SC neurons to acoustic stimuli in the intact cat were modulated by eye position in the direction consistent with the predictions of the "motor error" hypothesis, but the shift accounted for only two-thirds of the initial deviation of the eyes. However, when the average horizontal sound localization error, which was approximately 35% of the target amplitude, was taken into account, the magnitude of the horizontal shifts in the SC auditory receptive fields matched the observed behavior. The modulation by eye position was not due to concomitant movements of the external ears, as confirmed by recordings carried out after immobilizing the pinnae of one cat. However, the pattern of modulation after pinnae immobilization was inconsistent with the observations in the intact cat, suggesting that, in the intact animal, information about the position of the pinnae may be taken into account.

Drug repositioning for enzyme modulator based on human metabolite-likeness.

PubMed

Lee, Yoon Hyeok; Choi, Hojae; Park, Seongyong; Lee, Boah; Yi, Gwan-Su

2017-05-31

Recently, the metabolite-likeness of the drug space has emerged and has opened a new possibility for exploring human metabolite-like candidates in drug discovery. However, the applicability of metabolite-likeness in drug discovery has been largely unexplored. Moreover, there are no reports on its applications for the repositioning of drugs to possible enzyme modulators, although enzyme-drug relations could be directly inferred from the similarity relationships between enzyme's metabolites and drugs. We constructed a drug-metabolite structural similarity matrix, which contains 1,861 FDA-approved drugs and 1,110 human intermediary metabolites scored with the Tanimoto similarity. To verify the metabolite-likeness measure for drug repositioning, we analyzed 17 known antimetabolite drugs that resemble the innate metabolites of their eleven target enzymes as the gold standard positives. Highly scored drugs were selected as possible modulators of enzymes for their corresponding metabolites. Then, we assessed the performance of metabolite-likeness with a receiver operating characteristic analysis and compared it with other drug-target prediction methods. We set the similarity threshold for drug repositioning candidates of new enzyme modulators based on maximization of the Youden's index. We also carried out literature surveys for supporting the drug repositioning results based on the metabolite-likeness. In this paper, we applied metabolite-likeness to repurpose FDA-approved drugs to disease-associated enzyme modulators that resemble human innate metabolites. All antimetabolite drugs were mapped with their known 11 target enzymes with statistically significant similarity values to the corresponding metabolites. The comparison with other drug-target prediction methods showed the higher performance of metabolite-likeness for predicting enzyme modulators. After that, the drugs scored higher than similarity score of 0.654 were selected as possible modulators of enzymes for their corresponding metabolites. In addition, we showed that drug repositioning results of 10 enzymes were concordant with the literature evidence. This study introduced a method to predict the repositioning of known drugs to possible modulators of disease associated enzymes using human metabolite-likeness. We demonstrated that this approach works correctly with known antimetabolite drugs and showed that the proposed method has better performance compared to other drug target prediction methods in terms of enzyme modulators prediction. This study as a proof-of-concept showed how to apply metabolite-likeness to drug repositioning as well as potential in further expansion as we acquire more disease associated metabolite-target protein relations.

Target Trailing With Safe Navigation for Maritime Autonomous Surface Vehicles

NASA Technical Reports Server (NTRS)

Wolf, Michael; Kuwata, Yoshiaki; Zarzhitsky, Dimitri V.

2013-01-01

This software implements a motion-planning module for a maritime autonomous surface vehicle (ASV). The module trails a given target while also avoiding static and dynamic surface hazards. When surface hazards are other moving boats, the motion planner must apply International Regulations for Avoiding Collisions at Sea (COLREGS). A key subset of these rules has been implemented in the software. In case contact with the target is lost, the software can receive and follow a "reacquisition route," provided by a complementary system, until the target is reacquired. The programmatic intention is that the trailed target is a submarine, although any mobile naval platform could serve as the target. The algorithmic approach to combining motion with a (possibly moving) goal location, while avoiding local hazards, may be applicable to robotic rovers, automated landing systems, and autonomous airships. The software operates in JPL s CARACaS (Control Architecture for Robotic Agent Command and Sensing) software architecture and relies on other modules for environmental perception data and information on the predicted detectability of the target, as well as the low-level interface to the boat controls.

The Geoinformatica free and open source software stack

NASA Astrophysics Data System (ADS)

Jolma, A.

2012-04-01

The Geoinformatica free and open source software (FOSS) stack is based mainly on three established FOSS components, namely GDAL, GTK+, and Perl. GDAL provides access to a very large selection of geospatial data formats and data sources, a generic geospatial data model, and a large collection of geospatial analytical and processing functionality. GTK+ and the Cairo graphics library provide generic graphics and graphical user interface capabilities. Perl is a programming language, for which there is a very large set of FOSS modules for a wide range of purposes and which can be used as an integrative tool for building applications. In the Geoinformatica stack, data storages such as FOSS RDBMS PostgreSQL with its geospatial extension PostGIS can be used below the three above mentioned components. The top layer of Geoinformatica consists of a C library and several Perl modules. The C library comprises a general purpose raster algebra library, hydrological terrain analysis functions, and visualization code. The Perl modules define a generic visualized geospatial data layer and subclasses for raster and vector data and graphs. The hydrological terrain functions are already rather old and they suffer for example from the requirement of in-memory rasters. Newer research conducted using the platform include basic geospatial simulation modeling, visualization of ecological data, linking with a Bayesian network engine for spatial risk assessment in coastal areas, and developing standards-based distributed water resources information systems in Internet. The Geoinformatica stack constitutes a platform for geospatial research, which is targeted towards custom analytical tools, prototyping and linking with external libraries. Writing custom analytical tools is supported by the Perl language and the large collection of tools that are available especially in GDAL and Perl modules. Prototyping is supported by the GTK+ library, the GUI tools, and the support for object-oriented programming in Perl. New feature types, geospatial layer classes, and tools as extensions with specific features can be defined, used, and studied. Linking with external libraries is possible using the Perl foreign function interface tools or with generic tools such as Swig. We are interested in implementing and testing linking Geoinformatica with existing or new more specific hydrological FOSS.

Reward modulation of contextual cueing: Repeated context overshadows repeated target location.

PubMed

Sharifian, Fariba; Contier, Oliver; Preuschhof, Claudia; Pollmann, Stefan

2017-10-01

Contextual cueing can be enhanced by reward. However, there is a debate if reward is associated with the repeated target-distractor configurations or with the repeated target locations that occur in both repeated and new displays. Based on neuroimaging evidence, we hypothesized that reward becomes associated with the target location only in new displays, but not in repeated displays, where the repeated target location is overshadowed by the more salient repeated target-distractor configuration. To test this hypothesis, we varied the reward value associated with the same target location in repeated and new displays. The results confirmed the overshadowing hypothesis in that search facilitation in repeated target-distractor configurations was modulated by the variable value associated with the target location. This effect was observed mainly in early learning.

Research on Radar Micro-Doppler Feature Parameter Estimation of Propeller Aircraft

NASA Astrophysics Data System (ADS)

He, Zhihua; Tao, Feixiang; Duan, Jia; Luo, Jingsheng

2018-01-01

The micro-motion modulation effect of the rotated propellers to radar echo can be a steady feature for aircraft target recognition. Thus, micro-Doppler feature parameter estimation is a key to accurate target recognition. In this paper, the radar echo of rotated propellers is modelled and simulated. Based on which, the distribution characteristics of the micro-motion modulation energy in time, frequency and time-frequency domain are analyzed. The micro-motion modulation energy produced by the scattering points of rotating propellers is accumulated using the Inverse-Radon (I-Radon) transform, which can be used to accomplish the estimation of micro-modulation parameter. Finally, it is proved that the proposed parameter estimation method is effective with measured data. The micro-motion parameters of aircraft can be used as the features of radar target recognition.

Spatiotemporal reconstruction of auditory steady-state responses to acoustic amplitude modulations: Potential sources beyond the auditory pathway.

PubMed

Farahani, Ehsan Darestani; Goossens, Tine; Wouters, Jan; van Wieringen, Astrid

2017-03-01

Investigating the neural generators of auditory steady-state responses (ASSRs), i.e., auditory evoked brain responses, with a wide range of screening and diagnostic applications, has been the focus of various studies for many years. Most of these studies employed a priori assumptions regarding the number and location of neural generators. The aim of this study is to reconstruct ASSR sources with minimal assumptions in order to gain in-depth insight into the number and location of brain regions that are activated in response to low- as well as high-frequency acoustically amplitude modulated signals. In order to reconstruct ASSR sources, we applied independent component analysis with subsequent equivalent dipole modeling to single-subject EEG data (young adults, 20-30 years of age). These data were based on white noise stimuli, amplitude modulated at 4, 20, 40, or 80Hz. The independent components that exhibited a significant ASSR were clustered among all participants by means of a probabilistic clustering method based on a Gaussian mixture model. Results suggest that a widely distributed network of sources, located in cortical as well as subcortical regions, is active in response to 4, 20, 40, and 80Hz amplitude modulated noises. Some of these sources are located beyond the central auditory pathway. Comparison of brain sources in response to different modulation frequencies suggested that the identified brain sources in the brainstem, the left and the right auditory cortex show a higher responsiveness to 40Hz than to the other modulation frequencies. Copyright © 2017 Elsevier Inc. All rights reserved.

Progress Toward Efficient Laminar Flow Analysis and Design

NASA Technical Reports Server (NTRS)

Campbell, Richard L.; Campbell, Matthew L.; Streit, Thomas

2011-01-01

A multi-fidelity system of computer codes for the analysis and design of vehicles having extensive areas of laminar flow is under development at the NASA Langley Research Center. The overall approach consists of the loose coupling of a flow solver, a transition prediction method and a design module using shell scripts, along with interface modules to prepare the input for each method. This approach allows the user to select the flow solver and transition prediction module, as well as run mode for each code, based on the fidelity most compatible with the problem and available resources. The design module can be any method that designs to a specified target pressure distribution. In addition to the interface modules, two new components have been developed: 1) an efficient, empirical transition prediction module (MATTC) that provides n-factor growth distributions without requiring boundary layer information; and 2) an automated target pressure generation code (ATPG) that develops a target pressure distribution that meets a variety of flow and geometry constraints. The ATPG code also includes empirical estimates of several drag components to allow the optimization of the target pressure distribution. The current system has been developed for the design of subsonic and transonic airfoils and wings, but may be extendable to other speed ranges and components. Several analysis and design examples are included to demonstrate the current capabilities of the system.

Network based management for multiplexed electric vehicle charging

DOEpatents

Gadh, Rajit; Chung, Ching Yen; Qui, Li

2017-04-11

A system for multiplexing charging of electric vehicles, comprising a server coupled to a plurality of charging control modules over a network. Each of said charging modules being connected to a voltage source such that each charging control module is configured to regulate distribution of voltage from the voltage source to an electric vehicle coupled to the charging control module. Data collection and control software is provided on the server for identifying a plurality of electric vehicles coupled to the plurality of charging control modules and selectively distributing charging of the plurality of charging control modules to multiplex distribution of voltage to the plurality of electric vehicles.

Did You Listen to the Beat? Auditory Steady-State Responses in the Human Electroencephalogram at 4 and 7 Hz Modulation Rates Reflect Selective Attention.

PubMed

Jaeger, Manuela; Bleichner, Martin G; Bauer, Anna-Katharina R; Mirkovic, Bojana; Debener, Stefan

2018-02-27

The acoustic envelope of human speech correlates with the syllabic rate (4-8 Hz) and carries important information for intelligibility, which is typically compromised in multi-talker, noisy environments. In order to better understand the dynamics of selective auditory attention to low frequency modulated sound sources, we conducted a two-stream auditory steady-state response (ASSR) selective attention electroencephalogram (EEG) study. The two streams consisted of 4 and 7 Hz amplitude and frequency modulated sounds presented from the left and right side. One of two streams had to be attended while the other had to be ignored. The attended stream always contained a target, allowing for the behavioral confirmation of the attention manipulation. EEG ASSR power analysis revealed a significant increase in 7 Hz power for the attend compared to the ignore conditions. There was no significant difference in 4 Hz power when the 4 Hz stream had to be attended compared to when it had to be ignored. This lack of 4 Hz attention modulation could be explained by a distracting effect of a third frequency at 3 Hz (beat frequency) perceivable when the 4 and 7 Hz streams are presented simultaneously. Taken together our results show that low frequency modulations at syllabic rate are modulated by selective spatial attention. Whether attention effects act as enhancement of the attended stream or suppression of to be ignored stream may depend on how well auditory streams can be segregated.

Wide-field fluorescence diffuse optical tomography with epi-illumination of sinusoidal pattern

NASA Astrophysics Data System (ADS)

Li, Tongxin; Gao, Feng; Chen, Weiting; Qi, Caixia; Yan, Panpan; Zhao, Huijuan

2017-02-01

We present a wide-field fluorescence tomography with epi-illumination of sinusoidal pattern. In this scheme, a DMD projector is employed as a spatial light modulator to generate independently wide-field sinusoidal illumination patterns at varying spatial frequencies on a sample, and then the emitted photons at the sample surface were captured with a EM-CCD camera. This method results in a significantly reduced number of the optical field measurements as compared to the point-source-scanning ones and thereby achieves a fast data acquisition that is desired for a dynamic imaging application. Fluorescence yield images are reconstructed using the normalized-Born formulated inversion of the diffusion model. Experimental reconstructions are presented on a phantom embedding the fluorescent targets and compared for a combination of the multiply frequencies. The results validate the ability of the method to determine the target relative depth and quantification with an increasing accuracy.

Divided attention modulates semantic activation: evidence from a nonletter-level prime task.

PubMed

Otsuka, Sachio; Kawaguchi, Jun

2007-12-01

Research has recently shown that semantic activation is modulated in proportion to the amount of attention required for letter-level processing of the prime (the attention modulation hypothesis; Smith, Bentin, & Spalek, 2001). In this study, we examined this hypothesis with an auditory divided-attention task. Participants were asked to decide whether the pitch of a probe tone presented with the prime word was higher or lower than the basic tone presented with the fixation cross. Their target task was lexical decision to the target word. Experiment 1 showed that semantic priming was modulated by the amount of attentional resources. Moreover, in Experiment 2, this modulation was also found in a situation that eliminated the possibility of participants' response strategies. Yet, Experiment 3 showed repetition priming to be unaffected. These results support an amended attention modulation hypothesis in which modulation is not limited to letter-level processing.

New microwave modulation LIDAR scheme for naval mine detection

NASA Astrophysics Data System (ADS)

Alem, Nour; Pellen, Fabrice; Le Jeune, Bernard

2017-10-01

In this paper, a new modulator design suited for hybrid Lidar-radar applications is proposed and implemented. This modulator delivers a stable and tunable modulated optical pulse. Modulation frequency is in the GHz range, and associated with a bandpass filtering at the detection allow detecting a target echo embedded in the backscattering noise. This principle is known as hybrid Lidar-radar. We expose in this article theoretical principle of this new modulator and its experimental implementation. As polarization filtering can be coupled with the hybrid Lidar-radar technique to further improve target return, polarimetric sensitivity of this modulator was investigated. Since, theoretical results mismatched the experimental ones, thus, further investigations were taken. Mechanical constraint induced by mirror mount caused birefringent behavior to the mirror substrate. As this effect was not homogeneously distributed in the material, we were not being able to compensate it by modelling. However, we propose an experimental approach to solve this problem.

Targeted modulation of reactive oxygen species in the vascular endothelium.

PubMed

Shuvaev, Vladimir V; Muzykantov, Vladimir R

2011-07-15

'Endothelial cells lining vascular luminal surface represent an important site of signaling and injurious effects of reactive oxygen species (ROS) produced by other cells and endothelium itself in ischemia, inflammation and other pathological conditions. Targeted delivery of ROS modulating enzymes conjugated with antibodies to endothelial surface molecules (vascular immunotargeting) provides site-specific interventions in the endothelial ROS, unattainable by other formulations including PEG-modified enzymes. Targeting of ROS generating enzymes (e.g., glucose oxidase) provides ROS- and site-specific models of endothelial oxidative stress, whereas targeting of antioxidant enzymes SOD and catalase offers site-specific quenching of superoxide anion and H(2)O(2). These targeted antioxidant interventions help to clarify specific role of endothelial ROS in vascular and pulmonary pathologies and provide basis for design of targeted therapeutics for treatment of these pathologies. In particular, antibody/catalase conjugates alleviate acute lung ischemia/reperfusion injury, whereas antibody/SOD conjugates inhibit ROS-mediated vasoconstriction and inflammatory endothelial signaling. Encapsulation in protease-resistant, ROS-permeable carriers targeted to endothelium prolongs protective effects of antioxidant enzymes, further diversifying the means for targeted modulation of endothelial ROS. Copyright © 2011 Elsevier B.V. All rights reserved.

Method and Apparatus for Characterizing Pressure Sensors using Modulated Light Beam Pressure

NASA Technical Reports Server (NTRS)

Youngquist, Robert C. (Inventor)

2003-01-01

Embodiments of apparatuses and methods are provided that use light sources instead of sound sources for characterizing and calibrating sensors for measuring small pressures to mitigate many of the problems with using sound sources. In one embodiment an apparatus has a light source for directing a beam of light on a sensing surface of a pressure sensor for exerting a force on the sensing surface. The pressure sensor generates an electrical signal indicative of the force exerted on the sensing surface. A modulator modulates the beam of light. A signal processor is electrically coupled to the pressure sensor for receiving the electrical signal.

Targeting brain cells with glutathione-modulated nanoliposomes: in vitro and in vivo study

PubMed Central

Salem, Heba F; Ahmed, Sayed M; Hassaballah, Ashraf E; Omar, Mahmoud M

2015-01-01

Background The blood–brain barrier prevents many drug moieties from reaching the central nervous system. Therefore, glutathione-modulated nanoliposomes have been engineered to enhance the targeting of flucytosine to the brain. Methods Glutathione-modulated nanoliposomes were prepared by thin-film hydration technique and evaluated in the primary brain cells of rats. Lecithin, cholesterol, and span 65 were mixed at 1:1:1 molar ratio. The molar percentage of PEGylated glutathione varied from 0 mol% to 0.75 mol%. The cellular binding and the uptake of the targeted liposomes were both monitored by epifluorescent microscope and flow cytometry techniques. A biodistribution and a pharmacokinetic study of flucytosine and flucytosine-loaded glutathione–modulated liposomes was carried out to evaluate the in vivo brain-targeting efficiency. Results The size of glutathione-modulated nanoliposomes was <100 nm and the zeta potential was more than −65 mV. The cumulative release reached 70% for certain formulations. The cellular uptake increased as molar percent of glutathione increased to reach the maximum at 0.75 mol%. The uptake of the targeted liposomes by brain cells of the rats was three times greater than that of the nontargeted liposomes. An in vivo study showed that the relative efficiency was 2.632±0.089 and the concentration efficiency was 1.590±0.049, and also, the drug-targeting index was 3.670±0.824. Conclusion Overall, these results revealed that glutathione-PEGylated nanoliposomes enhance the effective delivery of flucytosine to brain and could become a promising new therapeutic option for the treatment of the brain infections. PMID:26229435

Locoregional control after intensity-modulated radiotherapy for nasopharyngeal carcinoma with an anatomy-based target definition.

PubMed

Kawashima, Mitsuhiko; Ariji, Takaki; Kameoka, Satoru; Ueda, Takashi; Kohno, Ryosuke; Nishio, Teiji; Arahira, Satoko; Motegi, Atsushi; Zenda, Sadamoto; Akimoto, Tetsuo; Tahara, Makoto; Hayashi, Ryuichi

2013-12-01

The objective of the study was to evaluate locoregional control after intensity-modulated radiotherapy for nasopharyngeal cancer using a target definition along with anatomical boundaries. Forty patients with biopsy-proven squamous cell or non-keratinizing carcinoma of the nasopharynx who underwent intensity-modulated radiotherapy between April 2006 and November 2009 were reviewed. There were 10 females and 30 males with a median age of 48 years (range, 17-74 years). More than half of the patients had T3/4 (n = 21) and/or N2/3 (n = 24) disease. Intensity-modulated radiotherapy was administered as 70 Gy/33 fractions with or without concomitant chemotherapy. The clinical target volume was contoured along with muscular fascia or periosteum, and the prescribed radiotherapy dose was determined for each anatomical compartment and lymph node level in the head and neck. One local recurrence was observed at Meckel's cave on the periphery of the high-risk clinical target volume receiving a total dose of <63 Gy. Otherwise, six locoregional failures were observed within irradiated volume receiving 70 Gy. Local and nodal control rates at 3 years were 91 and 89%, respectively. Adverse events were acceptable, and 25 (81%) of 31 patients who were alive without recurrence at 2 years had xerostomia of ≤Grade 1. The overall survival rate at 3 years was 87%. Target definition along with anatomically defined boundaries was feasible without compromise of the therapeutic ratio. It is worth testing this method further to minimize the unnecessary irradiated volume and to standardize the target definition in intensity-modulated radiotherapy for nasopharyngeal cancer.

eRNA: a graphic user interface-based tool optimized for large data analysis from high-throughput RNA sequencing

PubMed Central

2014-01-01

Background RNA sequencing (RNA-seq) is emerging as a critical approach in biological research. However, its high-throughput advantage is significantly limited by the capacity of bioinformatics tools. The research community urgently needs user-friendly tools to efficiently analyze the complicated data generated by high throughput sequencers. Results We developed a standalone tool with graphic user interface (GUI)-based analytic modules, known as eRNA. The capacity of performing parallel processing and sample management facilitates large data analyses by maximizing hardware usage and freeing users from tediously handling sequencing data. The module miRNA identification” includes GUIs for raw data reading, adapter removal, sequence alignment, and read counting. The module “mRNA identification” includes GUIs for reference sequences, genome mapping, transcript assembling, and differential expression. The module “Target screening” provides expression profiling analyses and graphic visualization. The module “Self-testing” offers the directory setups, sample management, and a check for third-party package dependency. Integration of other GUIs including Bowtie, miRDeep2, and miRspring extend the program’s functionality. Conclusions eRNA focuses on the common tools required for the mapping and quantification analysis of miRNA-seq and mRNA-seq data. The software package provides an additional choice for scientists who require a user-friendly computing environment and high-throughput capacity for large data analysis. eRNA is available for free download at https://sourceforge.net/projects/erna/?source=directory. PMID:24593312

eRNA: a graphic user interface-based tool optimized for large data analysis from high-throughput RNA sequencing.

PubMed

Yuan, Tiezheng; Huang, Xiaoyi; Dittmar, Rachel L; Du, Meijun; Kohli, Manish; Boardman, Lisa; Thibodeau, Stephen N; Wang, Liang

2014-03-05

RNA sequencing (RNA-seq) is emerging as a critical approach in biological research. However, its high-throughput advantage is significantly limited by the capacity of bioinformatics tools. The research community urgently needs user-friendly tools to efficiently analyze the complicated data generated by high throughput sequencers. We developed a standalone tool with graphic user interface (GUI)-based analytic modules, known as eRNA. The capacity of performing parallel processing and sample management facilitates large data analyses by maximizing hardware usage and freeing users from tediously handling sequencing data. The module miRNA identification" includes GUIs for raw data reading, adapter removal, sequence alignment, and read counting. The module "mRNA identification" includes GUIs for reference sequences, genome mapping, transcript assembling, and differential expression. The module "Target screening" provides expression profiling analyses and graphic visualization. The module "Self-testing" offers the directory setups, sample management, and a check for third-party package dependency. Integration of other GUIs including Bowtie, miRDeep2, and miRspring extend the program's functionality. eRNA focuses on the common tools required for the mapping and quantification analysis of miRNA-seq and mRNA-seq data. The software package provides an additional choice for scientists who require a user-friendly computing environment and high-throughput capacity for large data analysis. eRNA is available for free download at https://sourceforge.net/projects/erna/?source=directory.

Active modulation of laser coded systems using near infrared video projection system based on digital micromirror device (DMD)

NASA Astrophysics Data System (ADS)

Khalifa, Aly A.; Aly, Hussein A.; El-Sherif, Ashraf F.

2016-02-01

Near infrared (NIR) dynamic scene projection systems are used to perform hardware in-the-loop (HWIL) testing of a unit under test operating in the NIR band. The common and complex requirement of a class of these units is a dynamic scene that is spatio-temporal variant. In this paper we apply and investigate active external modulation of NIR laser in different ranges of temporal frequencies. We use digital micromirror devices (DMDs) integrated as the core of a NIR projection system to generate these dynamic scenes. We deploy the spatial pattern to the DMD controller to simultaneously yield the required amplitude by pulse width modulation (PWM) of the mirror elements as well as the spatio-temporal pattern. Desired modulation and coding of high stable, high power visible (Red laser at 640 nm) and NIR (Diode laser at 976 nm) using the combination of different optical masks based on DMD were achieved. These spatial versatile active coding strategies for both low and high frequencies in the range of kHz for irradiance of different targets were generated by our system and recorded using VIS-NIR fast cameras. The temporally-modulated laser pulse traces were measured using array of fast response photodetectors. Finally using a high resolution spectrometer, we evaluated the NIR dynamic scene projection system response in terms of preserving the wavelength and band spread of the NIR source after projection.

Multiple frequency optical mixer and demultiplexer and apparatus for remote sensing

NASA Technical Reports Server (NTRS)

Chen, Jeffrey R. (Inventor)

2010-01-01

A pulsed laser system includes a modulator module configured to provide pulsed electrical signals and a plurality of solid-state seed sources coupled to the modulator module and configured to operate, responsive to the pulsed electrical signals, in a pulse mode. Each of the plurality of solid-state seed sources is tuned to a different frequency channel separated from any adjacent frequency channel by a frequency offset. The pulsed laser system also includes a combiner that combines outputs from each of the solid state seed sources into a single optical path and an optical doubler and demultiplexer coupled to the single optical path and providing each doubled seed frequency on a separate output path.

Acoustic imaging microscope

DOEpatents

Deason, Vance A.; Telschow, Kenneth L.

2006-10-17

An imaging system includes: an object wavefront source and an optical microscope objective all positioned to direct an object wavefront onto an area of a vibrating subject surface encompassed by a field of view of the microscope objective, and to direct a modulated object wavefront reflected from the encompassed surface area through a photorefractive material; and a reference wavefront source and at least one phase modulator all positioned to direct a reference wavefront through the phase modulator and to direct a modulated reference wavefront from the phase modulator through the photorefractive material to interfere with the modulated object wavefront. The photorefractive material has a composition and a position such that interference of the modulated object wavefront and modulated reference wavefront occurs within the photorefractive material, providing a full-field, real-time image signal of the encompassed surface area.

Mitochondria As Sources and Targets of Methane.

PubMed

Mészáros, András Tamás; Szilágyi, Ágnes Lilla; Juhász, László; Tuboly, Eszter; Érces, Dániel; Varga, Gabriella; Hartmann, Petra

2017-01-01

This review summarizes the current knowledge on the role of mitochondria in the context of hypoxic cell biology, while providing evidence of how these mechanisms are modulated by methane (CH 4 ). Recent studies have unambiguously confirmed CH 4 bioactivity in various in vitro and in vivo experimental models and established the possibility that CH 4 can affect many aspects of mitochondrial physiology. To date, no specific binding of CH 4 to any enzymes or receptors have been reported, and it is probable that many of its effects are related to physico-chemical properties of the non-polar molecule. (i) Mitochondria themselves can be sources of endogenous CH 4 generation under oxido-reductive stress conditions; chemical inhibition of the mitochondrial electron transport chain with site-specific inhibitors leads to increased formation of CH 4 in eukaryote cells, in plants, and in animals. (ii) Conventionally believed as physiologically inert, studies cited in this review demonstrate that exogenous CH 4 modulates key events of inflammation. The anti-apoptotic effects of exogenously administered CH 4 are also recognized, and these properties also suggest that CH 4 -mediated intracellular signaling is closely associated with mitochondria. (iii) Mitochondrial substrate oxidation is coupled with the reduction of molecular oxygen, thus providing energy for cellular metabolism. Interestingly, recent in vivo studies have shown improved basal respiration and modulated mitochondrial oxidative phosphorylation by exogenous CH 4 . Overall, these data suggest that CH 4 liberation and effectiveness in eukaryotes are both linked to hypoxic events and redox regulation and support the notion that CH 4 has therapeutic roles in mammalian pathophysiologies.

Mitochondria As Sources and Targets of Methane

PubMed Central

Mészáros, András Tamás; Szilágyi, Ágnes Lilla; Juhász, László; Tuboly, Eszter; Érces, Dániel; Varga, Gabriella; Hartmann, Petra

2017-01-01

This review summarizes the current knowledge on the role of mitochondria in the context of hypoxic cell biology, while providing evidence of how these mechanisms are modulated by methane (CH4). Recent studies have unambiguously confirmed CH4 bioactivity in various in vitro and in vivo experimental models and established the possibility that CH4 can affect many aspects of mitochondrial physiology. To date, no specific binding of CH4 to any enzymes or receptors have been reported, and it is probable that many of its effects are related to physico-chemical properties of the non-polar molecule. (i) Mitochondria themselves can be sources of endogenous CH4 generation under oxido-reductive stress conditions; chemical inhibition of the mitochondrial electron transport chain with site-specific inhibitors leads to increased formation of CH4 in eukaryote cells, in plants, and in animals. (ii) Conventionally believed as physiologically inert, studies cited in this review demonstrate that exogenous CH4 modulates key events of inflammation. The anti-apoptotic effects of exogenously administered CH4 are also recognized, and these properties also suggest that CH4-mediated intracellular signaling is closely associated with mitochondria. (iii) Mitochondrial substrate oxidation is coupled with the reduction of molecular oxygen, thus providing energy for cellular metabolism. Interestingly, recent in vivo studies have shown improved basal respiration and modulated mitochondrial oxidative phosphorylation by exogenous CH4. Overall, these data suggest that CH4 liberation and effectiveness in eukaryotes are both linked to hypoxic events and redox regulation and support the notion that CH4 has therapeutic roles in mammalian pathophysiologies. PMID:29181377

Improved linearity using harmonic error rejection in a full-field range imaging system

NASA Astrophysics Data System (ADS)

Payne, Andrew D.; Dorrington, Adrian A.; Cree, Michael J.; Carnegie, Dale A.

2008-02-01

Full field range imaging cameras are used to simultaneously measure the distance for every pixel in a given scene using an intensity modulated illumination source and a gain modulated receiver array. The light is reflected from an object in the scene, and the modulation envelope experiences a phase shift proportional to the target distance. Ideally the waveforms are sinusoidal, allowing the phase, and hence object range, to be determined from four measurements using an arctangent function. In practice these waveforms are often not perfectly sinusoidal, and in some cases square waveforms are instead used to simplify the electronic drive requirements. The waveforms therefore commonly contain odd harmonics which contribute a nonlinear error to the phase determination, and therefore an error in the range measurement. We have developed a unique sampling method to cancel the effect of these harmonics, with the results showing an order of magnitude improvement in the measurement linearity without the need for calibration or lookup tables, while the acquisition time remains unchanged. The technique can be applied to existing range imaging systems without having to change or modify the complex illumination or sensor systems, instead only requiring a change to the signal generation and timing electronics.

CWDM for very-short-reach and optical-backplane interconnections

NASA Astrophysics Data System (ADS)

Laha, Michael J.

2002-06-01

Course Wavelength Division Multiplexing (CWDM) provides access to next generation optical interconnect data rates by utilizing conventional electro-optical components that are widely available in the market today. This is achieved through the use of CWDM multiplexers and demultiplexers that integrate commodity type active components, lasers and photodiodes, into small optical subassemblies. In contrast to dense wavelength division multiplexing (DWDM), in which multiple serial data streams are combined to create aggregate data pipes perhaps 100s of gigabits wide, CWDM uses multiple laser sources contained in one module to create a serial equivalent data stream. For example, four 2.5 Gb/s lasers are multiplexed to create a 10 Gb/s data pipe. The advantages of CWDM over traditional serial optical interconnects include lower module power consumption, smaller packaging, and a superior electrical interface. This discussion will detail the concept of CWDM and design parameters that are considered when productizing a CWDM module into an industry standard optical interconnect. Additionally, a scalable parallel CWDM hybrid architecture will be described that allows the transport of large amounts of data from rack to rack in an economical fashion. This particular solution is targeted at solving optical backplane bottleneck problems predicted for the next generation terabit and petabit routers.

Copper signaling in the brain and beyond.

PubMed

Ackerman, Cheri M; Chang, Christopher J

2018-03-30

Transition metals have been recognized and studied primarily in the context of their essential roles as structural and metabolic cofactors for biomolecules that compose living systems. More recently, an emerging paradigm of transition-metal signaling, where dynamic changes in transitional metal pools can modulate protein function, cell fate, and organism health and disease, has broadened our view of the potential contributions of these essential nutrients in biology. Using copper as a canonical example of transition-metal signaling, we highlight key experiments where direct measurement and/or visualization of dynamic copper pools, in combination with biochemical, physiological, and behavioral studies, have deciphered sources, targets, and physiological effects of copper signals.

Full Service

NASA Technical Reports Server (NTRS)

Morring, Frank, Jr.

2004-01-01

NASA is moving ahead with the sole-source procurement of a Canadian robot to service the Hubble Space Telescope, gaining confidence the International Space Station (ISS) technology can perform all of the tasks shuttle-launched astronauts were scheduled to do before the Columbia accident changed everything. The U.S. agency is negotiating with MD Robotics, a MacDonald Dettwiler unit located in Brampton, Ontario, for a version of the Special Purpose Dexterous Manipulator (SPDM) the company developed for the ISS. The SPDM would be the business end of a throwaway module designed to replace batteries and gyroscopes, pull old instruments and install new ones before plunging to a targeted reentry over the Pacific.

Solar photovoltaic power systems: an electric utility R & d perspective.

PubMed

Demeo, E A; Taylor, R W

1984-04-20

Solar photovoltaic technology is receiving increasing attention as a prospective source of bulk, electric utility power within the next 10 to 20 years. Successful development will require solar energy conversion efficiencies of about 15 percent for photovoltaic flat-plate modules, or about 25 percent for photovoltaic cells using highly concentrated sunlight. Three different cell technologies have a better than even chance of achieving these target efficiencies with costs and operating lifetimes that would allow significant use by electric utilities. The challenge for the next decade is to push photovoltaic technology to its physical limits while expanding markets and user confidence with currently available systems.

Work continues on Leonardo, the Multi-Purpose Logistics Module, in the Space Station Processing Faci

NASA Technical Reports Server (NTRS)

1999-01-01

Workers in the Space Station Processing Facility work on Leonardo, the Multipurpose Logistics Module (MPLM) built by the Agenzia Spaziale Italiana (ASI). The MPLM, a reusable logistics carrier, will be the primary delivery system used to resupply and return International Space Station cargo requiring a pressurized environment. Leonardo is the first of three MPLM carriers for the International Space Station. It is scheduled to be launched on Space Shuttle Mission STS-102, targeted for June 2000. Leonardo shares space in the SSPF with the Shuttle Radar Topography Mission (SRTM), targeted for launch in September 1999, and Destiny, the U.S. Lab module, targeted for mission STS-98 in late April 2000.

Differential targeting of Gbetagamma-subunit signaling with small molecules.

PubMed

Bonacci, Tabetha M; Mathews, Jennifer L; Yuan, Chujun; Lehmann, David M; Malik, Sundeep; Wu, Dianqing; Font, Jose L; Bidlack, Jean M; Smrcka, Alan V

2006-04-21

G protein betagamma subunits have potential as a target for therapeutic treatment of a number of diseases. We performed virtual docking of a small-molecule library to a site on Gbetagamma subunits that mediates protein interactions. We hypothesized that differential targeting of this surface could allow for selective modulation of Gbetagamma subunit functions. Several compounds bound to Gbetagamma subunits with affinities from 0.1 to 60 muM and selectively modulated functional Gbetagamma-protein-protein interactions in vitro, chemotactic peptide signaling pathways in HL-60 leukocytes, and opioid receptor-dependent analgesia in vivo. These data demonstrate an approach for modulation of G protein-coupled receptor signaling that may represent an important therapeutic strategy.

CADDIS Volume 2. Sources, Stressors and Responses: Metals - Point Sources from Industry

EPA Pesticide Factsheets

Introduction to the metals module, when to list metals as a candidate cause, ways to measure metals, simple and detailed conceptual diagrams for metals, metals module references and literature reviews.

How bees distinguish patterns by green and blue modulation

PubMed Central

Horridge, Adrian

2015-01-01

In the 1920s, Mathilde Hertz found that trained bees discriminated between shapes or patterns of similar size by something related to total length of contrasting contours. This input is now interpreted as modulation in green and blue receptor channels as flying bees scan in the horizontal plane. Modulation is defined as total contrast irrespective of sign multiplied by length of edge displaying that contrast, projected to vertical, therefore, combining structure and contrast in a single input. Contrast is outside the eye; modulation is a phasic response in receptor pathways inside. In recent experiments, bees trained to distinguish color detected, located, and measured three independent inputs and the angles between them. They are the tonic response of the blue receptor pathway and modulation of small-field green or (less preferred) blue receptor pathways. Green and blue channels interacted intimately at a peripheral level. This study explores in more detail how various patterns are discriminated by these cues. The direction of contrast at a boundary was not detected. Instead, bees located and measured total modulation generated by horizontal scanning of contrasts, irrespective of pattern. They also located the positions of isolated vertical edges relative to other landmarks and distinguished the angular widths between vertical edges by green or blue modulation alone. The preferred inputs were the strongest green modulation signal and angular width between outside edges, irrespective of color. In the absence of green modulation, the remaining cue was a measure and location of blue modulation at edges. In the presence of green modulation, blue modulation was inhibited. Black/white patterns were distinguished by the same inputs in blue and green receptor channels. Left–right polarity and mirror images could be discriminated by retinotopic green modulation alone. Colors in areas bounded by strong green contrast were distinguished as more or less blue than the background. The blue content could also be summed over the whole target. There were no achromatic patterns for bees and no evidence that they detected black, white, or gray levels apart from the differences in blue content or modulation at edges. Most of these cues would be sensitive to background color but some were influenced by changes in illumination. The bees usually learned only to avoid the unrewarded target. Exactly the same preferences of the same inputs were used in the detection of single targets as in discrimination between two targets. PMID:28539796

miRNA-Mediated Relationships between Cis-SNP Genotypes and Transcript Intensities in Lymphocyte Cell Lines

PubMed Central

Zhang, Wensheng; Edwards, Andrea; Zhu, Dongxiao; Flemington, Erik K.; Deininger, Prescott; Zhang, Kun

2012-01-01

In metazoans, miRNAs regulate gene expression primarily through binding to target sites in the 3′ UTRs (untranslated regions) of messenger RNAs (mRNAs). Cis-acting variants within, or close to, a gene are crucial in explaining the variability of gene expression measures. Single nucleotide polymorphisms (SNPs) in the 3′ UTRs of genes can affect the base-pairing between miRNAs and mRNAs, and hence disrupt existing target sites (in the reference sequence) or create novel target sites, suggesting a possible mechanism for cis regulation of gene expression. Moreover, because the alleles of different SNPs within a DNA sequence of limited length tend to be in strong linkage disequilibrium (LD), we hypothesize the variants of miRNA target sites caused by SNPs potentially function as bridges linking the documented cis-SNP markers to the expression of the associated genes. A large-scale analysis was herein performed to test this hypothesis. By systematically integrating multiple latest information sources, we found 21 significant gene-level SNP-involved miRNA-mediated post-transcriptional regulation modules (SNP-MPRMs) in the form of SNP-miRNA-mRNA triplets in lymphocyte cell lines for the CEU and YRI populations. Among the cognate genes, six including ALG8, DGKE, GNA12, KLF11, LRPAP1, and MMAB are related to multiple genetic diseases such as depressive disorder and Type-II diabetes. Furthermore, we found that ∼35% of the documented transcript intensity-related cis-SNPs (∼950) in a recent publication are identical to, or in significant linkage disequilibrium (LD) (p<0.01) with, one or multiple SNPs located in miRNA target sites. Based on these associations (or identities), 69 significant exon-level SNP-MPRMs and 12 disease genes were further determined for two populations. These results provide concrete in silico evidence for the proposed hypothesis. The discovered modules warrant additional follow-up in independent laboratory studies. PMID:22348086

Metrical expectations from preceding prosody influence perception of lexical stress

PubMed Central

Brown, Meredith; Salverda, Anne Pier; Dilley, Laura C.; Tanenhaus, Michael K.

2015-01-01

Two visual-world experiments tested the hypothesis that expectations based on preceding prosody influence the perception of suprasegmental cues to lexical stress. The results demonstrate that listeners’ consideration of competing alternatives with different stress patterns (e.g., ‘jury/gi’raffe) can be influenced by the fundamental frequency and syllable timing patterns across material preceding a target word. When preceding stressed syllables distal to the target word shared pitch and timing characteristics with the first syllable of the target word, pictures of alternatives with primary lexical stress on the first syllable (e.g., jury) initially attracted more looks than alternatives with unstressed initial syllables (e.g., giraffe). This effect was modulated when preceding unstressed syllables had pitch and timing characteristics similar to the initial syllable of the target word, with more looks to alternatives with unstressed initial syllables (e.g., giraffe) than to those with stressed initial syllables (e.g., jury). These findings suggest that expectations about the acoustic realization of upcoming speech include information about metrical organization and lexical stress, and that these expectations constrain the initial interpretation of suprasegmental stress cues. These distal prosody effects implicate on-line probabilistic inferences about the sources of acoustic-phonetic variation during spoken-word recognition. PMID:25621583

In Vivo Fluorescence Resonance Energy Transfer Imaging for Targeted Anti-Cancer Drug Delivery Kinetics

NASA Astrophysics Data System (ADS)

Webb, Kevin; Gaind, Vaibhav; Tsai, Hsiaorho; Bentz, Brian; Chelvam, Venkatesh; Low, Philip

2012-02-01

We describe an approach for the evaluation of targeted anti-cancer drug delivery in vivo. The method emulates the drug release and activation process through acceptor release from a targeted donor-acceptor pair that exhibits fluorescence resonance energy transfer (FRET). In this case, folate targeting of the cancer cells is used - 40 % of all human cancers, including ovarian, lung, breast, kidney, brain and colon cancer, over-express folate receptors. We demonstrate the reconstruction of the spatially-dependent FRET parameters in a mouse model and in tissue phantoms. The FRET parameterization is incorporated into a source for a diffusion equation model for photon transport in tissue, in a variant of optical diffusion tomography (ODT) called FRET-ODT. In addition to the spatially-dependent tissue parameters in the diffusion model (absorption and diffusion coefficients), the FRET parameters (donor-acceptor distance and yield) are imaged as a function of position. Modulated light measurements are made with various laser excitation positions and a gated camera. More generally, our method provides a new vehicle for studying disease at the molecular level by imaging FRET parameters in deep tissue, and allows the nanometer FRET ruler to be utilized in deep tissue.

Multi-wavelength time-coincident optical communications system and methods thereof

NASA Technical Reports Server (NTRS)

Lekki, John (Inventor); Nguyen, Quang-Viet (Inventor)

2009-01-01

An optical communications transmitter includes a oscillator source, producing a clock signal, a data source, producing a data signal, a modulating circuit for modulating the clock signal using the data signal to produce modulating signals, optical drivers, receiving the modulating signals and producing optical driving signals based on the modulating signals and optical emitters, producing small numbers of photons based on the optical driving signals. The small numbers of photons are time-correlated between at least two separate optical transmission wavelengths and quantum states and the small number of photons can be detected by a receiver to reform the data signal.

Numerical models analysis of energy conversion process in air-breathing laser propulsion

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

Hong Yanji; Song Junling; Cui Cunyan

Energy source was considered as a key essential in this paper to describe energy conversion process in air-breathing laser propulsion. Some secondary factors were ignored when three independent modules, ray transmission module, energy source term module and fluid dynamic module, were established by simultaneous laser radiation transportation equation and fluid mechanics equation. The incidence laser beam was simulated based on ray tracing method. The calculated results were in good agreement with those of theoretical analysis and experiments.

[Modulating expression of key genes within β-carotene synthetic pathway in recombinant Escherichia coli with RBS library to improve β-carotene production].

PubMed

Dai, Guanping; Sun, Tao; Miao, Liangtian; Li, Qingyan; Xiao, Dongguang; Zhang, Xueli

2014-08-01

β-carotene belongs to carotenoids family, widely applied in pharmaceuticals, neutraceuticals, cosmetics and food industries. In this study, three key genes (dxs, idi, and crt operon) within β-carotene synthetic pathway in recombinant Escherichia coli strain CAR005 were modulated with RBS Library to improve β-carotene production. There were 7%, 11% and 17% increase of β-carotene yield respectively after modulating dxs, idi and crt operon genes with RBS Library, demonstrating that modulating gene expression with regulatory parts libraries would have more opportunities to obtain optimal production of target compound. Combined modulation of crt operon, dxs and idi genes led to 35% increase of β-carotene yield compared to parent strain CAR005. The optimal gene expression strength identified in single gene modulation would not be the optimal strength when used in combined modulation. Our study provides a new strategy for improving production of target compound through modulation of gene expression.

Dispatching packets on a global combining network of a parallel computer

DOEpatents

Almasi, Gheorghe [Ardsley, NY; Archer, Charles J [Rochester, MN

2011-07-19

Methods, apparatus, and products are disclosed for dispatching packets on a global combining network of a parallel computer comprising a plurality of nodes connected for data communications using the network capable of performing collective operations and point to point operations that include: receiving, by an origin system messaging module on an origin node from an origin application messaging module on the origin node, a storage identifier and an operation identifier, the storage identifier specifying storage containing an application message for transmission to a target node, and the operation identifier specifying a message passing operation; packetizing, by the origin system messaging module, the application message into network packets for transmission to the target node, each network packet specifying the operation identifier and an operation type for the message passing operation specified by the operation identifier; and transmitting, by the origin system messaging module, the network packets to the target node.

Application of quantum-dot multi-wavelength lasers and silicon photonic ring resonators to data-center optical interconnects

NASA Astrophysics Data System (ADS)

Beckett, Douglas J. S.; Hickey, Ryan; Logan, Dylan F.; Knights, Andrew P.; Chen, Rong; Cao, Bin; Wheeldon, Jeffery F.

2018-02-01

Quantum dot comb sources integrated with silicon photonic ring-resonator filters and modulators enable the realization of optical sub-components and modules for both inter- and intra-data-center applications. Low-noise, multi-wavelength, single-chip, laser sources, PAM4 modulation and direct detection allow a practical, scalable, architecture for applications beyond 400 Gb/s. Multi-wavelength, single-chip light sources are essential for reducing power dissipation, space and cost, while silicon photonic ring resonators offer high-performance with space and power efficiency.

Cas13d Is a Compact RNA-Targeting Type VI CRISPR Effector Positively Modulated by a WYL-Domain-Containing Accessory Protein.

PubMed

Yan, Winston X; Chong, Shaorong; Zhang, Huaibin; Makarova, Kira S; Koonin, Eugene V; Cheng, David R; Scott, David A

2018-04-19

Bacterial class 2 CRISPR-Cas systems utilize a single RNA-guided protein effector to mitigate viral infection. We aggregated genomic data from multiple sources and constructed an expanded database of predicted class 2 CRISPR-Cas systems. A search for novel RNA-targeting systems identified subtype VI-D, encoding dual HEPN domain-containing Cas13d effectors and putative WYL-domain-containing accessory proteins (WYL1 and WYL-b1 through WYL-b5). The median size of Cas13d proteins is 190 to 300 aa smaller than that of Cas13a-Cas13c. Despite their small size, Cas13d orthologs from Eubacterium siraeum (Es) and Ruminococcus sp. (Rsp) are active in both CRISPR RNA processing and targeting, as well as collateral RNA cleavage, with no target-flanking sequence requirements. The RspWYL1 protein stimulates RNA cleavage by both EsCas13d and RspCas13d, demonstrating a common regulatory mechanism for divergent Cas13d orthologs. The small size, minimal targeting constraints, and modular regulation of Cas13d effectors further expands the CRISPR toolkit for RNA manipulation and detection. Copyright © 2018 Elsevier Inc. All rights reserved.

Within-Hemifield Competition in Early Visual Areas Limits the Ability to Track Multiple Objects with Attention

PubMed Central

Alvarez, George A.; Cavanagh, Patrick

2014-01-01

It is much easier to divide attention across the left and right visual hemifields than within the same visual hemifield. Here we investigate whether this benefit of dividing attention across separate visual fields is evident at early cortical processing stages. We measured the steady-state visual evoked potential, an oscillatory response of the visual cortex elicited by flickering stimuli, of moving targets and distractors while human observers performed a tracking task. The amplitude of responses at the target frequencies was larger than that of the distractor frequencies when participants tracked two targets in separate hemifields, indicating that attention can modulate early visual processing when it is divided across hemifields. However, these attentional modulations disappeared when both targets were tracked within the same hemifield. These effects were not due to differences in task performance, because accuracy was matched across the tracking conditions by adjusting target speed (with control conditions ruling out effects due to speed alone). To investigate later processing stages, we examined the P3 component over central-parietal scalp sites that was elicited by the test probe at the end of the trial. The P3 amplitude was larger for probes on targets than on distractors, regardless of whether attention was divided across or within a hemifield, indicating that these higher-level processes were not constrained by visual hemifield. These results suggest that modulating early processing stages enables more efficient target tracking, and that within-hemifield competition limits the ability to modulate multiple target representations within the hemifield maps of the early visual cortex. PMID:25164651

Power-Combined GaN Amplifier with 2.28-W Output Power at 87 GHz

NASA Technical Reports Server (NTRS)

Fung, King Man; Ward, John; Chattopadhyay, Goutam; Lin, Robert H.; Samoska, Lorene A.; Kangaslahti, Pekka P.; Mehdi, Imran; Lambrigtsen, Bjorn H.; Goldsmith, Paul F.; Soria, Mary M.;

Prototyping of beam position monitor for medium energy beam transport section of RAON heavy ion accelerator

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

Jang, Hyojae, E-mail: lkcom@ibs.re.kr; Jin, Hyunchang; Jang, Ji-Ho

2016-02-15

A heavy ion accelerator, RAON is going to be built by Rare Isotope Science Project in Korea. Its target is to accelerate various stable ions such as uranium, proton, and xenon from electron cyclotron resonance ion source and some rare isotopes from isotope separation on-line. The beam shaping, charge selection, and modulation should be applied to the ions from these ion sources because RAON adopts a superconducting linear accelerator structure for beam acceleration. For such treatment, low energy beam transport, radio frequency quadrupole, and medium energy beam transport (MEBT) will be installed in injector part of RAON accelerator. Recently, developmentmore » of a prototype of stripline beam position monitor (BPM) to measure the position of ion beams in MEBT section is under way. In this presentation, design of stripline, electromagnetic (EM) simulation results, and RF measurement test results obtained from the prototyped BPM will be described.« less

Neuronal basis of covert spatial attention in the frontal eye field.

PubMed

Thompson, Kirk G; Biscoe, Keri L; Sato, Takashi R

2005-10-12

The influential "premotor theory of attention" proposes that developing oculomotor commands mediate covert visual spatial attention. A likely source of this attentional bias is the frontal eye field (FEF), an area of the frontal cortex involved in converting visual information into saccade commands. We investigated the link between FEF activity and covert spatial attention by recording from FEF visual and saccade-related neurons in monkeys performing covert visual search tasks without eye movements. Here we show that the source of attention signals in the FEF is enhanced activity of visually responsive neurons. At the time attention is allocated to the visual search target, nonvisually responsive saccade-related movement neurons are inhibited. Therefore, in the FEF, spatial attention signals are independent of explicit saccade command signals. We propose that spatially selective activity in FEF visually responsive neurons corresponds to the mental spotlight of attention via modulation of ongoing visual processing.

Final Report for PV Incubator Subcontract No. NAT-0-99013-01: June 14, 2010 - March 2, 2012

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

Ghosal, K.

2012-04-01

The goal of the subcontract is to scale up Semprius' novel micro-cell based modules to an annualized rate of 500 kW of receivers and 10 kW of modules, in support of the DOE 2020 Sunshot Initiative goals. The statement of work (SOW) was broken up into two Phases. Phase I was directed towards process development efforts towards addressing fundamental manufacturing metrics such as yield, die per wafer, automation and throughput. Phase II objectives are to scale to an annualized production rate of 500 kW of receivers and 10 kW of modules, while improving cell efficiency, module efficiency and transfer yield.more » Semprius has met all the technical milestones and deliverables for the contract. All subtasks were completed earlier than expected and the results exceeded the technical targets. In particular, 3J cell efficiency of 41.2% exceeded the target of 38%, module efficiency of 28.3% exceeded the target of 28% and transfer yield of 96.4% exceeds the target of 95%, with all tasks completed well ahead of schedule. Also, devices fabricated from 1st use GaAs substrates and substrates with two re-uses have been shown to be identical.« less

A Novel c-VEP BCI Paradigm for Increasing the Number of Stimulus Targets Based on Grouping Modulation With Different Codes.

PubMed

Wei, Qingguo; Liu, Yonghui; Gao, Xiaorong; Wang, Yijun; Yang, Chen; Lu, Zongwu; Gong, Huayuan

2018-06-01

In an existing brain-computer interface (BCI) based on code modulated visual evoked potentials (c-VEP), a method with which to increase the number of targets without increasing code length has not yet been established. In this paper, a novel c-VEP BCI paradigm, namely, grouping modulation with different codes that have good autocorrelation and crosscorrelation properties, is presented to increase the number of targets and information transfer rate (ITR). All stimulus targets are divided into several groups and each group of targets are modulated by a distinct pseudorandom binary code and its circularly shifting codes. Canonical correlation analysis is applied to each group for yielding a spatial filter and templates for all targets in a group are constructed based on spatially filtered signals. Template matching is applied to each group and the attended target is recognized by finding the maximal correlation coefficients of all groups. Based on the paradigm, a BCI with a total of 48 targets divided into three groups was implemented; 12 and 10 subjects participated in an off-line and a simulated online experiments, respectively. Data analysis of the offline experiment showed that the paradigm can massively increase the number of targets from 16 to 48 at the cost of slight compromise in accuracy (95.49% vs. 92.85%). Results of the simulated online experiment suggested that although the averaged accuracy across subjects of all three groups of targets was lower than that of a single group of targets (91.67% vs. 94.9%), the average ITR of the former was substantially higher than that of the later (181 bits/min vs. 135.6 bit/min) due to the large increase of the number of targets. The proposed paradigm significantly improves the performance of the c-VEP BCI, and thereby facilitates its practical applications such as high-speed spelling.

Multiple source/multiple target fluid transfer apparatus

DOEpatents

Turner, Terry D.

1997-01-01

A fluid transfer apparatus includes: a) a plurality of orifices for connection with fluid sources; b) a plurality of orifices for connection with fluid targets; c) a set of fluid source conduits and fluid target conduits associated with the orifices; d) a pump fluidically interposed between the source and target conduits to transfer fluid therebetween; e) a purge gas conduit in fluid communication with the fluid source conduits, fluid target conduits and pump to receive and pass a purge gas under pressure; f) a solvent conduit in fluid communication with the fluid source conduits, fluid target conduits and pump to receive and pass solvent, the solvent conduit including a solvent valve; g) pump control means for controlling operation of the pump; h) purge gas valve control means for controlling operation of the purge gas valve to selectively impart flow of purge gas to the fluid source conduits, fluid target conduits and pump; i) solvent valve control means for controlling operation of the solvent valve to selectively impart flow of solvent to the fluid source conduits, fluid target conduits and pump; and j) source and target valve control means for controlling operation of the fluid source conduit valves and the fluid target conduit valves to selectively impart passage of fluid between a selected one of the fluid source conduits and a selected one of the fluid target conduits through the pump and to enable passage of solvent or purge gas through selected fluid source conduits and selected fluid target conduits.

Multiple source/multiple target fluid transfer apparatus

DOEpatents

Turner, T.D.

1997-08-26

A fluid transfer apparatus includes: (a) a plurality of orifices for connection with fluid sources; (b) a plurality of orifices for connection with fluid targets; (c) a set of fluid source conduits and fluid target conduits associated with the orifices; (d) a pump fluidically interposed between the source and target conduits to transfer fluid there between; (e) a purge gas conduit in fluid communication with the fluid source conduits, fluid target conduits and pump to receive and pass a purge gas under pressure; (f) a solvent conduit in fluid communication with the fluid source conduits, fluid target conduits and pump to receive and pass solvent, the solvent conduit including a solvent valve; (g) pump control means for controlling operation of the pump; (h) purge gas valve control means for controlling operation of the purge gas valve to selectively impart flow of purge gas to the fluid source conduits, fluid target conduits and pump; (i) solvent valve control means for controlling operation of the solvent valve to selectively impart flow of solvent to the fluid source conduits, fluid target conduits and pump; and (j) source and target valve control means for controlling operation of the fluid source conduit valves and the fluid target conduit valves to selectively impart passage of fluid between a selected one of the fluid source conduits and a selected one of the fluid target conduits through the pump and to enable passage of solvent or purge gas through selected fluid source conduits and selected fluid target conduits. 6 figs.

Fiber-based polarization-sensitive Mueller matrix optical coherence tomography with continuous source polarization modulation.

PubMed

Jiao, Shuliang; Todorović, Milos; Stoica, George; Wang, Lihong V

2005-09-10

We report on a new configuration of fiber-based polarization-sensitive Mueller matrix optical coherence tomography that permits the acquisition of the round-trip Jones matrix of a biological sample using only one light source and a single depth scan. In this new configuration, a polarization modulator is used in the source arm to continuously modulate the incident polarization state for both the reference and the sample arms. The Jones matrix of the sample can be calculated from the two frequency terms in the two detection channels. The first term is modulated by the carrier frequency, which is determined by the longitudinal scanning mechanism, whereas the other term is modulated by the beat frequency between the carrier frequency and the second harmonic of the modulation frequency of the polarization modulator. One important feature of this system is that, for the first time to our knowledge, the Jones matrix of the sample can be calculated with a single detection channel and a single measurement when diattenuation is negligible. The system was successfully tested by imaging both standard polarization elements and biological samples.

Open source challenges for hospital information system (HIS) in developing countries: a pilot project in Mali.

PubMed

Bagayoko, Cheick-Oumar; Dufour, Jean-Charles; Chaacho, Saad; Bouhaddou, Omar; Fieschi, Marius

2010-04-16

We are currently witnessing a significant increase in use of Open Source tools in the field of health. Our study aims to research the potential of these software packages for developing countries. Our experiment was conducted at the Centre Hospitalier Mere Enfant in Mali. After reviewing several Open Source tools in the field of hospital information systems, Mediboard software was chosen for our study. To ensure the completeness of Mediboard in relation to the functionality required for a hospital information system, its features were compared to those of a well-defined comprehensive record management tool set up at the University Hospital "La Timone" of Marseilles in France. It was then installed on two Linux servers: a first server for testing and validation of different modules, and a second one for the deployed full implementation. After several months of use, we have evaluated the usability aspects of the system including feedback from end-users through a questionnaire. Initial results showed the potential of Open Source in the field of health IT for developing countries like Mali.Five main modules have been fully implemented: patient administrative and medical records management of hospital activities, tracking of practitioners' activities, infrastructure management and the billing system. This last component of the system has been fully developed by the local Mali team.The evaluation showed that the system is broadly accepted by all the users who participated in the study. 77% of the participants found the system useful; 85% found it easy; 100% of them believe the system increases the reliability of data. The same proportion encourages the continuation of the experiment and its expansion throughout the hospital. In light of the results, we can conclude that the objective of our study was reached. However, it is important to take into account the recommendations and the challenges discussed here to avoid several potential pitfalls specific to the context of Africa.Our future work will target the full integration of the billing module in Mediboard and an expanded implementation throughout the hospital.

Open source challenges for hospital information system (HIS) in developing countries: a pilot project in Mali

PubMed Central

2010-01-01

Background We are currently witnessing a significant increase in use of Open Source tools in the field of health. Our study aims to research the potential of these software packages for developing countries. Our experiment was conducted at the Centre Hospitalier Mere Enfant in Mali. Methods After reviewing several Open Source tools in the field of hospital information systems, Mediboard software was chosen for our study. To ensure the completeness of Mediboard in relation to the functionality required for a hospital information system, its features were compared to those of a well-defined comprehensive record management tool set up at the University Hospital "La Timone" of Marseilles in France. It was then installed on two Linux servers: a first server for testing and validation of different modules, and a second one for the deployed full implementation. After several months of use, we have evaluated the usability aspects of the system including feedback from end-users through a questionnaire. Results Initial results showed the potential of Open Source in the field of health IT for developing countries like Mali. Five main modules have been fully implemented: patient administrative and medical records management of hospital activities, tracking of practitioners' activities, infrastructure management and the billing system. This last component of the system has been fully developed by the local Mali team. The evaluation showed that the system is broadly accepted by all the users who participated in the study. 77% of the participants found the system useful; 85% found it easy; 100% of them believe the system increases the reliability of data. The same proportion encourages the continuation of the experiment and its expansion throughout the hospital. Conclusions In light of the results, we can conclude that the objective of our study was reached. However, it is important to take into account the recommendations and the challenges discussed here to avoid several potential pitfalls specific to the context of Africa. Our future work will target the full integration of the billing module in Mediboard and an expanded implementation throughout the hospital. PMID:20398366

Electrical system for pulse-width modulated control of a power inverter using phase-shifted carrier signals and related operating methods

DOEpatents

Welchko, Brian A [Torrance, CA

2012-02-14

Systems and methods are provided for pulse-width modulated control of power inverter using phase-shifted carrier signals. An electrical system comprises an energy source and a motor. The motor has a first set of windings and a second set of windings, which are electrically isolated from each other. An inverter module is coupled between the energy source and the motor and comprises a first set of phase legs coupled to the first set of windings and a second set of phase legs coupled to the second set of windings. A controller is coupled to the inverter module and is configured to achieve a desired power flow between the energy source and the motor by modulating the first set of phase legs using a first carrier signal and modulating the second set of phase legs using a second carrier signal. The second carrier signal is phase-shifted relative to the first carrier signal.

Parallel, exhaustive processing underlies logarithmic search functions: Visual search with cortical magnification.

PubMed

Wang, Zhiyuan; Lleras, Alejandro; Buetti, Simona

2018-04-17

Our lab recently found evidence that efficient visual search (with a fixed target) is characterized by logarithmic Reaction Time (RT) × Set Size functions whose steepness is modulated by the similarity between target and distractors. To determine whether this pattern of results was based on low-level visual factors uncontrolled by previous experiments, we minimized the possibility of crowding effects in the display, compensated for the cortical magnification factor by magnifying search items based on their eccentricity, and compared search performance on such displays to performance on displays without magnification compensation. In both cases, the RT × Set Size functions were found to be logarithmic, and the modulation of the log slopes by target-distractor similarity was replicated. Consistent with previous results in the literature, cortical magnification compensation eliminated most target eccentricity effects. We conclude that the log functions and their modulation by target-distractor similarity relations reflect a parallel exhaustive processing architecture for early vision.

A Design of a Modular GPHS-Stirling Power System for a Lunar Habitation Module

NASA Technical Reports Server (NTRS)

Schmitz, Paul C.; Penswick, L. Barry; Shaltens, Richard K.

2005-01-01

Lunar habitation modules need electricity and potentially heat to operate. Because of the low amounts of radiation emitted by General Purpose Heat Source (GPHS) modules, power plants incorporating these as heat sources could be placed in close proximity to habitation modules. A design concept is discussed for a high efficiency power plant based on a GPHS assembly integrated with a Stirling convertor. This system could provide both electrical power and heat, if required, for a lunar habitation module. The conceptual GPHS/Stirling system is modular in nature and made up of a basic 5.5 KWe Stirling convertor/GPHS module assembly, convertor controller/PMAD electronics, waste heat radiators, and associated thermal insulation. For the specific lunar application under investigation eight modules are employed to deliver 40 KWe to the habitation module. This design looks at three levels of Stirling convertor technology and addresses the issues of integrating the Stirling convertors with the GPHS heat sources assembly using proven technology whenever possible. In addition, issues related to the high-temperature heat transport system, power management, convertor control, vibration isolation, and potential system packaging configurations to ensure safe operation during all phases of deployment will be discussed.

Image change detection systems, methods, and articles of manufacture

DOEpatents

Jones, James L.; Lassahn, Gordon D.; Lancaster, Gregory D.

2010-01-05

Aspects of the invention relate to image change detection systems, methods, and articles of manufacture. According to one aspect, a method of identifying differences between a plurality of images is described. The method includes loading a source image and a target image into memory of a computer, constructing source and target edge images from the source and target images to enable processing of multiband images, displaying the source and target images on a display device of the computer, aligning the source and target edge images, switching displaying of the source image and the target image on the display device, to enable identification of differences between the source image and the target image.

Glutamate synaptic inputs to ventral tegmental area neurons in the rat derive primarily from subcortical sources.

PubMed

Omelchenko, N; Sesack, S R

2007-05-25

Dopamine and GABA neurons in the ventral tegmental area project to the nucleus accumbens and prefrontal cortex and modulate locomotor and reward behaviors as well as cognitive and affective processes. Both midbrain cell types receive synapses from glutamate afferents that provide an essential control of behaviorally-linked activity patterns, although the sources of glutamate inputs have not yet been completely characterized. We used antibodies against the vesicular glutamate transporter subtypes 1 and 2 (VGlut1 and VGlut2) to investigate the morphology and synaptic organization of axons containing these proteins as putative markers of glutamate afferents from cortical versus subcortical sites, respectively, in rats. We also characterized the ventral tegmental area cell populations receiving VGlut1+ or VGlut2+ synapses according to their transmitter phenotype (dopamine or GABA) and major projection target (nucleus accumbens or prefrontal cortex). By light and electron microscopic examination, VGlut2+ as opposed to VGlut1+ axon terminals were more numerous, had a larger average size, synapsed more proximally, and were more likely to form convergent synapses onto the same target. Both axon types formed predominantly asymmetric synapses, although VGlut2+ terminals more often formed synapses with symmetric morphology. No absolute selectivity was observed for VGlut1+ or VGlut2+ axons to target any particular cell population. However, the synapses onto mesoaccumbens neurons more often involved VGlut2+ terminals, whereas mesoprefrontal neurons received relatively equal synaptic inputs from VGlut1+ and VGlut2+ profiles. The distinct morphological features of VGlut1 and VGlut2 positive axons suggest that glutamate inputs from presumed cortical and subcortical sources, respectively, differ in the nature and intensity of their physiological actions on midbrain neurons. More specifically, our findings imply that subcortical glutamate inputs to the ventral tegmental area expressing VGlut2 predominate over cortical sources of excitation expressing VGlut1 and are more likely to drive the behaviorally-linked bursts in dopamine cells that signal future expectancy or attentional shifting.

Thermal Neutron Point Source Imaging using a Rotating Modulation Collimator (RMC)

DTIC Science & Technology

2010-03-01

Source Details.........................................................................................37 3.5 Simulation of RMC in MCNP ...passed through the masks at each rotation angle. ................................. 42 19. Figure 19: MCNP Generate Modulation Profile for Cadmium. The...Cadmium. The multi-energetic neutron source simulation from MCNP is used for this plot. The energy is values are shown per energy bin. The

Adaptive electron beam shaping using a photoemission gun and spatial light modulator

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

Maxson, Jared; Lee, Hyeri; Bartnik, Adam C.

The need for precisely defined beam shapes in photoelectron sources has been well established. In this paper, we use a spatial light modulator and simple shaping algorithm to create arbitrary, detailed transverse laser shapes with high fidelity. We transmit this shaped laser to the photocathode of a high voltage dc gun. Using beam currents where space charge is negligible, and using an imaging solenoid and fluorescent viewscreen, we show that the resultant beam shape preserves these detailed features with similar fidelity. Next, instead of transmitting a shaped laser profile, we use an active feedback on the unshaped electron beam imagemore » to create equally accurate and detailed shapes. We demonstrate that this electron beam feedback has the added advantage of correcting for electron optical aberrations, yielding shapes without skew. The method may serve to provide precisely defined electron beams for low current target experiments, space-charge dominated beam commissioning, as well as for online adaptive correction of photocathode quantum efficiency degradation.« less

Adaptive electron beam shaping using a photoemission gun and spatial light modulator

NASA Astrophysics Data System (ADS)

Maxson, Jared; Lee, Hyeri; Bartnik, Adam C.; Kiefer, Jacob; Bazarov, Ivan

2015-02-01

The need for precisely defined beam shapes in photoelectron sources has been well established. In this paper, we use a spatial light modulator and simple shaping algorithm to create arbitrary, detailed transverse laser shapes with high fidelity. We transmit this shaped laser to the photocathode of a high voltage dc gun. Using beam currents where space charge is negligible, and using an imaging solenoid and fluorescent viewscreen, we show that the resultant beam shape preserves these detailed features with similar fidelity. Next, instead of transmitting a shaped laser profile, we use an active feedback on the unshaped electron beam image to create equally accurate and detailed shapes. We demonstrate that this electron beam feedback has the added advantage of correcting for electron optical aberrations, yielding shapes without skew. The method may serve to provide precisely defined electron beams for low current target experiments, space-charge dominated beam commissioning, as well as for online adaptive correction of photocathode quantum efficiency degradation.

Butyrate modulating effects on pro-inflammatory pathways in human intestinal epithelial cells.

PubMed

Elce, A; Amato, F; Zarrilli, F; Calignano, A; Troncone, R; Castaldo, G; Canani, R B

2017-10-13

Butyrate acts as energy source for intestinal epithelial cells and as key mediator of several immune processes, modulating gene expression mainly through histone deacetylation inhibition. Thanks to these effects, butyrate has been proposed for the treatment of many intestinal diseases. Aim of this study was to investigate the effect of butyrate on the expression of a large series of target genes encoding proteins involved in pro-inflammatory pathways. We performed quantitative real-time-PCR analysis of the expression of 86 genes encoding proteins bearing to pro-inflammatory pathways, before and after butyrate exposure, in primary epithelial cells derived from human small intestine and colon. Butyrate significantly down-regulated the expression of genes involved in inflammatory response, among which nuclear factor kappa beta, interferon-gamma, Toll like 2 receptor and tumour necrosis factor-alpha. Further confirmations of these data, including studies at protein level, would support the use of butyrate as effective therapeutic strategy in intestinal inflammatory disorders.

Adaptive electron beam shaping using a photoemission gun and spatial light modulator

DOE PAGES

Maxson, Jared; Lee, Hyeri; Bartnik, Adam C.; ...

2015-02-01

The need for precisely defined beam shapes in photoelectron sources has been well established. In this paper, we use a spatial light modulator and simple shaping algorithm to create arbitrary, detailed transverse laser shapes with high fidelity. We transmit this shaped laser to the photocathode of a high voltage dc gun. Using beam currents where space charge is negligible, and using an imaging solenoid and fluorescent viewscreen, we show that the resultant beam shape preserves these detailed features with similar fidelity. Next, instead of transmitting a shaped laser profile, we use an active feedback on the unshaped electron beam imagemore » to create equally accurate and detailed shapes. We demonstrate that this electron beam feedback has the added advantage of correcting for electron optical aberrations, yielding shapes without skew. The method may serve to provide precisely defined electron beams for low current target experiments, space-charge dominated beam commissioning, as well as for online adaptive correction of photocathode quantum efficiency degradation.« less

Super-resolution structured illumination in optically thick specimens without fluorescent tagging

NASA Astrophysics Data System (ADS)

Hoffman, Zachary R.; DiMarzio, Charles A.

2017-11-01

This research extends the work of Hoffman et al. to provide both sectioning and super-resolution using random patterns within thick specimens. Two methods of processing structured illumination in reflectance have been developed without the need for a priori knowledge of either the optical system or the modulation patterns. We explore the use of two deconvolution algorithms that assume either Gaussian or sparse priors. This paper will show that while both methods accomplish their intended objective, the sparse priors method provides superior resolution and contrast against all tested targets, providing anywhere from ˜1.6× to ˜2× resolution enhancement. The methods developed here can reasonably be implemented to work without a priori knowledge about the patterns or point spread function. Further, all experiments are run using an incoherent light source, unknown random modulation patterns, and without the use of fluorescent tagging. These additional modifications are challenging, but the generalization of these methods makes them prime candidates for clinical application, providing super-resolved noninvasive sectioning in vivo.

Tomotherapy as a tool in image-guided radiation therapy (IGRT): theoretical and technological aspects

PubMed Central

Yartsev, S; Kron, T; Van Dyk, J

2007-01-01

Helical tomotherapy (HT) is a novel treatment approach that combines Intensity-Modulate Radiation Therapy (IMRT) delivery with in-built image guidance using megavoltage (MV) CT scanning. The technique utilises a 6 MV linear accelerator mounted on a CT type ring gantry. The beam is collimated to a fan beam, which is intensity modulated using a binary multileaf collimator (MLC). As the patient advances slowly through the ring gantry, the linac rotates around the patient with a leaf-opening pattern optimised to deliver a highly conformal dose distribution to the target in the helical beam trajectory. The unit also allows the acquisition of MVCT images using the same radiation source detuned to reduce its effective energy to 3.5 MV, making the dose required for imaging less than 3 cGy. This paper discusses the major features of HT and describes the advantages and disadvantages of this approach in the context of the commercial Hi-ART system. PMID:21614257

Ultra high frequency imaging acoustic microscope

DOEpatents

Deason, Vance A.; Telschow, Kenneth L.

2006-05-23

An imaging system includes: an object wavefront source and an optical microscope objective all positioned to direct an object wavefront onto an area of a vibrating subject surface encompassed by a field of view of the microscope objective, and to direct a modulated object wavefront reflected from the encompassed surface area through a photorefractive material; and a reference wavefront source and at least one phase modulator all positioned to direct a reference wavefront through the phase modulator and to direct a modulated reference wavefront from the phase modulator through the photorefractive material to interfere with the modulated object wavefront. The photorefractive material has a composition and a position such that interference of the modulated object wavefront and modulated reference wavefront occurs within the photorefractive material, providing a full-field, real-time image signal of the encompassed surface area.

Computer Generated Holography with Intensity-Graded Patterns

PubMed Central

Conti, Rossella; Assayag, Osnath; de Sars, Vincent; Guillon, Marc; Emiliani, Valentina

2016-01-01

Computer Generated Holography achieves patterned illumination at the sample plane through phase modulation of the laser beam at the objective back aperture. This is obtained by using liquid crystal-based spatial light modulators (LC-SLMs), which modulate the spatial phase of the incident laser beam. A variety of algorithms is employed to calculate the phase modulation masks addressed to the LC-SLM. These algorithms range from simple gratings-and-lenses to generate multiple diffraction-limited spots, to iterative Fourier-transform algorithms capable of generating arbitrary illumination shapes perfectly tailored on the base of the target contour. Applications for holographic light patterning include multi-trap optical tweezers, patterned voltage imaging and optical control of neuronal excitation using uncaging or optogenetics. These past implementations of computer generated holography used binary input profile to generate binary light distribution at the sample plane. Here we demonstrate that using graded input sources, enables generating intensity graded light patterns and extend the range of application of holographic light illumination. At first, we use intensity-graded holograms to compensate for LC-SLM position dependent diffraction efficiency or sample fluorescence inhomogeneity. Finally we show that intensity-graded holography can be used to equalize photo evoked currents from cells expressing different levels of chanelrhodopsin2 (ChR2), one of the most commonly used optogenetics light gated channels, taking into account the non-linear dependence of channel opening on incident light. PMID:27799896

Center Finding Algorithm on slit mask point source for IGRINS (Immersion GRating INfrared Spectrograph)

NASA Astrophysics Data System (ADS)

Lee, Hye-In; Pak, Soojong; Lee, Jae-Joon; Mace, Gregory N.; Jaffe, Daniel Thomas

2017-06-01

We developed an observation control software for the IGRINS (Immersion Grating Infrared Spectrograph) silt-viewing camera module, which points the astronomical target onto the spectroscopy slit and sends tracking feedbacks to the telescope control system (TCS). The point spread function (PSF) image is not following symmetric Gaussian profile. In addition, bright targets are easily saturated and shown as a donut shape. It is not trivial to define and find the center of the asymmetric PSF especially when most of the stellar PSF falls inside the slit. We made a center balancing algorithm (CBA) which derives the expected center position along the slit-width axis by referencing the stray flux ratios of both upper and lower sides of the slit. We compared accuracies of the CBA and those of a two-dimensional Gaussian fitting (2DGA) through simulations in order to evaluate the center finding algorithms. These methods were then verified with observational data. In this poster, we present the results of our tests and suggest a new algorithm for centering targets in the slit image of a spectrograph.

Covert laser remote sensing and vibrometry

NASA Technical Reports Server (NTRS)

Maleki, Lutfollah (Inventor); Yu, Nan (Inventor); Matsko, Andrey B. (Inventor); Savchenkov, Anatoliy (Inventor)

2012-01-01

Designs of single-beam laser vibrometry systems and methods. For example, a method for detecting vibrations of a target based on optical sensing is provided to include operating a laser to produce a laser probe beam at a laser frequency and modulated at a modulation frequency onto a target; collecting light at or near the laser to collect light from the target while the target is being illuminated by the laser probe beam through an optical receiver aperture; using a narrow-band optical filter centered at the laser frequency to filter light collected from the optical receiver aperture to transmit light at the laser frequency while blocking light at other frequencies; using an optical detector to convert filtered light from the narrow-band optical filter to produce a receiver electrical signal; using a lock-in amplifier to detect and amplify the receiver electrical signal at the modulation frequency while rejecting signal components at other frequencies to produce an amplified receiver electrical signal; processing the amplified receiver electrical signal to extract information on vibrations of the target carried by reflected laser probe beam in the collected light; and controlling optical power of the laser probe beam at the target to follow optical power of background illumination at the target.

A neural mechanism for detecting the distance of a selected target by modulating the FM sweep rate of biosonar in echolocation of bat.

PubMed

Kamata, Eigo; Inoue, Satoru; Zheng, MeiHong; Kashimori, Yoshiki; Kambara, Takeshi

2004-01-01

Most species of bats making echolocation use frequency modulated (FM) ultrasonic pulses to measure the distance to targets. These bats detect with a high accuracy the arrival time differences between emitted pulses and their echoes generated by targets. In order to clarify the neural mechanism for echolocation, we present neural model of inferior colliculus (IC), medial geniculate body (MGB) and auditory cortex (AC) along which information of echo delay times is processed. The bats increase the downward frequency sweep rate of emitted FM pulse as they approach the target. The functional role of this modulation of sweep rate is not yet clear. In order to investigate the role, we calculated the response properties of our models of IC, MGB, and AC changing the target distance and the sweep rate. We found based on the simulations that the distance of a target in various ranges may be encoded the most clearly into the activity pattern of delay time map network in AC, when the sweep rate of FM pulse used is coincided with the observed value which the bats adopt for each range of target distance.

Factors modulating the delivery and effect of enzymatic cargo conjugated with antibodies targeted to the pulmonary endothelium

PubMed Central

Shuvaev, Vladimir V.; Christofidou-Solomidou, Melpo; Scherpereel, Arnaud; Simone, Eric; Arguiri, Evguenia; Tliba, Samira; Pick, Jeremy; Kennel, Stephen; Albelda, Steven M.; Muzykantov, Vladimir R.

2007-01-01

Vascular drug targeting may improve therapies, yet a thorough understanding of the factors that regulate effects of drugs directed to the endothelium is needed to translate this approach into the clinical domain. To define factors modulating the efficacy and effects of endothelial targeting, we used a model enzyme (glucose oxidase, GOX) coupled with monoclonal antibodies (anti-TM34 or anti-TM201) to distinct epitopes of thrombomodulin, a surface determinant enriched in the pulmonary endothelium. GOX delivery results in conversion of glucose and oxygen into H2O2 leading to lung damage, a clear physiologic endpoint. Results of in vivo studies in mice showed that the efficiency of cargo delivery and its effect are influenced by a number of factors including: 1) The level of pulmonary uptake of the targeting antibody (anti-TM201 was more efficient than anti-TM34); 2) The amount of an active drug delivered to the target; 3) The amount of target antigen on the endothelium (animals with suppressed TM levels showed less targeting); and, 4) The substrate availability for the enzyme cargo in the target tissue (hyperoxia augmented GOX-induced injury). Therefore, both activity of the conjugates and biological factors control targeting and effects of enzymatic cargo. Understanding the nature of such “modulating biological factors” will hopefully allow optimization and ultimately applications of drug targeting for “individualized” pharmacotherapy. PMID:17270308

Cholinergic Modulation of Frontoparietal Cortical Network Dynamics Supporting Supramodal Attention.

PubMed

Ljubojevic, Vladimir; Luu, Paul; Gill, Patrick Robert; Beckett, Lee-Anne; Takehara-Nishiuchi, Kaori; De Rosa, Eve

2018-04-18

A critical function of attention is to support a state of readiness to enhance stimulus detection, independent of stimulus modality. The nucleus basalis magnocellularis (NBM) is the major source of the neurochemical acetylcholine (ACh) for frontoparietal cortical networks thought to support attention. We examined a potential supramodal role of ACh in a frontoparietal cortical attentional network supporting target detection. We recorded local field potentials (LFPs) in the prelimbic frontal cortex (PFC) and the posterior parietal cortex (PPC) to assess whether ACh contributed to a state of readiness to alert rats to an impending presentation of visual or olfactory targets in one of five locations. Twenty male Long-Evans rats underwent training and then lesions of the NBM using the selective cholinergic immunotoxin 192 IgG-saporin (0.3 μg/μl; ACh-NBM-lesion) to reduce cholinergic afferentation of the cortical mantle. Postsurgery, ACh-NBM-lesioned rats had less correct responses and more omissions than sham-lesioned rats, which changed parametrically as we increased the attentional demands of the task with decreased target duration. This parametric deficit was found equally for both sensory targets. Accurate detection of visual and olfactory targets was associated specifically with increased LFP coherence, in the beta range, between the PFC and PPC, and with increased beta power in the PPC before the target's appearance in sham-lesioned rats. Readiness-associated changes in brain activity and visual and olfactory target detection were attenuated in the ACh-NBM-lesioned group. Accordingly, ACh may support supramodal attention via modulating activity in a frontoparietal cortical network, orchestrating a state of readiness to enhance target detection. SIGNIFICANCE STATEMENT We examined whether the neurochemical acetylcholine (ACh) contributes to a state of readiness for target detection, by engaging frontoparietal cortical attentional networks independent of modality. We show that ACh supported alerting attention to an impending presentation of either visual or olfactory targets. Using local field potentials, enhanced stimulus detection was associated with an anticipatory increase in power in the beta oscillation range before the target's appearance within the posterior parietal cortex (PPC) as well as increased synchrony, also in beta, between the prefrontal cortex and PPC. These readiness-associated changes in brain activity and behavior were attenuated in rats with reduced cortical ACh. Thus, ACh may act, in a supramodal manner, to prepare frontoparietal cortical attentional networks for target detection. Copyright © 2018 the authors 0270-6474/18/383988-18$15.00/0.

Chemical proteomics for target discovery of head-to-tail cyclized mini-proteins

NASA Astrophysics Data System (ADS)

Hellinger, Roland; Thell, Kathrin; Vasileva, Mina; Muhammad, Taj; Gunasekera, Sunithi; Kümmel, Daniel; Göransson, Ulf; Becker, Christian W.; Gruber, Christian W.

2017-10-01

Target deconvolution is one of the most challenging tasks in drug discovery, but a key step in drug development. In contrast to small molecules, there is a lack of validated and robust methodologies for target elucidation of peptides. In particular, it is difficult to apply these methods to cyclic and cysteine-stabilized peptides since they exhibit reduced amenability to chemical modification and affinity capture; however, such ribosomal synthesized and post-translationally modified peptide natural products are rich sources of promising drug candidates. For example, plant-derived circular peptides called cyclotides have recently attracted much attention due to their immunosuppressive effects and oral activity in the treatment of multiple sclerosis in mice, but their molecular target has hitherto not been reported. In this study a chemical proteomics approach using photo-affinity crosslinking was developed to determine a target of the circular peptide [T20K]kalata B1. Using this prototypic nature-derived peptide enabled the identification of a possible modulation of 14-3-3 proteins. This biochemical interaction was validated via competition pull down assays as well as a cellular reporter assay indicating an effect on 14-3-3-dependent transcriptional activity. As proof of concept, the presented approach may be applicable for target elucidation of various cyclic peptides and mini-proteins, in particular cyclotides, which represent a promising class of molecules in drug discovery and development.

Cytokines and cytokine networks target neurons to modulate long-term potentiation.

PubMed

Prieto, G Aleph; Cotman, Carl W

2017-04-01

Cytokines play crucial roles in the communication between brain cells including neurons and glia, as well as in the brain-periphery interactions. In the brain, cytokines modulate long-term potentiation (LTP), a cellular correlate of memory. Whether cytokines regulate LTP by direct effects on neurons or by indirect mechanisms mediated by non-neuronal cells is poorly understood. Elucidating neuron-specific effects of cytokines has been challenging because most brain cells express cytokine receptors. Moreover, cytokines commonly increase the expression of multiple cytokines in their target cells, thus increasing the complexity of brain cytokine networks even after single-cytokine challenges. Here, we review evidence on both direct and indirect-mediated modulation of LTP by cytokines. We also describe novel approaches based on neuron- and synaptosome-enriched systems to identify cytokines able to directly modulate LTP, by targeting neurons and synapses. These approaches can test multiple samples in parallel, thus allowing the study of multiple cytokines simultaneously. Hence, a cytokine networks perspective coupled with neuron-specific analysis may contribute to delineation of maps of the modulation of LTP by cytokines. Copyright © 2017 Elsevier Ltd. All rights reserved.

Cytokines and cytokine networks target neurons to modulate long-term potentiation

PubMed Central

Prieto, G. Aleph; Cotman, Carl W.

2017-01-01

Cytokines play crucial roles in the communication between brain cells including neurons and glia, as well as in the brain-periphery interactions. In the brain, cytokines modulate long-term potentiation (LTP), a cellular correlate of memory. Whether cytokines regulate LTP by direct effects on neurons or by indirect mechanisms mediated by non-neuronal cells is poorly understood. Elucidating neuron-specific effects of cytokines has been challenging because most brain cells express cytokine receptors. Moreover, cytokines commonly increase the expression of multiple cytokines in their target cells, thus increasing the complexity of brain cytokine networks even after single-cytokine challenges. Here, we review evidence on both direct and indirect-mediated modulation of LTP by cytokines. We also describe novel approaches based on neuron- and synaptosome-enriched systems to identify cytokines able to directly modulate LTP, by targeting neurons and synapses. These approaches can test multiple samples in parallel, thus allowing the study of multiple cytokines simultaneously. Hence, a cytokine networks perspective coupled with neuron-specific analysis may contribute to delineation of maps of the modulation of LTP by cytokines. PMID:28377062

Identification of cancer-cytotoxic modulators of PDE3A by predictive chemogenomics | Office of Cancer Genomics

Cancer.gov

High cancer death rates indicate the need for new anticancer therapeutic agents. Approaches to discovering new cancer drugs include target-based drug discovery and phenotypic screening. Here, we identified phosphodiesterase 3A modulators as cell-selective cancer cytotoxic compounds through phenotypic compound library screening and target deconvolution by predictive chemogenomics.

Differential Targeting of Gβγ-Subunit Signaling with Small Molecules

NASA Astrophysics Data System (ADS)

Bonacci, Tabetha M.; Mathews, Jennifer L.; Yuan, Chujun; Lehmann, David M.; Malik, Sundeep; Wu, Dianqing; Font, Jose L.; Bidlack, Jean M.; Smrcka, Alan V.

2006-04-01

G protein βγ subunits have potential as a target for therapeutic treatment of a number of diseases. We performed virtual docking of a small-molecule library to a site on Gβγ subunits that mediates protein interactions. We hypothesized that differential targeting of this surface could allow for selective modulation of Gβγ subunit functions. Several compounds bound to Gβγ subunits with affinities from 0.1 to 60 μM and selectively modulated functional Gβγ-protein-protein interactions in vitro, chemotactic peptide signaling pathways in HL-60 leukocytes, and opioid receptor-dependent analgesia in vivo. These data demonstrate an approach for modulation of G protein-coupled receptor signaling that may represent an important therapeutic strategy.

10 CFR 39.55 - Tritium neutron generator target sources.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 10 Energy 1 2010-01-01 2010-01-01 false Tritium neutron generator target sources. 39.55 Section 39... Equipment § 39.55 Tritium neutron generator target sources. (a) Use of a tritium neutron generator target....77. (b) Use of a tritium neutron generator target source, containing quantities exceeding 1,110 GBg...

10 CFR 39.55 - Tritium neutron generator target sources.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 10 Energy 1 2011-01-01 2011-01-01 false Tritium neutron generator target sources. 39.55 Section 39... Equipment § 39.55 Tritium neutron generator target sources. (a) Use of a tritium neutron generator target....77. (b) Use of a tritium neutron generator target source, containing quantities exceeding 1,110 GBg...

10 CFR 39.55 - Tritium neutron generator target sources.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 10 Energy 1 2014-01-01 2014-01-01 false Tritium neutron generator target sources. 39.55 Section 39... Equipment § 39.55 Tritium neutron generator target sources. (a) Use of a tritium neutron generator target....77. (b) Use of a tritium neutron generator target source, containing quantities exceeding 1,110 GBg...

10 CFR 39.55 - Tritium neutron generator target sources.

Code of Federal Regulations, 2013 CFR

2013-01-01

... 10 Energy 1 2013-01-01 2013-01-01 false Tritium neutron generator target sources. 39.55 Section 39... Equipment § 39.55 Tritium neutron generator target sources. (a) Use of a tritium neutron generator target....77. (b) Use of a tritium neutron generator target source, containing quantities exceeding 1,110 GBg...

10 CFR 39.55 - Tritium neutron generator target sources.

Code of Federal Regulations, 2012 CFR

2012-01-01

... 10 Energy 1 2012-01-01 2012-01-01 false Tritium neutron generator target sources. 39.55 Section 39... Equipment § 39.55 Tritium neutron generator target sources. (a) Use of a tritium neutron generator target....77. (b) Use of a tritium neutron generator target source, containing quantities exceeding 1,110 GBg...

Developing Sensitive and Selective Nanosensors: A Single Molecule - Multiple Excitation Source Approach. Altairnano Lithium Ion Nano-scaled Titanate Oxide Cell and Module Abuse Testing

DTIC Science & Technology

2012-03-13

Source Approach Part II. Altairnano Lithium Ion Nano-scaled Titanate Oxide Cell and Module Abuse Testing 14. ABSTRACT 16. SECURITY CLASSIFICATION OF...Lithium Ion Nano-scaled Titanate Oxide Cell and Module Abuse Testing Report Title ABSTRACT This final report for Contract W911NF-09-C-0135 transmits the...prototype development. The second (Part II.) is "Altairnano Lithium Ion Nano-scaled Titanate Oxide Cell and Module Abuse Test Report". The

The Basal Ganglia Striosomes Affect the Modulation of Conflicts by Subliminal Information-Evidence from X-Linked Dystonia Parkinsonism.

PubMed

Beste, Christian; Mückschel, Moritz; Rosales, Raymond; Domingo, Aloysius; Lee, Lillian; Ng, Arlene; Klein, Christine; Münchau, Alexander

2018-07-01

Cognitive control is relevant when distracting information induces behavioral conflicts. Such conflicts can be produced consciously and by subliminally processed information. Interestingly, both sources of conflict interact suggesting that they share neural mechanisms. Here, we ask whether conjoint effects between different sources of conflict are modulated by microstructural basal ganglia dysfunction. To this end, we carried out an electroencephalography study and examined event-related potentials (ERPs) including source localization using a combined flanker-subliminal priming task in patients with X-linked dystonia Parkinsonism (XDP) and a group of healthy controls. XDP in its early stages is known to predominantly affect the basal ganglia striosomes. The results suggest that conjoint effects between subliminal and conscious sources of conflicts are modulated by the striosomes and were stronger in XDP patients. The neurophysiological data indicate that this effect is related to modulations in conflict monitoring and response selection (N2 ERP) mechanisms engaging the anterior cingulate cortex. Bottom-up perceptual gating, attentional selection, and motor response activation processes in response to the stimuli (P1, N1, and lateralized readiness potential ERPs) were unaffected. Taken together, these data indicate that striosomes modulate the processing of conscious and subliminal sources of conflict suggesting that microstructural basal ganglia properties are relevant for cognitive control.

Analysis of Technology for Compact Coherent Lidar

NASA Technical Reports Server (NTRS)

Amzajerdian, Farzin

1997-01-01

In view of the recent advances in the area of solid state and semiconductor lasers has created new possibilities for the development of compact and reliable coherent lidars for a wide range of applications. These applications include: Automated Rendezvous and Capture, wind shear and clear air turbulence detection, aircraft wake vortex detection, and automobile collision avoidance. The work performed by the UAH personnel under this Delivery Order, concentrated on design and analyses of a compact coherent lidar system capable of measuring range and velocity of hard targets, and providing air mass velocity data. The following is the scope of this work. a. Investigate various laser sources and optical signal detection configurations in support of a compact and lightweight coherent laser radar to be developed for precision range and velocity measurements of hard and fuzzy targets. Through interaction with MSFC engineers, the most suitable laser source and signal detection technique that can provide a reliable compact and lightweight laser radar design will be selected. b. Analyze and specify the coherent laser radar system configuration and assist with its optical and electronic design efforts. Develop a system design including its optical layout design. Specify all optical components and provide the general requirements of the electronic subsystems including laser beam modulator and demodulator drivers, detector electronic interface, and the signal processor. c. Perform a thorough performance analysis to predict the system measurement range and accuracy. This analysis will utilize various coherent laser radar sensitivity formulations and different target models.

Treatment planning optimisation in proton therapy

PubMed Central

McGowan, S E; Burnet, N G; Lomax, A J

2013-01-01

ABSTRACT. The goal of radiotherapy is to achieve uniform target coverage while sparing normal tissue. In proton therapy, the same sources of geometric uncertainty are present as in conventional radiotherapy. However, an important and fundamental difference in proton therapy is that protons have a finite range, highly dependent on the electron density of the material they are traversing, resulting in a steep dose gradient at the distal edge of the Bragg peak. Therefore, an accurate knowledge of the sources and magnitudes of the uncertainties affecting the proton range is essential for producing plans which are robust to these uncertainties. This review describes the current knowledge of the geometric uncertainties and discusses their impact on proton dose plans. The need for patient-specific validation is essential and in cases of complex intensity-modulated proton therapy plans the use of a planning target volume (PTV) may fail to ensure coverage of the target. In cases where a PTV cannot be used, other methods of quantifying plan quality have been investigated. A promising option is to incorporate uncertainties directly into the optimisation algorithm. A further development is the inclusion of robustness into a multicriteria optimisation framework, allowing a multi-objective Pareto optimisation function to balance robustness and conformity. The question remains as to whether adaptive therapy can become an integral part of a proton therapy, to allow re-optimisation during the course of a patient's treatment. The challenge of ensuring that plans are robust to range uncertainties in proton therapy remains, although these methods can provide practical solutions. PMID:23255545

Electron intensity modulation for mixed-beam radiation therapy with an x-ray multi-leaf collimator

NASA Astrophysics Data System (ADS)

Weinberg, Rebecca

The current standard treatment for head and neck cancer at our institution uses intensity-modulated x-ray therapy (IMRT), which improves target coverage and sparing of critical structures by delivering complex fluence patterns from a variety of beam directions to conform dose distributions to the shape of the target volume. The standard treatment for breast patients is field-in-field forward-planned IMRT, with initial tangential fields and additional reduced-weight tangents with blocking to minimize hot spots. For these treatment sites, the addition of electrons has the potential of improving target coverage and sparing of critical structures due to rapid dose falloff with depth and reduced exit dose. In this work, the use of mixed-beam therapy (MBT), i.e., combined intensity-modulated electron and x-ray beams using the x-ray multi-leaf collimator (MLC), was explored. The hypothesis of this study was that addition of intensity-modulated electron beams to existing clinical IMRT plans would produce MBT plans that were superior to the original IMRT plans for at least 50% of selected head and neck and 50% of breast cases. Dose calculations for electron beams collimated by the MLC were performed with Monte Carlo methods. An automation system was created to facilitate communication between the dose calculation engine and the treatment planning system. Energy and intensity modulation of the electron beams was accomplished by dividing the electron beams into 2x2-cm2 beamlets, which were then beam-weight optimized along with intensity-modulated x-ray beams. Treatment plans were optimized to obtain equivalent target dose coverage, and then compared with the original treatment plans. MBT treatment plans were evaluated by participating physicians with respect to target coverage, normal structure dose, and overall plan quality in comparison with original clinical plans. The physician evaluations did not support the hypothesis for either site, with MBT selected as superior in 1 out of the 15 head and neck cases (p=1) and 6 out of 18 breast cases (p=0.95). While MBT was not shown to be superior to IMRT, reductions were observed in doses to critical structures distal to the target along the electron beam direction and to non-target tissues, at the expense of target coverage and dose homogeneity.

Cryogenic hydrogen fuel for controlled inertial confinement fusion (formation of reactor-scale cryogenic targets)

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

Aleksandrova, I. V.; Koresheva, E. R., E-mail: elena.koresheva@gmail.com; Krokhin, O. N.

2016-12-15

In inertial fusion energy research, considerable attention has recently been focused on low-cost fabrication of a large number of targets by developing a specialized layering module of repeatable operation. The targets must be free-standing, or unmounted. Therefore, the development of a target factory for inertial confinement fusion (ICF) is based on methods that can ensure a cost-effective target production with high repeatability. Minimization of the amount of tritium (i.e., minimization of time and space at all production stages) is a necessary condition as well. Additionally, the cryogenic hydrogen fuel inside the targets must have a structure (ultrafine layers—the grain sizemore » should be scaled back to the nanometer range) that supports the fuel layer survivability under target injection and transport through the reactor chamber. To meet the above requirements, significant progress has been made at the Lebedev Physical Institute (LPI) in the technology developed on the basis of rapid fuel layering inside moving free-standing targets (FST), also referred to as the FST layering method. Owing to the research carried out at LPI, unique experience has been gained in the development of the FST-layering module for target fabrication with an ultrafine fuel layer, including a reactor- scale target design. This experience can be used for the development of the next-generation FST-layering module for construction of a prototype of a target factory for power laser facilities and inertial fusion power plants.« less

Investigating local network interactions underlying first- and second-order processing.

PubMed

Ellemberg, Dave; Allen, Harriet A; Hess, Robert F

2004-01-01

We compared the spatial lateral interactions for first-order cues to those for second-order cues, and investigated spatial interactions between these two types of cues. We measured the apparent modulation depth of a target Gabor at fixation, in the presence and the absence of horizontally flanking Gabors. The Gabors' gratings were either added to (first-order) or multiplied with (second-order) binary 2-D noise. Apparent "contrast" or modulation depth (i.e., the perceived difference between the high and low luminance regions for the first-order stimulus, or between the high and low contrast regions for the second-order stimulus) was measured with a modulation depth-matching paradigm. For each observer, the first- and second-order Gabors were equated for apparent modulation depth without the flankers. Our results indicate that at the smallest inter-element spacing, the perceived reduction in modulation depth is significantly smaller for the second-order than for the first-order stimuli. Further, lateral interactions operate over shorter distances and the spatial frequency and orientation tuning of the suppression effect are broader for second- than first-order stimuli. Finally, first- and second-order information interact in an asymmetrical fashion; second-order flankers do not reduce the apparent modulation depth of the first-order target, whilst first-order flankers reduce the apparent modulation depth of the second-order target.

First and second generation γ-secretase modulators (GSMs) modulate amyloid-β (Aβ) peptide production through different mechanisms.

PubMed

Borgegard, Tomas; Juréus, Anders; Olsson, Fredrik; Rosqvist, Susanne; Sabirsh, Alan; Rotticci, Didier; Paulsen, Kim; Klintenberg, Rebecka; Yan, Hongmei; Waldman, Magnus; Stromberg, Kia; Nord, Johan; Johansson, Jonas; Regner, Anna; Parpal, Santiago; Malinowsky, David; Radesater, Ann-Cathrin; Li, Tingsheng; Singh, Rajeshwar; Eriksson, Hakan; Lundkvist, Johan

2012-04-06

γ-Secretase-mediated cleavage of amyloid precursor protein (APP) results in the production of Alzheimer disease-related amyloid-β (Aβ) peptides. The Aβ42 peptide in particular plays a pivotal role in Alzheimer disease pathogenesis and represents a major drug target. Several γ-secretase modulators (GSMs), such as the nonsteroidal anti-inflammatory drugs (R)-flurbiprofen and sulindac sulfide, have been suggested to modulate the Alzheimer-related Aβ production by targeting the APP. Here, we describe novel GSMs that are selective for Aβ modulation and do not impair processing of Notch, EphB2, or EphA4. The GSMs modulate Aβ both in cell and cell-free systems as well as lower amyloidogenic Aβ42 levels in the mouse brain. Both radioligand binding and cellular cross-competition experiments reveal a competitive relationship between the AstraZeneca (AZ) GSMs and the established second generation GSM, E2012, but a noncompetitive interaction between AZ GSMs and the first generation GSMs (R)-flurbiprofen and sulindac sulfide. The binding of a (3)H-labeled AZ GSM analog does not co-localize with APP but overlaps anatomically with a γ-secretase targeting inhibitor in rodent brains. Combined, these data provide compelling evidence of a growing class of in vivo active GSMs, which are selective for Aβ modulation and have a different mechanism of action compared with the original class of GSMs described.

Kilohertz binary phase modulator for pulsed laser sources using a digital micromirror device.

PubMed

Hoffmann, Maximilian; Papadopoulos, Ioannis N; Judkewitz, Benjamin

2018-01-01

The controlled modulation of an optical wavefront is required for aberration correction, digital phase conjugation, or patterned photostimulation. For most of these applications, it is desirable to control the wavefront modulation at the highest rates possible. The digital micromirror device (DMD) presents a cost-effective solution to achieve high-speed modulation and often exceeds the speed of the more conventional liquid crystal spatial light modulator but is inherently an amplitude modulator. Furthermore, spatial dispersion caused by DMD diffraction complicates its use with pulsed laser sources, such as those used in nonlinear microscopy. Here we introduce a DMD-based optical design that overcomes these limitations and achieves dispersion-free high-speed binary phase modulation. We show that this phase modulation can be used to switch through binary phase patterns at the rate of 20 kHz in two-photon excitation fluorescence applications.

Kilohertz binary phase modulator for pulsed laser sources using a digital micromirror device

NASA Astrophysics Data System (ADS)

Hoffmann, Maximilian; Papadopoulos, Ioannis N.; Judkewitz, Benjamin

2018-01-01

The controlled modulation of an optical wavefront is required for aberration correction, digital phase conjugation or patterned photostimulation. For most of these applications it is desirable to control the wavefront modulation at the highest rates possible. The digital micromirror device (DMD) presents a cost-effective solution to achieve high-speed modulation and often exceeds the speed of the more conventional liquid crystal spatial light modulator, but is inherently an amplitude modulator. Furthermore, spatial dispersion caused by DMD diffraction complicates its use with pulsed laser sources, such as those used in nonlinear microscopy. Here we introduce a DMD-based optical design that overcomes these limitations and achieves dispersion-free high-speed binary phase modulation. We show that this phase modulation can be used to switch through binary phase patterns at the rate of 20 kHz in two-photon excitation fluorescence applications.

System and method of modulating electrical signals using photoconductive wide bandgap semiconductors as variable resistors

DOEpatents

Harris, John Richardson; Caporaso, George J; Sampayan, Stephen E

2013-10-22

A system and method for producing modulated electrical signals. The system uses a variable resistor having a photoconductive wide bandgap semiconductor material construction whose conduction response to changes in amplitude of incident radiation is substantially linear throughout a non-saturation region to enable operation in non-avalanche mode. The system also includes a modulated radiation source, such as a modulated laser, for producing amplitude-modulated radiation with which to direct upon the variable resistor and modulate its conduction response. A voltage source and an output port, are both operably connected to the variable resistor so that an electrical signal may be produced at the output port by way of the variable resistor, either generated by activation of the variable resistor or propagating through the variable resistor. In this manner, the electrical signal is modulated by the variable resistor so as to have a waveform substantially similar to the amplitude-modulated radiation.

MO-G-17A-01: Innovative High-Performance PET Imaging System for Preclinical Imaging and Translational Researches

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

Sun, X; Lou, K; Rice University, Houston, TX

Purpose: To develop a practical and compact preclinical PET with innovative technologies for substantially improved imaging performance required for the advanced imaging applications. Methods: Several key components of detector, readout electronics and data acquisition have been developed and evaluated for achieving leapfrogged imaging performance over a prototype animal PET we had developed. The new detector module consists of an 8×8 array of 1.5×1.5×30 mm{sup 3} LYSO scintillators with each end coupled to a latest 4×4 array of 3×3 mm{sup 2} Silicon Photomultipliers (with ∼0.2 mm insensitive gap between pixels) through a 2.0 mm thick transparent light spreader. Scintillator surface andmore » reflector/coupling were designed and fabricated to reserve air-gap to achieve higher depth-of-interaction (DOI) resolution and other detector performance. Front-end readout electronics with upgraded 16-ch ASIC was newly developed and tested, so as the compact and high density FPGA based data acquisition and transfer system targeting 10M/s coincidence counting rate with low power consumption. The new detector module performance of energy, timing and DOI resolutions with the data acquisition system were evaluated. Initial Na-22 point source image was acquired with 2 rotating detectors to assess the system imaging capability. Results: No insensitive gaps at the detector edge and thus it is capable for tiling to a large-scale detector panel. All 64 crystals inside the detector were clearly separated from a flood-source image. Measured energy, timing, and DOI resolutions are around 17%, 2.7 ns and 1.96 mm (mean value). Point source image is acquired successfully without detector/electronics calibration and data correction. Conclusion: Newly developed advanced detector and readout electronics will be enable achieving targeted scalable and compact PET system in stationary configuration with >15% sensitivity, ∼1.3 mm uniform imaging resolution, and fast acquisition counting rate capability for substantially improved imaging and quantification performance for small animal imaging and image-guided radiotherapy applications. This work was supported by a research award RP120326 from Cancer Prevention and Research Institute of Texas.« less

Within-hemifield competition in early visual areas limits the ability to track multiple objects with attention.

PubMed

Störmer, Viola S; Alvarez, George A; Cavanagh, Patrick

2014-08-27

It is much easier to divide attention across the left and right visual hemifields than within the same visual hemifield. Here we investigate whether this benefit of dividing attention across separate visual fields is evident at early cortical processing stages. We measured the steady-state visual evoked potential, an oscillatory response of the visual cortex elicited by flickering stimuli, of moving targets and distractors while human observers performed a tracking task. The amplitude of responses at the target frequencies was larger than that of the distractor frequencies when participants tracked two targets in separate hemifields, indicating that attention can modulate early visual processing when it is divided across hemifields. However, these attentional modulations disappeared when both targets were tracked within the same hemifield. These effects were not due to differences in task performance, because accuracy was matched across the tracking conditions by adjusting target speed (with control conditions ruling out effects due to speed alone). To investigate later processing stages, we examined the P3 component over central-parietal scalp sites that was elicited by the test probe at the end of the trial. The P3 amplitude was larger for probes on targets than on distractors, regardless of whether attention was divided across or within a hemifield, indicating that these higher-level processes were not constrained by visual hemifield. These results suggest that modulating early processing stages enables more efficient target tracking, and that within-hemifield competition limits the ability to modulate multiple target representations within the hemifield maps of the early visual cortex. Copyright © 2014 the authors 0270-6474/14/3311526-08$15.00/0.

A Modularity-Based Method Reveals Mixed Modules from Chemical-Gene Heterogeneous Network

PubMed Central

Song, Jianglong; Tang, Shihuan; Liu, Xi; Gao, Yibo; Yang, Hongjun; Lu, Peng

2015-01-01

For a multicomponent therapy, molecular network is essential to uncover its specific mode of action from a holistic perspective. The molecular system of a Traditional Chinese Medicine (TCM) formula can be represented by a 2-class heterogeneous network (2-HN), which typically includes chemical similarities, chemical-target interactions and gene interactions. An important premise of uncovering the molecular mechanism is to identify mixed modules from complex chemical-gene heterogeneous network of a TCM formula. We thus proposed a novel method (MixMod) based on mixed modularity to detect accurate mixed modules from 2-HNs. At first, we compared MixMod with Clauset-Newman-Moore algorithm (CNM), Markov Cluster algorithm (MCL), Infomap and Louvain on benchmark 2-HNs with known module structure. Results showed that MixMod was superior to other methods when 2-HNs had promiscuous module structure. Then these methods were tested on a real drug-target network, in which 88 disease clusters were regarded as real modules. MixMod could identify the most accurate mixed modules from the drug-target 2-HN (normalized mutual information 0.62 and classification accuracy 0.4524). In the end, MixMod was applied to the 2-HN of Buchang naoxintong capsule (BNC) and detected 49 mixed modules. By using enrichment analysis, we investigated five mixed modules that contained primary constituents of BNC intestinal absorption liquid. As a matter of fact, the findings of in vitro experiments using BNC intestinal absorption liquid were found to highly accord with previous analysis. Therefore, MixMod is an effective method to detect accurate mixed modules from chemical-gene heterogeneous networks and further uncover the molecular mechanism of multicomponent therapies, especially TCM formulae. PMID:25927435

Taking time to feel our body: Steady increases in heartbeat perception accuracy and decreases in alexithymia over 9 months of contemplative mental training.

PubMed

Bornemann, Boris; Singer, Tania

2017-03-01

The ability to accurately perceive signals from the body has been shown to be important for physical and psychological health as well as understanding one's emotions. Despite the importance of this skill, often indexed by heartbeat perception accuracy (HBPa), little is known about its malleability. Here, we investigated whether contemplative mental practice can increase HBPa. In the context of a 9-month mental training study, the ReSource Project, two matched cohorts (n = 77 and n = 79) underwent three training modules of 3 months' duration that targeted attentional and interoceptive abilities (Presence module), socio-affective (Affect module), and socio-cognitive (Perspective module) abilities. A third cohort (n = 78) underwent 3 months of practice (Affect module) and a retest control group (n = 84) did not undergo any training. HBPa was measured with a heartbeat tracking task before and after each training module. Emotional awareness was measured by the Toronto Alexithymia Scale (TAS). Participants with TAS scores > 60 at screening were excluded. HBPa was found to increase steadily over the training, with significant and small- to medium-sized effects emerging after 6 months (Cohen's d = .173) and 9 months (d = .273) of mental training. Changes in HBPa were concomitant with and predictive of changes in emotional awareness. Our results suggest that HBPa can indeed be trained through intensive contemplative practice. The effect takes longer than the 8 weeks of typical mindfulness courses to reach meaningful magnitude. These increments in interoceptive accuracy and the related improvements in emotional awareness point to opportunities for improving physical and psychological health through contemplative mental training. © 2016 Society for Psychophysiological Research.

Universal sensor interface module (USIM)

NASA Astrophysics Data System (ADS)

King, Don; Torres, A.; Wynn, John

1999-01-01

A universal sensor interface model (USIM) is being developed by the Raytheon-TI Systems Company for use with fields of unattended distributed sensors. In its production configuration, the USIM will be a multichip module consisting of a set of common modules. The common module USIM set consists of (1) a sensor adapter interface (SAI) module, (2) digital signal processor (DSP) and associated memory module, and (3) a RF transceiver model. The multispectral sensor interface is designed around a low-power A/D converted, whose input/output interface consists of: -8 buffered, sampled inputs from various devices including environmental, acoustic seismic and magnetic sensors. The eight sensor inputs are each high-impedance, low- capacitance, differential amplifiers. The inputs are ideally suited for interface with discrete or MEMS sensors, since the differential input will allow direct connection with high-impedance bridge sensors and capacitance voltage sources. Each amplifier is connected to a 22-bit (Delta) (Sigma) A/D converter to enable simultaneous samples. The low power (Delta) (Sigma) converter provides 22-bit resolution at sample frequencies up to 142 hertz (used for magnetic sensors) and 16-bit resolution at frequencies up to 1168 hertz (used for acoustic and seismic sensors). The video interface module is based around the TMS320C5410 DSP. It can provide sensor array addressing, video data input, data calibration and correction. The processor module is based upon a MPC555. It will be used for mode control, synchronization of complex sensors, sensor signal processing, array processing, target classification and tracking. Many functions of the A/D, DSP and transceiver can be powered down by using variable clock speeds under software command or chip power switches. They can be returned to intermediate or full operation by DSP command. Power management may be based on the USIM's internal timer, command from the USIM transceiver, or by sleep mode processing management. The low power detection mode is implemented by monitoring any of the sensor analog outputs at lower sample rates for detection over a software controllable threshold.

Taking "The Math You Need When You Need It" Modules Beyond Introductory Geology Courses

NASA Astrophysics Data System (ADS)

Baer, E. M.; Wenner, J. M.; Burn, H. E.

2012-12-01

"The Math You Need, When You Need It" (TMYN) modules are finding use well beyond the courses for which they were originally written. However, faculty survey responses indicate that the modules are used in similar ways, suggesting that the overall design of the modules is effective. TMYN modules are online resources designed to help students develop quantitative skills in conjunction with introductory geology courses. Since 2010, 29 faculty members at 26 institutions used these asynchronous resources at in 68 different courses nationwide, impacting about 3000 students. After each use of the modules, instructors responded to a survey about their use of the modules and the impact on each course and student cohort. Of the 29 instructors, 16 responded with a total of 36 implementations, a 52% response rate. Survey responses indicate use of TMYN modules in classes well beyond their original design. The modules were originally designed for students in introductory geology classes, especially those targeted at non-geoscience majors. Sixty-nine percent (22/32) of TMYN courses included introductory geology courses such as Physical Geology, Earth System Science and Environmental Geology. The remainder of courses included multiple uses in oceanography and meteorology courses and more specialized geoscience courses such as geomorphology, structural geology and hydrology. Surveys suggest that only 63% of courses that used TMYN (20/32) were targeted to students in general education courses. Nine percent (3/32) of courses were targeted to STEM majors and 19% (6/32) were specifically targeted to geoscience majors, including upper-level courses. Despite the wide variety of institutions, instructors, classes, and student educational goals, faculty incorporated the modules into their curriculum in as originally designed, indicating that the overall design of the modules is effective. Twenty-two respondents indicate that modules were assigned immediately prior to using a skill in the classroom (either in lab exercises or a lecture period). Almost all instructors employed pre- and posttests to gauge learning. More than ¾ of survey respondents introduced the modules within the first week of class. In all but one instance, students were instructed to complete an online quiz immediately after working through the online modules and most (77%) designed these post-module quizzes as formative assessments allowing at least 3 attempts. The grades on these modules contributed to students' grades but were relatively low stakes with 88% reporting that the modules contributed to less than 10% of a student's course grade. Given the use beyond the introductory geology classroom and the similarity of the use of these modules in a wide variety of courses, it appears that the design of the modules is sound. However, previous studies have indicated that mathematical skills are not easily transferred (e.g. Bassok. and Holyoak, 1989) suggesting the adaptation of the modules for use outside the geosciences.

Acceptance and Commitment Therapy modules: Differential impact on treatment processes and outcomes.

PubMed

Villatte, Jennifer L; Vilardaga, Roger; Villatte, Matthieu; Plumb Vilardaga, Jennifer C; Atkins, David C; Hayes, Steven C

2016-02-01

A modular, transdiagnostic approach to treatment design and implementation may increase the public health impact of evidence-based psychosocial interventions. Such an approach relies on algorithms for selecting and implementing treatment components intended to have a specific therapeutic effect, yet there is little evidence for how components function independent of their treatment packages when employed in clinical service settings. This study aimed to demonstrate the specificity of treatment effects for two components of Acceptance and Commitment Therapy (ACT), a promising candidate for modularization. A randomized, nonconcurrent, multiple-baseline across participants design was used to examine component effects on treatment processes and outcomes in 15 adults seeking mental health treatment. The ACT OPEN module targeted acceptance and cognitive defusion; the ACT ENGAGED module targeted values-based activation and persistence. According to Tau-U analyses, both modules produced significant improvements in psychiatric symptoms, quality of life, and targeted therapeutic processes. ACT ENGAGED demonstrated greater improvements in quality of life and values-based activation. ACT OPEN showed greater improvements in symptom severity, acceptance, and defusion. Both modules improved awareness and non-reactivity, which were mutually targeted, though using distinct intervention procedures. Both interventions demonstrated high treatment acceptability, completion, and patient satisfaction. Treatment effects were maintained at 3-month follow up. ACT components should be considered for inclusion in a modular approach to implementing evidence-based psychosocial interventions for adults. Copyright © 2015 Elsevier Ltd. All rights reserved.

An fMRI investigation into the effect of preceding stimuli during visual oddball tasks.

PubMed

Fajkus, Jiří; Mikl, Michal; Shaw, Daniel Joel; Brázdil, Milan

2015-08-15

This study investigates the modulatory effect of stimulus sequence on neural responses to novel stimuli. A group of 34 healthy volunteers underwent event-related functional magnetic resonance imaging while performing a three-stimulus visual oddball task, involving randomly presented frequent stimuli and two types of infrequent stimuli - targets and distractors. We developed a modified categorization of rare stimuli that incorporated the type of preceding rare stimulus, and analyzed the event-related functional data according to this sequence categorization; specifically, we explored hemodynamic response modulation associated with increasing rare-to-rare stimulus interval. For two consecutive targets, a modulation of brain function was evident throughout posterior midline and lateral temporal cortex, while responses to targets preceded by distractors were modulated in a widely distributed fronto-parietal system. As for distractors that follow targets, brain function was modulated throughout a set of posterior brain structures. For two successive distractors, however, no significant modulation was observed, which is consistent with previous studies and our primary hypothesis. The addition of the aforementioned technique extends the possibilities of conventional oddball task analysis, enabling researchers to explore the effects of the whole range of rare stimuli intervals. This methodology can be applied to study a wide range of associated cognitive mechanisms, such as decision making, expectancy and attention. Copyright © 2015 Elsevier B.V. All rights reserved.

Cue and Target Processing Modulate the Onset of Inhibition of Return

ERIC Educational Resources Information Center

Gabay, Shai; Chica, Ana B.; Charras, Pom; Funes, Maria J.; Henik, Avishai

2012-01-01

Inhibition of return (IOR) is modulated by task set and appears later in discrimination tasks than in detection tasks. Several hypotheses have been suggested to account for this difference. We tested three of these hypotheses in two experiments by examining the influence of cue and target level of processing on the onset of IOR. In the first…

Fuzzy Logic Controlled Solar Module for Driving Three- Phase Induction Motor

NASA Astrophysics Data System (ADS)

Afiqah Zainal, Nurul; Sooi Tat, Chan; Ajisman

2016-02-01

Renewable energy produced by solar module gives advantages for generated three- phase induction motor in remote area. But, solar module's ou tput is uncertain and complex. Fuzzy logic controller is one of controllers that can handle non-linear system and maximum power of solar module. Fuzzy logic controller used for Maximum Power Point Tracking (MPPT) technique to control Pulse-Width Modulation (PWM) for switching power electronics circuit. DC-DC boost converter used to boost up photovoltaic voltage to desired output and supply voltage source inverter which controlled by three-phase PWM generated by microcontroller. IGBT switched Voltage source inverter (VSI) produced alternating current (AC) voltage from direct current (DC) source to control speed of three-phase induction motor from boost converter output. Results showed that, the output power of solar module is optimized and controlled by using fuzzy logic controller. Besides that, the three-phase induction motor can be drive and control using VSI switching by the PWM signal generated by the fuzzy logic controller. This concluded that the non-linear system can be controlled and used in driving three-phase induction motor.

Continuously phase-modulated standing surface acoustic waves for separation of particles and cells in microfluidic channels containing multiple pressure nodes

NASA Astrophysics Data System (ADS)

Lee, Junseok; Rhyou, Chanryeol; Kang, Byungjun; Lee, Hyungsuk

2017-04-01

This paper describes continuously phase-modulated standing surface acoustic waves (CPM-SSAW) and its application for particle separation in multiple pressure nodes. A linear change of phase in CPM-SSAW applies a force to particles whose magnitude depends on their size and contrast factors. During continuous phase modulation, we demonstrate that particles with a target dimension are translated in the direction of moving pressure nodes, whereas smaller particles show oscillatory movements. The rate of phase modulation is optimized for separation of target particles from the relationship between mean particle velocity and period of oscillation. The developed technique is applied to separate particles of a target dimension from the particle mixture. Furthermore, we also demonstrate human keratinocyte cells can be separated in the cell and bead mixture. The separation technique is incorporated with a microfluidic channel spanning multiple pressure nodes, which is advantageous over separation in a single pressure node in terms of throughput.

Solid-state Marx based two-switch voltage modulator for the On-Line Isotope Mass Separator accelerator at the European Organization for Nuclear Research

NASA Astrophysics Data System (ADS)

Redondo, L. M.; Silva, J. Fernando; Canacsinh, H.; Ferrão, N.; Mendes, C.; Soares, R.; Schipper, J.; Fowler, A.

2010-07-01

A new circuit topology is proposed to replace the actual pulse transformer and thyratron based resonant modulator that supplies the 60 kV target potential for the ion acceleration of the On-Line Isotope Mass Separator accelerator, the stability of which is critical for the mass resolution downstream separator, at the European Organization for Nuclear Research. The improved modulator uses two solid-state switches working together, each one based on the Marx generator concept, operating as series and parallel switches, reducing the stress on the series stacked semiconductors, and also as auxiliary pulse generator in order to fulfill the target requirements. Preliminary results of a 10 kV prototype, using 1200 V insulated gate bipolar transistors and capacitors in the solid-state Marx circuits, ten stages each, with an electrical equivalent circuit of the target, are presented, demonstrating both the improved voltage stability and pulse flexibility potential wanted for this new modulator.

Retrieving self-vocalized information: An event-related potential (ERP) study on the effect of retrieval orientation.

PubMed

Rosburg, Timm; Johansson, Mikael; Sprondel, Volker; Mecklinger, Axel

2014-11-18

Retrieval orientation refers to a pre-retrieval process and conceptualizes the specific form of processing that is applied to a retrieval cue. In the current event-related potential (ERP) study, we sought to find evidence for an involvement of the auditory cortex when subjects attempt to retrieve vocalized information, and hypothesized that adopting retrieval orientation would be beneficial for retrieval accuracy. During study, participants saw object words that they subsequently vocalized or visually imagined. At test, participants had to identify object names of one study condition as targets and to reject object names of the second condition together with new items. Target category switched after half of the test trials. Behaviorally, participants responded less accurately and more slowly to targets of the vocalize condition than to targets of the imagine condition. ERPs to new items varied at a single left electrode (T7) between 500 and 800ms, indicating a moderate retrieval orientation effect in the subject group as a whole. However, whereas the effect was strongly pronounced in participants with high retrieval accuracy, it was absent in participants with low retrieval accuracy. A current source density (CSD) mapping of the retrieval orientation effect indicated a source over left temporal regions. Independently from retrieval accuracy, the ERP retrieval orientation effect was surprisingly also modulated by test order. Findings are suggestive for an involvement of the auditory cortex in retrieval attempts of vocalized information and confirm that adopting retrieval orientation is potentially beneficial for retrieval accuracy. The effects of test order on retrieval-related processes might reflect a stronger focus on the newness of items in the more difficult test condition when participants started with this condition. Copyright © 2014 Elsevier Inc. All rights reserved.

Integrating scientific data for drug discovery and development using the Life Sciences Grid.

PubMed

Dow, Ernst R; Hughes, James B; Stephens, Susie M; Narayan, Vaibhav A; Bishop, Richard W

2009-06-01

There are many daunting challenges for companies who wish to bring novel drugs to market. The information complexity around potential drug targets has increased greatly with the introduction of microarrays, high-throughput screening and other technological advances over the past decade, but has not yet fundamentally increased our understanding of how to modify a disease with pharmaceuticals. Further, the bar has been raised in getting a successful drug to market as just being new is no longer enough: the drug must demonstrate improved performance compared with the ever increasing generic pharmacopeia to gain support from payers and government authorities. In addition, partly as a consequence of a climate of concern regarding the safety of drugs, regulatory authorities have approved fewer new molecular entities compared to historical norms over the past few years. To overcome these challenges, the pharmaceutical industry must fully embrace information technology to bring better understood compounds to market. An important first step in addressing an unmet medical need is in understanding the disease and identifying the physiological target(s) to be modulated by the drug. Deciding which targets to pursue for a given disease requires a multidisciplinary effort that integrates heterogeneous data from many sources, including genetic variations of populations, changes in gene expression and biochemical assays. The Life Science Grid was developed to provide a flexible framework to integrate such diverse biological, chemical and disease information to help scientists make better-informed decisions. The Life Science Grid has been used to rapidly and effectively integrate scientific information in the pharmaceutical industry and has been placed in the open source community to foster collaboration in the life sciences community.

Analysis of structure and deformation behavior of AISI 316L tensile specimens from the second operational target module at the Spallation Neutron Source

DOE PAGES

Gussev, Maxim N.; McClintock, David A.; Garner, Frank

2015-08-05

In an earlier publication, tensile testing was performed on specimens removed from the first two operational targets of the Spallation Neutron Source (SNS). There were several anomalous features in the results. First, some specimens had very large elongations (up to 57%) while others had significantly smaller values. Second, there was a larger than the usual amount of data scatter in the elongation results. Third, the stress-strain diagrams of nominally similar specimens spanned a wide range of behavior ranging from expected irradiation-induced hardening to varying levels of force drop after yield point and indirect signs of "traveling deformation wave" behavior associatedmore » with strain-induced martensite formation. To investigate the cause(s) of such variable tensile behavior, several specimens from Target 2, spanning the range of observed tensile behavior, were chosen for detailed microstructural examination using electron backscattering analysis (EBSD). It was also shown that the steel employed in the construction of the target contained an unexpected bimodal grain size distribution, containing very large out-of-specification grains surrounded by necklaces of grains of within-specification sizes. The large grains were frequently comparable to the width of the gauge section of the tensile specimen. Moreover, the propensity to form martensite during deformation was shown to be accelerated by radiation but also to be very sensitive to the relative orientation of the grains with respect to the tensile axis. Specimens having large grains in the gauge that were most favorably oriented for production of martensite strongly exhibited the traveling deformation wave phenomenon, while those specimens with less favorably oriented grains had lesser or no degree of the wave effect, thereby accounting for the larger than expected data scatter.« less

A variable-step-size robust delta modulator.

NASA Technical Reports Server (NTRS)

Song, C. L.; Garodnick, J.; Schilling, D. L.

1971-01-01

Description of an analytically obtained optimum adaptive delta modulator-demodulator configuration. The device utilizes two past samples to obtain a step size which minimizes the mean square error for a Markov-Gaussian source. The optimum system is compared, using computer simulations, with a linear delta modulator and an enhanced Abate delta modulator. In addition, the performance is compared to the rate distortion bound for a Markov source. It is shown that the optimum delta modulator is neither quantization nor slope-overload limited. The highly nonlinear equations obtained for the optimum transmitter and receiver are approximated by piecewise-linear equations in order to obtain system equations which can be transformed into hardware. The derivation of the experimental system is presented.

Source-to-incident-flux relation in a Tokamak blanket module

NASA Astrophysics Data System (ADS)

Imel, G. R.

The next-generation Tokamak experiments, including the Tokamak fusion test reactor (TFTR), will utilize small blanket modules to measure performance parameters such as tritium breeding profiles, power deposition profiles, and neutron flux profiles. Specifically, a neutron calorimeter (simply a neutron moderating blanket module) which permits inferring the incident 14 MeV flux based on measured temperature profiles was proposed for TFTR. The problem of how to relate this total scalar flux to the fusion neutron source is addressed. This relation is necessary since the calorimeter is proposed as a total fusion energy monitor. The methods and assumptions presented was valid for the TFTR Lithium Breeding Module (LBM), as well as other modules on larger Tokamak reactors.

Metabolism as a Target for Modulation in Autoimmune Diseases.

PubMed

Huang, Nick; Perl, Andras

2018-05-05

Metabolic pathways are now well recognized as important regulators of immune differentiation and activation, and thus influence the development of autoimmune diseases such as systemic lupus erythematosus (SLE). The mechanistic target of rapamycin (mTOR) has emerged as a key sensor of metabolic stress and an important mediator of proinflammatory lineage specification. Metabolic pathways control the production of mitochondrial reactive oxygen species (ROS), which promote mTOR activation and also modulate the antigenicity of proteins, lipids, and DNA, thus placing ROS at the heart of metabolic disturbances during pathogenesis of SLE. Therefore, we review here the pathways that control ROS production and mTOR activation and identify targets for safe therapeutic modulation of the signaling network that underlies autoimmune diseases, focusing on SLE. Copyright © 2018. Published by Elsevier Ltd.

Multi-voxel pattern analysis reveals increased memory targeting and reduced use of retrieved details during single-agenda source monitoring

PubMed Central

McDuff, Susan G. R.; Frankel, Hillary C.; Norman, Kenneth A.

2009-01-01

We used multi-voxel pattern analysis (MVPA) of fMRI data to gain insight into how subjects’ retrieval agendas influence source memory judgments (was item X studied using source Y?). In Experiment 1, we used a single-agenda test where subjects judged whether items were studied with the targeted source or not. In Experiment 2, we used a multi-agenda test where subjects judged whether items were studied using the targeted source, studied using a different source, or nonstudied. To evaluate the differences between single- and multi-agenda source monitoring, we trained a classifier to detect source-specific fMRI activity at study, and then we applied the classifier to data from the test phase. We focused on trials where the targeted source and the actual source differed, so we could use MVPA to track neural activity associated with both the targeted source and the actual source. Our results indicate that single-agenda monitoring was associated with increased focus on the targeted source (as evidenced by increased targeted-source activity, relative to baseline) and reduced use of information relating to the actual, non-target source. In the multi-agenda experiment, high-levels of actual-source activity were associated with increased correct rejections, suggesting that subjects were using recollection of actual-source information to avoid source memory errors. In the single-agenda experiment, there were comparable levels of actual-source activity (suggesting that recollection was taking place), but the relationship between actual-source activity and behavior was absent (suggesting that subjects were failing to make proper use of this information). PMID:19144851

Increased Anatomical Specificity of Neuromodulation via Modulated Focused Ultrasound

PubMed Central

Mehić, Edin; Xu, Julia M.; Caler, Connor J.; Coulson, Nathaniel K.; Moritz, Chet T.; Mourad, Pierre D.

2014-01-01

Transcranial ultrasound can alter brain function transiently and nondestructively, offering a new tool to study brain function now and inform future therapies. Previous research on neuromodulation implemented pulsed low-frequency (250–700 kHz) ultrasound with spatial peak temporal average intensities (ISPTA) of 0.1–10 W/cm2. That work used transducers that either insonified relatively large volumes of mouse brain (several mL) with relatively low-frequency ultrasound and produced bilateral motor responses, or relatively small volumes of brain (on the order of 0.06 mL) with relatively high-frequency ultrasound that produced unilateral motor responses. This study seeks to increase anatomical specificity to neuromodulation with modulated focused ultrasound (mFU). Here, ‘modulated’ means modifying a focused 2-MHz carrier signal dynamically with a 500-kHz signal as in vibro-acoustography, thereby creating a low-frequency but small volume (approximately 0.015 mL) source of neuromodulation. Application of transcranial mFU to lightly anesthetized mice produced various motor movements with high spatial selectivity (on the order of 1 mm) that scaled with the temporal average ultrasound intensity. Alone, mFU and focused ultrasound (FUS) each induced motor activity, including unilateral motions, though anatomical location and type of motion varied. Future work should include larger animal models to determine the relative efficacy of mFU versus FUS. Other studies should determine the biophysical processes through which they act. Also of interest is exploration of the potential research and clinical applications for targeted, transcranial neuromodulation created by modulated focused ultrasound, especially mFU’s ability to produce compact sources of ultrasound at the very low frequencies (10–100s of Hertz) that are commensurate with the natural frequencies of the brain. PMID:24504255

Semantic priming in the lexical decision task: roles of prospective prime-generated expectancies and retrospective semantic matching.

PubMed

Neely, J H; Keefe, D E; Ross, K L

1989-11-01

In semantic priming paradigms for lexical decisions, the probability that a word target is semantically related to its prime (the relatedness proportion) has been confounded with the probability that a target is a nonword, given that it is unrelated to its prime (the nonword ratio). This study unconfounded these two probabilities in a lexical decision task with category names as primes and with high- and low-dominance exemplars as targets. Semantic priming for high-dominance exemplars was modulated by the relatedness proportion and, to a lesser degree, by the nonword ratio. However, the nonword ratio exerted a stronger influence than did the relatedness proportion on semantic priming for low-dominance exemplars and on the nonword facilitation effect (i.e., the superiority in performance for nonword targets that follow a category name rather than a neutral XXX prime). These results suggest that semantic priming for lexical decisions is affected by both a prospective prime-generated expectancy, modulated by the relatedness proportion, and a retrospective target/prime semantic matching process, modulated by the nonword ratio.

Ultrasound modulation of bioluminescence generated inside a turbid medium

NASA Astrophysics Data System (ADS)

Ahmad, Junaid; Jayet, Baptiste; Hill, Philip J.; Mather, Melissa L.; Dehghani, Hamid; Morgan, Stephen P.

2017-03-01

In vivo bioluminescence imaging (BLI) has poor spatial resolution owing to strong light scattering by tissue, which also affects quantitative accuracy. This paper proposes a hybrid acousto-optic imaging platform that images bioluminescence modulated at ultrasound (US) frequency inside an optically scattering medium. This produces an US modulated light within the tissue that reduces the effects of light scattering and improves the spatial resolution. The system consists of a continuously excited 3.5 MHz US transducer applied to a tissue like phantom of known optical properties embedded with bio-or chemiluminescent sources that are used to mimic in vivo experiments. Scanning US over the turbid medium modulates the luminescent sources deep inside tissue at several US scan points. These modulated signals are recorded by a photomultiplier tube and lock-in detection to generate a 1D profile. Indeed, high frequency US enables small focal volume to improve spatial resolution, but this leads to lower signal-to-noise ratio. First experimental results show that US enables localization of a small luminescent source (around 2 mm wide) deep ( 20 mm) inside a tissue phantom having a scattering coefficient of 80 cm-1. Two sources separated by 10 mm could be resolved 20 mm inside a chicken breast.

Analysis of dead zone sources in a closed-loop fiber optic gyroscope.

PubMed

Chong, Kyoung-Ho; Choi, Woo-Seok; Chong, Kil-To

2016-01-01

Analysis of the dead zone is among the intensive studies in a closed-loop fiber optic gyroscope. In a dead zone, a gyroscope cannot detect any rotation and produces a zero bias. In this study, an analysis of dead zone sources is performed in simulation and experiments. In general, the problem is mainly due to electrical cross coupling and phase modulation drift. Electrical cross coupling is caused by interference between modulation voltage and the photodetector. The cross-coupled signal produces spurious gyro bias and leads to a dead zone if it is larger than the input rate. Phase modulation drift as another dead zone source is due to the electrode contamination, the piezoelectric effect of the LiNbO3 substrate, or to organic fouling. This modulation drift lasts for a short or long period of time like a lead-lag filter response and produces gyro bias error, noise spikes, or dead zone. For a more detailed analysis, the cross-coupling effect and modulation phase drift are modeled as a filter and are simulated in both the open-loop and closed-loop modes. The sources of dead zone are more clearly analyzed in the simulation and experimental results.

Tether deployment monitoring system, phase 2

NASA Technical Reports Server (NTRS)

1989-01-01

An operational Tether Deployment Monitoring System (TEDEMS) was constructed that would show system functionality in a terrestrial environment. The principle function of the TEDEMS system is the launching and attachment of reflective targets onto the tether during its deployment. These targets would be tracked with a radar antenna that was pointed towards the targets by a positioning system. A spring powered launcher for the targets was designed and fabricated. An instrumentation platform and launcher were also developed. These modules are relatively heavy and will influence tether deployment scenarios, unless they are released with a velocity and trajectory closely matching that of the tether. Owing to the tracking range limitations encountered during field trails of the Radar system, final TEDEMS system integration was not completed. The major module not finished was the system control computer. The lack of this device prevented any subsystem testing or field trials to be conducted. Other items only partially complete were the instrumentation platform launcher and modules and the radar target launcher. The work completed and the tests performed suggest that the proposed system continues to be a feasible approach to tether monitoring, although additional effort is still necessary to increase the range at which modules can be detected. The equipment completed and tested, to the extent stated, is available to NASA for use on any future program that requires tether tracking capability.

Distributed source pollutant transport module based on BTOPMC: a case study of the Laixi River basin in the Sichuan province of southwest China

NASA Astrophysics Data System (ADS)

Zhang, Hongbo; Ao, Tianqi; Gusyev, Maksym; Ishidaira, Hiroshi; Magome, Jun; Takeuchi, Kuniyoshi

2018-06-01

Nitrogen and phosphorus concentrations in Chinese river catchments are contributed by agricultural non-point and industrial point sources causing deterioration of river water quality and degradation of ecosystem functioning for a long distance downstream. To evaluate these impacts, a distributed pollutant transport module was developed on the basis of BTOPMC (Block-Wise Use of TOPMODEL with Muskingum-Cunge Method), a grid-based distributed hydrological model, using the water flow routing process of BTOPMC as the carrier of pollutant transport due a direct runoff. The pollutant flux at each grid is simulated based on mass balance of pollutants within the grid and surface water transport of these pollutants occurs between grids in the direction of the water flow on daily time steps. The model was tested in the study area of the Lu county area situated in the Laixi River basin in the Sichuan province of southwest China. The simulated concentrations of nitrogen and phosphorus are compared with the available monthly data at several water quality stations. These results demonstrate a greater pollutant concentration in the beginning of high flow period indicating the main mechanism of pollution transport. From these preliminary results, we suggest that the distributed pollutant transport model can reflect the characteristics of the pollutant transport and reach the expected target.

A portable fluorescence microscopic imaging system for cholecystectomy

NASA Astrophysics Data System (ADS)

Ye, Jian; Yang, Chaoyu; Gan, Qi; Ma, Rong; Zhang, Zeshu; Chang, Shufang; Shao, Pengfei; Zhang, Shiwu; Liu, Chenhai; Xu, Ronald

2016-03-01

In this paper we proposed a portable fluorescence microscopic imaging system to prevent iatrogenic biliary injuries from occurring during cholecystectomy due to misidentification of the cystic structures. The system consisted of a light source module, a CMOS camera, a Raspberry Pi computer and a 5 inch HDMI LCD. Specifically, the light source module was composed of 690 nm and 850 nm LEDs, allowing the CMOS camera to simultaneously acquire both fluorescence and background images. The system was controlled by Raspberry Pi using Python programming with the OpenCV library under Linux. We chose Indocyanine green(ICG) as a fluorescent contrast agent and then tested fluorescence intensities of the ICG aqueous solution at different concentration levels by our fluorescence microscopic system compared with the commercial Xenogen IVIS system. The spatial resolution of the proposed fluorescence microscopic imaging system was measured by a 1951 USAF resolution target and the dynamic response was evaluated quantitatively with an automatic displacement platform. Finally, we verified the technical feasibility of the proposed system in mouse models of bile duct, performing both correct and incorrect gallbladder resection. Our experiments showed that the proposed system can provide clear visualization of the confluence between the cystic duct and common bile duct or common hepatic duct, suggesting that this is a potential method for guiding cholecystectomy. The proposed portable system only cost a total of $300, potentially promoting its use in resource-limited settings.

N-Terminomics TAILS Identifies Host Cell Substrates of Poliovirus and Coxsackievirus B3 3C Proteinases That Modulate Virus Infection

PubMed Central

Jagdeo, Julienne M.; Dufour, Antoine; Klein, Theo; Solis, Nestor; Kleifeld, Oded; Kizhakkedathu, Jayachandran; Luo, Honglin; Overall, Christopher M.

2018-01-01

ABSTRACT Enteroviruses encode proteinases that are essential for processing of the translated viral polyprotein. In addition, viral proteinases also target host proteins to manipulate cellular processes and evade innate antiviral responses to promote replication and infection. Although some host protein substrates of enterovirus proteinases have been identified, the full repertoire of targets remains unknown. We used a novel quantitative in vitro proteomics-based approach, termed terminal amine isotopic labeling of substrates (TAILS), to identify with high confidence 72 and 34 new host protein targets of poliovirus and coxsackievirus B3 (CVB3) 3C proteinases (3Cpros) in HeLa cell and cardiomyocyte HL-1 cell lysates, respectively. We validated a subset of candidate substrates that are targets of poliovirus 3Cpro in vitro including three common protein targets, phosphoribosylformylglycinamidine synthetase (PFAS), hnRNP K, and hnRNP M, of both proteinases. 3Cpro-targeted substrates were also cleaved in virus-infected cells but not noncleavable mutant proteins designed from the TAILS-identified cleavage sites. Knockdown of TAILS-identified target proteins modulated infection both negatively and positively, suggesting that cleavage by 3Cpro promotes infection. Indeed, expression of a cleavage-resistant mutant form of the endoplasmic reticulum (ER)-Golgi vesicle-tethering protein p115 decreased viral replication and yield. As the first comprehensive study to identify and validate functional enterovirus 3Cpro substrates in vivo, we conclude that N-terminomics by TAILS is an effective strategy to identify host targets of viral proteinases in a nonbiased manner. IMPORTANCE Enteroviruses are positive-strand RNA viruses that encode proteases that cleave the viral polyprotein into the individual mature viral proteins. In addition, viral proteases target host proteins in order to modulate cellular pathways and block antiviral responses in order to facilitate virus infection. Although several host protein targets have been identified, the entire list of proteins that are targeted is not known. In this study, we used a novel unbiased proteomics approach to identify ∼100 novel host targets of the enterovirus 3C protease, thus providing further insights into the network of cellular pathways that are modulated to promote virus infection. PMID:29437971

In-Depth Study of the Interaction, Sensitivity, and Gating Modulation by PUFAs on K+ Channels; Interaction and New Targets

PubMed Central

Moreno, Cristina; de la Cruz, Alicia; Valenzuela, Carmen

2016-01-01

Voltage gated potassium channels (KV) are membrane proteins that allow selective flow of K+ ions in a voltage-dependent manner. These channels play an important role in several excitable cells as neurons, cardiomyocytes, and vascular smooth muscle. Over the last 20 years, it has been shown that omega-3 polyunsaturated fatty acids (PUFAs) enhance or decrease the activity of several cardiac KV channels. PUFAs-dependent modulation of potassium ion channels has been reported to be cardioprotective. However, the precise cellular mechanism underlying the cardiovascular benefits remained unclear in part because new PUFAs targets and signaling pathways continue being discovered. In this review, we will focus on recent data available concerning the following aspects of the KV channel modulation by PUFAs: (i) the exact residues involved in PUFAs-KV channels interaction; (ii) the structural PUFAs determinants important for their effects on KV channels; (iii) the mechanism of the gating modulation of KV channels and, finally, (iv) the PUFAs modulation of a few new targets present in smooth muscle cells (SMC), KCa1.1, K2P, and KATP channels, involved in vascular relaxation. PMID:27933000

Mechanical stress-controlled tunable active frequency-selective surface

NASA Astrophysics Data System (ADS)

Huang, Bo-Cin; Hong, Jian-Wei; Lo, Cheng-Yao

2017-01-01

This study proposes a tunable active frequency-selective surface (AFSS) realized by mechanically expanding or contracting a split-ring resonator (SRR) array. The proposed AFSS transfers mechanical stress from its elastic substrate to the top of the SRR, thereby achieving electromagnetic (EM) modulation without the need for an additional external power supply, meeting the requirements for the target application: the invisibility cloak. The operating mechanism of the proposed AFSS differs from those of other AFSSs, supporting modulations in arbitrary frequencies in the target range. The proposed stress-controlled or strain-induced EM modulation proves the existence of an identical and linear relationship between the strain gradient and the frequency shift, implying its suitability for other EM modulation ranges and applications.

Diffusion spectral imaging modules correlate with EEG LORETA neuroimaging modules.

PubMed

Thatcher, Robert W; North, Duane M; Biver, Carl J

2012-05-01

The purpose of this study was to test the hypothesis that the highest temporal correlations between 3-dimensional EEG current source density corresponds to anatomical Modules of high synaptic connectivity. Eyes closed and eyes open EEG was recorded from 19 scalp locations with a linked ears reference from 71 subjects age 13-42 years. LORETA was computed from 1 to 30 Hz in 2,394 cortical gray matter voxels that were grouped into six anatomical Modules corresponding to the ROIs in the Hagmann et al.'s [2008] diffusion spectral imaging (DSI) study. All possible cross-correlations between voxels within a DSI Module were compared with the correlations between Modules. The Hagmann et al. [ 2008] Module correlation structure was replicated in the correlation structure of EEG three-dimensional current source density. EEG Temporal correlation between brain regions is related to synaptic density as measured by diffusion spectral imaging. Copyright © 2011 Wiley-Liss, Inc.

Microscopy imaging system and method employing stimulated raman spectroscopy as a contrast mechanism

DOEpatents

Xie, Xiaoliang Sunney [Lexington, MA; Freudiger, Christian [Boston, MA; Min, Wei [Cambridge, MA

2011-09-27

A microscopy imaging system includes a first light source for providing a first train of pulses at a first center optical frequency .omega..sub.1, a second light source for providing a second train of pulses at a second center optical frequency .omega..sub.2, a modulator system, an optical detector, and a processor. The modulator system is for modulating a beam property of the second train of pulses at a modulation frequency f of at least 100 kHz. The optical detector is for detecting an integrated intensity of substantially all optical frequency components of the first train of pulses from the common focal volume by blocking the second train of pulses being modulated. The processor is for detecting, a modulation at the modulation frequency f, of the integrated intensity of the optical frequency components of the first train of pulses to provide a pixel of an image for the microscopy imaging system.

The neuronal mechanisms underlying improvement of impulsivity in ADHD by theta/beta neurofeedback.

PubMed

Bluschke, Annet; Broschwitz, Felicia; Kohl, Simon; Roessner, Veit; Beste, Christian

2016-08-12

Neurofeedback is increasingly recognized as an intervention to treat core symptoms of attention deficit hyperactivity disorder (ADHD). Despite the large number of studies having been carried out to evaluate its effectiveness, it is widely elusive what neuronal mechanisms related to the core symptoms of ADHD are modulated by neurofeedback. 19 children with ADHD undergoing 8 weeks of theta/beta neurofeedback and 17 waiting list controls performed a Go/Nogo task in a pre-post design. We used neurophysiological measures combining high-density EEG recording with source localization analyses using sLORETA. Compared to the waiting list ADHD control group, impulsive behaviour measured was reduced after neurofeedback treatment. The effects of neurofeedback were very specific for situations requiring inhibitory control over responses. The neurophysiological data shows that processes of perceptual gating, attentional selection and resource allocation processes were not affected by neurofeedback. Rather, neurofeedback effects seem to be based on the modulation of response inhibition processes in medial frontal cortices. The study shows that specific neuronal mechanisms underlying impulsivity are modulated by theta/beta neurofeedback in ADHD. The applied neurofeedback protocol could be particularly suitable to address inhibitory control. The study validates assumed functional neuroanatomical target regions of an established neurofeedback protocol on a neurophysiological level.

The neuronal mechanisms underlying improvement of impulsivity in ADHD by theta/beta neurofeedback

PubMed Central

Bluschke, Annet; Broschwitz, Felicia; Kohl, Simon; Roessner, Veit; Beste, Christian

2016-01-01

Neurofeedback is increasingly recognized as an intervention to treat core symptoms of attention deficit hyperactivity disorder (ADHD). Despite the large number of studies having been carried out to evaluate its effectiveness, it is widely elusive what neuronal mechanisms related to the core symptoms of ADHD are modulated by neurofeedback. 19 children with ADHD undergoing 8 weeks of theta/beta neurofeedback and 17 waiting list controls performed a Go/Nogo task in a pre-post design. We used neurophysiological measures combining high-density EEG recording with source localization analyses using sLORETA. Compared to the waiting list ADHD control group, impulsive behaviour measured was reduced after neurofeedback treatment. The effects of neurofeedback were very specific for situations requiring inhibitory control over responses. The neurophysiological data shows that processes of perceptual gating, attentional selection and resource allocation processes were not affected by neurofeedback. Rather, neurofeedback effects seem to be based on the modulation of response inhibition processes in medial frontal cortices. The study shows that specific neuronal mechanisms underlying impulsivity are modulated by theta/beta neurofeedback in ADHD. The applied neurofeedback protocol could be particularly suitable to address inhibitory control. The study validates assumed functional neuroanatomical target regions of an established neurofeedback protocol on a neurophysiological level. PMID:27514985

Identifying Rhodamine Dye Plume Sources in Near-Shore Oceanic Environments by Integration of Chemical and Visual Sensors

PubMed Central

Tian, Yu; Kang, Xiaodong; Li, Yunyi; Li, Wei; Zhang, Aiqun; Yu, Jiangchen; Li, Yiping

2013-01-01

This article presents a strategy for identifying the source location of a chemical plume in near-shore oceanic environments where the plume is developed under the influence of turbulence, tides and waves. This strategy includes two modules: source declaration (or identification) and source verification embedded in a subsumption architecture. Algorithms for source identification are derived from the moth-inspired plume tracing strategies based on a chemical sensor. The in-water test missions, conducted in November 2002 at San Clemente Island (California, USA) in June 2003 in Duck (North Carolina, USA) and in October 2010 at Dalian Bay (China), successfully identified the source locations after autonomous underwater vehicles tracked the rhodamine dye plumes with a significant meander over 100 meters. The objective of the verification module is to verify the declared plume source using a visual sensor. Because images taken in near shore oceanic environments are very vague and colors in the images are not well-defined, we adopt a fuzzy color extractor to segment the color components and recognize the chemical plume and its source by measuring color similarity. The source verification module is tested by images taken during the CPT missions. PMID:23507823

Precision-guided antimicrobial peptide as a targeted modulator of human microbial ecology.

PubMed

Guo, Lihong; McLean, Jeffrey S; Yang, Youngik; Eckert, Randal; Kaplan, Christopher W; Kyme, Pierre; Sheikh, Omid; Varnum, Brian; Lux, Renate; Shi, Wenyuan; He, Xuesong

2015-06-16

One major challenge to studying human microbiome and its associated diseases is the lack of effective tools to achieve targeted modulation of individual species and study its ecological function within multispecies communities. Here, we show that C16G2, a specifically targeted antimicrobial peptide, was able to selectively kill cariogenic pathogen Streptococcus mutans with high efficacy within a human saliva-derived in vitro oral multispecies community. Importantly, a significant shift in the overall microbial structure of the C16G2-treated community was revealed after a 24-h recovery period: several bacterial species with metabolic dependency or physical interactions with S. mutans suffered drastic reduction in their abundance, whereas S. mutans' natural competitors, including health-associated Streptococci, became dominant. This study demonstrates the use of targeted antimicrobials to modulate the microbiome structure allowing insights into the key community role of specific bacterial species and also indicates the therapeutic potential of C16G2 to achieve a healthy oral microbiome.

Preparation of multilayered nanocrystalline thin films with composition-modulated interfaces

NASA Astrophysics Data System (ADS)

Biro, D.; Barna, P. B.; Székely, L.; Geszti, O.; Hattori, T.; Devenyi, A.

2008-06-01

The properties of multilayer thin film structures depend on the morphology and structure of interfaces. A broad interface, in which the composition is varying, can enhance, e.g., the hardness of multilayer thin films. In the present experiments multilayers of TiAlN and CrN as well as TiAlN, CrN and MoS 2 were studied by using unbalanced magnetron sputter sources. The sputter sources were arranged side by side on an arc. This arrangement permits development of a transition zone between the layers, where the composition changes continuously. The multilayer system was deposited by one-fold oscillating movement of substrates in front of sputter sources. Thicknesses of layers could be changed both by oscillation frequency and by the power applied to sputter sources. Ti/Al: 50/50 at%, pure chromium and MoS 2 targets were used in the sputter sources. The depositions were performed in an Ar-N 2 mixture at 0.22 Pa working pressure. The sputtering power of the TiAl source was feed-back adjusted in fuzzy-logic mode in order to avoid fluctuation of the TiAl target sputter rate due to poisoning of the target surface. Structure characterization of films deposited on <1 0 0> Si wafers covered by thermally grown SiO 2 was performed by cross-sectional transmission electron microscopy. At first a 100 nm thick Cr base layer was deposited on the substrate to improve adhesion, which was followed by a CrN transition layer. The CrN transition layer was followed by a 100 nm thick TiAlN/CrN multilayer system. The TiAlN/CrN/MoS 2 multilayer system was deposited on the surface of this underlayer system. The underlayer systems Cr, CrN and TiAlN/CrN were crystalline with columnar structure according to the morphology of zone T of the structure zone models. The column boundaries contained segregated phases showing up in the under-focused TEM images. The surface of the underlayer system was wavy due to dome-shaped columns. The nanometer-scaled TiAlN/CrN/MoS 2 multilayer system followed this waviness. Crystallinity of the TiAlN and CrN layers in the multilayer system decreases with increasing thickness of the MoS 2 layer.

Light-emitting diode-based multiwavelength diffuse optical tomography system guided by ultrasound

PubMed Central

Yuan, Guangqian; Alqasemi, Umar; Chen, Aaron; Yang, Yi; Zhu, Quing

2014-01-01

Abstract. Laser diodes are widely used in diffuse optical tomography (DOT) systems but are typically expensive and fragile, while light-emitting diodes (LEDs) are cheaper and are also available in the near-infrared (NIR) range with adequate output power for imaging deeply seated targets. In this study, we introduce a new low-cost DOT system using LEDs of four wavelengths in the NIR spectrum as light sources. The LEDs were modulated at 20 kHz to avoid ambient light. The LEDs were distributed on a hand-held probe and a printed circuit board was mounted at the back of the probe to separately provide switching and driving current to each LED. Ten optical fibers were used to couple the reflected light to 10 parallel photomultiplier tube detectors. A commercial ultrasound system provided simultaneous images of target location and size to guide the image reconstruction. A frequency-domain (FD) laser-diode-based system with ultrasound guidance was also used to compare the results obtained from those of the LED-based system. Results of absorbers embedded in intralipid and inhomogeneous tissue phantoms have demonstrated that the LED-based system provides a comparable quantification accuracy of targets to the FD system and has the potential to image deep targets such as breast lesions. PMID:25473884

Metrical expectations from preceding prosody influence perception of lexical stress.

PubMed

Brown, Meredith; Salverda, Anne Pier; Dilley, Laura C; Tanenhaus, Michael K

2015-04-01

Two visual-world experiments tested the hypothesis that expectations based on preceding prosody influence the perception of suprasegmental cues to lexical stress. The results demonstrate that listeners' consideration of competing alternatives with different stress patterns (e.g., 'jury/gi'raffe) can be influenced by the fundamental frequency and syllable timing patterns across material preceding a target word. When preceding stressed syllables distal to the target word shared pitch and timing characteristics with the first syllable of the target word, pictures of alternatives with primary lexical stress on the first syllable (e.g., jury) initially attracted more looks than alternatives with unstressed initial syllables (e.g., giraffe). This effect was modulated when preceding unstressed syllables had pitch and timing characteristics similar to the initial syllable of the target word, with more looks to alternatives with unstressed initial syllables (e.g., giraffe) than to those with stressed initial syllables (e.g., jury). These findings suggest that expectations about the acoustic realization of upcoming speech include information about metrical organization and lexical stress and that these expectations constrain the initial interpretation of suprasegmental stress cues. These distal prosody effects implicate online probabilistic inferences about the sources of acoustic-phonetic variation during spoken-word recognition. (c) 2015 APA, all rights reserved.

Therapeutically targeting mitochondrial redox signalling alleviates endothelial dysfunction in preeclampsia.

PubMed

McCarthy, Cathal; Kenny, Louise C

2016-09-08

Aberrant placentation generating placental oxidative stress is proposed to play a critical role in the pathophysiology of preeclampsia. Unfortunately, therapeutic trials of antioxidants have been uniformly disappointing. There is provisional evidence implicating mitochondrial dysfunction as a source of oxidative stress in preeclampsia. Here we provide evidence that mitochondrial reactive oxygen species mediates endothelial dysfunction and establish that directly targeting mitochondrial scavenging may provide a protective role. Human umbilical vein endothelial cells exposed to 3% plasma from women with pregnancies complicated by preeclampsia resulted in a significant decrease in mitochondrial function with a subsequent significant increase in mitochondrial superoxide generation compared to cells exposed to plasma from women with uncomplicated pregnancies. Real-time PCR analysis showed increased expression of inflammatory markers TNF-α, TLR-9 and ICAM-1 respectively in endothelial cells treated with preeclampsia plasma. MitoTempo is a mitochondrial-targeted antioxidant, pre-treatment of cells with MitoTempo protected against hydrogen peroxide-induced cell death. Furthermore MitoTempo significantly reduced mitochondrial superoxide production in cells exposed to preeclampsia plasma by normalising mitochondrial metabolism. MitoTempo significantly altered the inflammatory profile of plasma treated cells. These novel data support a functional role for mitochondrial redox signaling in modulating the pathogenesis of preeclampsia and identifies mitochondrial-targeted antioxidants as potential therapeutic candidates.

Family 46 Carbohydrate-binding Modules Contribute to the Enzymatic Hydrolysis of Xyloglucan and β-1,3-1,4-Glucans through Distinct Mechanisms.

PubMed

Venditto, Immacolata; Najmudin, Shabir; Luís, Ana S; Ferreira, Luís M A; Sakka, Kazuo; Knox, J Paul; Gilbert, Harry J; Fontes, Carlos M G A

2015-04-24

Structural carbohydrates comprise an extraordinary source of energy that remains poorly utilized by the biofuel sector as enzymes have restricted access to their substrates within the intricacy of plant cell walls. Carbohydrate active enzymes (CAZYmes) that target recalcitrant polysaccharides are modular enzymes containing noncatalytic carbohydrate-binding modules (CBMs) that direct enzymes to their cognate substrate, thus potentiating catalysis. In general, CBMs are functionally and structurally autonomous from their associated catalytic domains from which they are separated through flexible linker sequences. Here, we show that a C-terminal CBM46 derived from BhCel5B, a Bacillus halodurans endoglucanase, does not interact with β-glucans independently but, uniquely, acts cooperatively with the catalytic domain of the enzyme in substrate recognition. The structure of BhCBM46 revealed a β-sandwich fold that abuts onto the region of the substrate binding cleft upstream of the active site. BhCBM46 as a discrete entity is unable to bind to β-glucans. Removal of BhCBM46 from BhCel5B, however, abrogates binding to β-1,3-1,4-glucans while substantially decreasing the affinity for decorated β-1,4-glucan homopolymers such as xyloglucan. The CBM46 was shown to contribute to xyloglucan hydrolysis only in the context of intact plant cell walls, but it potentiates enzymatic activity against purified β-1,3-1,4-glucans in solution or within the cell wall. This report reveals the mechanism by which a CBM can promote enzyme activity through direct interaction with the substrate or by targeting regions of the plant cell wall where the target glucan is abundant. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

Modulation of Target Recollection and Recollection Rejection Networks Due to Retrieval Facilitation and Interference

ERIC Educational Resources Information Center

Bowman, Caitlin R.; Sine, Shalome L.; Dennis, Nancy A.

2017-01-01

To better understand neural recollection processing, we induced interference in target recollection by presenting related lures before their respective targets and facilitated recollection rejection of lures by presenting targets before their related lures. Target recollection following interference recruited visual and prefrontal cortices,…

SU-F-T-81: Treating Nose Skin Using Energy and Intensity Modulated Electron Beams with Monte Carlo Based Dose Calculation

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

Jin, L; Fan, J; Eldib, A

Purpose: Treating nose skin with an electron beam is of a substantial challenge due to uneven nose surfaces and tissue heterogeneity, and consequently could have a great uncertainty of dose accuracy on the target. This work explored the method using Monte Carlo (MC)-based energy and intensity modulated electron radiotherapy (MERT), which would be delivered with a photon MLC in a standard medical linac (Artiste). Methods: The traditional treatment on the nose skin involves the usage of a bolus, often with a single energy electron beam. This work avoided using the bolus, and utilized mixed energies of electron beams. An in-housemore » developed Monte Carlo (MC)-based dose calculation/optimization planning system was employed for treatment planning. Phase space data (6, 9, 12 and 15 MeV) were used as an input source for MC dose calculations for the linac. To reduce the scatter-caused penumbra, a short SSD (61 cm) was used. A clinical case of the nose skin, which was previously treated with a single 9 MeV electron beam, was replanned with the MERT method. The resultant dose distributions were compared with the plan previously clinically used. The dose volume histogram of the MERT plan is calculated to examine the coverage of the planning target volume (PTV) and critical structure doses. Results: The target coverage and conformality in the MERT plan are improved as compared to the conventional plan. The MERT can provide more sufficient target coverage and less normal tissue dose underneath the nose skin. Conclusion: Compared to the conventional treatment technique, using MERT for the nose skin treatment has shown the dosimetric advantages in the PTV coverage and conformality. In addition, this technique eliminates the necessity of the cutout and bolus, which makes the treatment more efficient and accurate.« less

Fast and Forceful: Modulation of Response Activation Induced by Shifts of Perceived Depth in Virtual 3D Space

PubMed Central

Plewan, Thorsten; Rinkenauer, Gerhard

2016-01-01

Reaction time (RT) can strongly be influenced by a number of stimulus properties. For instance, there was converging evidence that perceived size rather than physical (i.e., retinal) size constitutes a major determinant of RT. However, this view has recently been challenged since within a virtual three-dimensional (3D) environment retinal size modulation failed to influence RT. In order to further investigate this issue in the present experiments response force (RF) was recorded as a supplemental measure of response activation in simple reaction tasks. In two separate experiments participants’ task was to react as fast as possible to the occurrence of a target located close to the observer or farther away while the offset between target locations was increased from Experiment 1 to Experiment 2. At the same time perceived target size (by varying the retinal size across depth planes) and target type (sphere vs. soccer ball) were modulated. Both experiments revealed faster and more forceful reactions when targets were presented closer to the observers. Perceived size and target type barely affected RT and RF in Experiment 1 but differentially affected both variables in Experiment 2. Thus, the present findings emphasize the usefulness of RF as a supplement to conventional RT measurement. On a behavioral level the results confirm that (at least) within virtual 3D space perceived object size neither strongly influences RT nor RF. Rather the relative position within egocentric (body-centered) space presumably indicates an object’s behavioral relevance and consequently constitutes an important modulator of visual processing. PMID:28018273

Pairwise domain adaptation module for CNN-based 2-D/3-D registration.

PubMed

Zheng, Jiannan; Miao, Shun; Jane Wang, Z; Liao, Rui

2018-04-01

Accurate two-dimensional to three-dimensional (2-D/3-D) registration of preoperative 3-D data and intraoperative 2-D x-ray images is a key enabler for image-guided therapy. Recent advances in 2-D/3-D registration formulate the problem as a learning-based approach and exploit the modeling power of convolutional neural networks (CNN) to significantly improve the accuracy and efficiency of 2-D/3-D registration. However, for surgery-related applications, collecting a large clinical dataset with accurate annotations for training can be very challenging or impractical. Therefore, deep learning-based 2-D/3-D registration methods are often trained with synthetically generated data, and a performance gap is often observed when testing the trained model on clinical data. We propose a pairwise domain adaptation (PDA) module to adapt the model trained on source domain (i.e., synthetic data) to target domain (i.e., clinical data) by learning domain invariant features with only a few paired real and synthetic data. The PDA module is designed to be flexible for different deep learning-based 2-D/3-D registration frameworks, and it can be plugged into any pretrained CNN model such as a simple Batch-Norm layer. The proposed PDA module has been quantitatively evaluated on two clinical applications using different frameworks of deep networks, demonstrating its significant advantages of generalizability and flexibility for 2-D/3-D medical image registration when a small number of paired real-synthetic data can be obtained.

IGF1R as a Key Target in High Risk, Metastatic Medulloblastoma

PubMed Central

Svalina, Matthew N.; Kikuchi, Ken; Abraham, Jinu; Lal, Sangeet; Davare, Monika A.; Settelmeyer, Teagan P.; Young, Michael C.; Peckham, Jennifer L.; Cho, Yoon-Jae; Michalek, Joel E.; Hernandez, Brian S.; Berlow, Noah E.; Jackson, Melanie; Guillaume, Daniel J.; Selden, Nathan R.; Bigner, Darell D.; Nazemi, Kellie J.; Green, Sarah C.; Corless, Christopher L.; Gultekin, Sakir; Mansoor, Atiya; Rubin, Brian P.; Woltjer, Randall; Keller, Charles

2016-01-01

Risk or presence of metastasis in medulloblastoma causes substantial treatment-related morbidity and overall mortality. Through the comparison of cytokines and growth factors in the cerebrospinal fluid (CSF) of metastatic medulloblastoma patients with factors also in conditioned media of metastatic MYC amplified medulloblastoma or leptomeningeal cells, we were led to explore the bioactivity of IGF1 in medulloblastoma by elevated CSF levels of IGF1, IGF-sequestering IGFBP3, IGFBP3-cleaving proteases (MMP and tPA), and protease modulators (TIMP1 and PAI-1). IGF1 led not only to receptor phosphorylation but also accelerated migration/adhesion in MYC amplified medulloblastoma cells in the context of appropriate matrix or meningothelial cells. Clinical correlation suggests a peri-/sub-meningothelial source of IGF-liberating proteases that could facilitate leptomeningeal metastasis. In parallel, studies of key factors responsible for cell autonomous growth in MYC amplified medulloblastoma prioritized IGF1R inhibitors. Together, our studies identify IGF1R as a high value target for clinical trials in high risk medulloblastoma. PMID:27255663

IGF1R as a Key Target in High Risk, Metastatic Medulloblastoma.

PubMed

Svalina, Matthew N; Kikuchi, Ken; Abraham, Jinu; Lal, Sangeet; Davare, Monika A; Settelmeyer, Teagan P; Young, Michael C; Peckham, Jennifer L; Cho, Yoon-Jae; Michalek, Joel E; Hernandez, Brian S; Berlow, Noah E; Jackson, Melanie; Guillaume, Daniel J; Selden, Nathan R; Bigner, Darell D; Nazemi, Kellie J; Green, Sarah C; Corless, Christopher L; Gultekin, Sakir; Mansoor, Atiya; Rubin, Brian P; Woltjer, Randall; Keller, Charles

2016-06-03

Risk or presence of metastasis in medulloblastoma causes substantial treatment-related morbidity and overall mortality. Through the comparison of cytokines and growth factors in the cerebrospinal fluid (CSF) of metastatic medulloblastoma patients with factors also in conditioned media of metastatic MYC amplified medulloblastoma or leptomeningeal cells, we were led to explore the bioactivity of IGF1 in medulloblastoma by elevated CSF levels of IGF1, IGF-sequestering IGFBP3, IGFBP3-cleaving proteases (MMP and tPA), and protease modulators (TIMP1 and PAI-1). IGF1 led not only to receptor phosphorylation but also accelerated migration/adhesion in MYC amplified medulloblastoma cells in the context of appropriate matrix or meningothelial cells. Clinical correlation suggests a peri-/sub-meningothelial source of IGF-liberating proteases that could facilitate leptomeningeal metastasis. In parallel, studies of key factors responsible for cell autonomous growth in MYC amplified medulloblastoma prioritized IGF1R inhibitors. Together, our studies identify IGF1R as a high value target for clinical trials in high risk medulloblastoma.

Auditory Attentional Control and Selection during Cocktail Party Listening

PubMed Central

Hill, Kevin T.

2010-01-01

In realistic auditory environments, people rely on both attentional control and attentional selection to extract intelligible signals from a cluttered background. We used functional magnetic resonance imaging to examine auditory attention to natural speech under such high processing-load conditions. Participants attended to a single talker in a group of 3, identified by the target talker's pitch or spatial location. A catch-trial design allowed us to distinguish activity due to top-down control of attention versus attentional selection of bottom-up information in both the spatial and spectral (pitch) feature domains. For attentional control, we found a left-dominant fronto-parietal network with a bias toward spatial processing in dorsal precentral sulcus and superior parietal lobule, and a bias toward pitch in inferior frontal gyrus. During selection of the talker, attention modulated activity in left intraparietal sulcus when using talker location and in bilateral but right-dominant superior temporal sulcus when using talker pitch. We argue that these networks represent the sources and targets of selective attention in rich auditory environments. PMID:19574393

Transdermal optogenetic peripheral nerve stimulation

NASA Astrophysics Data System (ADS)

Maimon, Benjamin E.; Zorzos, Anthony N.; Bendell, Rhys; Harding, Alexander; Fahmi, Mina; Srinivasan, Shriya; Calvaresi, Peter; Herr, Hugh M.

2017-06-01

Objective: A fundamental limitation in both the scientific utility and clinical translation of peripheral nerve optogenetic technologies is the optical inaccessibility of the target nerve due to the significant scattering and absorption of light in biological tissues. To date, illuminating deep nerve targets has required implantable optical sources, including fiber-optic and LED-based systems, both of which have significant drawbacks. Approach: Here we report an alternative approach involving transdermal illumination. Utilizing an intramuscular injection of ultra-high concentration AAV6-hSyn-ChR2-EYFP in rats. Main results: We demonstrate transdermal stimulation of motor nerves at 4.4 mm and 1.9 mm depth with an incident laser power of 160 mW and 10 mW, respectively. Furthermore, we employ this technique to accurately control ankle position by modulating laser power or position on the skin surface. Significance: These results have the potential to enable future scientific optogenetic studies of pathologies implicated in the peripheral nervous system for awake, freely-moving animals, as well as a basis for future clinical studies.

Finding quasi-modules of human and viral miRNAs: a case study of human cytomegalovirus (HCMV)

PubMed Central

2012-01-01

Background MicroRNAs (miRNAs) are important regulators of gene expression encoded by a variety of organisms, including viruses. Although the function of most of the viral miRNAs is currently unknown, there is evidence that both viral and host miRNAs contribute to the interactions between viruses and their hosts. miRNAs constitute a complex combinatorial network, where one miRNA may target many genes and one gene may be targeted by multiple miRNAs. In particular, viral and host miRNAs may also have mutual target genes. Based on published evidence linking viral and host miRNAs there are three modes of mutual regulation: competing, cooperating, and compensating modes. Results In this paper we explore the compensating mode of mutual regulation upon Human Cytomegalovirus (HCMV) infection, when host miRNAs are down regulated and viral miRNAs compensate by mimicking their function. To achieve this, we develop a new algorithm which finds groups, called quasi-modules, of viral and host miRNAs and their mutual target genes, and use a new host miRNA expression data for HCMV-infected and uninfected cells. For two of the reported quasi-modules, supporting evidence from biological and medical literature is provided. Conclusions The modules found by our method may advance the understanding of the role of miRNAs in host-viral interactions, and the genes in these modules may serve as candidates for further experimental validation. PMID:23206407

Eye-Pursuit and Reafferent Head Movement Signals Carried by Pursuit Neurons in the Caudal Part of the Frontal Eye Fields during Head-Free Pursuit

PubMed Central

Kasahara, Satoshi; Akao, Teppei; Kurkin, Sergei; Peterson, Barry W.

2009-01-01

Eye and head movements are coordinated during head-free pursuit. To examine whether pursuit neurons in frontal eye fields (FEF) carry gaze-pursuit commands that drive both eye-pursuit and head-pursuit, monkeys whose heads were free to rotate about a vertical axis were trained to pursue a juice feeder with their head and a target with their eyes. Initially the feeder and target moved synchronously with the same visual angle. FEF neurons responding to this gaze-pursuit were tested for eye-pursuit of target motion while the feeder was stationary and for head-pursuit while the target was stationary. The majority of pursuit neurons exhibited modulation during head-pursuit, but their preferred directions during eye-pursuit and head-pursuit were different. Although peak modulation occurred during head movements, the onset of discharge usually was not aligned with the head movement onset. The minority of neurons whose discharge onset was so aligned discharged after the head movement onset. These results do not support the idea that the head-pursuit–related modulation reflects head-pursuit commands. Furthermore, modulation similar to that during head-pursuit was obtained by passive head rotation on stationary trunk. Our results suggest that FEF pursuit neurons issue gaze or eye movement commands during gaze-pursuit and that the head-pursuit–related modulation primarily reflects reafferent signals resulting from head movements. PMID:18483002

Career Education for Mental Health Workers. Techniques of Intervention. Human Service Instructional Series. Module No. 4.

ERIC Educational Resources Information Center

Malchon, Margaret J.

This module on techniques of intervention is one of a set of six developed to prepare human services workers for the changing mental health service delivery system. Following notes on the target population (community college students), module length (51 class hours), and suggested class size (15-25 students), the module contains the following…

Maximizing the Use of a Web-Based Soils Module: Targeting Diverse Populations

ERIC Educational Resources Information Center

Lippert, Robert

2006-01-01

This article deals with an on-line soils module project. The two goals for this part of the project were to determine if an on-line soils module could be successfully used for asynchronous instruction of two diverse populations and to determine which demographic factors are related to test performance. The module was presented to an eighth-grade…

Sound stream segregation: a neuromorphic approach to solve the “cocktail party problem” in real-time

PubMed Central

Thakur, Chetan Singh; Wang, Runchun M.; Afshar, Saeed; Hamilton, Tara J.; Tapson, Jonathan C.; Shamma, Shihab A.; van Schaik, André

2015-01-01

The human auditory system has the ability to segregate complex auditory scenes into a foreground component and a background, allowing us to listen to specific speech sounds from a mixture of sounds. Selective attention plays a crucial role in this process, colloquially known as the “cocktail party effect.” It has not been possible to build a machine that can emulate this human ability in real-time. Here, we have developed a framework for the implementation of a neuromorphic sound segregation algorithm in a Field Programmable Gate Array (FPGA). This algorithm is based on the principles of temporal coherence and uses an attention signal to separate a target sound stream from background noise. Temporal coherence implies that auditory features belonging to the same sound source are coherently modulated and evoke highly correlated neural response patterns. The basis for this form of sound segregation is that responses from pairs of channels that are strongly positively correlated belong to the same stream, while channels that are uncorrelated or anti-correlated belong to different streams. In our framework, we have used a neuromorphic cochlea as a frontend sound analyser to extract spatial information of the sound input, which then passes through band pass filters that extract the sound envelope at various modulation rates. Further stages include feature extraction and mask generation, which is finally used to reconstruct the targeted sound. Using sample tonal and speech mixtures, we show that our FPGA architecture is able to segregate sound sources in real-time. The accuracy of segregation is indicated by the high signal-to-noise ratio (SNR) of the segregated stream (90, 77, and 55 dB for simple tone, complex tone, and speech, respectively) as compared to the SNR of the mixture waveform (0 dB). This system may be easily extended for the segregation of complex speech signals, and may thus find various applications in electronic devices such as for sound segregation and speech recognition. PMID:26388721

Sound stream segregation: a neuromorphic approach to solve the "cocktail party problem" in real-time.

PubMed

Thakur, Chetan Singh; Wang, Runchun M; Afshar, Saeed; Hamilton, Tara J; Tapson, Jonathan C; Shamma, Shihab A; van Schaik, André

2015-01-01

The human auditory system has the ability to segregate complex auditory scenes into a foreground component and a background, allowing us to listen to specific speech sounds from a mixture of sounds. Selective attention plays a crucial role in this process, colloquially known as the "cocktail party effect." It has not been possible to build a machine that can emulate this human ability in real-time. Here, we have developed a framework for the implementation of a neuromorphic sound segregation algorithm in a Field Programmable Gate Array (FPGA). This algorithm is based on the principles of temporal coherence and uses an attention signal to separate a target sound stream from background noise. Temporal coherence implies that auditory features belonging to the same sound source are coherently modulated and evoke highly correlated neural response patterns. The basis for this form of sound segregation is that responses from pairs of channels that are strongly positively correlated belong to the same stream, while channels that are uncorrelated or anti-correlated belong to different streams. In our framework, we have used a neuromorphic cochlea as a frontend sound analyser to extract spatial information of the sound input, which then passes through band pass filters that extract the sound envelope at various modulation rates. Further stages include feature extraction and mask generation, which is finally used to reconstruct the targeted sound. Using sample tonal and speech mixtures, we show that our FPGA architecture is able to segregate sound sources in real-time. The accuracy of segregation is indicated by the high signal-to-noise ratio (SNR) of the segregated stream (90, 77, and 55 dB for simple tone, complex tone, and speech, respectively) as compared to the SNR of the mixture waveform (0 dB). This system may be easily extended for the segregation of complex speech signals, and may thus find various applications in electronic devices such as for sound segregation and speech recognition.

On-Orbit Lunar Modulation Transfer Function Measurements for the Moderate Resolution Imaging Spectroradiometer

NASA Technical Reports Server (NTRS)

Choi, Taeyong; Xiong, Xiaoxiong; Wang, Zhipeng

2013-01-01

Spatial quality of an imaging sensor can be estimated by evaluating its modulation transfer function (MTF) from many different sources such as a sharp edge, a pulse target, or bar patterns with different spatial frequencies. These well-defined targets are frequently used for prelaunch laboratory tests, providing very reliable and accurate MTF measurements. A laboratory-quality edge input source was included in the spatial-mode operation of the Spectroradiometric Calibration Assembly (SRCA), which is one of the onboard calibrators of the Moderate Resolution Imaging Spectroradiometer (MODIS). Since not all imaging satellites have such an instrument, SRCA MTF estimations can be used as a reference for an on-orbit lunar MTF algorithm and results. In this paper, the prelaunch spatial quality characterization process from the Integrated Alignment Collimator and SRCA is briefly discussed. Based on prelaunch MTF calibration using the SRCA, a lunar MTF algorithm is developed and applied to the lifetime on-orbit Terra and Aqua MODIS lunar collections. In each lunar collection, multiple scan-directionMoon-to-background transition profiles are aligned by the subpixel edge locations from a parametric Fermi function fit. Corresponding accumulated edge profiles are filtered and interpolated to obtain the edge spread function (ESF). The MTF is calculated by applying a Fourier transformation on the line spread function through a simple differentiation of the ESF. The lifetime lunar MTF results are analyzed and filtered by a relationship with the Sun-Earth-MODIS angle. Finally, the filtered lunarMTF values are compared to the SRCA MTF results. This comparison provides the level of accuracy for on-orbit MTF estimations validated through prelaunch SRCA measurements. The lunar MTF values had larger uncertainty than the SRCA MTF results; however, the ratio mean of lunarMTF fit and SRCA MTF values is within 2% in the 250- and 500-m bands. Based on the MTF measurement uncertainty range, the suggested lunar MTF algorithm can be applied to any on-orbit imaging sensor with lunar calibration capability.

The Modulation of Exogenous Spatial Cueing on Spatial Stroop Interference: Evidence of a Set for "Cue-Target Event Segregation"

ERIC Educational Resources Information Center

Funes, Maria Jesus; Lupianez, Juan; Milliken, Bruce

2008-01-01

Two experiments are reported that test whether the modulation of exogenous cuing effects by the presence of a distractor at the location opposite the target (altering the time course of cueing effects, Lupianez et al., 1999, 2001) is due to the fast reorienting of attention or to a set for preventing the integration of the cue and the target…

TALE-PvuII fusion proteins--novel tools for gene targeting.

PubMed

Yanik, Mert; Alzubi, Jamal; Lahaye, Thomas; Cathomen, Toni; Pingoud, Alfred; Wende, Wolfgang

2013-01-01

Zinc finger nucleases (ZFNs) consist of zinc fingers as DNA-binding module and the non-specific DNA-cleavage domain of the restriction endonuclease FokI as DNA-cleavage module. This architecture is also used by TALE nucleases (TALENs), in which the DNA-binding modules of the ZFNs have been replaced by DNA-binding domains based on transcription activator like effector (TALE) proteins. Both TALENs and ZFNs are programmable nucleases which rely on the dimerization of FokI to induce double-strand DNA cleavage at the target site after recognition of the target DNA by the respective DNA-binding module. TALENs seem to have an advantage over ZFNs, as the assembly of TALE proteins is easier than that of ZFNs. Here, we present evidence that variant TALENs can be produced by replacing the catalytic domain of FokI with the restriction endonuclease PvuII. These fusion proteins recognize only the composite recognition site consisting of the target site of the TALE protein and the PvuII recognition sequence (addressed site), but not isolated TALE or PvuII recognition sites (unaddressed sites), even at high excess of protein over DNA and long incubation times. In vitro, their preference for an addressed over an unaddressed site is > 34,000-fold. Moreover, TALE-PvuII fusion proteins are active in cellula with minimal cytotoxicity.

Post-targeting strategy for ready-to-use targeted nanodelivery post cargo loading.

PubMed

Zhu, J Y; Hu, J J; Zhang, M K; Yu, W Y; Zheng, D W; Wang, X Q; Feng, J; Zhang, X Z

2017-12-14

Based on boronate formation, this study reports a post-targeting methodology capable of readily installing versatile targeting modules onto a cargo-loaded nanoplatform in aqueous mediums. This permits the targeted nanodelivery of broad-spectrum therapeutics (drug/gene) in a ready-to-use manner while overcoming the PEGylation-dilemma that frequently occurs in conventional targeting approaches.

Low profile, highly configurable, current sharing paralleled wide band gap power device power module

DOEpatents

McPherson, Brice; Killeen, Peter D.; Lostetter, Alex; Shaw, Robert; Passmore, Brandon; Hornberger, Jared; Berry, Tony M

2016-08-23

A power module with multiple equalized parallel power paths supporting multiple parallel bare die power devices constructed with low inductance equalized current paths for even current sharing and clean switching events. Wide low profile power contacts provide low inductance, short current paths, and large conductor cross section area provides for massive current carrying. An internal gate & source kelvin interconnection substrate is provided with individual ballast resistors and simple bolted construction. Gate drive connectors are provided on either left or right size of the module. The module is configurable as half bridge, full bridge, common source, and common drain topologies.

PyEEG: an open source Python module for EEG/MEG feature extraction.

PubMed

Bao, Forrest Sheng; Liu, Xin; Zhang, Christina

2011-01-01

Computer-aided diagnosis of neural diseases from EEG signals (or other physiological signals that can be treated as time series, e.g., MEG) is an emerging field that has gained much attention in past years. Extracting features is a key component in the analysis of EEG signals. In our previous works, we have implemented many EEG feature extraction functions in the Python programming language. As Python is gaining more ground in scientific computing, an open source Python module for extracting EEG features has the potential to save much time for computational neuroscientists. In this paper, we introduce PyEEG, an open source Python module for EEG feature extraction.

PyEEG: An Open Source Python Module for EEG/MEG Feature Extraction

PubMed Central

Bao, Forrest Sheng; Liu, Xin; Zhang, Christina

2011-01-01

Computer-aided diagnosis of neural diseases from EEG signals (or other physiological signals that can be treated as time series, e.g., MEG) is an emerging field that has gained much attention in past years. Extracting features is a key component in the analysis of EEG signals. In our previous works, we have implemented many EEG feature extraction functions in the Python programming language. As Python is gaining more ground in scientific computing, an open source Python module for extracting EEG features has the potential to save much time for computational neuroscientists. In this paper, we introduce PyEEG, an open source Python module for EEG feature extraction. PMID:21512582

New extension software modules to enhance searching and display of transcriptome data in Tripal databases

PubMed Central

Chen, Ming; Henry, Nathan; Almsaeed, Abdullah; Zhou, Xiao; Wegrzyn, Jill; Ficklin, Stephen

2017-01-01

Abstract Tripal is an open source software package for developing biological databases with a focus on genetic and genomic data. It consists of a set of core modules that deliver essential functions for loading and displaying data records and associated attributes including organisms, sequence features and genetic markers. Beyond the core modules, community members are encouraged to contribute extension modules to build on the Tripal core and to customize Tripal for individual community needs. To expand the utility of the Tripal software system, particularly for RNASeq data, we developed two new extension modules. Tripal Elasticsearch enables fast, scalable searching of the entire content of a Tripal site as well as the construction of customized advanced searches of specific data types. We demonstrate the use of this module for searching assembled transcripts by functional annotation. A second module, Tripal Analysis Expression, houses and displays records from gene expression assays such as RNA sequencing. This includes biological source materials (biomaterials), gene expression values and protocols used to generate the data. In the case of an RNASeq experiment, this would reflect the individual organisms and tissues used to produce sequencing libraries, the normalized gene expression values derived from the RNASeq data analysis and a description of the software or code used to generate the expression values. The module will load data from common flat file formats including standard NCBI Biosample XML. Data loading, display options and other configurations can be controlled by authorized users in the Drupal administrative backend. Both modules are open source, include usage documentation, and can be found in the Tripal organization’s GitHub repository. Database URL: Tripal Elasticsearch module: https://github.com/tripal/tripal_elasticsearch Tripal Analysis Expression module: https://github.com/tripal/tripal_analysis_expression PMID:29220446

Congruency effects in the remote distractor paradigm: evidence for top-down modulation.

PubMed

Born, Sabine; Kerzel, Dirk

2009-08-10

In three experiments, we examined effects of target-distractor similarity in the remote distractor effect (RDE). Observers made saccades to peripheral targets that were either gray or green. Foveal or peripheral distractors were presented at the same time. The distractors could either share the target's defining property (congruent) or be different from the target (incongruent). Congruent distractors slowed down saccadic reaction times more than incongruent distractors. The increase of the RDE with target-distractor congruency depended on task demands. The more participants had to rely on the target property to locate the target, the larger the congruency effect. We conclude that the RDE can be modulated in a top-down manner. Alternative explanations such as persisting memory traces for the target property or differences in stimulus arrangement were considered but discarded. Our claim is in line with models of saccade generation which assume that the structures underlying the RDE (e.g. the superior colliculus) receive bottom-up as well as top-down information.

Aquaporins: important but elusive drug targets

PubMed Central

Verkman, Alan S.; Anderson, Marc O.; Papadopoulos, Marios C.

2014-01-01

The aquaporins (AQPs) are a family of small, integral membrane proteins that facilitate water transport across the plasma membranes of cells in response to osmotic gradients. Data from knockout mice support the involvement of AQPs in epithelial fluid secretion, cell migration, brain oedema and adipocyte metabolism, which suggests that modulation of AQP function or expression could have therapeutic potential in oedema, cancer, obesity, brain injury, glaucoma and several other conditions. Moreover, loss-of-function mutations in human AQPs cause congenital cataracts (AQP0) and nephrogenic diabetes insipidus (AQP2), and autoantibodies against AQP4 cause the autoimmune demyelinating disease neuromyelitis optica. Although some potential AQP modulators have been identified, challenges associated with the development of better modulators include the druggability of the target and the suitability of the assay methods used to identify modulators. PMID:24625825

Features of Modularly Assembled Compounds That Impart Bioactivity Against an RNA Target

PubMed Central

Rzuczek, Suzanne G.; Gao, Yu; Tang, Zhen-Zhi; Thornton, Charles A.; Kodadek, Thomas; Disney, Matthew D.

2013-01-01

Transcriptomes provide a myriad of potential RNAs that could be the targets of therapeutics or chemical genetic probes of function. Cell permeable small molecules, however, generally do not exploit these targets, owing to the difficulty in the design of high affinity, specific small molecules targeting RNA. As part of a general program to study RNA function using small molecules, we designed bioactive, modularly assembled small molecules that target the non-coding expanded RNA repeat that causes myotonic dystrophy type 1 (DM1), r(CUG)exp. Herein, we present a rigorous study to elucidate features in modularly assembled compounds that afford bioactivity. Different modular assembly scaffolds were investigated including polyamines, α-peptides, β-peptides, and peptide tertiary amides (PTAs). Based on activity as assessed by improvement of DM1-associated defects, stability against proteases, cellular permeability, and toxicity, we discovered that constrained backbones, namely PTAs, are optimal. Notably, we determined that r(CUG)exp is the target of the optimal PTA in cellular models and that the optimal PTA improves DM1-associated defects in a mouse model. Biophysical analyses were employed to investigate potential sources of bioactivity. These investigations show that modularly assembled compounds have increased residence times on their targets and faster on rates than the RNA-binding modules from which they were derived and faster on rates than the protein that binds r(CUG)exp, the inactivation of which gives rise to DM1-associated defects. These studies provide information about features of small molecules that are programmable for targeting RNA, allowing for the facile optimization of therapeutics or chemical probes against other cellular RNA targets. PMID:24032410

Features of modularly assembled compounds that impart bioactivity against an RNA target.

PubMed

Rzuczek, Suzanne G; Gao, Yu; Tang, Zhen-Zhi; Thornton, Charles A; Kodadek, Thomas; Disney, Matthew D

2013-10-18

Transcriptomes provide a myriad of potential RNAs that could be the targets of therapeutics or chemical genetic probes of function. Cell-permeable small molecules, however, generally do not exploit these targets, owing to the difficulty in the design of high affinity, specific small molecules targeting RNA. As part of a general program to study RNA function using small molecules, we designed bioactive, modularly assembled small molecules that target the noncoding expanded RNA repeat that causes myotonic dystrophy type 1 (DM1), r(CUG)(exp). Herein, we present a rigorous study to elucidate features in modularly assembled compounds that afford bioactivity. Different modular assembly scaffolds were investigated, including polyamines, α-peptides, β-peptides, and peptide tertiary amides (PTAs). On the basis of activity as assessed by improvement of DM1-associated defects, stability against proteases, cellular permeability, and toxicity, we discovered that constrained backbones, namely, PTAs, are optimal. Notably, we determined that r(CUG)(exp) is the target of the optimal PTA in cellular models and that the optimal PTA improves DM1-associated defects in a mouse model. Biophysical analyses were employed to investigate potential sources of bioactivity. These investigations show that modularly assembled compounds have increased residence times on their targets and faster on rates than the RNA-binding modules from which they were derived. Moreover, they have faster on rates than the protein that binds r(CUG)(exp), the inactivation of which gives rise to DM1-associated defects. These studies provide information about features of small molecules that are programmable for targeting RNA, allowing for the facile optimization of therapeutics or chemical probes against other cellular RNA targets.

Optimization of combined electron and photon beams for breast cancer

NASA Astrophysics Data System (ADS)

Xiong, W.; Li, J.; Chen, L.; Price, R. A.; Freedman, G.; Ding, M.; Qin, L.; Yang, J.; Ma, C.-M.

2004-05-01

Recently, intensity-modulated radiation therapy and modulated electron radiotherapy have gathered a growing interest for the treatment of breast and head and neck tumours. In this work, we carried out a study to combine electron and photon beams to achieve differential dose distributions for multiple target volumes simultaneously. A Monte Carlo based treatment planning system was investigated, which consists of a set of software tools to perform accurate dose calculation, treatment optimization, leaf sequencing and plan analysis. We compared breast treatment plans generated using this home-grown optimization and dose calculation software for different treatment techniques. Five different planning techniques have been developed for this study based on a standard photon beam whole breast treatment and an electron beam tumour bed cone down. Technique 1 includes two 6 MV tangential wedged photon beams followed by an anterior boost electron field. Technique 2 includes two 6 MV tangential intensity-modulated photon beams and the same boost electron field. Technique 3 optimizes two intensity-modulated photon beams based on a boost electron field. Technique 4 optimizes two intensity-modulated photon beams and the weight of the boost electron field. Technique 5 combines two intensity-modulated photon beams with an intensity-modulated electron field. Our results show that technique 2 can reduce hot spots both in the breast and the tumour bed compared to technique 1 (dose inhomogeneity is reduced from 34% to 28% for the target). Techniques 3, 4 and 5 can deliver a more homogeneous dose distribution to the target (with dose inhomogeneities for the target of 22%, 20% and 9%, respectively). In many cases techniques 3, 4 and 5 can reduce the dose to the lung and heart. It is concluded that combined photon and electron beam therapy may be advantageous for treating breast cancer compared to conventional treatment techniques using tangential wedged photon beams followed by a boost electron field.

Cancer-linked targets modulated by curcumin

PubMed Central

Hasima, Noor; Aggarwal, Bharat B

2012-01-01

In spite of major advances in oncology, the World Health Organization predicts that cancer incidence will double within the next two decades. Although it is well understood that cancer is a hyperproliferative disorder mediated through dysregulation of multiple cell signaling pathways, most cancer drug development remains focused on modulation of specific targets, mostly one at a time, with agents referred to as “targeted therapies,” “smart drugs,” or “magic bullets.” How many cancer targets there are is not known, and how many targets must be attacked to control cancer growth is not well understood. Although more than 90% of cancer-linked deaths are due to metastasis of the tumor to vital organs, most drug targeting is focused on killing the primary tumor. Besides lacking specificity, the targeted drugs induce toxicity and side effects that sometimes are greater problems than the disease itself. Furthermore, the cost of some of these drugs is so high that most people cannot afford them. The present report describes the potential anticancer properties of curcumin, a component of the Indian spice turmeric (Curcuma longa), known for its safety and low cost. Curcumin can selectively modulate multiple cell signaling pathways linked to inflammation and to survival, growth, invasion, angiogenesis, and metastasis of cancer cells. More clinical trials of curcumin are needed to prove its usefulness in the cancer setting. PMID:23301199

ATAQS: A computational software tool for high throughput transition optimization and validation for selected reaction monitoring mass spectrometry

PubMed Central

2011-01-01

Background Since its inception, proteomics has essentially operated in a discovery mode with the goal of identifying and quantifying the maximal number of proteins in a sample. Increasingly, proteomic measurements are also supporting hypothesis-driven studies, in which a predetermined set of proteins is consistently detected and quantified in multiple samples. Selected reaction monitoring (SRM) is a targeted mass spectrometric technique that supports the detection and quantification of specific proteins in complex samples at high sensitivity and reproducibility. Here, we describe ATAQS, an integrated software platform that supports all stages of targeted, SRM-based proteomics experiments including target selection, transition optimization and post acquisition data analysis. This software will significantly facilitate the use of targeted proteomic techniques and contribute to the generation of highly sensitive, reproducible and complete datasets that are particularly critical for the discovery and validation of targets in hypothesis-driven studies in systems biology. Result We introduce a new open source software pipeline, ATAQS (Automated and Targeted Analysis with Quantitative SRM), which consists of a number of modules that collectively support the SRM assay development workflow for targeted proteomic experiments (project management and generation of protein, peptide and transitions and the validation of peptide detection by SRM). ATAQS provides a flexible pipeline for end-users by allowing the workflow to start or end at any point of the pipeline, and for computational biologists, by enabling the easy extension of java algorithm classes for their own algorithm plug-in or connection via an external web site. This integrated system supports all steps in a SRM-based experiment and provides a user-friendly GUI that can be run by any operating system that allows the installation of the Mozilla Firefox web browser. Conclusions Targeted proteomics via SRM is a powerful new technique that enables the reproducible and accurate identification and quantification of sets of proteins of interest. ATAQS is the first open-source software that supports all steps of the targeted proteomics workflow. ATAQS also provides software API (Application Program Interface) documentation that enables the addition of new algorithms to each of the workflow steps. The software, installation guide and sample dataset can be found in http://tools.proteomecenter.org/ATAQS/ATAQS.html PMID:21414234

Modular Open-Source Software for Item Factor Analysis

ERIC Educational Resources Information Center

Pritikin, Joshua N.; Hunter, Micheal D.; Boker, Steven M.

2015-01-01

This article introduces an item factor analysis (IFA) module for "OpenMx," a free, open-source, and modular statistical modeling package that runs within the R programming environment on GNU/Linux, Mac OS X, and Microsoft Windows. The IFA module offers a novel model specification language that is well suited to programmatic generation…

Optogenetic control of mitochondrial metabolism and Ca2+ signaling by mitochondria-targeted opsins.

PubMed

Tkatch, Tatiana; Greotti, Elisa; Baranauskas, Gytis; Pendin, Diana; Roy, Soumitra; Nita, Luliaoana I; Wettmarshausen, Jennifer; Prigge, Matthias; Yizhar, Ofer; Shirihai, Orian S; Fishman, Daniel; Hershfinkel, Michal; Fleidervish, Ilya A; Perocchi, Fabiana; Pozzan, Tullio; Sekler, Israel

2017-06-27

Key mitochondrial functions such as ATP production, Ca 2+ uptake and release, and substrate accumulation depend on the proton electrochemical gradient (ΔμH + ) across the inner membrane. Although several drugs can modulate ΔμH + , their effects are hardly reversible, and lack cellular specificity and spatial resolution. Although channelrhodopsins are widely used to modulate the plasma membrane potential of excitable cells, mitochondria have thus far eluded optogenetic control. Here we describe a toolkit of optometabolic constructs based on selective targeting of channelrhodopsins with distinct functional properties to the inner mitochondrial membrane of intact cells. We show that our strategy enables a light-dependent control of the mitochondrial membrane potential (Δψ m ) and coupled mitochondrial functions such as ATP synthesis by oxidative phosphorylation, Ca 2+ dynamics, and respiratory metabolism. By directly modulating Δψ m , the mitochondria-targeted opsins were used to control complex physiological processes such as spontaneous beats in cardiac myocytes and glucose-dependent ATP increase in pancreatic β-cells. Furthermore, our optometabolic tools allow modulation of mitochondrial functions in single cells and defined cell regions.

Compact x-ray source and panel

DOEpatents

Sampayon, Stephen E [Manteca, CA

2008-02-12

A compact, self-contained x-ray source, and a compact x-ray source panel having a plurality of such x-ray sources arranged in a preferably broad-area pixelized array. Each x-ray source includes an electron source for producing an electron beam, an x-ray conversion target, and a multilayer insulator separating the electron source and the x-ray conversion target from each other. The multi-layer insulator preferably has a cylindrical configuration with a plurality of alternating insulator and conductor layers surrounding an acceleration channel leading from the electron source to the x-ray conversion target. A power source is connected to each x-ray source of the array to produce an accelerating gradient between the electron source and x-ray conversion target in any one or more of the x-ray sources independent of other x-ray sources in the array, so as to accelerate an electron beam towards the x-ray conversion target. The multilayer insulator enables relatively short separation distances between the electron source and the x-ray conversion target so that a thin panel is possible for compactness. This is due to the ability of the plurality of alternating insulator and conductor layers of the multilayer insulators to resist surface flashover when sufficiently high acceleration energies necessary for x-ray generation are supplied by the power source to the x-ray sources.

Nanoparticles that Communicate In Vivo to Amplify Tumour Targeting

PubMed Central

von Maltzahn, Geoffrey; Park, Ji-Ho; Lin, Kevin Y.; Singh, Neetu; Schwöppe, Christian; Mesters, Rolf; Berdel, Wolfgang E.; Ruoslahti, Erkki; Sailor, Michael J.; Bhatia, Sangeeta N.

2012-01-01

Nanomedicines have enormous potential to improve the precision of cancer therapy, yet our ability to efficiently home these materials to regions of disease in vivo remains very limited. Inspired by the ability for communication to improve targeting in biological systems, such inflammatory cell recruitment to sites of disease, we construct systems where synthetic biological and nanotechnological components communicate to amplify disease targeting in vivo. These systems are composed of ‘Signalling’ modules (nanoparticles or engineered proteins) that target tumours and then locally active the coagulation cascade to broadcast tumour location to clot-targeted ‘Receiving’ nanoparticles in circulation that carry a diagnostic or therapeutic cargo, thereby amplifying their delivery. We show that communicating nanoparticle systems can be composed from multiple types of Signalling and Receiving modules, can transmit information via multiple molecular pathways in coagulation, can operate autonomously, and can target over 40-fold higher doses of chemotherapeutics to tumours than non-communicating controls. PMID:21685903

Nanoparticles that communicate in vivo to amplify tumour targeting

NASA Astrophysics Data System (ADS)

von Maltzahn, Geoffrey; Park, Ji-Ho; Lin, Kevin Y.; Singh, Neetu; Schwöppe, Christian; Mesters, Rolf; Berdel, Wolfgang E.; Ruoslahti, Erkki; Sailor, Michael J.; Bhatia, Sangeeta N.

2011-07-01

Nanomedicines have enormous potential to improve the precision of cancer therapy, yet our ability to efficiently home these materials to regions of disease in vivo remains very limited. Inspired by the ability of communication to improve targeting in biological systems, such as inflammatory-cell recruitment to sites of disease, we construct systems where synthetic biological and nanotechnological components communicate to amplify disease targeting in vivo. These systems are composed of ‘signalling’ modules (nanoparticles or engineered proteins) that target tumours and then locally activate the coagulation cascade to broadcast tumour location to clot-targeted ‘receiving’ nanoparticles in circulation that carry a diagnostic or therapeutic cargo, thereby amplifying their delivery. We show that communicating nanoparticle systems can be composed of multiple types of signalling and receiving modules, can transmit information through multiple molecular pathways in coagulation, can operate autonomously and can target over 40 times higher doses of chemotherapeutics to tumours than non-communicating controls.

Repetition priming across distinct contexts: effects of lexical status, word frequency, and retrieval test.

PubMed

Coane, Jennifer H; Balota, David A

2010-12-01

Repetition priming, the facilitation observed when a target is preceded by an identity prime, is a robust phenomenon that occurs across a variety of conditions. Oliphant (1983), however, failed to observe repetition priming for targets embedded in the instructions to an experiment in a subsequent lexical decision task. In the present experiments, we examined the roles of priming context (list or instructions), target lexicality, and target frequency in both lexical decision and episodic recognition performance. Initial encoding context did not modulate priming in lexical decision or recognition memory for low-frequency targets or nonwords, whereas context strongly modulated episodic recognition for high-frequency targets. The results indicate that priming across contexts is sensitive to the distinctiveness of the trace and the reliance on episodic retrieval mechanisms. These results also shed light on the influence of event boundaries, such that priming occurs across different events for relatively distinct (low-frequency) items.

Power Amplifier Module with 734-mW Continuous Wave Output Power

NASA Technical Reports Server (NTRS)

Fung, King Man; Samoska, Lorene A.; Kangaslahti, Pekka P.; Lamgrigtsen, Bjorn H.; Goldsmith, Paul F.; Lin, Robert H.; Soria, Mary M.; Cooperrider, Joelle T.; Micovic, Moroslav; Kurdoghlian, Ara

2010-01-01

Research findings were reported from an investigation of new gallium nitride (GaN) monolithic millimeter-wave integrated circuit (MMIC) power amplifiers (PAs) targeting the highest output power and the highest efficiency for class-A operation in W-band (75-110 GHz). W-band PAs are a major component of many frequency multiplied submillimeter-wave LO signal sources. For spectrometer arrays, substantial W-band power is required due to the passive lossy frequency multipliers-to generate higher frequency signals in nonlinear Schottky diode-based LO sources. By advancing PA technology, the LO system performance can be increased with possible cost reductions compared to current GaAs PAs. High-power, high-efficiency GaN PAs are cross-cutting and can enable more efficient local oscillator distribution systems for new astrophysics and planetary receivers and heterodyne array instruments. It can also allow for a new, electronically scannable solid-state array technology for future Earth science radar instruments and communications platforms.

Increasing seed size and quality by manipulating BIG SEEDS1 in legume species

PubMed Central

Ge, Liangfa; Yu, Jianbin; Wang, Hongliang; Luth, Diane; Bai, Guihua; Wang, Kan

2016-01-01

Plant organs, such as seeds, are primary sources of food for both humans and animals. Seed size is one of the major agronomic traits that have been selected in crop plants during their domestication. Legume seeds are a major source of dietary proteins and oils. Here, we report a conserved role for the BIG SEEDS1 (BS1) gene in the control of seed size and weight in the model legume Medicago truncatula and the grain legume soybean (Glycine max). BS1 encodes a plant-specific transcription regulator and plays a key role in the control of the size of plant organs, including seeds, seed pods, and leaves, through a regulatory module that targets primary cell proliferation. Importantly, down-regulation of BS1 orthologs in soybean by an artificial microRNA significantly increased soybean seed size, weight, and amino acid content. Our results provide a strategy for the increase in yield and seed quality in legumes. PMID:27791139

An auto-adaptive optimization approach for targeting nonpoint source pollution control practices.

PubMed

Chen, Lei; Wei, Guoyuan; Shen, Zhenyao

2015-10-21

To solve computationally intensive and technically complex control of nonpoint source pollution, the traditional genetic algorithm was modified into an auto-adaptive pattern, and a new framework was proposed by integrating this new algorithm with a watershed model and an economic module. Although conceptually simple and comprehensive, the proposed algorithm would search automatically for those Pareto-optimality solutions without a complex calibration of optimization parameters. The model was applied in a case study in a typical watershed of the Three Gorges Reservoir area, China. The results indicated that the evolutionary process of optimization was improved due to the incorporation of auto-adaptive parameters. In addition, the proposed algorithm outperformed the state-of-the-art existing algorithms in terms of convergence ability and computational efficiency. At the same cost level, solutions with greater pollutant reductions could be identified. From a scientific viewpoint, the proposed algorithm could be extended to other watersheds to provide cost-effective configurations of BMPs.

Context-Aware Adaptive Hybrid Semantic Relatedness in Biomedical Science

NASA Astrophysics Data System (ADS)

Emadzadeh, Ehsan

Text mining of biomedical literature and clinical notes is a very active field of research in biomedical science. Semantic analysis is one of the core modules for different Natural Language Processing (NLP) solutions. Methods for calculating semantic relatedness of two concepts can be very useful in solutions solving different problems such as relationship extraction, ontology creation and question / answering [1--6]. Several techniques exist in calculating semantic relatedness of two concepts. These techniques utilize different knowledge sources and corpora. So far, researchers attempted to find the best hybrid method for each domain by combining semantic relatedness techniques and data sources manually. In this work, attempts were made to eliminate the needs for manually combining semantic relatedness methods targeting any new contexts or resources through proposing an automated method, which attempted to find the best combination of semantic relatedness techniques and resources to achieve the best semantic relatedness score in every context. This may help the research community find the best hybrid method for each context considering the available algorithms and resources.

Recruit LEP Students for Vocational Programs. One of Four Performance-Based Modules To Prepare Vocational Educators To Serve LEP Students.

ERIC Educational Resources Information Center

Friedenberg, Joan E.; And Others

This module is one in a series of four performance-based modules developed to prepare vocational educators to serve limited English proficient (LEP) students. It is designed to help new and experienced vocational recruiters target their recruiting efforts for LEP persons. The module is made up of a series of five learning experiences, some…

Micro-vibration detection with heterodyne holography based on time-averaged method

NASA Astrophysics Data System (ADS)

Qin, XiaoDong; Pan, Feng; Chen, ZongHui; Hou, XueQin; Xiao, Wen

2017-02-01

We propose a micro-vibration detection method by introducing heterodyne interferometry to time-averaged holography. This method compensates for the deficiency of time-average holography in quantitative measurements and widens its range of application effectively. Acousto-optic modulators are used to modulate the frequencies of the reference beam and the object beam. Accurate detection of the maximum amplitude of each point in the vibration plane is performed by altering the frequency difference of both beams. The range of amplitude detection of plane vibration is extended. In the stable vibration mode, the distribution of the maximum amplitude of each point is measured and the fitted curves are plotted. Hence the plane vibration mode of the object is demonstrated intuitively and detected quantitatively. We analyzed the method in theory and built an experimental system with a sine signal as the excitation source and a typical piezoelectric ceramic plate as the target. The experimental results indicate that, within a certain error range, the detected vibration mode agrees with the intrinsic vibration characteristics of the object, thus proving the validity of this method.

Not letting the left leg know what the right leg is doing: limb-specific locomotor adaptation to sensory-cue conflict.

PubMed

Durgin, Frank H; Fox, Laura F; Hoon Kim, Dong

2003-11-01

We investigated the phenomenon of limb-specific locomotor adaptation in order to adjudicate between sensory-cue-conflict theory and motor-adaptation theory. The results were consistent with cue-conflict theory in demonstrating that two different leg-specific hopping aftereffects are modulated by the presence of conflicting estimates of self-motion from visual and nonvisual sources. Experiment 1 shows that leg-specific increases in forward drift during attempts to hop in place on one leg while blindfolded vary according to the relationship between visual information and motor activity during an adaptation to outdoor forward hopping. Experiment 2 shows that leg-specific changes in performance on a blindfolded hopping-to-target task are similarly modulated by the presence of cue conflict during adaptation to hopping on a treadmill. Experiment 3 shows that leg-specific aftereffects from hopping additionally produce inadvertent turning during running in place while blindfolded. The results of these experiments suggest that these leg-specific locomotor aftereffects are produced by sensory-cue conflict rather than simple motor adaptation.

Automatic flatness detection system for micro part

NASA Astrophysics Data System (ADS)

Luo, Yi; Wang, Xiaodong; Shan, Zhendong; Li, Kehong

2016-01-01

An automatic flatness detection system for micro rings is developed. It is made up of machine vision module, ring supporting module and control system. An industry CCD camera with the resolution of 1628×1236 pixel, a telecentric with magnification of two, and light sources are used to collect the vision information. A rotary stage with a polished silicon wafer is used to support the ring. The silicon wafer provides a mirror image and doubles the gap caused by unevenness of the ring. The control system comprise an industry computer and software written in LabVIEW Get Kernel and Convolute Function are selected to reduce noise and distortion, Laplacian Operator is used to sharp the image, and IMAQ Threshold function is used to separate the target object from the background. Based on this software, system repeating precision is 2.19 μm, less than one pixel. The designed detection system can easily identify the ring warpage larger than 5 μm, and if the warpage is less than 25 μm, it can be used in ring assembly and satisfied the final positionary and perpendicularity error requirement of the component.

Ghost imaging with bucket detection and point detection

NASA Astrophysics Data System (ADS)

Zhang, De-Jian; Yin, Rao; Wang, Tong-Biao; Liao, Qing-Hua; Li, Hong-Guo; Liao, Qinghong; Liu, Jiang-Tao

2018-04-01

We experimentally investigate ghost imaging with bucket detection and point detection in which three types of illuminating sources are applied: (a) pseudo-thermal light source; (b) amplitude modulated true thermal light source; (c) amplitude modulated laser source. Experimental results show that the quality of ghost images reconstructed with true thermal light or laser beam is insensitive to the usage of bucket or point detector, however, the quality of ghost images reconstructed with pseudo-thermal light in bucket detector case is better than that in point detector case. Our theoretical analysis shows that the reason for this is due to the first order transverse coherence of the illuminating source.

Use of potassium chloride and flavor enhancers in low sodium Cheddar cheese.

PubMed

Grummer, J; Bobowski, N; Karalus, M; Vickers, Z; Schoenfuss, T

2013-03-01

We investigated use of potassium chloride (KCl) to maintain both the salty flavor and to replace the preservative effects of salt when reducing the sodium content in natural cheese. Because salt replacers can affect flavor because of inherent off-flavors, such as bitter and metallic, we examined the use of flavor enhancers for their ability to modulate some of these undesirable sensory effects. Stirred-curd Cheddar-style cheese was manufactured using 2 cheese-making procedures (different curd knife sizes and target salting titratable acidities), in duplicate. Curd was salted with sodium chloride (NaCl) or 60% reduced sodium blends of NaCl and KCl (2 different sources). Curd was also salted at a 60% reduced sodium rate with NaCl and KCl with added flavor enhancers. A hydrolyzed vegetable protein/yeast extract blend, a natural "potassium-blocking type" flavor, disodium inosinate, or disodium guanylate were each blended with the reduced sodium salt blend and added to curd at the salting step. The resulting blocks of cheese were aged for 5 mo and evaluated monthly for chemical, microbial, and sensory differences. At 5 mo of aging, we measured liking for the cheeses using a consumer panel. Overall, cheeses were well liked by the consumer panel, and the scores of reduced sodium cheese with 2 different KCl sources were not different from those of the full-sodium control. The addition of flavor enhancers to Cheddar curd had mixed results, with one improving the consumer flavor liking only slightly over KCl, and one (disodium inosinate) significantly reducing consumer flavor liking scores, presumably due to the amount of umami flavor it contributed. Potassium chloride replacement salts sourced from different manufacturers affected the chemical and flavor properties of cheese, and changes to pH and temperature targets may be necessary to yield cheese with the moisture and pH targets desired. The cheese-making procedure used also influenced flavors observed, which resulted in higher levels of brothy flavor in cheese made with smaller curd knives and a higher target salting titratable acidity. This effect resulted in lower consumer liking scores. Copyright © 2013 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

Radio over fiber transceiver employing phase modulation of an optical broadband source.

PubMed

Grassi, Fulvio; Mora, José; Ortega, Beatriz; Capmany, José

2010-10-11

This paper proposes a low-cost RoF transceiver for multichannel SCM/WDM signal distribution suitable for future broadband access networks. The transceiver is based on the phase modulation of an optical broadband source centered at third transmission window. Prior to phase modulation the optical broadband source output signal is launched into a Mach-Zehnder interferometer structure, as key device enabling radio signals propagation over the optical link. Furthermore, an optical CWDM is employed to create a multichannel scenario by performing the spectral slicing of the modulated optical signal into a number of channels each one conveying the information from the central office to different base stations. The operation range is up to 20 GHz with a modulation bandwidth around of 500 MHz. Experimental results of the transmission of SCM QPSK and 64-QAM data through 20 Km of SMF exhibit good EVM results in the operative range determined by the phase-to-intensity conversion process. The proposed approach shows a great suitability for WDM networks based on RoF signal transport and also represents a cost-effective solution for passive optical networks.

A promising new mechanism of ionizing radiation detection for positron emission tomography: Modulation of optical properties

PubMed Central

Tao, Li; Daghighian, Henry M.; Levin, Craig S.

2016-01-01

Using conventional scintillation detection, the fundamental limit in positron emission tomography (PET) time resolution is strongly dependent on the inherent temporal variances generated during the scintillation process, yielding an intrinsic physical limit for the coincidence time resolution of around 100 ps. On the other hand, modulation mechanisms of the optical properties of a material exploited in the optical telecommunications industry can be orders of magnitude faster. In this paper we borrow from the concept of optics pump-probe measurement to for the first time study whether ionizing radiation can produce modulations of optical properties, which can be utilized as a novel method for radiation detection. We show that a refractive index modulation of approximately 5 × 10−6 is induced by interactions in a cadmium telluride (CdTe) crystal from a 511 keV photon source. Furthermore, using additional radionuclide sources, we show that the amplitude of the optical modulation signal varies linearly with both the detected event rate and average photon energy of the radiation source. PMID:27716640

A compact, all-optical, THz wave generator based on self-modulation in a slab photonic crystal waveguide with a single sub-nanometer graphene layer.

PubMed

Asadi, R; Ouyang, Z; Mohammd, M M

2015-07-14

We design a compact, all-optical THz wave generator based on self-modulation in a 1-D slab photonic crystal (PhC) waveguide with a single sub-nanometer graphene layer by using enhanced nonlinearity of graphene. It has been shown that at the bandgap edge of higher bands of a 1-D slab PhC, through only one sub-nanometer graphene layer we can obtain a compact, high modulation factor (about 0.98 percent), self-intensity modulator at a high frequency (about 0.6 THz) and low threshold intensity (about 15 MW per square centimeter), and further a compact, all-optical THz wave generator by integrating the self-modulator with a THz photodiode or photonic mixer. Such a THz source is expected to have a relatively high efficiency compared with conventional sources based on optical methods. The proposed THz source can find wide applications in THz science and technology, e.g., in THz imaging, THz sensors and detectors, THz communication systems, and THz optical integrated logic circuits.

A machine-learned analysis of human gene polymorphisms modulating persisting pain points at major roles of neuroimmune processes.

PubMed

Kringel, Dario; Lippmann, Catharina; Parnham, Michael J; Kalso, Eija; Ultsch, Alfred; Lötsch, Jörn

2018-06-19

Human genetic research has implicated functional variants of more than one hundred genes in the modulation of persisting pain. Artificial intelligence and machine learning techniques may combine this knowledge with results of genetic research gathered in any context, which permits the identification of the key biological processes involved in chronic sensitization to pain. Based on published evidence, a set of 110 genes carrying variants reported to be associated with modulation of the clinical phenotype of persisting pain in eight different clinical settings was submitted to unsupervised machine-learning aimed at functional clustering. Subsequently, a mathematically supported subset of genes, comprising those most consistently involved in persisting pain, was analyzed by means of computational functional genomics in the Gene Ontology knowledgebase. Clustering of genes with evidence for a modulation of persisting pain elucidated a functionally heterogeneous set. The situation cleared when the focus was narrowed to a genetic modulation consistently observed throughout several clinical settings. On this basis, two groups of biological processes, the immune system and nitric oxide signaling, emerged as major players in sensitization to persisting pain, which is biologically highly plausible and in agreement with other lines of pain research. The present computational functional genomics-based approach provided a computational systems-biology perspective on chronic sensitization to pain. Human genetic control of persisting pain points to the immune system as a source of potential future targets for drugs directed against persisting pain. Contemporary machine-learned methods provide innovative approaches to knowledge discovery from previous evidence. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

WGCNA: an R package for weighted correlation network analysis.

PubMed

Langfelder, Peter; Horvath, Steve

2008-12-29

Correlation networks are increasingly being used in bioinformatics applications. For example, weighted gene co-expression network analysis is a systems biology method for describing the correlation patterns among genes across microarray samples. Weighted correlation network analysis (WGCNA) can be used for finding clusters (modules) of highly correlated genes, for summarizing such clusters using the module eigengene or an intramodular hub gene, for relating modules to one another and to external sample traits (using eigengene network methodology), and for calculating module membership measures. Correlation networks facilitate network based gene screening methods that can be used to identify candidate biomarkers or therapeutic targets. These methods have been successfully applied in various biological contexts, e.g. cancer, mouse genetics, yeast genetics, and analysis of brain imaging data. While parts of the correlation network methodology have been described in separate publications, there is a need to provide a user-friendly, comprehensive, and consistent software implementation and an accompanying tutorial. The WGCNA R software package is a comprehensive collection of R functions for performing various aspects of weighted correlation network analysis. The package includes functions for network construction, module detection, gene selection, calculations of topological properties, data simulation, visualization, and interfacing with external software. Along with the R package we also present R software tutorials. While the methods development was motivated by gene expression data, the underlying data mining approach can be applied to a variety of different settings. The WGCNA package provides R functions for weighted correlation network analysis, e.g. co-expression network analysis of gene expression data. The R package along with its source code and additional material are freely available at http://www.genetics.ucla.edu/labs/horvath/CoexpressionNetwork/Rpackages/WGCNA.

WGCNA: an R package for weighted correlation network analysis

PubMed Central

Langfelder, Peter; Horvath, Steve

2008-01-01

Background Correlation networks are increasingly being used in bioinformatics applications. For example, weighted gene co-expression network analysis is a systems biology method for describing the correlation patterns among genes across microarray samples. Weighted correlation network analysis (WGCNA) can be used for finding clusters (modules) of highly correlated genes, for summarizing such clusters using the module eigengene or an intramodular hub gene, for relating modules to one another and to external sample traits (using eigengene network methodology), and for calculating module membership measures. Correlation networks facilitate network based gene screening methods that can be used to identify candidate biomarkers or therapeutic targets. These methods have been successfully applied in various biological contexts, e.g. cancer, mouse genetics, yeast genetics, and analysis of brain imaging data. While parts of the correlation network methodology have been described in separate publications, there is a need to provide a user-friendly, comprehensive, and consistent software implementation and an accompanying tutorial. Results The WGCNA R software package is a comprehensive collection of R functions for performing various aspects of weighted correlation network analysis. The package includes functions for network construction, module detection, gene selection, calculations of topological properties, data simulation, visualization, and interfacing with external software. Along with the R package we also present R software tutorials. While the methods development was motivated by gene expression data, the underlying data mining approach can be applied to a variety of different settings. Conclusion The WGCNA package provides R functions for weighted correlation network analysis, e.g. co-expression network analysis of gene expression data. The R package along with its source code and additional material are freely available at . PMID:19114008

Stable optical frequency comb generation and applications in arbitrary waveform generation, signal processing and optical data mining

NASA Astrophysics Data System (ADS)

Ozharar, Sarper

This thesis focuses on the generation and applications of stable optical frequency combs. Optical frequency combs are defined as equally spaced optical frequencies with a fixed phase relation among themselves. The conventional source of optical frequency combs is the optical spectrum of the modelocked lasers. In this work, we investigated alternative methods for optical comb generation, such as dual sine wave phase modulation, which is more practical and cost effective compared to modelocked lasers stabilized to a reference. Incorporating these comblines, we have generated tunable RF tones using the serrodyne technique. The tuning range was +/-1 MHz, limited by the electronic waveform generator, and the RF carrier frequency is limited by the bandwidth of the photodetector. Similarly, using parabolic phase modulation together with time division multiplexing, RF chirp extension has been realized. Another application of the optical frequency combs studied in this thesis is real time data mining in a bit stream. A novel optoelectronic logic gate has been developed for this application and used to detect an 8 bit long target pattern. Also another approach based on orthogonal Hadamard codes have been proposed and explained in detail. Also novel intracavity modulation schemes have been investigated and applied for various applications such as (a) improving rational harmonic modelocking for repetition rate multiplication and pulse to pulse amplitude equalization, (b) frequency skewed pulse generation for ranging and (c) intracavity active phase modulation in amplitude modulated modelocked lasers for supermode noise spur suppression and integrated jitter reduction. The thesis concludes with comments on the future work and next steps to improve some of the results presented in this work.

Towards an autonomous sensor architecture for persistent area protection

NASA Astrophysics Data System (ADS)

Thomas, Paul A.; Marshall, Gillian F.; Stubbins, Daniel J.; Faulkner, David A.

2016-10-01

The majority of sensor installations for area protection (e.g. critical national infrastructure, military forward operating bases, etc.) make use of banks of screens each containing one or more sensor feeds, such that the burden of combining data from the various sources, understanding the situation, and controlling the sensors all lies with the human operator. Any automation in the system is generally heavily bespoke for the particular installation, leading to an inflexible system which is difficult to change or upgrade. We have developed a modular system architecture consisting of intelligent autonomous sensor modules, a high level decision making module, a middleware integration layer and an end-user GUI. The modules are all effectively "plug and play", and we have demonstrated that it is relatively simple to incorporate legacy sensors into the architecture. We have extended our previously-reported SAPIENT demonstration system to operate with a larger number and variety of sensor modules, over an extended area, detecting and classifying a wider variety of "threat activities", both vehicular and pedestrian. We report the results of a demonstration of the SAPIENT system containing multiple autonomous sensor modules with a range of modalities including laser scanners, radar, TI, EO, acoustic and seismic sensors. They operate from a combination of mains, generator and battery power, and communicate with the central "hub" over Ethernet, point-to-point wireless links and Wi-Fi. The system has been configured to protect an extended area in a complex semi-urban environment. We discuss the operation of the SAPIENT system in a realistic demonstration environment (which included significant activity not under trial control), showing sensor cueing, multi-modal sensor fusion, threat prioritisation and target hand-off.

Chloride channels as drug targets

PubMed Central

Verkman, Alan S.; Galietta, Luis J. V.

2013-01-01

Chloride channels represent a relatively under-explored target class for drug discovery as elucidation of their identity and physiological roles has lagged behind that of many other drug targets. Chloride channels are involved in a wide range of biological functions, including epithelial fluid secretion, cell-volume regulation, neuroexcitation, smooth-muscle contraction and acidification of intracellular organelles. Mutations in several chloride channels cause human diseases, including cystic fibrosis, macular degeneration, myotonia, kidney stones, renal salt wasting and hyperekplexia. Chloride-channel modulators have potential applications in the treatment of some of these disorders, as well as in secretory diarrhoeas, polycystic kidney disease, osteoporosis and hypertension. Modulators of GABAA (γ-aminobutyric acid A) receptor chloride channels are in clinical use and several small-molecule chloride-channel modulators are in preclinical development and clinical trials. Here, we discuss the broad opportunities that remain in chloride-channel-based drug discovery. PMID:19153558

TALE-mediated modulation of transcriptional enhancers in vivo.

PubMed

Crocker, Justin; Stern, David L

2013-08-01

We tested whether transcription activator-like effectors (TALEs) could mediate repression and activation of endogenous enhancers in the Drosophila genome. TALE repressors (TALERs) targeting each of the five even-skipped (eve) stripe enhancers generated repression specifically of the focal stripes. TALE activators (TALEAs) targeting the eve promoter or enhancers caused increased expression primarily in cells normally activated by the promoter or targeted enhancer, respectively. This effect supports the view that repression acts in a dominant fashion on transcriptional activators and that the activity state of an enhancer influences TALE binding or the ability of the VP16 domain to enhance transcription. In these assays, the Hairy repression domain did not exhibit previously described long-range transcriptional repression activity. The phenotypic effects of TALER and TALEA expression in larvae and adults are consistent with the observed modulations of eve expression. TALEs thus provide a novel tool for detection and functional modulation of transcriptional enhancers in their native genomic context.

Infrared dim small target segmentation method based on ALI-PCNN model

NASA Astrophysics Data System (ADS)

Zhao, Shangnan; Song, Yong; Zhao, Yufei; Li, Yun; Li, Xu; Jiang, Yurong; Li, Lin

2017-10-01

Pulse Coupled Neural Network (PCNN) is improved by Adaptive Lateral Inhibition (ALI), while a method of infrared (IR) dim small target segmentation based on ALI-PCNN model is proposed in this paper. Firstly, the feeding input signal is modulated by lateral inhibition network to suppress background. Then, the linking input is modulated by ALI, and linking weight matrix is generated adaptively by calculating ALI coefficient of each pixel. Finally, the binary image is generated through the nonlinear modulation and the pulse generator in PCNN. The experimental results show that the segmentation effect as well as the values of contrast across region and uniformity across region of the proposed method are better than the OTSU method, maximum entropy method, the methods based on conventional PCNN and visual attention, and the proposed method has excellent performance in extracting IR dim small target from complex background.

Cost-effective bidirectional digitized radio-over-fiber systems employing sigma delta modulation

NASA Astrophysics Data System (ADS)

Lee, Kyung Woon; Jung, HyunDo; Park, Jung Ho

2016-11-01

We propose a cost effective digitized radio-over-fiber (D-RoF) system employing a sigma delta modulation (SDM) and a bidirectional transmission technique using phase modulated downlink and intensity modulated uplink. SDM is transparent to different radio access technologies and modulation formats, and more suitable for a downlink of wireless system because a digital to analog converter (DAC) can be avoided at the base station (BS). Also, Central station and BS share the same light source by using a phase modulation for the downlink and an intensity modulation for the uplink transmission. Avoiding DACs and light sources have advantages in terms of cost reduction, power consumption, and compatibility with conventional wireless network structure. We have designed a cost effective bidirectional D-RoF system using a low pass SDM and measured the downlink and uplink transmission performance in terms of error vector magnitude, signal spectra, and constellations, which are based on the 10MHz LTE 64-QAM standard.

The NASA Goddard Group's Source Monitoring Database and Program

NASA Astrophysics Data System (ADS)

Gipson, John; Le Bail, Karine; Ma, Chopo

2014-12-01

Beginning in 2003, the Goddard VLBI group developed a program to purposefully monitor when sources were observed and to increase the observations of ``under-observed'' sources. The heart of the program consists of a MySQL database that keeps track of, on a session-by-session basis: the number of observations that are scheduled for a source, the number of observations that are successfully correlated, and the number of observations that are used in a session. In addition, there is a table that contains the target number of successful sessions over the last twelve months. Initially this table just contained two categories. Sources in the geodetic catalog had a target of 12 sessions/year; the remaining ICRF-1 defining sources had a target of two sessions/year. All other sources did not have a specific target. As the program evolved, different kinds of sources with different observing targets were added. During the scheduling process, the scheduler has the option of automatically selecting N sources which have not met their target. We discuss the history and present some results of this successful program.

Two small RNAs, CrcY and CrcZ, act in concert to sequester the Crc global regulator in Pseudomonas putida, modulating catabolite repression.

PubMed

Moreno, Renata; Fonseca, Pilar; Rojo, Fernando

2012-01-01

The Crc protein is a translational repressor that recognizes a specific target at some mRNAs, controlling catabolite repression and co-ordinating carbon metabolism in pseudomonads. In Pseudomonas aeruginosa, the levels of free Crc protein are controlled by CrcZ, a sRNA that sequesters Crc, acting as an antagonist. We show that, in Pseudomonas putida, the levels of free Crc are controlled by CrcZ and by a novel 368 nt sRNA named CrcY. CrcZ and CrcY, which contain six potential targets for Crc, were able to bind Crc specifically in vitro. The levels of CrcZ and CrcY were low under conditions generating a strong catabolite repression, and increased strongly when catabolite repression was absent. Deletion of either crcZ or crcY had no effect on catabolite repression, but the simultaneous absence of both sRNAs led to constitutive catabolite repression that compromised growth on some carbon sources. Overproduction of CrcZ or CrcY significantly reduced repression. We propose that CrcZ and CrcY act in concert, sequestering and modulating the levels of free Crc according to metabolic conditions. The CbrA/CbrB two-component system activated crcZ transcription, but had little effect on crcY. CrcY was detected in P. putida, Pseudomonas fluorescens and Pseudomonas syringae, but not in P. aeruginosa. © 2011 Blackwell Publishing Ltd.

MZmine 2: Modular framework for processing, visualizing, and analyzing mass spectrometry-based molecular profile data

PubMed Central

2010-01-01

Background Mass spectrometry (MS) coupled with online separation methods is commonly applied for differential and quantitative profiling of biological samples in metabolomic as well as proteomic research. Such approaches are used for systems biology, functional genomics, and biomarker discovery, among others. An ongoing challenge of these molecular profiling approaches, however, is the development of better data processing methods. Here we introduce a new generation of a popular open-source data processing toolbox, MZmine 2. Results A key concept of the MZmine 2 software design is the strict separation of core functionality and data processing modules, with emphasis on easy usability and support for high-resolution spectra processing. Data processing modules take advantage of embedded visualization tools, allowing for immediate previews of parameter settings. Newly introduced functionality includes the identification of peaks using online databases, MSn data support, improved isotope pattern support, scatter plot visualization, and a new method for peak list alignment based on the random sample consensus (RANSAC) algorithm. The performance of the RANSAC alignment was evaluated using synthetic datasets as well as actual experimental data, and the results were compared to those obtained using other alignment algorithms. Conclusions MZmine 2 is freely available under a GNU GPL license and can be obtained from the project website at: http://mzmine.sourceforge.net/. The current version of MZmine 2 is suitable for processing large batches of data and has been applied to both targeted and non-targeted metabolomic analyses. PMID:20650010

N-Terminomics TAILS Identifies Host Cell Substrates of Poliovirus and Coxsackievirus B3 3C Proteinases That Modulate Virus Infection.

PubMed

Jagdeo, Julienne M; Dufour, Antoine; Klein, Theo; Solis, Nestor; Kleifeld, Oded; Kizhakkedathu, Jayachandran; Luo, Honglin; Overall, Christopher M; Jan, Eric

2018-04-15

Enteroviruses encode proteinases that are essential for processing of the translated viral polyprotein. In addition, viral proteinases also target host proteins to manipulate cellular processes and evade innate antiviral responses to promote replication and infection. Although some host protein substrates of enterovirus proteinases have been identified, the full repertoire of targets remains unknown. We used a novel quantitative in vitro proteomics-based approach, termed t erminal a mine i sotopic l abeling of s ubstrates (TAILS), to identify with high confidence 72 and 34 new host protein targets of poliovirus and coxsackievirus B3 (CVB3) 3C proteinases (3C pro s) in HeLa cell and cardiomyocyte HL-1 cell lysates, respectively. We validated a subset of candidate substrates that are targets of poliovirus 3C pro in vitro including three common protein targets, phosphoribosylformylglycinamidine synthetase (PFAS), hnRNP K, and hnRNP M, of both proteinases. 3C pro -targeted substrates were also cleaved in virus-infected cells but not noncleavable mutant proteins designed from the TAILS-identified cleavage sites. Knockdown of TAILS-identified target proteins modulated infection both negatively and positively, suggesting that cleavage by 3C pro promotes infection. Indeed, expression of a cleavage-resistant mutant form of the endoplasmic reticulum (ER)-Golgi vesicle-tethering protein p115 decreased viral replication and yield. As the first comprehensive study to identify and validate functional enterovirus 3C pro substrates in vivo , we conclude that N-terminomics by TAILS is an effective strategy to identify host targets of viral proteinases in a nonbiased manner. IMPORTANCE Enteroviruses are positive-strand RNA viruses that encode proteases that cleave the viral polyprotein into the individual mature viral proteins. In addition, viral proteases target host proteins in order to modulate cellular pathways and block antiviral responses in order to facilitate virus infection. Although several host protein targets have been identified, the entire list of proteins that are targeted is not known. In this study, we used a novel unbiased proteomics approach to identify ∼100 novel host targets of the enterovirus 3C protease, thus providing further insights into the network of cellular pathways that are modulated to promote virus infection. Copyright © 2018 Jagdeo et al.

A Natural Chimeric Pseudomonas Bacteriocin with Novel Pore-Forming Activity Parasitizes the Ferrichrome Transporter.

PubMed

Ghequire, Maarten G K; Kemland, Lieselore; Anoz-Carbonell, Ernesto; Buchanan, Susan K; De Mot, René

2017-02-21

Modular bacteriocins represent a major group of secreted protein toxins with a narrow spectrum of activity, involved in interference competition between Gram-negative bacteria. These antibacterial proteins include a domain for binding to the target cell and a toxin module at the carboxy terminus. Self-inhibition of producers is provided by coexpression of linked immunity genes that transiently inhibit the toxin's activity through formation of bacteriocin-immunity complexes or by insertion in the inner membrane, depending on the type of toxin module. We demonstrate strain-specific inhibitory activity for PmnH, a Pseudomonas bacteriocin with an unprecedented dual-toxin architecture, hosting both a colicin M domain, potentially interfering with peptidoglycan synthesis, and a novel colicin N-type domain, a pore-forming module distinct from the colicin Ia-type domain in Pseudomonas aeruginosa pyocin S5. A downstream-linked gene product confers PmnH immunity upon susceptible strains. This protein, ImnH, has a transmembrane topology similar to that of Pseudomonas colicin M-like and pore-forming immunity proteins, although homology with either of these is essentially absent. The enhanced killing activity of PmnH under iron-limited growth conditions reflects parasitism of the ferrichrome-type transporter for entry into target cells, a strategy shown here to be used as well by monodomain colicin M-like bacteriocins from pseudomonads. The integration of a second type of toxin module in a bacteriocin gene could offer a competitive advantage against bacteria displaying immunity against only one of both toxic activities. IMPORTANCE In their continuous struggle for ecological space, bacteria face a huge load of contenders, including phylogenetically related strains that compete for the same niche. One important group of secreted antibacterial proteins assisting in eliminating these rivals are modular bacteriocins of Gram-negative bacteria, comprising a domain for docking onto the cell envelope of a target cell, a translocation domain enabling subsequent cellular entry, and a toxin module that kills target cells via enzymatic or pore-forming activity. We here demonstrate the antagonistic function of a Pseudomonas bacteriocin with unique architecture that combines a putative enzymatic colicin M-like domain and a novel pore-forming toxin module. For target cell recognition and entry, this bacteriocin hybrid takes advantage of the ferrichrome transporter, also parasitized by enzymatic Pseudomonas bacteriocins devoid of the pore-forming module. Bacteriocins with an expanded toxin potential may represent an inventive bacterial strategy to alleviate immunity in target cells. Copyright © 2017 Ghequire et al.

Description of the dynamic infrared background/target simulator (DIBS)

NASA Astrophysics Data System (ADS)

Lujan, Ignacio

1988-01-01

The purpose of the Dynamic Infrared Background/Target Simulator (DIBS) is to project dynamic infrared scenes to a test sensor; e.g., a missile seeker that is sensitive to infrared energy. The projected scene will include target(s) and background. This system was designed to present flicker-free infrared scenes in the 8 micron to 12 micron wavelength region. The major subassemblies of the DIBS are the laser write system (LWS), vanadium dioxide modulator assembly, scene data buffer (SDB), and the optical image translator (OIT). This paper describes the overall concept and design of the infrared scene projector followed by some details of the LWS and VO2 modulator. Also presented are brief descriptions of the SDB and OIT.

BEST medical radioisotope production cyclotrons

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

Sabaiduc, Vasile; Milton, Bruce; Suthanthiran, Krishnan

2013-04-19

Best Cyclotron Systems Inc (BCSI) is currently developing 14 MeV, 25 MeV, 35MeV and 70MeV cyclotrons for radioisotope production and research applications as well as the entire spectrum of targets and nuclear synthesis modules for the production of Positron Emission Tomography (PET), Single Photon Emission Computed Tomography (SPECT) and radiation therapy isotopes. The company is a subsidiary of Best Medical International, renowned in the field of medical instrumentation and radiation therapy. All cyclotrons have external negative hydrogen ion sources, four radial sectors with two dees in opposite valleys, cryogenic vacuum system and simultaneous beam extraction on opposite lines. The beammore » intensity ranges from 400 {mu}A to 1000 {mu}A, depending on the cyclotron energy and application.« less

Absolute colorimetric characterization of a DSLR camera

NASA Astrophysics Data System (ADS)

Guarnera, Giuseppe Claudio; Bianco, Simone; Schettini, Raimondo

2014-03-01

A simple but effective technique for absolute colorimetric camera characterization is proposed. It offers a large dynamic range requiring just a single, off-the-shelf target and a commonly available controllable light source for the characterization. The characterization task is broken down in two modules, respectively devoted to absolute luminance estimation and to colorimetric characterization matrix estimation. The characterized camera can be effectively used as a tele-colorimeter, giving an absolute estimation of the XYZ data in cd=m2. The user is only required to vary the f - number of the camera lens or the exposure time t, to better exploit the sensor dynamic range. The estimated absolute tristimulus values closely match the values measured by a professional spectro-radiometer.

BEST medical radioisotope production cyclotrons

NASA Astrophysics Data System (ADS)

Sabaiduc, Vasile; Milton, Bruce; Suthanthiran, Krishnan; Gelbart, W. Z.; Johnson, Richard R.

2013-04-01

Best Cyclotron Systems Inc (BCSI) is currently developing 14 MeV, 25 MeV, 35MeV and 70MeV cyclotrons for radioisotope production and research applications as well as the entire spectrum of targets and nuclear synthesis modules for the production of Positron Emission Tomography (PET), Single Photon Emission Computed Tomography (SPECT) and radiation therapy isotopes. The company is a subsidiary of Best Medical International, renowned in the field of medical instrumentation and radiation therapy. All cyclotrons have external negative hydrogen ion sources, four radial sectors with two dees in opposite valleys, cryogenic vacuum system and simultaneous beam extraction on opposite lines. The beam intensity ranges from 400 μA to 1000 μA, depending on the cyclotron energy and application [1].

Single-shot thermal ghost imaging using wavelength-division multiplexing

NASA Astrophysics Data System (ADS)

Deng, Chao; Suo, Jinli; Wang, Yuwang; Zhang, Zhili; Dai, Qionghai

2018-01-01

Ghost imaging (GI) is an emerging technique that reconstructs the target scene from its correlated measurements with a sequence of patterns. Restricted by the multi-shot principle, GI usually requires long acquisition time and is limited in observation of dynamic scenes. To handle this problem, this paper proposes a single-shot thermal ghost imaging scheme via a wavelength-division multiplexing technique. Specifically, we generate thousands of correlated patterns simultaneously by modulating a broadband light source with a wavelength dependent diffuser. These patterns carry the scene's spatial information and then the correlated photons are coupled into a spectrometer for the final reconstruction. This technique increases the speed of ghost imaging and promotes the applications in dynamic ghost imaging with high scalability and compatibility.

Dipole source localization of event-related brain activity indicative of an early visual selective attention deficit in ADHD children.

PubMed

Jonkman, L M; Kenemans, J L; Kemner, C; Verbaten, M N; van Engeland, H

2004-07-01

This study was aimed at investigating whether attention-deficit hyperactivity disorder (ADHD) children suffer from specific early selective attention deficits in the visual modality with the aid of event-related brain potentials (ERPs). Furthermore, brain source localization was applied to identify brain areas underlying possible deficits in selective visual processing in ADHD children. A two-channel visual color selection task was administered to 18 ADHD and 18 control subjects in the age range of 7-13 years and ERP activity was derived from 30 electrodes. ADHD children exhibited lower perceptual sensitivity scores resulting in poorer target selection. The ERP data suggested an early selective-attention deficit as manifested in smaller frontal positive activity (frontal selection positivity; FSP) in ADHD children around 200 ms whereas later occipital and fronto-central negative activity (OSN and N2b; 200-400 ms latency) appeared to be unaffected. Source localization explained the FSP by posterior-medial equivalent dipoles in control subjects, which may reflect the contribution of numerous surrounding areas. ADHD children have problems with selective visual processing that might be caused by a specific early filtering deficit (absent FSP) occurring around 200 ms. The neural sources underlying these problems have to be further identified. Source localization also suggested abnormalities in the 200-400 ms time range, pertaining to the distribution of attention-modulated activity in lateral frontal areas.

Small Molecule Chemical Probes of MicroRNA Function

PubMed Central

Velagapudi, Sai Pradeep; Vummidi, Balayeshwanth R.; Disney, Matthew D.

2015-01-01

MicroRNAs (miRNAs) are small, non-coding RNAs that control protein expression. Aberrant miRNA expression has been linked to various human diseases, and thus miRNAs have been explored as diagnostic markers and therapeutic targets. Although it is challenging to target RNA with small molecules in general, there have been successful campaigns that have identified small molecule modulators of miRNA function by targeting various pathways. For example, small molecules that modulate transcription and target nuclease processing sites in miRNA precursors have been identified. Herein, we describe challenges in developing chemical probes that target miRNAs and highlight aspects of miRNA cellular biology elucidated by using small molecule chemical probes. We expect that this area will expand dramatically in the near future as strides are made to understand small molecule recognition of RNA from a fundamental perspective. PMID:25500006

APPARATUS FOR MEASURING NEUTRON CROSS SECTIONS

DOEpatents

Cranberg, L.

1959-07-14

An apparatus is described for analyzing the nuclear reaction products resulting from impingement of nuclear particles against a selected target material and automatically recording the number of reaction prcducts in selected energy levels. The target is bombarded by ions from a particle accelerator and the target potential is cyclicly varied over a particular energy range by a modulator. A nuclear reaction detector is lccated adjacent the target to produce pulses for each reaction product. The output from the detector and the modulator are coupled to a function sampler, for generating a pulse in respcnse to each detected event having an amplitude proportional to the amplitude of the instantaneous target potential. The later pulses are coupled to a multichannel analyzer, whereby nuclear reactions are recorded in appropriate channels of the analyzer in correspcndence with the magnitude of the energy of the impinging ions.

Passive state preparation in the Gaussian-modulated coherent-states quantum key distribution

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

Qi, Bing; Evans, Philip G.; Grice, Warren P.

In the Gaussian-modulated coherent-states (GMCS) quantum key distribution (QKD) protocol, Alice prepares quantum states actively: For each transmission, Alice generates a pair of Gaussian-distributed random numbers, encodes them on a weak coherent pulse using optical amplitude and phase modulators, and then transmits the Gaussian-modulated weak coherent pulse to Bob. Here we propose a passive state preparation scheme using a thermal source. In our scheme, Alice splits the output of a thermal source into two spatial modes using a beam splitter. She measures one mode locally using conjugate optical homodyne detectors, and transmits the other mode to Bob after applying appropriatemore » optical attenuation. Under normal conditions, Alice's measurement results are correlated to Bob's, and they can work out a secure key, as in the active state preparation scheme. Given the initial thermal state generated by the source is strong enough, this scheme can tolerate high detector noise at Alice's side. Furthermore, the output of the source does not need to be single mode, since an optical homodyne detector can selectively measure a single mode determined by the local oscillator. Preliminary experimental results suggest that the proposed scheme could be implemented using an off-the-shelf amplified spontaneous emission source.« less

Passive state preparation in the Gaussian-modulated coherent-states quantum key distribution

DOE PAGES

Qi, Bing; Evans, Philip G.; Grice, Warren P.

2018-01-01

In the Gaussian-modulated coherent-states (GMCS) quantum key distribution (QKD) protocol, Alice prepares quantum states actively: For each transmission, Alice generates a pair of Gaussian-distributed random numbers, encodes them on a weak coherent pulse using optical amplitude and phase modulators, and then transmits the Gaussian-modulated weak coherent pulse to Bob. Here we propose a passive state preparation scheme using a thermal source. In our scheme, Alice splits the output of a thermal source into two spatial modes using a beam splitter. She measures one mode locally using conjugate optical homodyne detectors, and transmits the other mode to Bob after applying appropriatemore » optical attenuation. Under normal conditions, Alice's measurement results are correlated to Bob's, and they can work out a secure key, as in the active state preparation scheme. Given the initial thermal state generated by the source is strong enough, this scheme can tolerate high detector noise at Alice's side. Furthermore, the output of the source does not need to be single mode, since an optical homodyne detector can selectively measure a single mode determined by the local oscillator. Preliminary experimental results suggest that the proposed scheme could be implemented using an off-the-shelf amplified spontaneous emission source.« less

Ivy and neurogliaform interneurons are a major target of μ opioid receptor modulation

PubMed Central

Krook-Magnuson, Esther; Luu, Lillian; Lee, Sang-Hun; Varga, Csaba; Soltesz, Ivan

2011-01-01

Mu opioid receptors (μORs) are selectively expressed on interneurons in area CA1 of the hippocampus. Fast-spiking, parvalbumin expressing, basket cells express μORs, but circumstantial evidence suggests that another major, unidentified, GABAergic cell class must also be modulated by μORs. Here we report that the abundant, dendritically targeting, neurogliaform family of cells (Ivy and neurogliaform cells) is a previously unrecognized target of direct modulation by μORs. Ivy and neurogliaform cells are not only numerous, but also have unique properties, including promiscuous gap junctions formed with various interneuronal subtypes, volume transmission, and the ability to produce a postsynaptic GABAB response after a single presynaptic spike. Using a mouse line expressing green fluorescent protein under the neuropeptide Y promoter, we find that across all layers of CA1, activation of μORs hyperpolarizes Ivy and neurogliaform cells. Further, paired recordings between synaptically coupled Ivy and pyramidal cells show that Ivy cell terminals are dramatically inhibited by μOR-activation. Effects in Ivy and neurogliaform cells are seen at similar concentrations of agonist as those producing inhibition in fast-spiking PV basket cells. We also report that Ivy cells display the recently described phenomenon of persistent firing, a state of continued firing in the absence of continued input, and that induction of persistent firing is inhibited by μOR-activation. Together these findings identify a major, previously unrecognized, target of μOR-modulation. Given the prominence of this cell type in and beyond CA1, as well as its unique role in microcircuitry, opioid modulation of neurogliaform cells has wide implications. PMID:22016519

Ivy and neurogliaform interneurons are a major target of μ-opioid receptor modulation.

PubMed

Krook-Magnuson, Esther; Luu, Lillian; Lee, Sang-Hun; Varga, Csaba; Soltesz, Ivan

2011-10-19

μ-Opioid receptors (μORs) are selectively expressed on interneurons in area CA1 of the hippocampus. Fast-spiking, parvalbumin-expressing, basket cells express μORs, but circumstantial evidence suggests that another major, unidentified, GABAergic cell class must also be modulated by μORs. Here we report that the abundant, dendritically targeting, neurogliaform family of cells (Ivy and neurogliaform cells) is a previously unrecognized target of direct modulation by μORs. Ivy and neurogliaform cells are not only numerous but also have unique properties, including promiscuous gap junctions formed with various interneuronal subtypes, volume transmission, and the ability to produce a postsynaptic GABA(B) response after a single presynaptic spike. Using a mouse line expressing green fluorescent protein under the neuropeptide Y promoter, we find that, across all layers of CA1, activation of μORs hyperpolarizes Ivy and neurogliaform cells. Furthermore, paired recordings between synaptically coupled Ivy and pyramidal cells show that Ivy cell terminals are dramatically inhibited by μOR activation. Effects in Ivy and neurogliaform cells are seen at similar concentrations of agonist as those producing inhibition in fast-spiking parvalbumin basket cells. We also report that Ivy cells display the recently described phenomenon of persistent firing, a state of continued firing in the absence of continued input, and that induction of persistent firing is inhibited by μOR activation. Together, these findings identify a major, previously unrecognized, target of μOR modulation. Given the prominence of this cell type in and beyond CA1, as well as its unique role in microcircuitry, opioid modulation of neurogliaform cells has wide implications.

Online education improves pediatric residents' understanding of atopic dermatitis.

PubMed

Craddock, Megan F; Blondin, Heather M; Youssef, Molly J; Tollefson, Megha M; Hill, Lauren F; Hanson, Janice L; Bruckner, Anna L

2018-01-01

Pediatricians manage skin conditions such as atopic dermatitis (AD) but report that their dermatologic training is inadequate. Online modules may enhance medical education when sufficient didactic or clinical teaching experiences are lacking. We assessed whether an online module about AD improved pediatric residents' knowledge and changed their clinical management of AD. Target and control cohorts of pediatric residents from two institutions were recruited. Target subjects took a 30-question test about AD early in their residency, reviewed the online module, and repeated the test 6 months and 1 year later. The control subjects, who had 1 year of clinical experience but had not reviewed the online module, also took the test. The mean percentage of correct answers was calculated and compared using two-sided, two-sample independent t tests and repeated-measures analysis of variance. For a subset of participants, clinical documentation from AD encounters was reviewed and 13 practice behaviors were compared using the Fisher exact test. Twenty-five subjects in the target cohort and 29 subjects in the control cohort completed the study. The target cohort improved from 18.0 ± 3.2 to 23.4 ± 3.4 correctly answered questions over 1 year (P < .001). This final value was greater than that of the control cohort (20.7 ± 4.5; P = .01). Meaningful differences in practice behaviors were not seen. Pediatric residents who reviewed an online module about AD demonstrated statistically significant improvement in disease-specific knowledge over time and had statistically significantly higher scores than controls. Online dermatology education may effectively supplement traditional clinical teaching. © 2017 Wiley Periodicals, Inc.

Open-Source Tools for Enhancing Full-Text Searching of OPACs: Use of Koha, Greenstone and Fedora

ERIC Educational Resources Information Center

Anuradha, K. T.; Sivakaminathan, R.; Kumar, P. Arun

2011-01-01

Purpose: There are many library automation packages available as open-source software, comprising two modules: staff-client module and online public access catalogue (OPAC). Although the OPAC of these library automation packages provides advanced features of searching and retrieval of bibliographic records, none of them facilitate full-text…

ISS Destiny Laboratory Smoke Detection Model

NASA Technical Reports Server (NTRS)

Brooker, John E.; Urban, David L.; Ruff, Gary A.

2007-01-01

Smoke transport and detection were modeled numerically in the ISS Destiny module using the NIST, Fire Dynamics Simulator code. The airflows in Destiny were modeled using the existing flow conditions and the module geometry included obstructions that simulate the currently installed hardware on orbit. The smoke source was modeled as a 0.152 by 0.152 m region that emitted smoke particulate ranging from 1.46 to 8.47 mg/s. In the module domain, the smoke source was placed in the center of each Destiny rack location and the model was run to determine the time required for the two smoke detectors to alarm. Overall the detection times were dominated by the circumferential flow, the axial flow from the intermodule ventilation and the smoke source strength.

Shielded Metal Arc Welding. Welding Module 4. Instructor's Guide.

ERIC Educational Resources Information Center

Missouri Univ., Columbia. Instructional Materials Lab.

This guide is intended to assist vocational educators in teaching an eight-unit module in shielded metal arc welding. The module is part of a welding curriculum that has been designed to be totally integrated with Missouri's Vocational Instruction Management System. The following topics are covered in the module: safety; theory, power sources, and…

On the Path to SunShot - The Role of Advancements in Solar Photovoltaic Efficiency, Reliability, and Costs

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

Woodhouse, Michael; Jones-Albertus, Rebecca; Feldman, David

2016-05-01

Although tremendous progress has been made in reducing the cost of PV systems, additional LCOE reductions of 40%–50% between 2015 and 2020 will be required to reach the SunShot Initiative’s targets (see Woodhouse et al. 2016). Understanding the tradeoffs between installed prices and other PV system characteristics—such as module efficiency, module degradation rate, and system lifetime—are vital. For example, with 29%-efficient modules and high reliability (a 50-year lifetime and a 0.2%/year module degradation rate), a residential PV system could achieve the SunShot LCOE goal with modules priced at almost $1.20/W. But change the lifetime to 10 years and the degradationmore » rate to 2%/year, and the system would need those very high-efficiency modules at zero cost to achieve the same LCOE. Although these examples are extreme, they serve to illustrate the wide range of technological combinations that could help drive PV toward the LCOE goals. SunShot’s PV roadmaps illustrate specific potential pathways to the target cost reductions.« less

Imidazoles and benzimidazoles as tubulin-modulators for anti-cancer therapy.

PubMed

Torres, Fernando C; García-Rubiño, M Eugenia; Lozano-López, César; Kawano, Daniel F; Eifler-Lima, Vera L; von Poser, Gilsane L; Campos, Joaquín M

2015-01-01

Imidazoles and benzimidazoles are privileged heterocyclic bioactive compounds used with success in the clinical practice of innumerous diseases. Although there are many advancements in cancer therapy, microtubules remain as one of the few macromolecular targets validated for planning active anti-cancer compounds, and the design of drugs that modulate microtubule dynamics in unknown sites of tubulin is one of the goals of the medicinal chemistry. The discussion of the role of new and commercially available imidazole and benzimidazole derivatives as tubulin modulators is scattered throughout scientific literature, and indicates that these compounds have a tubulin modulation mechanism different from that of tubulin modulators clinically available, such as paclitaxel, docetaxel, vincristine and vinblastine. In fact, recent literature indicates that these derivatives inhibit microtubule formation binding to the colchicine site, present good pharmacokinetic properties and are capable of overcoming multidrug resistance in many cell lines. The understanding of the mechanisms involved in the imidazoles/benzimidazoles modulation of microtubule dynamics is very important to develop new strategies to overcome the resistance to anti-cancer drugs and to discover new biomarkers and targets for cancer chemotherapy.

System and Method for Generating a Frequency Modulated Linear Laser Waveform

NASA Technical Reports Server (NTRS)

Pierrottet, Diego F. (Inventor); Petway, Larry B. (Inventor); Amzajerdian, Farzin (Inventor); Barnes, Bruce W. (Inventor); Lockard, George E. (Inventor); Hines, Glenn D. (Inventor)

2017-01-01

A system for generating a frequency modulated linear laser waveform includes a single frequency laser generator to produce a laser output signal. An electro-optical modulator modulates the frequency of the laser output signal to define a linear triangular waveform. An optical circulator passes the linear triangular waveform to a band-pass optical filter to filter out harmonic frequencies created in the waveform during modulation of the laser output signal, to define a pure filtered modulated waveform having a very narrow bandwidth. The optical circulator receives the pure filtered modulated laser waveform and transmits the modulated laser waveform to a target.

System and Method for Generating a Frequency Modulated Linear Laser Waveform

NASA Technical Reports Server (NTRS)

Pierrottet, Diego F. (Inventor); Petway, Larry B. (Inventor); Amzajerdian, Farzin (Inventor); Barnes, Bruce W. (Inventor); Lockard, George E. (Inventor); Hines, Glenn D. (Inventor)

2014-01-01

A system for generating a frequency modulated linear laser waveform includes a single frequency laser generator to produce a laser output signal. An electro-optical modulator modulates the frequency of the laser output signal to define a linear triangular waveform. An optical circulator passes the linear triangular waveform to a band-pass optical filter to filter out harmonic frequencies created in the waveform during modulation of the laser output signal, to define a pure filtered modulated waveform having a very narrow bandwidth. The optical circulator receives the pure filtered modulated laser waveform and transmits the modulated laser waveform to a target.

Algorithms for a very high speed universal noiseless coding module

NASA Technical Reports Server (NTRS)

Rice, Robert F.; Yeh, Pen-Shu

1991-01-01

The algorithmic definitions and performance characterizations are presented for a high performance adaptive coding module. Operation of at least one of these (single chip) implementations is expected to exceed 500 Mbits/s under laboratory conditions. Operation of a companion decoding module should operate at up to half the coder's rate. The module incorporates a powerful noiseless coder for Standard Form Data Sources (i.e., sources whose symbols can be represented by uncorrelated non-negative integers where the smaller integers are more likely than the larger ones). Performance close to data entropies can be expected over a Dynamic Range of from 1.5 to 12 to 14 bits/sample (depending on the implementation).

Long-term memory biases auditory spatial attention.

PubMed

Zimmermann, Jacqueline F; Moscovitch, Morris; Alain, Claude

2017-10-01

Long-term memory (LTM) has been shown to bias attention to a previously learned visual target location. Here, we examined whether memory-predicted spatial location can facilitate the detection of a faint pure tone target embedded in real world audio clips (e.g., soundtrack of a restaurant). During an initial familiarization task, participants heard audio clips, some of which included a lateralized target (p = 50%). On each trial participants indicated whether the target was presented from the left, right, or was absent. Following a 1 hr retention interval, participants were presented with the same audio clips, which now all included a target. In Experiment 1, participants showed memory-based gains in response time and d'. Experiment 2 showed that temporal expectations modulate attention, with greater memory-guided attention effects on performance when temporal context was reinstated from learning (i.e., when timing of the target within audio clips was not changed from initially learned timing). Experiment 3 showed that while conscious recall of target locations was modulated by exposure to target-context associations during learning (i.e., better recall with higher number of learning blocks), the influence of LTM associations on spatial attention was not reduced (i.e., number of learning blocks did not affect memory-guided attention). Both Experiments 2 and 3 showed gains in performance related to target-context associations, even for associations that were not explicitly remembered. Together, these findings indicate that memory for audio clips is acquired quickly and is surprisingly robust; both implicit and explicit LTM for the location of a faint target tone modulated auditory spatial attention. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

Summary of the XIII International Workshop on Polarized Sources, Targets and Polarimetry

NASA Astrophysics Data System (ADS)

Rathmann, F.

2011-01-01

The workshops on polarized sources, targets, and polarimetry are held every two years. The present meeting took place in Ferrara, Italy, and was organized by the University of Ferrara. Sessions on Polarized Proton and Deuterium Sources, Polarized Electron Sources, Polarimetry, Polarized Solid Targets, and Polarized Internal Targets, highlighted topics, recent developments, and progress in the field. A session decicated to Future Facilities provided an overview of a number of new activities in the spin-physics sector at facilities that are currently in the planning stage. Besides presenting a broad overview of polarized ion sources, electron sources, solid and gaseous targets, and their neighboring fields, the workshop also addressed the application of polarized atoms in applied sciences and medicine that is becoming increasingly important.

Stimulated Raman scattering microscopy by Nyquist modulation of a two-branch ultrafast fiber source.

PubMed

Riek, Claudius; Kocher, Claudius; Zirak, Peyman; Kölbl, Christoph; Fimpel, Peter; Leitenstorfer, Alfred; Zumbusch, Andreas; Brida, Daniele

2016-08-15

A highly stable setup for stimulated Raman scattering (SRS) microscopy is presented. It is based on a two-branch femtosecond Er:fiber laser operating at a 40 MHz repetition rate. One of the outputs is directly modulated at the Nyquist frequency with an integrated electro-optic modulator (EOM). This compact source combines a jitter-free pulse synchronization with a broad tunability and allows for shot-noise limited SRS detection. The performance of the SRS microscope is illustrated with measurements on samples from material science and cell biology.

Simulation verification techniques study. Task report 4: Simulation module performance parameters and performance standards

NASA Technical Reports Server (NTRS)

1974-01-01

Shuttle simulation software modules in the environment, crew station, vehicle configuration and vehicle dynamics categories are discussed. For each software module covered, a description of the module functions and operational modes, its interfaces with other modules, its stored data, inputs, performance parameters and critical performance parameters is given. Reference data sources which provide standards of performance are identified for each module. Performance verification methods are also discussed briefly.

Optically coupled methods for microwave impedance microscopy

NASA Astrophysics Data System (ADS)

Johnston, Scott R.; Ma, Eric Yue; Shen, Zhi-Xun

2018-04-01

Scanning Microwave Impedance Microscopy (MIM) measurement of photoconductivity with 50 nm resolution is demonstrated using a modulated optical source. The use of a modulated source allows for the measurement of photoconductivity in a single scan without a reference region on the sample, as well as removing most topographical artifacts and enhancing signal to noise as compared with unmodulated measurement. A broadband light source with a tunable monochrometer is then used to measure energy resolved photoconductivity with the same methodology. Finally, a pulsed optical source is used to measure local photo-carrier lifetimes via MIM, using the same 50 nm resolution tip.

Spatial Light Modulators as Optical Crossbar Switches

NASA Technical Reports Server (NTRS)

Juday, Richard

2003-01-01

A proposed method of implementing cross connections in an optical communication network is based on the use of a spatial light modulator (SLM) to form controlled diffraction patterns that connect inputs (light sources) and outputs (light sinks). Sources would typically include optical fibers and/or light-emitting diodes; sinks would typically include optical fibers and/or photodetectors. The sources and/or sinks could be distributed in two dimensions; that is, on planes. Alternatively or in addition, sources and/or sinks could be distributed in three dimensions -- for example, on curved surfaces or in more complex (including random) three-dimensional patterns.

Discriminating Simulated Vocal Tremor Source Using Amplitude Modulation Spectra

PubMed Central

Carbonell, Kathy M.; Lester, Rosemary A.; Story, Brad H.; Lotto, Andrew J.

2014-01-01

Objectives/Hypothesis Sources of vocal tremor are difficult to categorize perceptually and acoustically. This paper describes a preliminary attempt to discriminate vocal tremor sources through the use of spectral measures of the amplitude envelope. The hypothesis is that different vocal tremor sources are associated with distinct patterns of acoustic amplitude modulations. Study Design Statistical categorization methods (discriminant function analysis) were used to discriminate signals from simulated vocal tremor with different sources using only acoustic measures derived from the amplitude envelopes. Methods Simulations of vocal tremor were created by modulating parameters of a vocal fold model corresponding to oscillations of respiratory driving pressure (respiratory tremor), degree of vocal fold adduction (adductory tremor) and fundamental frequency of vocal fold vibration (F0 tremor). The acoustic measures were based on spectral analyses of the amplitude envelope computed across the entire signal and within select frequency bands. Results The signals could be categorized (with accuracy well above chance) in terms of the simulated tremor source using only measures of the amplitude envelope spectrum even when multiple sources of tremor were included. Conclusions These results supply initial support for an amplitude-envelope based approach to identify the source of vocal tremor and provide further evidence for the rich information about talker characteristics present in the temporal structure of the amplitude envelope. PMID:25532813

Id-1 gene and gene products as therapeutic targets for treatment of breast cancer and other types of carcinoma

DOEpatents

Desprez, Pierre-Yves; Campisi, Judith

2014-08-19

A method for treatment of breast cancer and other types of cancer. The method comprises targeting and modulating Id-1 gene expression, if any, for the Id-1 gene, or gene products in breast or other epithelial cancers in a patient by delivering products that modulate Id-1 gene expression. When expressed, Id-1 gene is a prognostic indicator that cancer cells are invasive and metastatic.

TALE-PvuII Fusion Proteins – Novel Tools for Gene Targeting

PubMed Central

Yanik, Mert; Alzubi, Jamal; Lahaye, Thomas; Cathomen, Toni; Pingoud, Alfred; Wende, Wolfgang

2013-01-01

Zinc finger nucleases (ZFNs) consist of zinc fingers as DNA-binding module and the non-specific DNA-cleavage domain of the restriction endonuclease FokI as DNA-cleavage module. This architecture is also used by TALE nucleases (TALENs), in which the DNA-binding modules of the ZFNs have been replaced by DNA-binding domains based on transcription activator like effector (TALE) proteins. Both TALENs and ZFNs are programmable nucleases which rely on the dimerization of FokI to induce double-strand DNA cleavage at the target site after recognition of the target DNA by the respective DNA-binding module. TALENs seem to have an advantage over ZFNs, as the assembly of TALE proteins is easier than that of ZFNs. Here, we present evidence that variant TALENs can be produced by replacing the catalytic domain of FokI with the restriction endonuclease PvuII. These fusion proteins recognize only the composite recognition site consisting of the target site of the TALE protein and the PvuII recognition sequence (addressed site), but not isolated TALE or PvuII recognition sites (unaddressed sites), even at high excess of protein over DNA and long incubation times. In vitro, their preference for an addressed over an unaddressed site is > 34,000-fold. Moreover, TALE-PvuII fusion proteins are active in cellula with minimal cytotoxicity. PMID:24349308

Grounding the Meanings in Sensorimotor Behavior using Reinforcement Learning

PubMed Central

Farkaš, Igor; Malík, Tomáš; Rebrová, Kristína

2012-01-01

The recent outburst of interest in cognitive developmental robotics is fueled by the ambition to propose ecologically plausible mechanisms of how, among other things, a learning agent/robot could ground linguistic meanings in its sensorimotor behavior. Along this stream, we propose a model that allows the simulated iCub robot to learn the meanings of actions (point, touch, and push) oriented toward objects in robot’s peripersonal space. In our experiments, the iCub learns to execute motor actions and comment on them. Architecturally, the model is composed of three neural-network-based modules that are trained in different ways. The first module, a two-layer perceptron, is trained by back-propagation to attend to the target position in the visual scene, given the low-level visual information and the feature-based target information. The second module, having the form of an actor-critic architecture, is the most distinguishing part of our model, and is trained by a continuous version of reinforcement learning to execute actions as sequences, based on a linguistic command. The third module, an echo-state network, is trained to provide the linguistic description of the executed actions. The trained model generalizes well in case of novel action-target combinations with randomized initial arm positions. It can also promptly adapt its behavior if the action/target suddenly changes during motor execution. PMID:22393319

Study of run time errors of the ATLAS pixel detector in the 2012 data taking period

NASA Astrophysics Data System (ADS)

Gandrajula, Reddy Pratap

The high resolution silicon Pixel detector is critical in event vertex reconstruction and in particle track reconstruction in the ATLAS detector. During the pixel data taking operation, some modules (Silicon Pixel sensor +Front End Chip+ Module Control Chip (MCC)) go to an auto-disable state, where the Modules don't send the data for storage. Modules become operational again after reconfiguration. The source of the problem is not fully understood. One possible source of the problem is traced to the occurrence of single event upset (SEU) in the MCC. Such a module goes to either a Timeout or Busy state. This report is the study of different types and rates of errors occurring in the Pixel data taking operation. Also, the study includes the error rate dependency on Pixel detector geometry.

Allosteric Modulators for the Treatment of Schizophrenia: Targeting Glutamatergic Networks

PubMed Central

Menniti, Frank S.; Lindsley, Craig W.; Conn, P. Jeffrey; Pandit, Jayvardhan; Zagouras, Panayiotis; Volkmann, Robert A.

2013-01-01

Schizophrenia is a highly debilitating mental disorder which afflicts approximately 1% of the global population. Cognitive and negative deficits account for the lifelong disability associated with schizophrenia, whose symptoms are not effectively addressed by current treatments. New medicines are needed to treat these aspects of the disease. Neurodevelopmental, neuropathological, genetic, and behavioral pharmacological data indicate that schizophrenia stems from a dysfunction of glutamate synaptic transmission, particularly in frontal cortical networks. A number of novel pre- and postsynaptic mechanisms affecting glutamatergic synaptic transmission have emerged as viable targets for schizophrenia. While developing orthosteric glutamatergic agents for these targets has proven extremely difficult, targeting allosteric sites of these targets has emerged as a promising alternative. From a medicinal chemistry perspective, allosteric sites provide an opportunity of finding agents with better drug-like properties and greater target specificity. Furthermore, allosteric modulators are better suited to maintaining the highly precise temporal and spatial aspects of glutamatergic synaptic transmission. Herein, we review neuropathological and genomic/genetic evidence underscoring the importance of glutamate synaptic dysfunction in the etiology of schizophrenia and make a case for allosteric targets for therapeutic intervention. We review progress in identifying allosteric modulators of AMPA receptors, NMDA receptors, and metabotropic glutamate receptors, all with the aim of restoring physiological glutamatergic synaptic transmission. Challenges remain given the complexity of schizophrenia and the difficulty in studying cognition in animals and humans. Nonetheless, important compounds have emerged from these efforts and promising preclinical and variable clinical validation has been achieved. PMID:23409764

Multi-target drugs to address multiple checkpoints in complex inflammatory pathologies: evolutionary cues for novel "first-in-class" anti-inflammatory drug candidates: a reviewer's perspective.

PubMed

Mathew, Geetha; Unnikrishnan, M K

2015-10-01

Inflammation is a complex, metabolically expensive process involving multiple signaling pathways and regulatory mechanisms which have evolved over evolutionary timescale. Addressing multiple targets of inflammation holistically, in moderation, is probably a more evolutionarily viable strategy, as compared to current therapy which addresses drug targets in isolation. Polypharmacology, addressing multiple targets, is commonly used in complex ailments, suggesting the superior safety and efficacy profile of multi-target (MT) drugs. Phenotypic drug discovery, which generated successful MT and first-in-class drugs in the past, is now re-emerging. A multi-pronged approach, which modulates the evolutionarily conserved, robust and pervasive cellular mechanisms of tissue repair, with AMPK at the helm, regulating the complex metabolic/immune/redox pathways underlying inflammation, is perhaps a more viable strategy than addressing single targets in isolation. Molecules that modulate multiple molecular mechanisms of inflammation in moderation (modulating TH cells toward the anti-inflammatory phenotype, activating AMPK, stimulating Nrf2 and inhibiting NFκB) might serve as a model for a novel Darwinian "first-in-class" therapeutic category that holistically addresses immune, redox and metabolic processes associated with inflammatory repair. Such a multimodal biological activity is supported by the fact that several non-calorific pleiotropic natural products with anti-inflammatory action have been incorporated into diet (chiefly guided by the adaptive development of olfacto-gustatory preferences over evolutionary timescales) rendering such molecules, endowed with evolutionarily privileged molecular scaffolds, naturally oriented toward multiple targets.

Application of a water quality model in the White Cart water catchment, Glasgow, UK.

PubMed

Liu, S; Tucker, P; Mansell, M; Hursthouse, A

2003-03-01

Water quality models of urban systems have previously focused on point source (sewerage system) inputs. Little attention has been given to diffuse inputs and research into diffuse pollution has been largely confined to agriculture sources. This paper reports on new research that is aimed at integrating diffuse inputs into an urban water quality model. An integrated model is introduced that is made up of four modules: hydrology, contaminant point sources, nutrient cycling and leaching. The hydrology module, T&T consists of a TOPMODEL (a TOPography-based hydrological MODEL), which simulates runoff from pervious areas and a two-tank model, which simulates runoff from impervious urban areas. Linked into the two-tank model, the contaminant point source module simulates the overflow from the sewerage system in heavy rain. The widely known SOILN (SOIL Nitrate model) is the basis of nitrogen cycle module. Finally, the leaching module consists of two functions: the production function and the transfer function. The production function is based on SLIM (Solute Leaching Intermediate Model) while the transfer function is based on the 'flushing hypothesis' which postulates a relationship between contaminant concentrations in the receiving water course and the extent to which the catchment is saturated. This paper outlines the modelling methodology and the model structures that have been developed. An application of this model in the White Cart catchment (Glasgow) is also included.

Methods, systems and apparatus for controlling operation of two alternating current (AC) machines

DOEpatents

Gallegos-Lopez, Gabriel [Torrance, CA; Nagashima, James M [Cerritos, CA; Perisic, Milun [Torrance, CA; Hiti, Silva [Redondo Beach, CA

2012-06-05

A system is provided for controlling two alternating current (AC) machines via a five-phase PWM inverter module. The system comprises a first control loop, a second control loop, and a current command adjustment module. The current command adjustment module operates in conjunction with the first control loop and the second control loop to continuously adjust current command signals that control the first AC machine and the second AC machine such that they share the input voltage available to them without compromising the target mechanical output power of either machine. This way, even when the phase voltage available to either one of the machines decreases, that machine outputs its target mechanical output power.

A high-speed BCI based on code modulation VEP

NASA Astrophysics Data System (ADS)

Bin, Guangyu; Gao, Xiaorong; Wang, Yijun; Li, Yun; Hong, Bo; Gao, Shangkai

2011-04-01

Recently, electroencephalogram-based brain-computer interfaces (BCIs) have attracted much attention in the fields of neural engineering and rehabilitation due to their noninvasiveness. However, the low communication speed of current BCI systems greatly limits their practical application. In this paper, we present a high-speed BCI based on code modulation of visual evoked potentials (c-VEP). Thirty-two target stimuli were modulated by a time-shifted binary pseudorandom sequence. A multichannel identification method based on canonical correlation analysis (CCA) was used for target identification. The online system achieved an average information transfer rate (ITR) of 108 ± 12 bits min-1 on five subjects with a maximum ITR of 123 bits min-1 for a single subject.

Targeting CB2-GPR55 Receptor Heteromers Modulates Cancer Cell Signaling*

PubMed Central

Moreno, Estefanía; Andradas, Clara; Medrano, Mireia; Caffarel, María M.; Pérez-Gómez, Eduardo; Blasco-Benito, Sandra; Gómez-Cañas, María; Pazos, M. Ruth; Irving, Andrew J.; Lluís, Carme; Canela, Enric I.; Fernández-Ruiz, Javier; Guzmán, Manuel; McCormick, Peter J.; Sánchez, Cristina

2014-01-01

The G protein-coupled receptors CB2 (CB2R) and GPR55 are overexpressed in cancer cells and human tumors. Because a modulation of GPR55 activity by cannabinoids has been suggested, we analyzed whether this receptor participates in cannabinoid effects on cancer cells. Here we show that CB2R and GPR55 form heteromers in cancer cells, that these structures possess unique signaling properties, and that modulation of these heteromers can modify the antitumoral activity of cannabinoids in vivo. These findings unveil the existence of previously unknown signaling platforms that help explain the complex behavior of cannabinoids and may constitute new targets for therapeutic intervention in oncology. PMID:24942731

[Comparison of SIB-IMRT treatment plans for upper esophageal carcinoma].

PubMed

Fu, Wei-hua; Wang, Lv-hua; Zhou, Zong-mei; Dai, Jian-rong; Hu, Yi-min

2003-06-01

To implement simultaneous integrated boost intensity-modulated radiotherapy(SIB-IMRT) plans for upper esophageal carcinoma and investigate the dose profiles of tumor and electively treated region and the dose to organs at risk (OARs). SIB-IMRT plans were designed for two patients with upper esophageal carcinoma. Two target volumes were predefined: PTV1, the target volume of the primary lesion, which was given to 67.2 Gy, and PTV2, the target volume of electively treated region, which was given to 50.4 Gy. With the same dose-volume constraints, but different beams arrangements (3, 5, 7, or 9 equispaced coplanar beams), four plans were generated. Indices, including dose distribution, dose volume histogram (DVH) and conformity index, were used for comparison of these plans. The plan with three intensity-modulated beams could produce good dose distribution for the two target volumes. The dose conformity to targets and the dose to OARs were improved as the beam number increased. The dose distributions in targets changed little when the beam number increased from 7 to 9. Five to seven intensity-modulated beams can produce desirable dose distributions for simultaneous integrated boost (SIB) treatment for upper esophageal carcinoma. The primary tumor can get higher equivalent dose by SIB treatments. It is easier and more efficient to design plans with equispaced coplanar beams. The efficacy of SIB-IMRT remains to be determined by the clinical outcome.

Visual motion modulates pattern sensitivity ahead, behind, and beside motion

PubMed Central

Arnold, Derek H.; Marinovic, Welber; Whitney, David

2014-01-01

Retinal motion can modulate visual sensitivity. For instance, low contrast drifting waveforms (targets) can be easier to detect when abutting the leading edges of movement in adjacent high contrast waveforms (inducers), rather than the trailing edges. This target-inducer interaction is contingent on the adjacent waveforms being consistent with one another – in-phase as opposed to out-of-phase. It has been suggested that this happens because there is a perceptually explicit predictive signal at leading edges of motion that summates with low contrast physical input – a ‘predictive summation’. Another possible explanation is a phase sensitive ‘spatial summation’, a summation of physical inputs spread across the retina (not predictive signals). This should be non-selective in terms of position – it should be evident at leading, adjacent, and at trailing edges of motion. To tease these possibilities apart, we examined target sensitivity at leading, adjacent, and trailing edges of motion. We also examined target sensitivity adjacent to flicker, and for a stimulus that is less susceptible to spatial summation, as it sums to grey across a small retinal expanse. We found evidence for spatial summation in all but the last condition. Finally, we examined sensitivity to an absence of signal at leading and trailing edges of motion, finding greater sensitivity at leading edges. These results are inconsistent with the existence of a perceptually explicit predictive signal in advance of drifting waveforms. Instead, we suggest that phase-contingent target-inducer modulations of sensitivity are explicable in terms of a directionally modulated spatial summation. PMID:24699250

Transcranial Direct Current Stimulation (tDCS) Targeting Left Dorsolateral Prefrontal Cortex Modulates Task-Induced Acute Pain in Healthy Volunteers

PubMed Central

Mariano, Timothy Y.; Wout, Mascha van't; Garnaat, Sarah L.; Rasmussen, Steven A.; Greenberg, Benjamin D.

2016-01-01

Objective Current chronic pain treatments target nociception rather than affective “suffering” and its associated functional and psychiatric comorbidities. Left dorsolateral prefrontal cortex (DLPFC) has been implicated in affective, cognitive, and attentional aspects of pain and is a primary target of neuromodulation for affective disorders. Transcranial direct current stimulation (tDCS) can noninvasively modulate cortical activity. The present study tests if anodal tDCS targeting left DLPFC will increase tolerability of acute painful stimuli versus cathodal tDCS. Methods Forty tDCS-naive healthy volunteers received anodal and cathodal stimulation targeting left DLPFC in two randomized and counterbalanced sessions. During stimulation, each participant performed cold pressor (CP) and breath holding (BH) tasks. We measured pain intensity with the Defense and Veterans Pain Rating Scale (DVPRS) before and after each task. Results Mixed ANOVA revealed no main effect of stimulation polarity for mean CP threshold, tolerance, or endurance, or mean BH time (all p > 0.27). However, DVPRS rise associated with CP was significantly smaller with anodal versus cathodal tDCS (p = 0.024). We further observed a significant tDCS polarity × stimulation order interaction (p = 0.042) on CP threshold suggesting task sensitization. Conclusions Although our results do not suggest that polarity of tDCS targeting left DLPFC differentially modulates tolerability of CP- and BH-related pain distress in healthy volunteers, there was a significant effect on DVPRS pain ratings. This contrasts with our previous findings that tDCS targeting left dorsal anterior cingulate cortex showed a trend towards higher mean CP tolerance with cathodal versus anodal stimulation. The present results may suggest tDCS-related effects on nociception or DLPFC-mediated attention, or preferential modulation of the affective valence of pain as captured by DVPRS. Sham-controlled clinical studies are needed. PMID:26814276

Transcranial Direct Current Stimulation (tDCS) Targeting Left Dorsolateral Prefrontal Cortex Modulates Task-Induced Acute Pain in Healthy Volunteers.

PubMed

Mariano, Timothy Y; Van't Wout, Mascha; Garnaat, Sarah L; Rasmussen, Steven A; Greenberg, Benjamin D

2016-04-01

Current chronic pain treatments target nociception rather than affective "suffering" and its associated functional and psychiatric comorbidities. The left dorsolateral prefrontal cortex (DLPFC) has been implicated in affective, cognitive, and attentional aspects of pain and is a primary target of neuromodulation for affective disorders. Transcranial direct current stimulation (tDCS) can non-invasively modulate cortical activity. The present study tests whether anodal tDCS targeting the left DLPFC will increase tolerability of acute painful stimuli vs cathodal tDCS. Forty tDCS-naive healthy volunteers received anodal and cathodal stimulation targeting the left DLPFC in two randomized and counterbalanced sessions. During stimulation, each participant performed cold pressor (CP) and breath holding (BH) tasks. We measured pain intensity with the Defense and Veterans Pain Rating Scale (DVPRS) before and after each task. Mixed ANOVA revealed no main effect of stimulation polarity for mean CP threshold, tolerance, or endurance, or mean BH time (allP > 0.27). However, DVPRS rise associated with CP was significantly smaller with anodal vs cathodal tDCS (P = 0.024). We further observed a significant tDCS polarity × stimulation order interaction (P = 0.042) on CP threshold, suggesting task sensitization. Although our results do not suggest that polarity of tDCS targeting the left DLPFC differentially modulates the tolerability of CP- and BH-related pain distress in healthy volunteers, there was a significant effect on DVPRS pain ratings. This contrasts with our previous findings that tDCS targeting the left dorsal anterior cingulate cortex showed a trend toward higher mean CP tolerance with cathodal vs anodal stimulation. The present results may suggest tDCS-related effects on nociception or DLPFC-mediated attention, or preferential modulation of the affective valence of pain as captured by the DVPRS. Sham-controlled clinical studies are needed. © 2015 American Academy of Pain Medicine. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

"Kill" the messenger: Targeting of cell-derived microparticles in lupus nephritis.

PubMed

Nielsen, Christoffer T; Rasmussen, Niclas S; Heegaard, Niels H H; Jacobsen, Søren

2016-07-01

Immune complex (IC) deposition in the glomerular basement membrane (GBM) is a key early pathogenic event in lupus nephritis (LN). The clarification of the mechanisms behind IC deposition will enable targeted therapy in the future. Circulating cell-derived microparticles (MPs) have been proposed as major sources of extracellular autoantigens and ICs and triggers of autoimmunity in LN. The overabundance of galectin-3-binding protein (G3BP) along with immunoglobulins and a few other proteins specifically distinguish circulating MPs in patients with systemic lupus erythematosus (SLE), and this is most pronounced in patients with active LN. G3BP co-localizes with deposited ICs in renal biopsies from LN patients supporting a significant presence of MPs in the IC deposits. G3BP binds strongly to glomerular basement membrane proteins and integrins. Accordingly, MP surface proteins, especially G3BP, may be essential for the deposition of ICs in kidneys and thus for the ensuing formation of MP-derived electron dense structures in the GBM, and immune activation in LN. This review focuses on the notion of targeting surface molecules on MPs as an entirely novel treatment strategy in LN. By targeting MPs, a double hit may be achieved by attenuating both the autoantigenic fueling of immune complexes and the triggering of the adaptive immune system. Thereby, early pathogenic events may be blocked in contrast to current treatment strategies that primarily target and modulate later events in the cellular and humoral immune response. Copyright © 2016 Elsevier B.V. All rights reserved.

Distributed Attention Is Implemented through Theta-Rhythmic Gamma Modulation.

PubMed

Landau, Ayelet Nina; Schreyer, Helene Marianne; van Pelt, Stan; Fries, Pascal

2015-08-31

When subjects monitor a single location, visual target detection depends on the pre-target phase of an ∼8 Hz brain rhythm. When multiple locations are monitored, performance decrements suggest a division of the 8 Hz rhythm over the number of locations, indicating that different locations are sequentially sampled. Indeed, when subjects monitor two locations, performance benefits alternate at a 4 Hz rhythm. These performance alternations were revealed after a reset of attention to one location. Although resets are common and important events for attention, it is unknown whether, in the absence of resets, ongoing attention samples stimuli in alternation. Here, we examined whether spatially specific attentional sampling can be revealed by ongoing pre-target brain rhythms. Visually induced gamma-band activity plays a role in spatial attention. Therefore, we hypothesized that performance on two simultaneously monitored stimuli can be predicted by a 4 Hz modulation of gamma-band activity. Brain rhythms were assessed with magnetoencephalography (MEG) while subjects monitored bilateral grating stimuli for a unilateral target event. The corresponding contralateral gamma-band responses were subtracted from each other to isolate spatially selective, target-related fluctuations. The resulting lateralized gamma-band activity (LGA) showed opposite pre-target 4 Hz phases for detected versus missed targets. The 4 Hz phase of pre-target LGA accounted for a 14.5% modulation in performance. These findings suggest that spatial attention is a theta-rhythmic sampling process that is continuously ongoing, with each sampling cycle being implemented through gamma-band synchrony. Copyright © 2015 Elsevier Ltd. All rights reserved.

Neuromuscular mechanisms and neural strategies in the control of time-varying muscle contractions.

PubMed

Erimaki, Sophia; Agapaki, Orsalia M; Christakos, Constantinos N

2013-09-01

The organization of the neural input to motoneurons that underlies time-varying muscle force is assumed to depend on muscle transfer characteristics and neural strategies or control modes utilizing sensory signals. We jointly addressed these interlinked, but previously studied individually and partially, issues for sinusoidal (range 0.5-5.0 Hz) force-tracking contractions of a human finger muscle. Using spectral and correlation analyses of target signal, force signal, and motor unit (MU) discharges, we studied 1) patterns of such discharges, allowing inferences on the motoneuronal input; 2) transformation of MU population activity (EMG) into quasi-sinusoidal force; and 3) relation of force oscillation to target, carrying information on the input's organization. A broad view of force control mechanisms and strategies emerged. Specifically, synchronized MU and EMG modulations, reflecting a frequency-modulated motoneuronal input, accompanied the force variations. Gain and delay drops between EMG modulation and force oscillation, critical for the appropriate organization of this input, occurred with increasing target frequency. According to our analyses, gain compensation was achieved primarily through rhythmical activation/deactivation of higher-threshold MUs and secondarily through the adaptation of the input's strength expected during tracking tasks. However, the input's timing was not adapted to delay behaviors and seemed to depend on the control modes employed. Thus, for low-frequency targets, the force oscillation was highly coherent with, but led, a target, this timing error being compatible with predictive feedforward control partly based on the target's derivatives. In contrast, the force oscillation was weakly coherent, but in phase, with high-frequency targets, suggesting control mainly based on a target's rhythm.

Reduced order modelling in searches for continuous gravitational waves - I. Barycentring time delays

NASA Astrophysics Data System (ADS)

Pitkin, M.; Doolan, S.; McMenamin, L.; Wette, K.

2018-06-01

The frequencies and phases of emission from extra-solar sources measured by Earth-bound observers are modulated by the motions of the observer with respect to the source, and through relativistic effects. These modulations depend critically on the source's sky-location. Precise knowledge of the modulations are required to coherently track the source's phase over long observations, for example, in pulsar timing, or searches for continuous gravitational waves. The modulations can be modelled as sky-location and time-dependent time delays that convert arrival times at the observer to the inertial frame of the source, which can often be the Solar system barycentre. We study the use of reduced order modelling for speeding up the calculation of this time delay for any sky-location. We find that the time delay model can be decomposed into just four basis vectors, and with these the delay for any sky-location can be reconstructed to sub-nanosecond accuracy. When compared to standard routines for time delay calculation in gravitational wave searches, using the reduced basis can lead to speed-ups of 30 times. We have also studied components of time delays for sources in binary systems. Assuming eccentricities <0.25, we can reconstruct the delays to within 100 s of nanoseconds, with best case speed-ups of a factor of 10, or factors of two when interpolating the basis for different orbital periods or time stamps. In long-duration phase-coherent searches for sources with sky-position uncertainties, or binary parameter uncertainties, these speed-ups could allow enhancements in their scopes without large additional computational burdens.

PST 2009: XIII International Workshop on Polarized Sources Targets and Polarimetry

NASA Astrophysics Data System (ADS)

Lenisa, Paolo

2011-05-01

The workshops on polarized sources, targets, and polarimetry are held every two years. In 2009 the meeting took place in Ferrara, Italy, and was organized by the University of Ferrara and INFN. Sessions on Polarized Proton and Deuterium Sources, Polarized Electron Sources, Polarimetry, Polarized Solid Targets, and Polarized Internal Targets, highlighted topics, recent developments, and progress in the field. A session dedicated to Future Facilities provided an overview of a number of new activities in the spin-physics sector at facilities that are currently in the planning stage. Besides presenting a broad overview of polarized ion sources, electron sources, solid and gaseous targets, and their neighbouring fields, the workshop also addressed the application of polarized atoms in applied sciences and medicine that is becoming increasingly important.

Incomplete Multisource Transfer Learning.

PubMed

Ding, Zhengming; Shao, Ming; Fu, Yun

2018-02-01

Transfer learning is generally exploited to adapt well-established source knowledge for learning tasks in weakly labeled or unlabeled target domain. Nowadays, it is common to see multiple sources available for knowledge transfer, each of which, however, may not include complete classes information of the target domain. Naively merging multiple sources together would lead to inferior results due to the large divergence among multiple sources. In this paper, we attempt to utilize incomplete multiple sources for effective knowledge transfer to facilitate the learning task in target domain. To this end, we propose an incomplete multisource transfer learning through two directional knowledge transfer, i.e., cross-domain transfer from each source to target, and cross-source transfer. In particular, in cross-domain direction, we deploy latent low-rank transfer learning guided by iterative structure learning to transfer knowledge from each single source to target domain. This practice reinforces to compensate for any missing data in each source by the complete target data. While in cross-source direction, unsupervised manifold regularizer and effective multisource alignment are explored to jointly compensate for missing data from one portion of source to another. In this way, both marginal and conditional distribution discrepancy in two directions would be mitigated. Experimental results on standard cross-domain benchmarks and synthetic data sets demonstrate the effectiveness of our proposed model in knowledge transfer from incomplete multiple sources.

Modulated method for efficient, narrow-bandwidth, laser Compton X-ray and gamma-ray sources

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

Barty, Christopher P. J.

A method of x-ray and gamma-ray generation via laser Compton scattering uses the interaction of a specially-formatted, highly modulated, long duration, laser pulse with a high-frequency train of high-brightness electron bunches to both create narrow bandwidth x-ray and gamma-ray sources and significantly increase the laser to Compton photon conversion efficiency.

Macroeconomic Activity Module - NEMS Documentation

EIA Publications

2016-01-01

Documents the objectives, analytical approach, and development of the National Energy Modeling System (NEMS) Macroeconomic Activity Module (MAM) used to develop the Annual Energy Outlook for 2016 (AEO2016). The report catalogues and describes the module assumptions, computations, methodology, parameter estimation techniques, and mainframe source code

Passive measurement-device-independent quantum key distribution with orbital angular momentum and pulse position modulation

NASA Astrophysics Data System (ADS)

Wang, Lian; Zhou, Yuan-yuan; Zhou, Xue-jun; Chen, Xiao

2018-03-01

Based on the orbital angular momentum and pulse position modulation, we present a novel passive measurement-device-independent quantum key distribution (MDI-QKD) scheme with the two-mode source. Combining with the tight bounds of the yield and error rate of single-photon pairs given in our paper, we conduct performance analysis on the scheme with heralded single-photon source. The numerical simulations show that the performance of our scheme is significantly superior to the traditional MDI-QKD in the error rate, key generation rate and secure transmission distance, since the application of orbital angular momentum and pulse position modulation can exclude the basis-dependent flaw and increase the information content for each single photon. Moreover, the performance is improved with the rise of the frame length. Therefore, our scheme, without intensity modulation, avoids the source side channels and enhances the key generation rate. It has greatly utility value in the MDI-QKD setups.

Signaling cascades modulate the speed of signal propagation through space.

PubMed

Govern, Christopher C; Chakraborty, Arup K

2009-01-01

Cells are not mixed bags of signaling molecules. As a consequence, signals must travel from their origin to distal locations. Much is understood about the purely diffusive propagation of signals through space. Many signals, however, propagate via signaling cascades. Here, we show that, depending on their kinetics, cascades speed up or slow down the propagation of signals through space, relative to pure diffusion. We modeled simple cascades operating under different limits of Michaelis-Menten kinetics using deterministic reaction-diffusion equations. Cascades operating far from enzyme saturation speed up signal propagation; the second mobile species moves more quickly than the first through space, on average. The enhanced speed is due to more efficient serial activation of a downstream signaling module (by the signaling molecule immediately upstream in the cascade) at points distal from the signaling origin, compared to locations closer to the source. Conversely, cascades operating under saturated kinetics, which exhibit zero-order ultrasensitivity, can slow down signals, ultimately localizing them to regions around the origin. Signal speed modulation may be a fundamental function of cascades, affecting the ability of signals to penetrate within a cell, to cross-react with other signals, and to activate distant targets. In particular, enhanced speeds provide a way to increase signal penetration into a cell without needing to flood the cell with large numbers of active signaling molecules; conversely, diminished speeds in zero-order ultrasensitive cascades facilitate strong, but localized, signaling.

Differential absorption lidar measurements of atmospheric water vapor using a pseudonoise code modulated AlGaAs laser. Thesis

NASA Technical Reports Server (NTRS)

Rall, Jonathan A. R.

1994-01-01

Lidar measurements using pseudonoise code modulated AlGaAs lasers are reported. Horizontal path lidar measurements were made at night to terrestrial targets at ranges of 5 and 13 km with 35 mW of average power and integration times of one second. Cloud and aerosol lidar measurements were made to thin cirrus clouds at 13 km altitude with Rayleigh (molecular) backscatter evident up to 9 km. Average transmitter power was 35 mW and measurement integration time was 20 minutes. An AlGaAs laser was used to characterize spectral properties of water vapor absorption lines at 811.617, 816.024, and 815.769 nm in a multipass absorption cell using derivative spectroscopy techniques. Frequency locking of an AlGaAs laser to a water vapor absorption line was achieved with a laser center frequency stability measured to better than one-fifth of the water vapor Doppler linewidth over several minutes. Differential absorption lidar measurements of atmospheric water vapor were made in both integrated path and range-resolved modes using an externally modulated AlGaAs laser. Mean water vapor number density was estimated from both integrated path and range-resolved DIAL measurements and agreed with measured humidity values to within 6.5 percent and 20 percent, respectively. Error sources were identified and their effects on estimates of water vapor number density calculated.

The Effect of Dynamic Pitch on Speech Recognition in Temporally Modulated Noise

ERIC Educational Resources Information Center

Shen, Jung; Souza, Pamela E.

2017-01-01

Purpose: This study investigated the effect of dynamic pitch in target speech on older and younger listeners' speech recognition in temporally modulated noise. First, we examined whether the benefit from dynamic-pitch cues depends on the temporal modulation of noise. Second, we tested whether older listeners can benefit from dynamic-pitch cues for…

Dosimetric effect of Elekta Beam Modulator micromultileaf in three-dimensional conformal radiotherapy and intensity-modulated radiotherapy for prostate cancer

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

Carosi, Alessandra, E-mail: alessandra.carosi@katamail.com; Ingrosso, Gianluca; Ponti, Elisabetta

2014-07-01

The purpose of this study is to analyze the dosimetric effect of Elekta Beam Modulator in 3-dimensional conformal radiation therapy (3DCRT) and in intensity-modulated radiation therapy (IMRT) for localized prostate cancer. We compared treatment plans developed with 2 different Elekta multileaf collimators (MLC): Beam Modulator micro-MLC (mMLC) (4-mm leaf width at the isocenter) and standard MLC (10-mm leaf width at the isocenter). The comparison was performed for 15 patients with localized prostate cancer in 3DCRT and IMRT delivery; a total of 60 treatment plans were processed. The dose-volume histograms were used to provide the quantitative comparison between plans. In particular,more » we analyzed differences between rectum and bladder sparing in terms of a set of appropriate Vx (percentage of organ at risk [OAR] volume receiving the x dose) and differences between target conformity and coverage in terms of coverage factor and conformation number. Our analysis demonstrates that in 3DCRT there is an advantage in the use of Elekta Beam Modulator mMLC in terms of organ sparing; in particular, a significant decrease in rectal V{sub 60} and V{sub 50} (p = 0.001) and in bladder V{sub 70} and V{sub 65} (p = 0.007 and 0.002, respectively) was found. Moreover, a better target dose conformity was obtained (p = 0.002). IMRT plans comparison demonstrated no significant differences between the use of the 4 or 10-mm MLCs. Our analysis shows that in 3DCRT the use of the Elekta Beam Modulator mMLC gives a gain in target conformity and in OARs dose sparing whereas in IMRT plans there is no advantage.« less