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Sample records for acoustic stimulation cas

  1. The effect of contralateral acoustic stimulation on spontaneous otoacoustic emissions.

    PubMed

    Zhao, Wei; Dhar, Sumitrajit

    2010-03-01

    Evoked otoacoustic emissions are often used to study the medial olivocochlear (MOC) efferents in humans. There has been concern that the emission-evoking stimulus may itself elicit efferent activity and alter the evoked otoacoustic emission. Spontaneous otoacoustic emissions (SOAEs) are hence advantageous as no external stimulation is necessary to record the response in the test ear. Contralateral acoustic stimulation (CAS) has been shown to suppress SOAE level and elevate SOAE frequency, but the time course of these effects is largely unknown. By utilizing the Choi-Williams distribution, here we report a gradual adaptation during the presence of CAS and an overshoot following CAS offset in both SOAE magnitude and frequency from six normal-hearing female human subjects. Furthermore, we have quantified the time constants of both magnitude and frequency shifts at the onset, presence, and offset of four levels of CAS. Most studies using contralateral elicitors do not stringently control the middle-ear muscle (MEM) reflex, leaving the results difficult to interpret. In addition to clinically available measures of the MEM reflex, we have incorporated a sensitive laboratory technique to monitor the MEM reflex in our subjects, allowing us to interpret the results with greater confidence.

  2. Motor cortex inhibition induced by acoustic stimulation.

    PubMed

    Kühn, Andrea A; Sharott, Andrew; Trottenberg, Thomas; Kupsch, Andreas; Brown, Peter

    2004-09-01

    The influence of the brainstem motor system on cerebral motor areas may play an important role in motor control in health and disease. A new approach to investigate this interaction in man is combining acoustic stimulation activating the startle system with transcranial magnetic stimulation (TMS) over the motor cortex. However, it is unclear whether the inhibition of TMS responses following acoustic stimulation occurs at the level of the motor cortex through reticulo-cortical projections or subcortically, perhaps through reticulo-spinal projections. We compared the influence of acoustic stimulation on motor effects elicited by TMS over motor cortical areas to those evoked with subcortical electrical stimulation (SES) through depth electrodes in five patients treated with deep brain stimulation for Parkinson's disease. SES bypasses the motor cortex, demonstrating any interaction with acoustic stimuli at the subcortical level. EMG was recorded from the contralateral biceps brachii muscle. Acoustic stimulation was delivered binaurally through headphones and used as a conditioning stimulus at an interstimulus interval of 50 ms. When TMS was used as the test stimulus, the area and amplitude of the conditioned motor response was significantly inhibited (area: 57.5+/-12.9%, amplitude: 47.9+/-7.4%, as percentage of unconditioned response) whereas facilitation occurred with SES (area: 110.1+/-4.3%, amplitude: 116.9+/-6.9%). We conclude that a startle-evoked activation of reticulo-cortical projections transiently inhibits the motor cortex.

  3. Electro-acoustic stimulation. Acoustic and electric pitch comparisons.

    PubMed

    McDermott, Hugh; Sucher, Catherine; Simpson, Andrea

    2009-01-01

    For simultaneous acoustic and electric stimulation to be perceived as complementary, it may be beneficial for hearing aids and cochlear implants (CI) to be adjusted to provide compatible pitch sensations. To this end, estimates of the pitch perceived for a set of acoustic and electric stimuli were obtained from 14 CI users who had usable low-frequency hearing, either in the non-implanted ear or in both ears. The subjects assigned numerical pitch estimates to each of 5 acoustic pure tones and 5 single-electrode electric pulse trains. On average, the acoustic frequency that corresponded in pitch to stimulation on the most apical electrode was approximately 480 Hz. This was about 1 octave lower than the frequency expected from Greenwood's frequency-place function applied to estimates of the electrode insertion angle based on X-ray images. Furthermore, evidence was found suggesting that pitch decreased with increasing duration of CI use. Pitch estimates from 5 subjects who completed the experiment before experiencing any other sounds through their CI were generally close to the values expected from a recently published frequency map for the cochlear spiral ganglion. Taken together, these findings suggest that some perceptual adaptation may occur that would compensate in part for the apparent mismatch between the intracochlear position of the electrodes and the acoustic frequencies assigned to them in the sound processor.

  4. A Systematic Review of Electric-Acoustic Stimulation

    PubMed Central

    Ching, Teresa Y. C.; Cowan, Robert

    2013-01-01

    Cochlear implant systems that combine electric and acoustic stimulation in the same ear are now commercially available and the number of patients using these devices is steadily increasing. In particular, electric-acoustic stimulation is an option for patients with severe, high frequency sensorineural hearing impairment. There have been a range of approaches to combining electric stimulation and acoustic hearing in the same ear. To develop a better understanding of fitting practices for devices that combine electric and acoustic stimulation, we conducted a systematic review addressing three clinical questions: what is the range of acoustic hearing in the implanted ear that can be effectively preserved for an electric-acoustic fitting?; what benefits are provided by combining acoustic stimulation with electric stimulation?; and what clinical fitting practices have been developed for devices that combine electric and acoustic stimulation? A search of the literature was conducted and 27 articles that met the strict evaluation criteria adopted for the review were identified for detailed analysis. The range of auditory thresholds in the implanted ear that can be successfully used for an electric-acoustic application is quite broad. The effectiveness of combined electric and acoustic stimulation as compared with electric stimulation alone was consistently demonstrated, highlighting the potential value of preservation and utilization of low frequency hearing in the implanted ear. However, clinical procedures for best fitting of electric-acoustic devices were varied. This clearly identified a need for further investigation of fitting procedures aimed at maximizing outcomes for recipients of electric-acoustic devices. PMID:23539259

  5. Effects of contralateral acoustic stimulation on spontaneous otoacoustic emissions and hearing threshold fine structure.

    PubMed

    Dewey, James B; Lee, Jungmee; Dhar, Sumitrajit

    2014-12-01

    Medial olivocochlear (MOC) influence on cochlear mechanics can be noninvasively, albeit indirectly, explored via the effects of contralateral acoustic stimulation (CAS) on otoacoustic emissions. CAS-mediated effects are particularly pronounced for spontaneous otoacoustic emissions (SOAEs), which are typically reduced in amplitude and shifted upward in frequency by CAS. We investigated whether similar frequency shifts and magnitude reductions were observed behaviorally in the fine structure of pure-tone hearing thresholds, a phenomenon thought to share a common underlying mechanism with SOAEs. In normal-hearing listeners, fine-resolution thresholds were obtained over a narrow frequency range centered on the frequency of an SOAE, both in the absence and presence of 60-dB SPL broadband CAS. While CAS shifted threshold fine structure patterns and SOAEs upward in frequency by a comparable amount, little reduction in the presence or depth of fine structure was observed at frequencies near those of SOAEs. In fact, CAS typically improved thresholds, particularly at threshold minima, and increased fine structure depth when reductions in the amplitude of the associated SOAE were less than 10 dB. Additional measurements made at frequencies distant from SOAEs, or near SOAEs that were more dramatically reduced in amplitude by the CAS, revealed that CAS tended to elevate thresholds and reduce threshold fine structure depth. The results suggest that threshold fine structure is sensitive to MOC-mediated changes in cochlear gain, but that SOAEs complicate the interpretation of threshold measurements at nearby frequencies, perhaps due to masking or other interference effects. Both threshold fine structure and SOAEs may be significant sources of intersubject and intrasubject variability in psychoacoustic investigations of MOC function.

  6. Frequency overlap between electric and acoustic stimulation and speech-perception benefit in patients with combined electric and acoustic stimulation

    PubMed Central

    Zhang, Ting; Spahr, Anthony J.; Dorman, Michael F.

    2010-01-01

    Objectives Our aim was to assess, for patients with a cochlear implant in one ear and low-frequency acoustic hearing in the contralateral ear, whether reducing the overlap in frequencies conveyed in the acoustic signal and those analyzed by the cochlear implant speech processor would improve speech recognition. Design The recognition of monosyllabic words in quiet and sentences in noise was evaluated in three listening configurations: electric stimulation alone, acoustic stimulation alone, and combined electric and acoustic stimulation. The acoustic stimuli were either unfiltered or low-pass (LP) filtered at 250 Hz, 500 Hz, or 750 Hz. The electric stimuli were either unfiltered or high-pass (HP) filtered at 250 Hz, 500 Hz or 750 Hz. In the combined condition the unfiltered acoustic signal was paired with the unfiltered electric signal, the 250 LP acoustic signal was paired with the 250 Hz HP electric signal, the 500 Hz LP acoustic signal was paired with the 500 Hz HP electric signal and the 750 Hz LP acoustic signal was paired with the 750 Hz HP electric signal. Results For both acoustic and electric signals performance increased as the bandwith increased. The highest level of performance in the combined condition was observed in the unfiltered acoustic plus unfiltered electric condition. Conclusions Reducing the overlap in frequency representation between acoustic and electric stimulation does not increase speech understanding scores for patients who have residual hearing in the ear contralateral to the implant. We find that acoustic information below 250 Hz significantly improves performance for patients who combine electric and acoustic stimulation and accounts for the majority of the speech-perception benefit when acoustic stimulation is combined with electric stimulation. PMID:19915474

  7. Assessment of a direct acoustic cochlear stimulator.

    PubMed

    Chatzimichalis, Michail; Sim, Jae Hoon; Huber, Alexander M

    2012-01-01

    This study aimed to assess the functional results of a new, active, acoustic-mechanical hearing implant, the Direct Acoustic Cochlear Stimulation Partial Implant (DACS PI), in a preclinical study. The DACS PI is an electromagnetic device fixed to the mastoid by screws and coupled to a standard stapes prosthesis by an artificial incus (AI). The function of the DACS PI-aided reconstruction was assessed by determining: (1) the maximum equivalent sound pressure level (SPL) of the implant, which was obtained from measurements of the volume displacement at the round window in normal and implanted ears, and (2) the quality at the coupling interface between the AI of the DACS and the stapes prosthesis, which was quantified from measurements of relative motions between the AI and the prosthesis. Both measurements were performed with fresh temporal bones using a scanning laser Doppler interferometry system. The expected maximum equivalent SPL with a typical driving voltage of 0.3 V was about 115-125 dB SPL up to 1.5 kHz in reconstruction with the DACS PI, and decreased with a roll-off slope of about 65 dB/decade, reaching 90 dB SPL at 8 kHz. The large roll-off relative to a normal ear was presumed to be a relatively high inductive impedance of the coil of the DACS PI actuator at higher frequencies. Good coupling quality between the AI and the prosthesis was achieved below the resonance (∼1.5 kHz) of the DACS PI for all tested stapes prostheses. Above the resonance, the SMart Piston, which is composed of a shape-memory alloy, had the best coupling quality.

  8. Evidence for a bipolar change in distortion product otoacoustic emissions during contralateral acoustic stimulation in humans

    NASA Astrophysics Data System (ADS)

    Müller, Jörg; Janssen, Thomas; Heppelmann, Guido; Wagner, Wolfgang

    2005-12-01

    The aim of this study was to investigate the activity of the medial olivocochlear (MOC) efferents during contralateral (CAS) and ipsilateral acoustic stimulation (IAS) by recording distortion product otoacoustic emission (DPOAE) suppression and DPOAE adaptation in humans. The main question was: do large bipolar changes in DPOAE level (transition from enhancement to suppression) also occur in humans when changing the primary tone level within a small range as described by Maison and Liberman for guinea pigs [J. Neurosci. 20, 4701-4707 (2000)]? In the present study, large bipolar changes in DPOAE level (14 dB on average across subjects) were found during CAS predominantly at frequencies where dips in the DPOAE fine structure occurred. Thus, effects of the second DPOAE source might be responsible for the observed bipolar effect. In contrast, comparable effects were not found during IAS as was reported in guinea pigs. Reproducibility of CAS DPOAEs was better than that for IAS DPOAEs. Thus, contralateral DPOAE suppression is suggested to be superior to ipsilateral DPOAE adaptation with regard to measuring the MOC reflex strength and for evaluating the vulnerability of the cochlea to acoustic overexposure in a clinical context.

  9. Effects of contralateral acoustic stimulation on otoacoustic emissions induced by swept tones.

    PubMed

    Shixiong Chen; Yanbing Jin; Lisheng Xu; Guanglin Li

    2015-08-01

    The medial olivocochlear complex (MOC) is an auditory nucleus that projects efferent nerve fibers to control the behaviors of both sides of the cochlea. Otoacoutsic emissions (OAEs) are by-products the activities of the outer hair cells (OHCs) in the cochlea and could be used as a noninvasive way to study the efferent control of the MOC. However, existing results regarding the efferent control are quite controversial and often restricted to a rather limited frequency range. In this study, a new method of measuring stimulus frequency otoacoustic emissions (SFOAEs) with the presence of a contralateral acoustic stimulation (CAS) was proposed to study the efferent control over the cochlea. SFOAEs were measured with swept tones with time varying frequencies so that SFOAE spectra with and without the presence of the CAS could be compared with high frequency-resolution. The results showed that there was consistent decrease in the amplitude of the swept-tone SFOAEs across a wide frequency range from 0.5 to 8 kHz when the CAS was presented, suggesting an outstanding attenuation of OHC activities by the efferent control from the MOC. The SFOAE decrease with the presence of the CAS might provide a new approach to measure the strength of the efferent control and to evaluate the functional status of the central auditory pathway.

  10. [Impact of the Overlap Region Between Acoustic and Electric Stimulation].

    PubMed

    Baumann, Uwe; Mocka, Moritz

    2017-02-08

    Patients with residual hearing in the low frequencies and ski-slope hearing loss with partial deafness at medium and high frequencies receive a cochlear implant treatment with electric-acoustic stimulation (EAS, "hybrid" stimulation). In the border region between electric and acoustic stimulation a superposition of the 2 types of stimulation is expected. The area of overlap is determined by the insertion depth of the stimulating electrode and the lower starting point of signal transmission provided by the CI speech processor. The study examined the influence of the variation of the electric-acoustic overlap area on speech perception in noise, whereby the width of the "transmission gap" between the 2 different stimulus modalities was varied by 2 different methods. The results derived from 9 experienced users of the MED-EL Duet 2 speech processor show that the electric-acoustic overlapping area and with it the crossover frequency between the acoustic part and the CI should be adjusted individually. Overall, speech reception thresholds (SRT) showed a wide variation of results in between subjects. Further studies shall investigate whether generalized procedures about the setting of the overlap between electric and acoustic stimulation are reasonable, whereby an increased number of subjects and a longer period of acclimatization prior to the conduction of hearing tests deemed necessary.

  11. Responses evoked from man by acoustic stimulation

    NASA Technical Reports Server (NTRS)

    Galambos, R.; Hecox, K.; Picton, T.

    1974-01-01

    Clicks and other acoustic stimuli evoke time-locked responses from the brain of man. The properties of the waves recordable within the interval from 1 to 10 msec after the stimuli strike the eardrum are discussed along with factors influencing the waves in the 100 to 500 msec epoch. So-called brainstem responses from a normal young adult are considered. No waves were observed for clicks to weak to be heard. With increasing stimulus strength the waves become larger in amplitude and their latency shortens.

  12. Acoustic Wave Stimulated Enhanced Oil Recovery

    NASA Astrophysics Data System (ADS)

    Reichmann, Sven; Giese, Rüdiger; Amro, Mohammed

    2013-04-01

    High demand and the finite oil deposits will be a problem in the future. To temper the impact of a shortage in crude oil, a lot of research in the field of enhanced oil recovery (EOR) is worldwide ongoing. Using seismic waves to stimulate recovery of oil is known as seismic-EOR. The development of a stimulation procedure using seismic sources and the evaluation of the obtained data in a real oil field is the aim of the project WAVE.O.R. The project is funded by the German scientific society for oil, gas and coal (DGMK). The Technical University of Freiberg (TUBAF) and the German Research Center for Geosciences (GFZ) in Potsdam developed a flooding cell connected with magnetostrictive actuators as sources for seismic energy. This device is eligible to survey the impact of different seismic stimulation parameter like frequency, alignment, amplitude and rock characteristics on oil recovery. The obtained laboratory data of flooding experiments using seismic waves were analyzed for key features like water breakthrough point, oil recovery and oil fraction. New approach has been developed, which consists of the connection of a principal component analysis with a clustering algorithm. This new technique allows us a better understanding and thus prediction of the recovery behavior of oil bearing sediments. The experiments show promising possibilities to enhance oil recovery with seismic stimulation. Especially the combination of different frequencies between 100 Hz and 4000 Hz had a positive impact on oil recovery. The responsible mechanisms were identified and discussed. Data obtained with the laboratory device will be applied in a field test using a borehole device developed by the GFZ in the project "Seismic Prediction While Drilling" (SPWD). For this purpose experiments are conducted to obtain the radiation pattern of the seismic sources used by the SPWD device in a borehole. In addition, the development of a control setup for the 1-D actuator array is an aim of the

  13. Direct Intracochlear Acoustic Stimulation Using a PZT Microactuator.

    PubMed

    Luo, Chuan; Omelchenko, Irina; Manson, Robert; Robbins, Carol; Oesterle, Elizabeth C; Cao, Guo Zhong; Shen, I Y; Hume, Clifford R

    2015-12-01

    Combined electric and acoustic stimulation has proven to be an effective strategy to improve hearing in some cochlear implant users. We describe an acoustic microactuator to directly deliver stimuli to the perilymph in the scala tympani. The 800 µm by 800 µm actuator has a silicon diaphragm driven by a piezoelectric thin film (e.g., lead-zirconium-titanium oxide or PZT). This device could also be used as a component of a bimodal acoustic-electric electrode array. In the current study, we established a guinea pig model to test the actuator for its ability to deliver auditory signals to the cochlea in vivo. The actuator was placed through the round window of the cochlea. Auditory brainstem response (ABR) thresholds, peak latencies, and amplitude growth were calculated for an ear canal speaker versus the intracochlear actuator for tone burst stimuli at 4, 8, 16, and 24 kHz. An ABR was obtained after removal of the probe to assess loss of hearing related to the procedure. In some animals, the temporal bone was harvested for histologic analysis of cochlear damage. We show that the device is capable of stimulating ABRs in vivo with latencies and growth functions comparable to stimulation in the ear canal. Further experiments will be necessary to evaluate the efficiency and safety of this modality in long-term auditory stimulation and its ability to be integrated with conventional cochlear implant arrays.

  14. Direct Intracochlear Acoustic Stimulation Using a PZT Microactuator

    PubMed Central

    Luo, Chuan; Omelchenko, Irina; Manson, Robert; Robbins, Carol; Oesterle, Elizabeth C.; Cao, Guo Zhong; Hume, Clifford R.

    2015-01-01

    Combined electric and acoustic stimulation has proven to be an effective strategy to improve hearing in some cochlear implant users. We describe an acoustic microactuator to directly deliver stimuli to the perilymph in the scala tympani. The 800 µm by 800 µm actuator has a silicon diaphragm driven by a piezoelectric thin film (e.g., lead-zirconium-titanium oxide or PZT). This device could also be used as a component of a bimodal acoustic-electric electrode array. In the current study, we established a guinea pig model to test the actuator for its ability to deliver auditory signals to the cochlea in vivo. The actuator was placed through the round window of the cochlea. Auditory brainstem response (ABR) thresholds, peak latencies, and amplitude growth were calculated for an ear canal speaker versus the intracochlear actuator for tone burst stimuli at 4, 8, 16, and 24 kHz. An ABR was obtained after removal of the probe to assess loss of hearing related to the procedure. In some animals, the temporal bone was harvested for histologic analysis of cochlear damage. We show that the device is capable of stimulating ABRs in vivo with latencies and growth functions comparable to stimulation in the ear canal. Further experiments will be necessary to evaluate the efficiency and safety of this modality in long-term auditory stimulation and its ability to be integrated with conventional cochlear implant arrays. PMID:26631107

  15. Klamath Falls: High-Power Acoustic Well Stimulation Technology

    SciTech Connect

    Black, Brian

    2006-07-24

    Acoustic well stimulation (AWS) technology uses high-power sonic waves from specific frequency spectra in an attempt to stimulate production in a damaged or low-production wellbore. AWS technology is one of the most promising technologies in the oil and gas industry, but it has proven difficult for the industry to develop an effective downhole prototype. This collaboration between Klamath Falls Inc. and the Rocky Mountain Oilfield Testing Center (RMOTC) included a series of tests using high-power ultrasonic tools to stimulate oil and gas production. Phase I testing was designed and implemented to verify tool functionality, power requirements, and capacity of high-power AWS tools. The purpose of Phase II testing was to validate the production response of wells with marginal production rates to AWS stimulation and to capture and identify any changes in the downhole environment after tool deployment. This final report presents methodology and results.

  16. The facilitation of motor actions by acoustic and electric stimulation.

    PubMed

    Marinovic, Welber; Milford, Magdalene; Carroll, Timothy; Riek, Stephan

    2015-12-01

    The presentation of a loud acoustic stimulus during the preparation of motor actions can both speed movement initiation and increase response vigor. Several recent studies have explored this phenomenon as a means to investigate the mechanisms and neural correlates of movement preparation. Here, we sought to determine the generality of this effect across sensory modalities, and in particular whether unexpected somatosensory stimulation can facilitate movements in a manner similar to loud sounds. We show that electric and acoustic stimuli can be similarly effective in inducing the early release of motor actions, in both reaction time and anticipatory timing tasks. Consistent with recent response activation models of motor preparation, we also demonstrate that increasing the intensity of electric stimuli induces both progressive decreases in reaction time and increases in response vigor. Additionally, we show that the early release of motor actions can be induced by electric stimuli targeting predominantly either muscle afferents or skin afferents. Finally, we show that simultaneous acoustic and electric stimulation leads to earlier releases of anticipatory actions than either unimodal stimulus. These findings may lead to new avenues for experimental and clinical exploitation of the effects of accessory sensory information on movement preparation and initiation.

  17. Muscarinic cholinergic inhibition of beta-adrenergic stimulation of phospholamban phosphorylation and CaS transport in guinea pig ventricles

    SciTech Connect

    Lindemann, J.P.; Watanabe, A.M.

    1985-10-25

    The effects of muscarinic cholinergic stimulation on beta-adrenergic induced increases in phospholamban phosphorylation and CaS transport were studied in intact myocardium. Isolated guinea pig ventricles were perfused via the coronary arteries with TSPi, after which membrane vesicles were isolated from individual hearts. Isoproterenol produced reversible increases in TSP incorporation into phospholamban. Associated with the increases in TSP incorporation were increases in the initial rate of phosphate-facilitated CaS uptake measured in aliquots of the same membrane vesicles isolated from the perfused hearts. The increases in TSP incorporation and calcium transport were significantly attenuated by the simultaneous administration of acetylcholine. Acetylcholine also attenuated increases in phospholamban phosphorylation and CaS uptake produced by the phosphodiesterase inhibitor isobutylmethylxanthine and forskolin. The contractile effects of all agents which increased cAMP levels (increased contractility and a reduction in the t1/2 of relaxation) were also attenuated by acetylcholine. The inhibitory effects of acetylcholine were associated with attenuation of the increases in cAMP levels produced by isoproterenol and isobutylmethylxanthine but not by forskolin. Acetylcholine also increased the rate of reversal of the functional and biochemical effects of isoproterenol by propranolol without affecting cAMP levels. These results suggest that cholinergic agonists inhibit the functional effects of beta-adrenergic stimulation in part by inhibition of phospholamban phosphorylation. This inhibition may be mediated by two potential mechanisms: inhibition of beta-adrenergic activation of adenylate cyclase and stimulation of dephosphorylation.

  18. Cochlear dead regions constrain the benefit of combining acoustic stimulation with electric stimulation

    PubMed Central

    Zhang, Ting; Dorman, Michael F.; Gifford, Rene; Moore, Brian C.J.

    2014-01-01

    Objective The aims of this study were to (i) detect the presence and edge frequency (fe) of a cochlear dead region in the ear with residual acoustic hearing for bimodal cochlear implant (CI) users, and (ii) determine whether amplification based on the presence or absence of a dead region would improve speech understanding and sound quality. Design Twenty two listeners with a CI in one ear and residual acoustic hearing in the non-implanted ear were tested. Eleven listeners had a cochlear dead region in the acoustic-hearing ear and eleven did not. Dead regions were assessed with the threshold equalizing noise (TEN) and the sweeping noise, psychophysical tuning curve (SWPTC) tests. Speech understanding was assessed with monosyllabic words and the AzBio sentences at +10 dB signal-to-noise ratio. Speech and music quality judgments were obtained with the Judgment of Sound Quality questionnaire. Results For this population, using shifted tips of the PTCs as a basis for diagnosis, the TEN had high sensitivity (0.91) and poor specificity (0.55). The value of fe was lower when estimated with the SWPTC test than with the TEN test. For the listeners with cochlear dead regions, speech understanding, speech quality and music quality were best when no amplification was applied for frequencies within the dead region. For listeners without dead regions, speech understanding was best with full-bandwidth amplification and was reduced when amplification was not applied when the audiometric threshold exceeded 80 dB HL. Conclusion Our data suggest that, to improve bimodal benefit for listeners who combine electric and acoustic stimulation, audiologists should routinely test for the presence of cochlear dead regions and determine amplification bandwidth accordingly. PMID:24950254

  19. A new brain stimulation method: Noninvasive transcranial magneto-acoustical stimulation

    NASA Astrophysics Data System (ADS)

    Yuan, Yi; Chen, Yu-Dong; Li, Xiao-Li

    2016-08-01

    We investigate transcranial magneto-acoustical stimulation (TMAS) for noninvasive brain neuromodulation in vivo. TMAS as a novel technique uses an ultrasound wave to induce an electric current in the brain tissue in the static magnetic field. It has the advantage of high spatial resolution and penetration depth. The mechanism of TMAS onto a neuron is analyzed by combining the TMAS principle and Hodgkin-Huxley neuron model. The anesthetized rats are stimulated by TMAS, resulting in the local field potentials which are recorded and analyzed. The simulation results show that TMAS can induce neuronal action potential. The experimental results indicate that TMAS can not only increase the amplitude of local field potentials but also enhance the effect of focused ultrasound stimulation on the neuromodulation. In summary, TMAS can accomplish brain neuromodulation, suggesting a potentially powerful noninvasive stimulation method to interfere with brain rhythms for diagnostic and therapeutic purposes. Project supported by the National Natural Science Foundation of China (Grant Nos. 61503321 and 61273063) and the Natural Science Foundation of Hebei Province, China (Grant No. F2014203161).

  20. Courtship Initiation Is Stimulated by Acoustic Signals in Drosophila melanogaster

    PubMed Central

    Ejima, Aki; Griffith, Leslie C.

    2008-01-01

    Finding a mating partner is a critical task for many organisms. It is in the interest of males to employ multiple sensory modalities to search for females. In Drosophila melanogaster, vision is thought to be the most important courtship stimulating cue at long distance, while chemosensory cues are used at relatively short distance. In this report, we show that when visual cues are not available, sounds produced by the female allow the male to detect her presence in a large arena. When the target female was artificially immobilized, the male spent a prolonged time searching before starting courtship. This delay in courtship initiation was completely rescued by playing either white noise or recorded fly movement sounds to the male, indicating that the acoustic and/or seismic stimulus produced by movement stimulates courtship initiation, most likely by increasing the general arousal state of the male. Mutant males expressing tetanus toxin (TNT) under the control of Gr68a-GAL4 had a defect in finding active females and a delay in courtship initiation in a large arena, but not in a small arena. Gr68a-GAL4 was found to be expressed pleiotropically not only in putative gustatory pheromone receptor neurons but also in mechanosensory neurons, suggesting that Gr68a-positive mechanosensory neurons, not gustatory neurons, provide motion detection necessary for courtship initiation. TNT/Gr68a males were capable of discriminating the copulation status and age of target females in courtship conditioning, indicating that female discrimination and formation of olfactory courtship memory are independent of the Gr68a-expressing neurons that subserve gustation and mechanosensation. This study suggests for the first time that mechanical signals generated by a female fly have a prominent effect on males' courtship in the dark and leads the way to studying how multimodal sensory information and arousal are integrated in behavioral decision making. PMID:18802468

  1. Stimulated emission of phonons in an acoustic cavity

    NASA Astrophysics Data System (ADS)

    Tilstra, Lieuwe Gijsbert

    2001-10-01

    This thesis will present experiments on stimulated emission of phonons in dilute ruby following complete population inversion of the Zeeman-split E(2E) Kramers doublet by selective pulsed optical pumping into its upper component. The resulting phonon avalanches are detected by use of the R1 luminescence emanating from the inverted zone, located near the end face where the laser beam enters the crystal. The phonons appear to team up into a highly directional phonon beam. The phonon frequency is tunable from, say, 10-100 GHz via the magnetic field splitting of the doublet. Remarkably, the population of the lower doublet component, which is a measure of the number of phonons generated, evolves with a sequence of distinct steps. The time interval in between these steps equals 2L/v, corresponding to the time the phonons need to return to the inverted zone by reflection at the opposite end face at a distance L. The end faces of the ruby crystal thus form an acoustic cavity. The phonon beam passes the inverted zone repeatedly to be amplified further, in a manner similar to light in an optical laser. In other words, the basic ingredients for a phonon laser have been established.

  2. A Stable but Reversible Integrated Surrogate Reporter for Assaying CRISPR/Cas9-Stimulated Homology-directed Repair.

    PubMed

    Wen, Yahong; Liao, Grace; Pritchard, Thomas; Zhao, Ting-Ting; Connelly, Jon P; Pruett-Miller, Shondra M; Blanc, Valerie; Davidson, Nicholas O; Madison, Blair B

    2017-02-22

    The discovery and application of CRISPR/Cas9 technology for genome editing has greatly accelerated targeted mutagenesis in a variety of organisms. CRISPR/Cas9-mediated site-specific cleavage is typically exploited for the generation of insertions or deletions (indels) following aberrant dsDNA repair via the endogenous non-homology end-joining (NHEJ) pathway, or alternatively, for enhancing homology directed repair (HDR) to facilitate the generation of a specific mutation (or knock-in). However, there is a need for efficient cellular assays that can measure Cas9/guide RNA (gRNA) activity. Reliable methods for enriching and identifying desired mutants are also lacking. Here we describe a method using the Piggybac transposon for stable genomic integration of an H2B-GFP reporter or a hygromycin resistance gene for assaying Cas9 target cleavage and homology-directed repair (HDR). The H2B-GFP fusion protein provides increased stability and an obvious pattern of nuclear localization. This method, called SRIRACCHA (i.e., a stable, but reversible, integrated reporter for assaying CRISPR/Cas-stimulated HDR activity), enables the enrichment of mutants via selection of GFP-positive or hygromycin-resistant mammalian cells (immortalized or non-immortalized) as a surrogate for the modification of the endogenous target site. Currently available hyperactive Piggybac transposase mutants allow both delivery and removal of the surrogate reporters, with minimal risk of generating undesirable mutations. This assay permits rapid screening for efficient gRNAs, and the accelerated identification of mutant clones, and is applicable to many cell types. We foresee the utility of this approach in contexts in which the maintenance of genomic integrity is essential, for example, when engineering cells for therapeutic purposes.

  3. The effect of static force on round window stimulation with the direct acoustic cochlea stimulator.

    PubMed

    Maier, Hannes; Salcher, Rolf; Schwab, Burkard; Lenarz, Thomas

    2013-07-01

    The Direct Acoustic Cochlea Stimulator Partial Implant (DACS PI, Phonak Acoustic Implants SA, Switzerland) is intended to stimulate the cochlea by a conventional stapedotomy piston that is crimped onto the DACS PI artificial incus. An alternative approach to the round window (RW) is successfully done with other devices, having the advantage of being also independent of the existence of middle ear structure (e.g. ossicles). Here the possibility of stimulating the RW with the DACS actuator is investigated including the impact of static force on sound transmission to the cochlea. The maximum equivalent sound pressure output with RW stimulation was determined experimentally in fresh human temporal bones. Experiments were performed in analogy to the ASTM standard (F2504.24930-1) method for the output determination of implantable middle ear hearing devices (IMEHDs) in human cadaveric temporal bones (TBs). ASTM compliant temporal bones were stimulated with a prosthesis having a spherical tip (∅0.5 mm) attached to the actuator. The stimulation was performed perpendicular to the round window membrane (RWM) at varying position relative to the RW and the resulting static force on the RW membrane was determined. At each position the displacement output of the DACS PI actuator and the stapes footplate (SFP) vibration in response to actuator stimulation was measured with a Laser Doppler Velocimeter (LDV). By comparison of the achieved output at the stapes footplate in response to sound and transducer stimulation the equivalent sound pressure level at the tympanic membrane at 1Vrms input voltage was calculated assuming that the SFP displacement in both conditions is a measure of perceived loudness, as it is done in the ASTM standard. Ten TB preparations within the acceptance range of the ASTM standard were used for analysis. The actuator driven stapes footplate displacement amplitude as well as the resulting equivalent sound pressure level was highly dependent on the static

  4. Plasticity in human pitch perception induced by tonotopically mismatched electro-acoustic stimulation.

    PubMed

    Reiss, L A J; Turner, C W; Karsten, S A; Gantz, B J

    2014-01-03

    Under normal conditions, the acoustic pitch percept of a pure tone is determined mainly by the tonotopic place of the stimulation along the cochlea. Unlike acoustic stimulation, electric stimulation of a cochlear implant (CI) allows for the direct manipulation of the place of stimulation in human subjects. CI sound processors analyze the range of frequencies needed for speech perception and allocate portions of this range to the small number of electrodes distributed in the cochlea. Because the allocation is assigned independently of the original resonant frequency of the basilar membrane associated with the location of each electrode, CI users who have access to residual hearing in either or both ears often have tonotopic mismatches between the acoustic and electric stimulation. Here we demonstrate plasticity of place pitch representations of up to three octaves in Hybrid CI users after experience with combined electro-acoustic stimulation. The pitch percept evoked by single CI electrodes, measured relative to acoustic tones presented to the non-implanted ear, changed over time in directions that reduced the electro-acoustic pitch mismatch introduced by the CI programming. This trend was particularly apparent when the allocations of stimulus frequencies to electrodes were changed over time, with pitch changes even reversing direction in some subjects. These findings show that pitch plasticity can occur more rapidly and on a greater scale in the mature auditory system than previously thought possible. Overall, the results suggest that the adult auditory system can impose perceptual order on disordered arrays of inputs.

  5. Plasticity in Human Pitch Perception Induced by Tonotopically Mismatched Electro-Acoustic Stimulation

    PubMed Central

    Reiss, Lina A.J.; Turner, Christopher W.; Karsten, Sue A.; Gantz, Bruce J.

    2013-01-01

    Under normal conditions, the acoustic pitch percept of a pure tone is determined mainly by the tonotopic place of the stimulation along the cochlea. Unlike acoustic stimulation, electric stimulation of a cochlear implant (CI) allows for the direct manipulation of the place of stimulation in human subjects. CI sound processors analyze the range of frequencies needed for speech perception and allocate portions of this range to the small number of electrodes distributed in the cochlea. Because the allocation is assigned independently of the original resonant frequency of the basilar membrane associated with the location of each electrode, CI users who have access to residual hearing in either or both ears often have tonotopic mismatches between the acoustic and electric stimulation. Here we demonstrate plasticity of place pitch representations of up to 3 octaves in Hybrid CI users after experience with combined electro-acoustic stimulation. The pitch percept evoked by single CI electrodes, measured relative to acoustic tones presented to the non-implanted ear, changed over time in directions that reduced the electro-acoustic pitch mismatch introduced by the CI programming. This trend was particularly apparent when the allocations of stimulus frequencies to electrodes were changed over time, with pitch changes even reversing direction in some subjects. These findings show that pitch plasticity can occur more rapidly and on a greater scale in the mature auditory system than previously thought possible. Overall, the results suggest that the adult auditory system can impose perceptual order on disordered arrays of inputs. PMID:24157931

  6. Comparison of auditory responses determined by acoustic stimulation and by mechanical round window stimulation at equivalent stapes velocities.

    PubMed

    Lee, JangWoo; Seong, KiWoong; Lee, Sang-Heun; Lee, Kyu-Yup; Cho, Jin-Ho

    2014-08-01

    Active middle ear implants (AMEIs) have been studied to overcome the limitations of conventional hearing aids such as howling, occlusion, and social discrimination. AMEIs usually drive the oval window (OW) by means of transmitting vibrational force through the ossicles and the vibrational force corresponding to sound is generated from a mechanical actuator. Recently, round window (RW) stimulation using an AMEI such as a floating mass transducer (FMT) to deliver sound to the cochlea has been introduced and hearing improvement in clinical use has been reported. Although previous studies demonstrated that the auditory response to RW stimulation was comparable to a sound-evoked auditory response, few studies have investigated the quantification of the physiologic performance of an AMEI through RW stimulation on the inner ear in vivo. There is no established relationship between the cochlear responses and mechanical stimulation to RW. The aim of this study is to assess the physiologic response in RW stimulation by an AMEI. The transferred energy through the RW to the inner ear could estimate the response corresponding to acoustic stimulation in order to quantify the AMEI output in the ossicular chain or OW stimulation. The parameters of the auditory brainstem responses (ABRs) were measured and compared based on stapes velocities similar enough to be regarded as the same for acoustic stimulation to the external auditory canal (EAC) and mechanical stimulation to the RW in an in vivo system. In conclusion, this study showed that the amplitudes and latencies of the ABRs of acoustic and RW stimulation showed significant differences at comparable stapes velocities in an in vivo system. These differences in the ABR amplitudes and latencies reflect different output functions of the cochlea in response to different stimulation pathways. Therefore, it is necessary to develop a new method for quantifying the output of the cochlea in the case of RW stimulation.

  7. Information From the Voice Fundamental Frequency (F0) Region Accounts for the Majority of the Benefit When Acoustic Stimulation Is Added to Electric Stimulation

    PubMed Central

    Zhang, Ting; Dorman, Michael F.; Spahr, Anthony J.

    2013-01-01

    Objectives The aim of this study was to determine the minimum amount of low-frequency acoustic information that is required to achieve speech perception benefit in listeners with a cochlear implant in one ear and low-frequency hearing in the other ear. Design The recognition of monosyllabic words in quiet and sentences in noise was evaluated in three listening conditions: electric stimulation alone, acoustic stimulation alone, and combined electric and acoustic stimulation. The acoustic stimuli presented to the nonimplanted ear were either low-pass-filtered at 125, 250, 500, or 750 Hz, or unfiltered (wideband). Results Adding low-frequency acoustic information to electrically stimulated information led to a significant improvement in word recognition in quiet and sentence recognition in noise. Improvement was observed in the electric and acoustic stimulation condition even when the acoustic information was limited to the 125-Hz-low-passed signal. Further improvement for the sentences in noise was observed when the acoustic signal was increased to wideband. Conclusions Information from the voice fundamental frequency (F0) region accounts for the majority of the speech perception benefit when acoustic stimulation is added to electric stimulation. We propose that, in quiet, low-frequency acoustic information leads to an improved representation of voicing, which in turn leads to a reduction in word candidates in the lexicon. In noise, the robust representation of voicing allows access to low-frequency acoustic landmarks that mark syllable structure and word boundaries. These landmarks can bootstrap word and sentence recognition. PMID:20050394

  8. Towards multifocal ultrasonic neural stimulation II: design considerations for an acoustic retinal prosthesis

    NASA Astrophysics Data System (ADS)

    Naor, Omer; Hertzberg, Yoni; Zemel, Esther; Kimmel, Eitan; Shoham, Shy

    2012-04-01

    Ultrasound waves, widely used as a non-invasive diagnostic modality, were recently shown to stimulate neuronal activity. Functionally meaningful stimulation, as is required in order to form a unified percept, requires the dynamic generation of simultaneous stimulation patterns. In this paper, we examine the general feasibility and properties of an acoustic retinal prosthesis, a new vision restoration strategy that will combine ultrasonic neuro-stimulation and ultrasonic field sculpting technology towards non-invasive artificial stimulation of surviving neurons in a degenerating retina. We explain the conceptual framework for such a device, study its feasibility in an in vivo ultrasonic retinal stimulation study and discuss the associated design considerations and tradeoffs. Finally, we simulate and experimentally validate a new holographic method—the angular spectrum-GSW—for efficient generation of uniform and accurate continuous ultrasound patterns. This method provides a powerful, flexible solution to the problem of projecting complex acoustic images onto structures like the retina.

  9. Suppression and facilitation of auditory neurons through coordinated acoustic and midbrain stimulation: investigating a deep brain stimulator for tinnitus

    NASA Astrophysics Data System (ADS)

    Offutt, Sarah J.; Ryan, Kellie J.; Konop, Alexander E.; Lim, Hubert H.

    2014-12-01

    Objective. The inferior colliculus (IC) is the primary processing center of auditory information in the midbrain and is one site of tinnitus-related activity. One potential option for suppressing the tinnitus percept is through deep brain stimulation via the auditory midbrain implant (AMI), which is designed for hearing restoration and is already being implanted in deaf patients who also have tinnitus. However, to assess the feasibility of AMI stimulation for tinnitus treatment we first need to characterize the functional connectivity within the IC. Previous studies have suggested modulatory projections from the dorsal cortex of the IC (ICD) to the central nucleus of the IC (ICC), though the functional properties of these projections need to be determined. Approach. In this study, we investigated the effects of electrical stimulation of the ICD on acoustic-driven activity within the ICC in ketamine-anesthetized guinea pigs. Main Results. We observed ICD stimulation induces both suppressive and facilitatory changes across ICC that can occur immediately during stimulation and remain after stimulation. Additionally, ICD stimulation paired with broadband noise stimulation at a specific delay can induce greater suppressive than facilitatory effects, especially when stimulating in more rostral and medial ICD locations. Significance. These findings demonstrate that ICD stimulation can induce specific types of plastic changes in ICC activity, which may be relevant for treating tinnitus. By using the AMI with electrode sites positioned with the ICD and the ICC, the modulatory effects of ICD stimulation can be tested directly in tinnitus patients.

  10. Combining acoustic and electric stimulation in the service of speech recognition

    PubMed Central

    Dorman, Michael F.; Gifford, Rene H.

    2010-01-01

    The majority of recently implanted, cochlear implant patients can potentially benefit from a hearing aid in the ear contralateral to the implant. When patients combine electric and acoustic stimulation, word recognition in quiet and sentence recognition in noise increase significantly. Several studies suggest that the acoustic information that leads to the increased level of performance resides mostly in the frequency region of the voice fundamental, e.g. 125 Hz for a male voice. Recent studies suggest that this information aids speech recognition in noise by improving the recognition of lexical boundaries or word onsets. In some noise environments, patients with bilateral implants can achieve similar levels of performance as patients who combine electric and acoustic stimulation. Patients who have undergone hearing preservation surgery, and who have electric stimulation from a cochlear implant and who have low-frequency hearing in both the implanted and not-implanted ears, achieve the best performance in a high noise environment. PMID:20874053

  11. A partial hearing animal model for chronic electro-acoustic stimulation

    NASA Astrophysics Data System (ADS)

    Irving, S.; Wise, A. K.; Millard, R. E.; Shepherd, R. K.; Fallon, J. B.

    2014-08-01

    Objective. Cochlear implants (CIs) have provided some auditory function to hundreds of thousands of people around the world. Although traditionally carried out only in profoundly deaf patients, the eligibility criteria for implantation have recently been relaxed to include many partially-deaf patients with useful levels of hearing. These patients receive both electrical stimulation from their implant and acoustic stimulation via their residual hearing (electro-acoustic stimulation; EAS) and perform very well. It is unclear how EAS improves speech perception over electrical stimulation alone, and little evidence exists about the nature of the interactions between electric and acoustic stimuli. Furthermore, clinical results suggest that some patients that undergo cochlear implantation lose some, if not all, of their residual hearing, reducing the advantages of EAS over electrical stimulation alone. A reliable animal model with clinically-relevant partial deafness combined with clinical CIs is important to enable these issues to be studied. This paper outlines such a model that has been successfully used in our laboratory. Approach. This paper outlines a battery of techniques used in our laboratory to generate, validate and examine an animal model of partial deafness and chronic CI use. Main results. Ototoxic deafening produced bilaterally symmetrical hearing thresholds in neonatal and adult animals. Electrical activation of the auditory system was confirmed, and all animals were chronically stimulated via adapted clinical CIs. Acoustic compound action potentials (CAPs) were obtained from partially-hearing cochleae, using the CI amplifier. Immunohistochemical analysis allows the effects of deafness and electrical stimulation on cell survival to be studied. Significance. This animal model has applications in EAS research, including investigating the functional interactions between electric and acoustic stimulation, and the development of techniques to maintain residual

  12. A partial hearing animal model for chronic electro-acoustic stimulation

    PubMed Central

    Irving, S.; Wise, A.K.; Millard, R.E.; Shepherd, R.K.; Fallon, J.B.

    2014-01-01

    Objective Cochlear implants (CIs) have provided some auditory function to hundreds of thousands of people around the world. Although traditionally carried out only in profoundly deaf patients, the eligibility criteria for implantation have recently been relaxed to include many partially-deaf patients with useful levels of hearing. These patients receive both electrical stimulation from their implant and acoustic stimulation via their residual hearing (electro-acoustic stimulation; EAS) and perform very well. It is unclear how EAS improves speech perception over electrical stimulation alone, and little evidence exists about the nature of the interactions between electric and acoustic stimuli. Furthermore, clinical results suggest that some patients that undergo cochlear implantation lose some, if not all, of their residual hearing, reducing the advantages of EAS over electrical stimulation alone. A reliable animal model with clinically-relevant partial deafness combined with clinical CIs is important to enable these issues to be studied. This manuscript outlines such a model that has been successfully used in our laboratory. Approach This manuscript outlines a battery of techniques used in our laboratory to generate, validate and examine an animal model of partial deafness and chronic CI use. Main Result Ototoxic deafening produced bilaterally symmetrical hearing thresholds in neonatal and adult animals. Electrical activation of the auditory system was confirmed, and all animals were chronically stimulated via adapted clinical CIs. Acoustic compound action potentials (CAPs) were obtained from partially-hearing cochleae, using the CI amplifier. Immunohistochemical analysis allows the effects of deafness and electrical stimulation on cell survival to be studied. Significance This animal model has applications in EAS research, including investigating the functional interactions between electric and acoustic stimulation, and the development of techniques to maintain

  13. Mandarin Speech Perception in Combined Electric and Acoustic Stimulation

    PubMed Central

    Li, Yongxin; Zhang, Guoping; Galvin, John J.; Fu, Qian-Jie

    2014-01-01

    For deaf individuals with residual low-frequency acoustic hearing, combined use of a cochlear implant (CI) and hearing aid (HA) typically provides better speech understanding than with either device alone. Because of coarse spectral resolution, CIs do not provide fundamental frequency (F0) information that contributes to understanding of tonal languages such as Mandarin Chinese. The HA can provide good representation of F0 and, depending on the range of aided acoustic hearing, first and second formant (F1 and F2) information. In this study, Mandarin tone, vowel, and consonant recognition in quiet and noise was measured in 12 adult Mandarin-speaking bimodal listeners with the CI-only and with the CI+HA. Tone recognition was significantly better with the CI+HA in noise, but not in quiet. Vowel recognition was significantly better with the CI+HA in quiet, but not in noise. There was no significant difference in consonant recognition between the CI-only and the CI+HA in quiet or in noise. There was a wide range in bimodal benefit, with improvements often greater than 20 percentage points in some tests and conditions. The bimodal benefit was compared to CI subjects’ HA-aided pure-tone average (PTA) thresholds between 250 and 2000 Hz; subjects were divided into two groups: “better” PTA (<50 dB HL) or “poorer” PTA (>50 dB HL). The bimodal benefit differed significantly between groups only for consonant recognition. The bimodal benefit for tone recognition in quiet was significantly correlated with CI experience, suggesting that bimodal CI users learn to better combine low-frequency spectro-temporal information from acoustic hearing with temporal envelope information from electric hearing. Given the small number of subjects in this study (n = 12), further research with Chinese bimodal listeners may provide more information regarding the contribution of acoustic and electric hearing to tonal language perception. PMID:25386962

  14. A crucial role for DOK1 in PDGF-BB-stimulated glioma cell invasion through p130Cas and Rap1 signalling.

    PubMed

    Barrett, Angela; Evans, Ian M; Frolov, Antonina; Britton, Gary; Pellet-Many, Caroline; Yamaji, Maiko; Mehta, Vedanta; Bandopadhyay, Rina; Li, Ningning; Brandner, Sebastian; Zachary, Ian C; Frankel, Paul

    2014-06-15

    DOK1 regulates platelet-derived growth factor (PDGF)-BB-stimulated glioma cell motility. Mechanisms regulating tumour cell motility are essential for invasion and metastasis. We report here that PDGF-BB-mediated glioma cell invasion and migration are dependent on the adaptor protein downstream of kinase 1 (DOK1). DOK1 is expressed in several glioma cell lines and in tumour biopsies from high-grade gliomas. DOK1 becomes tyrosine phosphorylated upon PDGF-BB stimulation of human glioma cells. Knockdown of DOK1 or expression of a DOK1 mutant (DOK1FF) containing Phe in place of Tyr at residues 362 and 398, resulted in inhibition of both the PDGF-BB-induced tyrosine phosphorylation of p130Cas (also known as BCAR1) and the activation of Rap1. DOK1 colocalises with tyrosine phosphorylated p130Cas at the cell membrane of PDGF-BB-treated cells. Expression of a non-tyrosine-phosphorylatable substrate domain mutant of p130Cas (p130Cas15F) inhibited PDGF-BB-mediated Rap1 activation. Knockdown of DOK1 and Rap1 inhibited PDGF-BB-induced chemotactic cell migration, and knockdown of DOK1 and Rap1 and expression of DOK1FF inhibited PDGF-mediated three-dimensional (3D) spheroid invasion. These data show a crucial role for DOK1 in the regulation of PDGF-BB-mediated tumour cell motility through a p130Cas-Rap1 signalling pathway. [Corrected

  15. Perturbation and Nonlinear Dynamic Analysis of Acoustic Phonatory Signal in Parkinsonian Patients Receiving Deep Brain Stimulation

    ERIC Educational Resources Information Center

    Lee, Victoria S.; Zhou, Xiao Ping; Rahn, Douglas A., III; Wang, Emily Q.; Jiang, Jack J.

    2008-01-01

    Nineteen PD patients who received deep brain stimulation (DBS), 10 non-surgical (control) PD patients, and 11 non-pathologic age- and gender-matched subjects performed sustained vowel phonations. The following acoustic measures were obtained on the sustained vowel phonations: correlation dimension (D[subscript 2]), percent jitter, percent shimmer,…

  16. Acoustic Energy: An Innovative Technology for Stimulating Oil Wells

    SciTech Connect

    Edgar, Dorland E.; Peters, Robert W.; Johnson, Donald O.; Paulsen, P. David; Roberts, Wayne

    2006-04-30

    The objective of this investigation was to demonstrate the effectiveness of sonication in reducing the viscosity of heavy crude oils. Sonication is the use of acoustic or sound energy to produce physical and/or chemical changes in materials, usually fluids. The goal of the first project phase was to demonstrate a proof of concept for the project objective. Batch tests of three commercially available, single-weight oils (30-, 90-, and 120-wt) were performed in the laboratory. Several observations and conclusions were made from this series of experiments. These include the following: (1) In general, the lower the acoustic frequency, the greater the efficiency in reducing the viscosity of the oils; (2) Sonication treatment of the three oils resulted in reductions in viscosity that ranged from a low of 31% to a high of 75%; and (3) The results of the first phase of the project successfully demonstrated that sonication could reduce the viscosity of oils of differing viscosity. The goal of the second project phase was to demonstrate the ability of sonication to reduce the viscosity of three crude oils ranging from a light crude to a heavy crude. The experiments also were designed to examine the benefits of two proprietary chemical additives used in conjunction with sonication. Acoustic frequencies ranging from 800 Hz to 1.6 kHz were used in these tests, and a reactor chamber was designed for flow-through operation with a capacity of one gallon (3.8 liters). The three crude oils selected for use in the testing program were: (1) a heavy crude from California with a viscosity of approximately 65,000 cP (API gravity about 12{sup o}), (2) a crude from Alabama with a significant water content and a viscosity of approximately 6,000 cP (API gravity about 22 {sup o}), and (3) a light crude from the Middle East with a viscosity of approximately 700 cP (API gravity about 32{sup o}). The principal conclusions derived from the second project phase include the following: (1) The

  17. The Codacs™ direct acoustic cochlear implant actuator: exploring alternative stimulation sites and their stimulation efficiency.

    PubMed

    Grossöhmichen, Martin; Salcher, Rolf; Kreipe, Hans-Heinrich; Lenarz, Thomas; Maier, Hannes

    2015-01-01

    This work assesses the efficiency of the Codacs system actuator (Cochlear Ltd., Sydney Australia) in different inner ear stimulation modalities. Originally the actuator was intended for direct perilymph stimulation after stapedotomy using a piston prosthesis. A possible alternative application is the stimulation of middle ear structures or the round window (RW). Here the perilymph stimulation with a K-piston through a stapes footplate (SFP) fenestration (N = 10) as well as stimulation of the stapes head (SH) with a Bell prosthesis (N = 9), SFP stimulation with an Omega/Aerial prosthesis (N = 8) and reverse RW stimulation (N = 10) were performed in cadaveric human temporal bones (TBs). Codacs actuator output is expressed as equivalent sound pressure level (eq. SPL) using RW and SFP displacement responses, measured by Laser Doppler velocimetry as reference. The axial actuator coupling force in stimulation of stapes and RW was adjusted to ~5 mN. The Bell prosthesis and Omega/Aerial prosthesis stimulation generated similar mean eq. SPLs (Bell: 127.5-141.8 eq. dB SPL; Omega/Aerial: 123.6-143.9 eq. dB SPL), being significantly more efficient than K-piston perilymph stimulation (108.6-131.6 eq. dB SPL) and RW stimulation (108.3-128.2 eq. dB SPL). Our results demonstrate that SH, SFP and RW are adequate alternative stimulation sites for the Codacs actuator using coupling prostheses and an axial coupling force of ~5 mN. Based on the eq. SPLs, all investigated methods were adequate for in vivo hearing aid applications, provided that experimental conditions including constant coupling force will be implemented.

  18. Prenatal features of Pena-Shokeir sequence with atypical response to acoustic stimulation.

    PubMed

    Pittyanont, Sirida; Jatavan, Phudit; Suwansirikul, Songkiat; Tongsong, Theera

    2016-09-01

    A fetal sonographic screening examination performed at 23 weeks showed polyhydramnios, micrognathia, fixed postures of all long bones, but no movement and no breathing. The fetus showed fetal heart rate acceleration but no movement when acoustic stimulation was applied with artificial larynx. All these findings persisted on serial examinations. The neonate was stillborn at 37 weeks and a final diagnosis of Pena-Shokeir sequence was made. In addition to typical sonographic features of Pena-Shokeir sequence, fetal heart rate accelerations with no movement in response to acoustic stimulation suggests that peripheral myopathy may possibly play an important role in the pathogenesis of the disease. © 2016 Wiley Periodicals, Inc. J Clin Ultrasound 44:459-462, 2016.

  19. Contrast Enhancement for Thermal Acoustic Breast Cancer Imaging via Resonant Stimulation

    DTIC Science & Technology

    2008-03-01

    Wang, “Time-domain reconstruction for thermoa- coustic tomography in a speherical geometry,” IEEE Trans. Med. Imag., vol. 21, no. 7, pp. 814–822, Jul...comply with a collection of information if it does not display a currently valid OMB control number. PLEASE DO NOT RETURN YOUR FORM TO THE ABOVE ADDRESS...excited into resonance via EM stimulation, the effective acoustic scattering cross-section may increase by a factor in excess of 100 based on

  20. THE PSYCHOPHYSICS OF LOW-FREQUENCY ACOUSTIC HEARING IN ELECTRIC AND ACOUSTIC STIMULATION (EAS) AND BIMODAL PATIENTS

    PubMed Central

    Gifford, Rene H.; Dorman, Michael F.

    2013-01-01

    This paper provides a review of the current literature on psychophysical properties of low-frequency hearing, both before and after implantation, with a focus on frequency selectivity, nonlinear cochlear processing, and speech perception in temporally modulated maskers for bimodal listeners as well as patients with hearing preservation in the implanted ear and receiving combined electric and acoustic stimulation (EAS). In this paper we review our work, the work of others, and report results not previously published for speech perception in steady-state and temporally fluctuating maskers; the degree of masking release and frequency resolution for 11 bimodal, 6 hearing preservation patients; and 5 control subjects with normal hearing. The results demonstrate that a small masking release is possible with acoustic hearing in just one ear, with the degree of masking release being correlated with the low-frequency pure tone average in the non-implanted ear; furthermore, frequency selectivity as defined by the width of the auditory filter was not correlated with the degree of masking release. Descriptions of the clinical utility of hearing preservation in the implanted ear for improving speech perception in complex listening environments, as well as directions for the future, are discussed. PMID:24244874

  1. Direct Acoustic Stimulation at the Lateral Canal: An Alternative Route to the Inner Ear?

    PubMed Central

    Walraevens, Joris; Desloovere, Christian; Wouters, Jan; Gérard, Jean-Marc

    2016-01-01

    Severe to profound mixed hearing loss is associated with hearing rehabilitation difficulties. Recently, promising results for speech understanding were obtained with a direct acoustic cochlear implant (DACI). The surgical implantation of a DACI with standard coupling through a stapedotomy can however be regarded as challenging. Therefore, in this experimental study, the feasibility of direct acoustic stimulation was investigated at an anatomically and surgically more accessible inner ear site. DACI stimulation of the intact, blue-lined and opened lateral semicircular canal (LC) was investigated and compared with standard oval window (OW) coupling. Additionally, stapes footplate fixation was induced. Round window (RW) velocity, as a measure of the performance of the device and its coupling efficiency, was determined in fresh-frozen human cadaver heads. Using single point laser Doppler vibrometry, RW velocity could reliably be measured in low and middle frequency range, and equivalent sound pressure level (LE) output was calculated. Results for the different conditions obtained in five heads were analyzed in subsequent frequency ranges. Comparing the difference in RW membrane velocity showed higher LE in the LC opened condition [mean: 103 equivalent dB SPL], than in LC intact or blue-lined conditions [63 and 74 equivalent dB SPL, respectively]. No difference was observed between the LC opened and the standard OW condition. Inducing stapes fixation, however, led to a difference in the low frequency range of LE compared to LC opened. In conclusion, this feasibility study showed promising results for direct acoustic stimulation at this specific anatomically and surgically more accessible inner ear site. Future studies are needed to address the impact of LC stimulation on cochlear micromechanics and on the vestibular system like dizziness and risks of hearing loss. PMID:27500399

  2. Direct Acoustic Stimulation at the Lateral Canal: An Alternative Route to the Inner Ear?

    PubMed

    Verhaert, Nicolas; Walraevens, Joris; Desloovere, Christian; Wouters, Jan; Gérard, Jean-Marc

    2016-01-01

    Severe to profound mixed hearing loss is associated with hearing rehabilitation difficulties. Recently, promising results for speech understanding were obtained with a direct acoustic cochlear implant (DACI). The surgical implantation of a DACI with standard coupling through a stapedotomy can however be regarded as challenging. Therefore, in this experimental study, the feasibility of direct acoustic stimulation was investigated at an anatomically and surgically more accessible inner ear site. DACI stimulation of the intact, blue-lined and opened lateral semicircular canal (LC) was investigated and compared with standard oval window (OW) coupling. Additionally, stapes footplate fixation was induced. Round window (RW) velocity, as a measure of the performance of the device and its coupling efficiency, was determined in fresh-frozen human cadaver heads. Using single point laser Doppler vibrometry, RW velocity could reliably be measured in low and middle frequency range, and equivalent sound pressure level (LE) output was calculated. Results for the different conditions obtained in five heads were analyzed in subsequent frequency ranges. Comparing the difference in RW membrane velocity showed higher LE in the LC opened condition [mean: 103 equivalent dB SPL], than in LC intact or blue-lined conditions [63 and 74 equivalent dB SPL, respectively]. No difference was observed between the LC opened and the standard OW condition. Inducing stapes fixation, however, led to a difference in the low frequency range of LE compared to LC opened. In conclusion, this feasibility study showed promising results for direct acoustic stimulation at this specific anatomically and surgically more accessible inner ear site. Future studies are needed to address the impact of LC stimulation on cochlear micromechanics and on the vestibular system like dizziness and risks of hearing loss.

  3. Two-Bubble Acoustic Tweezing Cytometry for Biomechanical Probing and Stimulation of Cells

    PubMed Central

    Chen, Di; Sun, Yubing; Gudur, Madhu S.R.; Hsiao, Yi-Sing; Wu, Ziqi; Fu, Jianping; Deng, Cheri X.

    2015-01-01

    The study of mechanotransduction relies on tools that are capable of applying mechanical forces to elicit and assess cellular responses. Here we report a new (to our knowledge) technique, called two-bubble acoustic tweezing cytometry (TB-ATC), for generating spatiotemporally controlled subcellular mechanical forces on live cells by acoustic actuation of paired microbubbles targeted to the cell adhesion receptor integrin. By measuring the ultrasound-induced activities of cell-bound microbubbles and the actin cytoskeleton contractile force responses, we determine that TB-ATC elicits mechanoresponsive cellular changes via cyclic, paired displacements of integrin-bound microbubbles driven by the attractive secondary acoustic radiation force (sARF) between the bubbles in an ultrasound field. We demonstrate the feasibility of dual-mode TB-ATC for both subcellular probing and mechanical stimulation. By exploiting the robust and unique interaction of ultrasound with microbubbles, TB-ATC provides distinct advantages for experimentation and quantification of applied forces and cellular responses for biomechanical probing and stimulation of cells. PMID:25564850

  4. Support of a patient-specific therapeutical acoustic stimulation in tinnitus by numerical modeling.

    PubMed

    Haab, L; Scheerer, M; Ruckert, J; Hannemann, R; Strauss, D J

    2012-01-01

    The pathogenesis of tinnitus involves multiple hierarchical levels of auditory processing and appraisal of sensory saliency. Early tinnitus onset is most likely attributed to homeostatic plasticity in the periphery, while the chronification and decompensation are tightly linked to brain areas for the allocation of attentional resources, such as e.g., the thalamocortical feedback loops and the limbic system. Increased spontaneous firing after sensory deafferentation might be sufficient to generate a phantom perception, yet the question why not every peripheral hearing loss automatically elicits a tinnitus sensation is still to be addressed. Utilizing quantitative modeling of multiple hierarchical levels in the auditory pathway, we demonstrate the effects of lateral inhibition on increased spontaneous firing and the resulting elevation of firing regularity and synchronization of neural activity. The presented therapeutical approach is based on the idea of disrupting the heightened regularity of the neural population response in the tinnitus frequency range. This neural activity regularity depends on lateral dispersion of common noise and thus is susceptible for edge effects and might be influenced by a change in neural activity in bordering frequency ranges by fitted acoustical stimulation. We propose the use of patient specifically adapted tailor-made notched acoustic stimulation, utilizing modeling results for the optimal adjustment of the stimulation frequencies to archive a therapeutical edge-effect.

  5. Cochlear Implant Electrode Effect on Sound Energy Transfer within the Cochlea during Acoustic Stimulation

    PubMed Central

    Greene, Nathaniel T.; Mattingly, Jameson K.; Jenkins, Herman A.; Tollin, Daniel J.; Easter, James R.; Cass, Stephen P.

    2015-01-01

    Hypothesis Cochlear implants (CI) designed for hearing preservation will not alter mechanical properties of the middle and inner ear as measured by intracochlear pressure (PIC) and stapes velocity (Vstap). Background CIs designed to provide combined electrical and acoustic stimulation (EAS) are now available. To maintain functional acoustic hearing, it is important to know if a CI electrode can alter middle or inner ear mechanics, as any alteration could contribute to elevated low-frequency thresholds in EAS patients. Methods Seven human cadaveric temporal bones were prepared, and pure-tone stimuli from 120Hz–10kHz were presented at a range of intensities up to 110 dB SPL. PIC in the scala vestibuli (PSV) and tympani (PST) were measured with fiber-optic pressure sensors concurrently with VStap using laser Doppler vibrometry. Five CI electrodes from two different manufacturers, with varying dimensions were inserted via a round window approach at six different depths (16–25 mm). Results The responses of PIC and VStap to acoustic stimulation were assessed as a function of stimulus frequency, normalized to SPL in the external auditory canal (EAC), in baseline and electrode inserted conditions. Responses measured with electrodes inserted were generally within ~5 dB of baseline, indicating little effect of cochlear implant electrode insertion on PIC and VStap. Overall, mean differences across conditions were small for all responses, and no substantial differences were consistently visible across electrode types. Conclusions Results suggest that the influence of a CI electrode on middle and inner ear mechanics is minimal, despite variation in electrode lengths and configurations. PMID:26333018

  6. Cristallisation par onde acoustique : le cas de l'héliumCrystallization by acoustic waves: the case of helium

    NASA Astrophysics Data System (ADS)

    Ben Amar, Martine; Brenner, Michael P.; Rice, James R.

    2003-09-01

    We establish a theoretical model to explain the nucleation of a crystal of helium by an acoustic over-pressure. We explain the interfacial laws for this ultra-fast cristallization, close to the sound speed. Assuming spherical symmetry and taking into account the experimental data, we recover the dynamics of the growth and melting during an over-pressure impulse. To cite this article: M. Ben Amar et al., C. R. Mecanique 331 (2003).

  7. The advantages of sound localization and speech perception of bilateral electric acoustic stimulation

    PubMed Central

    Moteki, Hideaki; Kitoh, Ryosuke; Tsukada, Keita; Iwasaki, Satoshi; Nishio, Shin-Ya

    2015-01-01

    Conclusion: Bilateral electric acoustic stimulation (EAS) effectively improved speech perception in noise and sound localization in patients with high-frequency hearing loss. Objective: To evaluate bilateral EAS efficacy of sound localization detection and speech perception in noise in two cases of high-frequency hearing loss. Methods: Two female patients, aged 38 and 45 years, respectively, received bilateral EAS sequentially. Pure-tone audiometry was performed preoperatively and postoperatively to evaluate the hearing preservation in the lower frequencies. Speech perception outcomes in quiet and noise and sound localization were assessed with unilateral and bilateral EAS. Results: Residual hearing in the lower frequencies was well preserved after insertion of a FLEX24 electrode (24 mm) using the round window approach. After bilateral EAS, speech perception improved in quiet and even more so in noise. In addition, the sound localization ability of both cases with bilateral EAS improved remarkably. PMID:25423260

  8. Effects of contextual cues on speech recognition in simulated electric-acoustic stimulation

    PubMed Central

    Kong, Ying-Yee; Donaldson, Gail; Somarowthu, Ala

    2015-01-01

    Low-frequency acoustic cues have shown to improve speech perception in cochlear-implant listeners. However, the mechanisms underlying this benefit are still not well understood. This study investigated the extent to which low-frequency cues can facilitate listeners' use of linguistic knowledge in simulated electric-acoustic stimulation (EAS). Experiment 1 examined differences in the magnitude of EAS benefit at the phoneme, word, and sentence levels. Speech materials were processed via noise-channel vocoding and lowpass (LP) filtering. The amount of spectral degradation in the vocoder speech was varied by applying different numbers of vocoder channels. Normal-hearing listeners were tested on vocoder-alone, LP-alone, and vocoder + LP conditions. Experiment 2 further examined factors that underlie the context effect on EAS benefit at the sentence level by limiting the low-frequency cues to temporal envelope and periodicity (AM + FM). Results showed that EAS benefit was greater for higher-context than for lower-context speech materials even when the LP ear received only low-frequency AM + FM cues. Possible explanations for the greater EAS benefit observed with higher-context materials may lie in the interplay between perceptual and expectation-driven processes for EAS speech recognition, and/or the band-importance functions for different types of speech materials. PMID:25994712

  9. Effects of contextual cues on speech recognition in simulated electric-acoustic stimulation.

    PubMed

    Kong, Ying-Yee; Donaldson, Gail; Somarowthu, Ala

    2015-05-01

    Low-frequency acoustic cues have shown to improve speech perception in cochlear-implant listeners. However, the mechanisms underlying this benefit are still not well understood. This study investigated the extent to which low-frequency cues can facilitate listeners' use of linguistic knowledge in simulated electric-acoustic stimulation (EAS). Experiment 1 examined differences in the magnitude of EAS benefit at the phoneme, word, and sentence levels. Speech materials were processed via noise-channel vocoding and lowpass (LP) filtering. The amount of spectral degradation in the vocoder speech was varied by applying different numbers of vocoder channels. Normal-hearing listeners were tested on vocoder-alone, LP-alone, and vocoder + LP conditions. Experiment 2 further examined factors that underlie the context effect on EAS benefit at the sentence level by limiting the low-frequency cues to temporal envelope and periodicity (AM + FM). Results showed that EAS benefit was greater for higher-context than for lower-context speech materials even when the LP ear received only low-frequency AM + FM cues. Possible explanations for the greater EAS benefit observed with higher-context materials may lie in the interplay between perceptual and expectation-driven processes for EAS speech recognition, and/or the band-importance functions for different types of speech materials.

  10. Stimulated Raman scattering in the presence of suprathermal ion acoustic fluctuations in inhomogeneous plasma

    NASA Astrophysics Data System (ADS)

    Barr, H. C.; Boyd, T. J. M.; Lukyanov, A. V.

    2000-03-01

    In this report a complex Raman scattering event against a background of nonthermal ion coustic waves in an inhomogenous plasma is considered. The complex Raman process is a five-wave interaction in which three-wave stimulated Raman scattering (SRS) is accompanied by the decay of the Raman Langmuir wave into either a second Langmuir wave (LD) or a second scattered light wave (ED) and an ion acoustic wave. An extension of Stokes’ theory is used to obtain expressions for the gain in the Raman Langmuir and scattered waves. It is shown that only very modest levels of ion waves are needed to produce duce a significant effect on the net Raman convective gain which proves to be sensitive to the source levels of the amplifying waves. For LD the gain from the Raman Langmuir wave source is suppressed while that from the secondary Langmuir wave is enhanced such that the net gain is increased or decreased depending on which of the two sources is greater. When the source levels of both Langmuir waves are at thermal levels, opposing effects mean no net change in the gain factor irrespective of the ion acoustic wave amplitude. For ED the gain is invariably suppressed for any source distributions. Two possible regimes of an enhanced effect have been identified: exact sidescattering for ED and the supersonic point vicinity for LD(ED). The theory thus provides a possible explanation for a variety of the observed effects in the interplay between SRS and stimulated Brillouin scattering, both of concern in laser fusion schemes.

  11. Effect of Digital Frequency Compression (DFC) on Speech Recognition in Candidates for Combined Electric and Acoustic Stimulation (EAS)

    ERIC Educational Resources Information Center

    Gifford, Rene H.; Dorman, Michael F.; Spahr, Anthony J.; McKarns, Sharon A.

    2007-01-01

    Purpose: To compare the effects of conventional amplification (CA) and digital frequency compression (DFC) amplification on the speech recognition abilities of candidates for a partial-insertion cochlear implant, that is, candidates for combined electric and acoustic stimulation (EAS). Method: The participants were 6 patients whose audiometric…

  12. Theoretical Analysis of Transcranial Magneto-Acoustical Stimulation with Hodgkin-Huxley Neuron Model

    PubMed Central

    Yuan, Yi; Chen, Yudong; Li, Xiaoli

    2016-01-01

    Transcranial magneto-acoustical stimulation (TMAS) is a novel stimulation technology in which an ultrasonic wave within a magnetostatic field generates an electric current in an area of interest in the brain to modulate neuronal activities. As a key part of the neural network, neurons transmit information in the nervous system. However, the effect of TMAS on the neuronal firing pattern remains unknown. To address this problem, we investigated the stimulatory mechanism of TMAS on neurons, by using a Hodgkin-Huxley neuron model. The simulation results indicated that the magnetostatic field intensity and ultrasonic power affect the amplitude and interspike interval of neuronal action potential under a continuous wave ultrasound. The simulation results also showed that the ultrasonic power, duty cycle and repetition frequency can alter the firing pattern of neural action potential under pulsed wave ultrasound. This study may help to reveal and explain the biological mechanism of TMAS and to provide a theoretical basis for TMAS in the treatment or rehabilitation of neuropsychiatric disorders. PMID:27148032

  13. Hearing preservation and clinical outcome of 32 consecutive electric acoustic stimulation (EAS) surgeries

    PubMed Central

    Moteki, Hideaki; Tsukada, Keita; Miyagawa, Maiko; Nishio, Shin-Ya; Takumi, Yutaka; Iwasaki, Satoshi; Kumakawa, Kozo; Naito, Yasushi; Takahashi, Haruo; Kanda, Yukihiko; Tono, Tetsuya

    2014-01-01

    Conclusions Our results indicated that electric acoustic stimulation (EAS) is beneficial for Japanese-speaking patients, including those with less residual hearing at lower frequencies. Comparable outcomes for the patients with less residual hearing indicated that current audiological criteria for EAS could be expanded. Successful hearing preservation results, together with the progressive nature of loss of residual hearing in these patients, mean that minimally invasive full insertion of medium/long electrodes in cochlear implantation (CI) surgery is a desirable solution. The minimally invasive concepts that have been obtained through EAS surgery are, in fact, crucial for all CI patients. Objectives This study was conducted to evaluate hearing preservation results and speech discrimination outcomes of hearing preservation surgeries using medium/long electrodes. Methods A total of 32 consecutive minimally invasive hearing preservation CIs (using a round window approach with deep insertion of a flexible electrode) were performed in 30 Japanese patients (two were bilateral cases), including patients with less residual hearing. Hearing preservation rates as well as speech discrimination/perception scores were investigated on a multicenter basis. Results Postoperative evaluation after full insertion of the flexible electrodes (24 mm, 31.5 mm) showed that residual hearing was well preserved in all 32 ears. In all patients, speech discrimination and perception scores were improved postoperatively. PMID:24834939

  14. A simulation study of harmonics regeneration in noise reduction for electric and acoustic stimulation

    PubMed Central

    Hu, Yi

    2010-01-01

    Recent research results show that combined electric and acoustic stimulation (EAS) significantly improves speech recognition in noise, and it is generally established that access to the improved F0 representation of target speech, along with the glimpse cues, provide the EAS benefits. Under noisy listening conditions, noise signals degrade these important cues by introducing undesired temporal-frequency components and corrupting harmonics structure. In this study, the potential of combining noise reduction and harmonics regeneration techniques was investigated to further improve speech intelligibility in noise by providing improved beneficial cues for EAS. Three hypotheses were tested: (1) noise reduction methods can improve speech intelligibility in noise for EAS; (2) harmonics regeneration after noise reduction can further improve speech intelligibility in noise for EAS; and (3) harmonics sideband constraints in frequency domain (or equivalently, amplitude modulation in temporal domain), even deterministic ones, can provide additional benefits. Test results demonstrate that combining noise reduction and harmonics regeneration can significantly improve speech recognition in noise for EAS, and it is also beneficial to preserve the harmonics sidebands under adverse listening conditions. This finding warrants further work into the development of algorithms that regenerate harmonics and the related sidebands for EAS processing under noisy conditions. PMID:21117763

  15. Design of a semi-implantable hearing device for direct acoustic cochlear stimulation.

    PubMed

    Bernhard, Hans; Stieger, Christof; Perriard, Yves

    2011-02-01

    A new hearing therapy based on direct acoustic cochlear stimulation was developed for the treatment of severe to profound mixed hearing loss. The device efficacy was validated in an initial clinical trial with four patients. This semi-implantable investigational device consists of an externally worn audio processor, a percutaneous connector, and an implantable microactuator. The actuator is placed in the mastoid bone, right behind the external auditory canal. It generates vibrations that are directly coupled to the inner ear fluids and that, therefore, bypass the external and the middle ear. The system is able to provide an equivalent sound pressure level of 125 dB over the frequency range between 125 and 8000 Hz. The hermetically sealed actuator is designed to provide maximal output power by keeping its dimensions small enough to enable implantation. A network model is used to simulate the dynamic characteristics of the actuator to adjust its transfer function to the characteristics of the middle ear. The geometry of the different actuator components is optimized using finite-element modeling.

  16. A simulation study of harmonics regeneration in noise reduction for electric and acoustic stimulation.

    PubMed

    Hu, Yi

    2010-05-01

    Recent research results show that combined electric and acoustic stimulation (EAS) significantly improves speech recognition in noise, and it is generally established that access to the improved F0 representation of target speech, along with the glimpse cues, provide the EAS benefits. Under noisy listening conditions, noise signals degrade these important cues by introducing undesired temporal-frequency components and corrupting harmonics structure. In this study, the potential of combining noise reduction and harmonics regeneration techniques was investigated to further improve speech intelligibility in noise by providing improved beneficial cues for EAS. Three hypotheses were tested: (1) noise reduction methods can improve speech intelligibility in noise for EAS; (2) harmonics regeneration after noise reduction can further improve speech intelligibility in noise for EAS; and (3) harmonics sideband constraints in frequency domain (or equivalently, amplitude modulation in temporal domain), even deterministic ones, can provide additional benefits. Test results demonstrate that combining noise reduction and harmonics regeneration can significantly improve speech recognition in noise for EAS, and it is also beneficial to preserve the harmonics sidebands under adverse listening conditions. This finding warrants further work into the development of algorithms that regenerate harmonics and the related sidebands for EAS processing under noisy conditions.

  17. Acoustic stimulation causes tonotopic alterations in the length of isolated outer hair cells from guinea pig hearing organ.

    PubMed Central

    Canlon, B; Brundin, L; Flock, A

    1988-01-01

    Isolated outer hair cells from the mammalian cochlea exhibit a motile response to electrical or chemical stimulation. Here we show that isolated outer hair cells can also respond to acoustic stimulation, in the form of a tone burst of 200 Hz, by either shortening or lengthening depending on their cochlear location. Cells from the apical region of the cochlea (long cells) responded by increasing their length, whereas those from more basal regions (short cells) responded by decreasing their length. Cells from intermediate positions showed an equal probability for either elongating or shortening. Both the elongating and shortening response was inhibited by 3 microM poly(L-lysine). It is suggested that this tonotopic and bidirectional acoustic response may be one of the active components underlying the specific phase and frequency displacement of the basilar membrane. Images PMID:3413135

  18. Frequency-specific adaptation in human auditory cortex depends on the spectral variance in the acoustic stimulation.

    PubMed

    Herrmann, Björn; Henry, Molly J; Obleser, Jonas

    2013-04-01

    In auditory cortex, activation and subsequent adaptation is strongest for regions responding best to a stimulated tone frequency and less for regions responding best to other frequencies. Previous attempts to characterize the spread of neural adaptation in humans investigated the auditory cortex N1 component of the event-related potentials. Importantly, however, more recent studies in animals show that neural response properties are not independent of the stimulation context. To link these findings in animals to human scalp potentials, we investigated whether contextual factors of the acoustic stimulation, namely, spectral variance, affect the spread of neural adaptation. Electroencephalograms were recorded while human participants listened to random tone sequences varying in spectral variance (narrow vs. wide). Spread of adaptation was investigated by modeling single-trial neural adaptation and subsequent recovery based on the spectro-temporal stimulation history. Frequency-specific neural responses were largest on the N1 component, and the modeled neural adaptation indices were strongly predictive of trial-by-trial amplitude variations. Yet the spread of adaption varied depending on the spectral variance in the stimulation, such that adaptation spread was broadened for tone sequences with wide spectral variance. Thus the present findings reveal context-dependent auditory cortex adaptation and point toward a flexibly adjusting auditory system that changes its response properties with the spectral requirements of the acoustic environment.

  19. Acoustics

    NASA Technical Reports Server (NTRS)

    Goodman, Jerry R.; Grosveld, Ferdinand

    2007-01-01

    The acoustics environment in space operations is important to maintain at manageable levels so that the crewperson can remain safe, functional, effective, and reasonably comfortable. High acoustic levels can produce temporary or permanent hearing loss, or cause other physiological symptoms such as auditory pain, headaches, discomfort, strain in the vocal cords, or fatigue. Noise is defined as undesirable sound. Excessive noise may result in psychological effects such as irritability, inability to concentrate, decrease in productivity, annoyance, errors in judgment, and distraction. A noisy environment can also result in the inability to sleep, or sleep well. Elevated noise levels can affect the ability to communicate, understand what is being said, hear what is going on in the environment, degrade crew performance and operations, and create habitability concerns. Superfluous noise emissions can also create the inability to hear alarms or other important auditory cues such as an equipment malfunctioning. Recent space flight experience, evaluations of the requirements in crew habitable areas, and lessons learned (Goodman 2003; Allen and Goodman 2003; Pilkinton 2003; Grosveld et al. 2003) show the importance of maintaining an acceptable acoustics environment. This is best accomplished by having a high-quality set of limits/requirements early in the program, the "designing in" of acoustics in the development of hardware and systems, and by monitoring, testing and verifying the levels to ensure that they are acceptable.

  20. Indication of direct acoustical cochlea stimulation in comparison to cochlear implants.

    PubMed

    Kludt, Eugen; Büchner, Andreas; Schwab, Burkard; Lenarz, Thomas; Maier, Hannes

    2016-10-01

    The new implantable hearing system Codacs™ was designed to close the treatment gap between active middle ear implants and cochlear implants in cases of severe-to-profound mixed hearing loss. The Codacs™ actuator is attached to conventional stapes prosthesis during the implantation and thereby provides acoustical stimulation through a stapedotomy to the cochlea. Cochlear implants (CIs) on the other hand are an established treatment option for profoundly deaf patients including mixed hearing losses that are possible candidates for the Codacs™. In this retrospective study, we compared the clinical outcome of 25 patients with the Codacs™ (≥3 month post-activation) to 54 CI patients (two years post-activation) with comparable pre-operative bone conduction (BC) thresholds that were potential candidates for both categories of devices. The word recognition score (Freiburg monosyllables test) in quiet was significantly (p < 0.05) better in the Codacs™ than in the corresponding CI patients for average pre-operative bone conduction below 60 dB HL and equal in patients with a pre-operative BC PTA between 60 and 70 dB HL. Speech in noise intelligibility (HSM sentences test at +10 dB SNR) was significantly (p < 0.001) better in Codacs™ (80% median) than in CI patients (25% median) in all tested groups. Our results indicate for patients with sufficient cochlear reserve that speech intelligibility in noise with the Codacs™ hearing implant is significantly better than with a CI. Further, results in Codacs™ were better predictable, encouraging the extension of the indication to patients with less cochlear reserve than reported here.

  1. Detection of dead regions in the cochlea: relevance for combined electric and acoustic stimulation.

    PubMed

    Moore, Brian C J; Glasberg, Brian; Schlueter, Anne

    2010-01-01

    A dead region is a region in the cochlea where the inner hair cells and/or the auditory neurones are functioning very poorly, if at all. People who are being considered for a combination of a cochlear implant and a hearing aid typically have a dead region in the parts of the cochlea that normally respond to medium and high frequencies, but have some functional hearing at lower frequencies. For such people, it may be useful to determine the edge frequency, f(e), of any dead region. This may be relevant to choosing the most appropriate insertion depth of the electrode array, and to the way that frequencies in the input signal are mapped to acoustic and electric stimulation. It may also be helpful in interpreting the results of research studies. This paper reviews methods for diagnosing dead regions and defining the value of f(e). It is argued that the value of f(e) cannot be determined reliably from the audiogram, although a dead region is likely to be present at a given frequency when the hearing loss at that frequency is 70 dB or more. When a sinusoidal signal is reported as sounding highly distorted or noise-like, a dead region may be present at the signal frequency, but again this is not a reliable indicator. The TEN test is a simple clinical method for diagnosis of dead regions. Where this test gives a positive diagnosis, it is recommended that psychophysical tuning curves be measured to define the value of f(e) more precisely.

  2. Investigation on optical and acoustic fields of stimulated Brillouin scattering in As2S3 suspended-core optical fibers

    NASA Astrophysics Data System (ADS)

    Xu, Qiang; Gao, Weiqing; Li, Xue; Ni, Chenquan; Chen, Xiangcai; Chen, Li; Zhang, Wei; Hu, Jigang; Chen, Xiangdong; Yuan, Zijun

    2016-10-01

    The optical and acoustic fields of stimulated Brillouin scattering (SBS) effect in the As2S3 chalcogenide suspended-core microstructured optical fibers (MOFs) are investigated by the finite-element method (FEM). The optical and acoustic fundamental modes at 1550 nm are analyzed with the core diameters of the MOFs varying from 1.0 to 6.0 μm. For each case, the holes of the MOFs are filled with different materials such as trichlormethane (CHCL3), alcohol and water. When the core diameter is 6.0 μm, the maximum peak intensity of the optical fundamental mode is in the case with air holes, while the minimum value is in the case filled with CHCL3. The ratio of difference is 0.66%. The minimum peak intensity of the acoustic fundamental mode is in the case with air holes, while the maximum value is in the case filled with water. The ratio of difference is 0.13%. The same rule occurs in the fiber cores of 4.5, 3.0 and 2.0 μm, where the decreases of 0.97%, 1.48%, 1.94% for optical field and the increases of 0.24%, 0.34%, 0.74% for acoustic field are obtained, respectively. When the core diameter is 1.0 μm, ratios of difference for optical and acoustic fields are much higher than those in the cases of 2.0-6.0 μm, which are 3.55% and 29.13%, respectively. The overlap factors between optical and acoustic fields are calculated, which are changed with the core diameter and the filled material in holes. Our results will be helpful to strengthen or suppress the SBS effect in practical applications.

  3. Electric and acoustic stimulation during movement preparation can facilitate movement execution in healthy participants and stroke survivors.

    PubMed

    Marinovic, Welber; Brauer, Sandra G; Hayward, Kathryn S; Carroll, Timothy J; Riek, Stephan

    2016-04-08

    There has been increasing interest in the use of loud acoustic stimulation (LAS) to gain insight into the preparation and initiation of motor actions. Typically, LAS presented during movement preparation in healthy participants culminates in the earlier than normal initiation of the prepared movement and an increase in the magnitude of the response. Recent reports have shown LAS can also facilitate movement in chronic stroke survivors. This suggests that current therapies for motor recovery after stroke might benefit from employing such alternate methods of triggering movement. In this study we sought to test a new way to facilitate motor actions that could be of relevance in clinical settings. Five individuals with chronic motor impairments due to stroke and eight healthy young adults performed a functional reaching task in response to a visual go-signal. On 30% of the trials, LAS or electric stimuli (collectively, sensory stimuli) were unexpectedly presented in synchrony with the go-signal. Both healthy and stroke participants reacted with shorter latencies and executed faster responses when sensory stimulation was synchronized with the go-signal. We have replicated previous findings showing acoustic stimuli can aid movement execution in chronic stroke survivors and demonstrated the same type of effect can be achieved using electric stimulation. Thus, these two types of sensory stimuli can be easily integrated with current devices available to assist people with stroke to engage in rehabilitation efforts.

  4. Acoustic evaluation of short-term effects of repetitive transcranial magnetic stimulation on motor aspects of speech in Parkinson's disease.

    PubMed

    Eliasova, I; Mekyska, J; Kostalova, M; Marecek, R; Smekal, Z; Rektorova, I

    2013-04-01

    Hypokinetic dysarthria in Parkinson's disease (PD) can be characterized by monotony of pitch and loudness, reduced stress, variable rate, imprecise consonants, and a breathy and harsh voice. Using acoustic analysis, we studied the effects of high-frequency repetitive transcranial magnetic stimulation (rTMS) applied over the primary orofacial sensorimotor area (SM1) and the left dorsolateral prefrontal cortex (DLPFC) on motor aspects of voiced speech in PD. Twelve non-depressed and non-demented men with PD (mean age 64.58 ± 8.04 years, mean PD duration 10.75 ± 7.48 years) and 21 healthy age-matched men (a control group, mean age 64 ± 8.55 years) participated in the speech study. The PD patients underwent two sessions of 10 Hz rTMS over the dominant hemisphere with 2,250 stimuli/day in a random order: (1) over the SM1; (2) over the left DLPFC in the "on" motor state. Speech examination comprised the perceptual rating of global speech performance and an acoustic analysis based upon a standardized speech task. The Mann-Whitney U test was used to compare acoustic speech variables between controls and PD patients. The Wilcoxon test was used to compare data prior to and after each stimulation in the PD group. rTMS applied over the left SM1 was associated with a significant increase in harmonic-to-noise ratio and net speech rate in the sentence tasks. With respect to the vowel task results, increased median values and range of Teager-Kaiser energy operator, increased vowel space area, and significant jitter decrease were observed after the left SM1 stimulation. rTMS over the left DLPFC did not induce any significant effects. The positive results of acoustic analysis were not reflected in a subjective rating of speech performance quality as assessed by a speech therapist. Our pilot results indicate that one session of rTMS applied over the SM1 may lead to measurable improvement in voice quality and intensity and an increase in speech rate and tongue movements

  5. Perception of power modulation of light in conjunction with acoustic stimulation

    NASA Astrophysics Data System (ADS)

    Hahlweg, Cornelius F.; Weyer, Cornelia; Gercke-Hahn, Harald; Gutzmann, Holger L.; Brahmann, Andre; Rothe, Hendrik

    2013-09-01

    The present paper is derived from an ongoing study on the human perception of combined optical and acoustical periodical stimuli. Originating from problems of occupational medicine concerning artificial illumination and certain machinery with coherent optical and acoustical emissions there are effects which are interesting in the context of Optics and Music. Because of the difficulties in evaluation of physical and psychological effects of such coherent stimuli in a first step we questioned if such coherence is perceivable at all. Concept, experimental set-up and first results are discussed in short.

  6. Observation of stimulated electron acoustic wave scattering: the case for nonlinear kinetic effects

    NASA Astrophysics Data System (ADS)

    Montgomery, D. S.; Cobble, J. A.; Fernandez, J. C.; Rose, H. A.; Focia, R. J.; Russell, D. A.

    2001-10-01

    Electrostatic waves with a frequency and phase velocity between an ion acoustic wave (IAW) and an electron plasma wave (EPW) have been observed with Thomson scattering in inhomogeneous plasmas, and in the backscattered spectrum for homogeneous single hot spot laser plasmas. We show that these waves are consistent with an electron-acoustic wave (EAW) that is a BGK-like mode due to electron trapping. The nonlinear dispersion relation for BGK-like EPW and EAW is discussed, and previous inhomogeneous Trident and Nova data are re-examined in this context. The possible implications of these results for backscattered SRS on the NIF are discussed.

  7. Pre- and post-stimulation characterization of geothermal well GRT-1, Rittershoffen, France: insights from acoustic image logs of hard fractured rock

    NASA Astrophysics Data System (ADS)

    Vidal, Jeanne; Genter, Albert; Schmittbuhl, Jean

    2016-08-01

    Geothermal well GRT-1 (Rittershoffen, Alsace) was drilled in 2012. Its open-hole section (extending down to a depth of 2.6 km) penetrated fractured sandstones and granite. In 2013, the well was subjected to Thermal, Chemical and Hydraulic (TCH) stimulation, which improved the injectivity index fivefold. The goal of the study was to assess the impact of the stimulation by comparing pre- and post-stimulation well-logging (acoustic and temperature [T] logs) and mud-logging data. This comparison revealed modifications of almost all the natural fractures. However, not all of these fractures are associated with permeability enhancement, and the post-stimulation T logs are important for characterizing this enhancement. Chemical alteration due to mechanical erosion at the tops and bottoms of the fractures was observed in the sandstones. These zones display indications of very small new permeability after the TCH stimulation. Because a major fault zone caved extensively where it crosses the borehole, it was not imaged in the acoustic logs. However, this originally permeable zone was enhanced as demonstrated by the T logs. Based on the natural injectivity of this fault zone, hydraulic erosion and thermal microcracking of its internal quartz veins are associated with this permeability enhancement. Although local changes in the borehole wall observed in the acoustic images cannot be directly linked to the improved injectivity index, the comparison of the acoustic image logs allows for identification of fracture zones impacted by the TCH stimulation.

  8. Contrast Enhancement for Thermal Acoustic Breast Cancer Imaging via Resonant Stimulation

    DTIC Science & Technology

    2009-03-01

    Olsen and J. C. Lin, “Acoustic imaging of a model of a human hand using pulsed microwave irradiation,” Bioelectromagnetics, vol. 4, pp. 397–400, 1983. [2...E. Steen and B. Olstad, “Volume rendering of 3-D medical ultrasound data using direct feature mapping,” IEEE Trans. Med. Imag., vol. 13, no. 6, pp

  9. Contrast Enhancement for Thermal Acoustic Breast Cancer Imaging via Resonant Stimulation

    DTIC Science & Technology

    2010-03-01

    data-independent and suf- fer from low -resolution, high sidelobe levels , and poor interference rejection capabilities. The data-adaptive ARMOR can...high-resolution, low sidelobe level , and much improved inter- ference suppression capability. APPENDIX THERMAL ACOUSTIC SIMULATIONS We consider the...dB main beam is matched to the tumor region well, and the sidelobe level is low . Fig. 2(b) is the DAS beampattern which is calculated using (16). It

  10. Theoretical study of stimulated and spontaneous Hawking effects from an acoustic black hole in a hydrodynamically flowing fluid of light

    NASA Astrophysics Data System (ADS)

    Grišins, Pjotrs; Nguyen, Hai Son; Bloch, Jacqueline; Amo, Alberto; Carusotto, Iacopo

    2016-10-01

    We propose an experiment to detect and characterize the analog Hawking radiation in an analog model of gravity consisting of a flowing exciton-polariton condensate. Under a suitably designed coherent pump configuration, the condensate features an acoustic event horizon for sound waves that at the semiclassical level is equivalent to an astrophysical black-hole horizon. We show that a continuous-wave pump-and-probe spectroscopy experiment allows to measure the analog Hawking temperature from the dependence of the stimulated Hawking effect on the pump-probe detuning. We anticipate the appearance of an emergent resonant cavity for sound waves between the pump beam and the horizon, which results in marked oscillations on top of an overall exponential frequency dependence. We finally analyze the spatial correlation function of density fluctuations and identify the hallmark features of the correlated pairs of Bogoliubov excitations created by the spontaneous Hawking process, as well as novel signatures characterizing the emergent cavity.

  11. Stimulated Scattering of Light from Ion Acoustic Waves in Collisional Multi-species Plasma.

    NASA Astrophysics Data System (ADS)

    Berger, Richard; Valeo, Ernest

    2003-10-01

    The dispersion properties of ion acoustic waves (IAW) are sensitive to the strength of ion-ion collisions,especially in multi-species plasma in which the different species have differing charge-to-mass ratios(Bychenkov et al., PRE 51, 1400 (1995)). Here, we consider the modification of the frequency and damping of the fast and slow acoustic modes in a plasma composed of light (low Z) and heavy (high Z) ions. In the fluid limit, kλ_lh <<1, the friction between the two species causes the damping whereas, in the collisionless limit, Landau damping of the light ions provides the dissipation. Collisions between light and heavy ions also affect the nonlinear response(P. W. Rambo, S. C. Wilks, and W. L. Kruer, Phys. Rev. Lett. 79), 83 (1997).. We examine the effects of collisions on the linear evolution of ion waves driven by the ponderomotive force of two light waves within the context of linear parametric instability theory. The simulation of the nonlinear evolution is done with a δ f model that evolves the background(E. J. Valeo and S. Brunner, Bull. Am. Phys. Soc. 46), QP1.137 (2001)., and includes the effects of collisions of light on heavy ions within the Lorentz model. The calculated effect of a small number of high Z ions on SBS in low Z plasmas will be compared with recent experimental results(Suter et al.,private communication). l

  12. Unexpected acoustic stimulation during action preparation reveals gradual re-specification of movement direction.

    PubMed

    Marinovic, Welber; Tresilian, James; Chapple, Jack L; Riek, Stephan; Carroll, Timothy J

    2017-02-17

    A loud acoustic stimulus (LAS) is often used as a tool to investigate motor preparation in simple reaction time (RT) tasks, where all movement parameters are known in advance. In this report, we used a LAS to examine direction specification in simple and choice RT tasks. This allowed us to investigate how the specification of movement direction unfolds during the preparation period. In two experiments, participants responded to the appearance of an imperative stimulus (IS) with a ballistic wrist force directed toward one of two targets. In probe trials, a LAS (120dBa) was delivered around the time of IS presentation. In Experiment 1, RTs in the simple RT task were faster when the LAS was presented, but the effect on the movement kinematics was negligible. In the Choice RT task, however, movement direction variability increased when the LAS was presented. In Experiment 2, when we primed movements toward one direction, our analyses revealed that the longer participants took to start a movement, the more accurate their responses became. Our results show not only that movement direction reprogramming occurs quickly and continuously, but also that LAS can be a valuable tool to obtain meaningful readouts of the motor system's preparatory state.

  13. Erratum: ?Stimulated Brillouin Backscattering and Ion Acoustic Wave Secondary Instability? [Phys. Plasmas 16, 032701 (2009)

    SciTech Connect

    Cohen, B I; Williams, E A; Berger, R L; Pesme, D; Riconda, C

    2009-04-20

    This Erratum addresses errors that occurred in some of the analysis in our recent publication (Ref. 1). The main elements of Ref. 1 are (1) the presentation of kinetic simulations of simulated Brillouin backscattering (SBS) and the accompanying secondary instability of the primary SBS ion acoustic wave (IAW) with and without the inclusion of the second harmonic of the primary IAW; (2) analyses of the four-wave (primary IAW, low-frequency IAW, and two sidebands of the primary IAW) and seven-wave (includes the second harmonic of the primary IAW and its two sidebands, as well as the four waves defined in the foregoing) dispersion relations for the secondary IAW instability; (3) comparisons of the results of solving the dispersion relations to the two particle simulations; (4) mode coupling calculations for SBS and the four-wave system of IAWs that model the particle simulations; and (5) a discussion and summary. However, the simplified 7-wave dispersion relation used in Ref. 1 propagated a typographical error in Eq.(44) in Ref. 2, the Pesme, Riconda, and Tikhonchuk (PRT) paper. This Erratum corrects Eq.(44) of Ref. 2 (discussed in more detail in an Erratum3 for Ref. 2) and revises Sec. IV of Ref. 1 by correcting the analysis and comparisons of the 4-wave and 7-wave dispersion relations, and the comparison of the 7-wave dispersion relation to the particle simulations. We find that the results of the corrected 7-wave dispersion relation are not profoundly different from the corresponding results in Ref. 1 and the 7-wave growth rates of the most unstable modes are more similar to the results of the 4-wave dispersion relation. The main results of Ref. 1 are unchanged: (1) the particle simulations exhibit a secondary IAW instability that is a modulational instability involving parallel and obliquely propagating IAWs; (2) the two types of particle simulation exhibit similar spectra, and the second harmonic IAW is a transient feature in the first particle simulation that is

  14. Effect of Digital Frequency Compression (DFC) on Speech Recognition in Candidates for Combined Electric and Acoustic Stimulation (EAS)

    PubMed Central

    Gifford, René H.; Dorman, Michael F.; Spahr, Anthony J.; McKarns, Sharon A.

    2008-01-01

    Purpose To compare the effects of conventional amplification (CA) and digital frequency compression (DFC) amplification on the speech recognition abilities of candidates for a partial-insertion cochlear implant, that is, candidates for combined electric and acoustic stimulation (EAS). Method The participants were 6 patients whose audiometric thresholds at 500 Hz and below were ≤60 dB HL and whose thresholds at 2000 Hz and above were ≥80 dB HL. Six tests of speech understanding were administered with CA and DFC. The Abbreviated Profile of Hearing Aid Benefit (APHAB) was also administered following use of CA and DFC. Results Group mean scores were not statistically different in the CA and DFC conditions. However, 2 patients received substantial benefit in DFC conditions. APHAB scores suggested increased ease of communication, but also increased aversive sound quality. Conclusion Results suggest that a relatively small proportion of individuals who meet EAS candidacy will receive substantial benefit from a DFC hearing aid and that a larger proportion will receive at least a small benefit when speech is presented against a background of noise. This benefit, however, comes at a cost—aversive sound quality. PMID:17905905

  15. Highly efficient Cas9-mediated transcriptional programming.

    PubMed

    Chavez, Alejandro; Scheiman, Jonathan; Vora, Suhani; Pruitt, Benjamin W; Tuttle, Marcelle; P R Iyer, Eswar; Lin, Shuailiang; Kiani, Samira; Guzman, Christopher D; Wiegand, Daniel J; Ter-Ovanesyan, Dmitry; Braff, Jonathan L; Davidsohn, Noah; Housden, Benjamin E; Perrimon, Norbert; Weiss, Ron; Aach, John; Collins, James J; Church, George M

    2015-04-01

    The RNA-guided nuclease Cas9 can be reengineered as a programmable transcription factor. However, modest levels of gene activation have limited potential applications. We describe an improved transcriptional regulator obtained through the rational design of a tripartite activator, VP64-p65-Rta (VPR), fused to nuclease-null Cas9. We demonstrate its utility in activating endogenous coding and noncoding genes, targeting several genes simultaneously and stimulating neuronal differentiation of human induced pluripotent stem cells (iPSCs).

  16. Stronger efferent suppression of cochlear neural potentials by contralateral acoustic stimulation in awake than in anesthetized chinchilla

    PubMed Central

    Aedo, Cristian; Tapia, Eduardo; Pavez, Elizabeth; Elgueda, Diego; Delano, Paul H.; Robles, Luis

    2015-01-01

    There are two types of sensory cells in the mammalian cochlea, inner hair cells, which make synaptic contact with auditory-nerve afferent fibers, and outer hair cells that are innervated by crossed and uncrossed medial olivocochlear (MOC) efferent fibers. Contralateral acoustic stimulation activates the uncrossed efferent MOC fibers reducing cochlear neural responses, thus modifying the input to the central auditory system. The chinchilla, among all studied mammals, displays the lowest percentage of uncrossed MOC fibers raising questions about the strength and frequency distribution of the contralateral-sound effect in this species. On the other hand, MOC effects on cochlear sensitivity have been mainly studied in anesthetized animals and since the MOC-neuron activity depends on the level of anesthesia, it is important to assess the influence of anesthesia in the strength of efferent effects. Seven adult chinchillas (Chinchilla laniger) were chronically implanted with round-window electrodes in both cochleae. We compared the effect of contralateral sound in awake and anesthetized condition. Compound action potentials (CAP) and cochlear microphonics (CM) were measured in the ipsilateral cochlea in response to tones in absence and presence of contralateral sound. Control measurements performed after middle-ear muscles section in one animal discarded any possible middle-ear reflex activation. Contralateral sound produced CAP amplitude reductions in all chinchillas, with suppression effects greater by about 1–3 dB in awake than in anesthetized animals. In contrast, CM amplitude increases of up to 1.9 dB were found in only three awake chinchillas. In both conditions the strongest efferent effects were produced by contralateral tones at frequencies equal or close to those of ipsilateral tones. Contralateral CAP suppressions for 1–6 kHz ipsilateral tones corresponded to a span of uncrossed MOC fiber innervation reaching at least the central third of the chinchilla

  17. Dissociation of psychophysical and EEG steady-state response measures of cross-modal temporal correspondence for amplitude modulated acoustic and vibrotactile stimulation.

    PubMed

    Timora, Justin R; Budd, Timothy W

    2013-09-01

    Research examining multisensory integration suggests that the correspondence of stimulus characteristics across modalities (cross-modal correspondence) can have a dramatic influence on both neurophysiological and perceptual responses to multimodal stimulation. The current study extends prior research by examining the cross-modal correspondence of amplitude modulation rate for simultaneous acoustic and vibrotactile stimulation using EEG and perceptual measures of sensitivity to amplitude modulation. To achieve this, psychophysical thresholds and steady-state responses (SSRs) were measured for acoustic and vibrotactile amplitude modulated (AM) stimulation for 21 and 40 Hz AM rates as a function of the cross-modal correspondence. The study design included three primary conditions to determine whether the changes in the SSR and psychophysical thresholds were due to the cross-modal temporal correspondence of amplitude modulated stimuli: NONE (AM in one modality only), SAME (the same AM rate for each modality) and DIFF (different AM rates for each modality). The results of the psychophysical analysis showed that AM detection thresholds for the simultaneous AM conditions (i.e., SAME and DIFF) were significantly higher (i.e., lower sensitivity) than AM detection thresholds for the stimulation of a single modality (i.e., NONE). SSR results showed significant effects of SAME and DIFF conditions on SSR activity. The different pattern of results for perceptual and SSR measures of cross-modal correspondence of AM rate indicates a dissociation between entrained cortical activity (i.e., SSR) and perception.

  18. Evolution of elastic and thermal properties during TMOS-gel formation determined by ringing bottle acoustic resonance spectroscopy, impulsive stimulated scattering, photopyroelectric spectroscopy and the hot ball method

    NASA Astrophysics Data System (ADS)

    Xu, Xiaodong; Agustin Flores Cuautle, Jose Jesus; Kouyate, Mansour; Bernardus Roozen, Nicolaas; Goossens, Jozefien; Menon, Preethy; Kuriakose Malayil, Maju; Salenbien, Robbe; Nair Rajesh, Ravindran; Glorieux, Christ; Griesmar, Pascal; Martinez, Loïc; Serfaty, Stéphane

    2016-03-01

    The evolution of the elastic and thermal properties of a tetramethylorthosilicate (TMOS)-based gel that exhibits an extraordinary ringing effect when enclosed in a bottle is investigated during the sol-gel transition. The results demonstrate the feasibility of three proposed experimental methods for monitoring of gels during their formation. The shear stiffening evolution during gelation is monitored by ringing bottle, resonant acoustic spectroscopy and by an ultrasonic technique using piezo electric excitation and detection. The evolution of the longitudinal modulus and the thermal diffusivity of the gel during stiffening are simultaneously determined by a combined photoacoustic and photothermal method based on heterodyne diffraction detection of impulsive stimulated scattering by, respectively, a propagating acoustic wave grating and a decaying thermal expansion grating that were both thermo elastically generated using a pulsed laser. Also, the feasibility of an inverse photopyroelectric method and a hot ball technique to monitor the thermal transport efficiency and thermal impedance of a forming gel by tracking the thermal conductivity, the thermal diffusivity, and the thermal effusivity is demonstrated. The network polymerization and stiffening during the sol-gel transition in TMOS-gel corresponds with substantial changes in the shear acoustic velocity and in all thermal properties, while the longitudinal acoustic velocity is only weakly affected.

  19. CAS77 and CAS7276: A Review.

    ERIC Educational Resources Information Center

    Harrison, Isom, Jr.

    This paper describes the content, organization, specifications, and methods of use of the CAS77 and CAS7276 online files of worldwide chemical literature, databases produced by Chemical Abstracts Service and available from System Development Corporation (SDC). The scope of the databases, their unit record, their data elements, their modes of…

  20. A Phase-Locking Analysis of Neuronal Firing Rhythms with Transcranial Magneto-Acoustical Stimulation Based on the Hodgkin-Huxley Neuron Model

    PubMed Central

    Yuan, Yi; Pang, Na; Chen, Yudong; Wang, Yi; Li, Xiaoli

    2017-01-01

    Transcranial magneto-acoustical stimulation (TMAS) uses ultrasonic waves and a static magnetic field to generate electric current in nerve tissues for the purpose of modulating neuronal activities. It has the advantage of high spatial resolution and penetration depth. Neuronal firing rhythms carry and transmit nerve information in neural systems. In this study, we investigated the phase-locking characteristics of neuronal firing rhythms with TMAS based on the Hodgkin-Huxley neuron model. The simulation results indicate that the modulation frequency of ultrasound can affect the phase-locking behaviors. The results of this study may help us to explain the potential firing mechanism of TMAS. PMID:28163679

  1. Acoustic tone or medial geniculate stimulation cue training in the rat is associated with neocortical neuroplasticity and reduced akinesia under haloperidol challenge.

    PubMed

    Brown, Andrew R; Hu, Bin; Kolb, Bryan; Teskey, G Campbell

    2010-12-06

    Sensory cues can improve movement deficits in Parkinson's disease, but little is known about the mechanisms involved. To investigate neuroplastic changes following sensorimotor cue training, rats were shaped to respond to acoustic tone or medial geniculate stimulation cues by retrieving a food reward. Neuroplasticity associated with training was assessed by changes in auditory neocortical evoked field potentials and dendritic morphology. Stimulation cue training was associated with changes in dendritic arbour length and complexity in auditory and motor neocortices, but was without effect on evoked electrophysiological responses. Tone cue training was associated with a significant increase in peak height of the evoked auditory response and then under haloperidol challenge, demonstrated reduced akinesia. Results indicate that cue-training induces neuroplastic changes that may be related to improved sensorimotor function under dopaminergic antagonism.

  2. Morphological Correlates of Hearing Loss after Cochlear Implantation and Electro-Acoustic Stimulation in a Hearing-Impaired Guinea Pig Model

    PubMed Central

    Reiss, Lina A.J.; Stark, Gemaine; Nguyen-Huynh, Anh T.; Spear, Kayce A.; Zhang, Hongzheng; Tanaka, Chiemi; Li, Hongzhe

    2016-01-01

    Hybrid or electro-acoustic stimulation (EAS) cochlear implants (CIs) are designed to provide high-frequency electric hearing together with residual low-frequency acoustic hearing. However, 30-50% of EAS CI recipients lose residual hearing after implantation. The objective of this study was to determine the mechanisms of EAS-induced hearing loss in an animal model with high-frequency hearing loss. Guinea pigs were exposed to 24 hours of noise (12-24 kHz at 116 dB) to induce a high-frequency hearing loss. After recovery, two groups of animals were implanted (n=6 per group), with one group receiving chronic acoustic and electric stimulation for 10 weeks, and the other group receiving no stimulation during this time frame. A third group (n=6) was not implanted, but received chronic acoustic stimulation. Auditory brainstem responses were recorded biweekly to monitor changes in hearing. The organ of Corti was immunolabeled with phalloidin, anti-CtBP2, and anti-GluR2 to quantify hair cells, ribbons and post-synaptic receptors. The lateral wall was immunolabeled with phalloidin and lectin to quantify stria vascularis capillary diameters. Bimodal or trimodal diameter distributions were observed; the number and location of peaks were objectively determined using the Aikake Information Criterion and Expectation Maximization algorithm. Noise exposure led to immediate hearing loss at 16-32 kHz for all groups. Cochlear implantation led to additional hearing loss at 4-8 kHz; this hearing loss was negatively and positively correlated with minimum and maximum peaks of the bimodal or trimodal distributions of stria vascularis capillary diameters, respectively. After chronic stimulation, no significant group changes in thresholds were seen; however, elevated thresholds at 1 kHz in implanted, stimulated animals were significantly correlated with decreased presynaptic ribbon and postsynaptic receptor counts. Inner and outer hair cell counts did not differ between groups and were not

  3. Morphological correlates of hearing loss after cochlear implantation and electro-acoustic stimulation in a hearing-impaired Guinea pig model.

    PubMed

    Reiss, Lina A J; Stark, Gemaine; Nguyen-Huynh, Anh T; Spear, Kayce A; Zhang, Hongzheng; Tanaka, Chiemi; Li, Hongzhe

    2015-09-01

    Hybrid or electro-acoustic stimulation (EAS) cochlear implants (CIs) are designed to provide high-frequency electric hearing together with residual low-frequency acoustic hearing. However, 30-50% of EAS CI recipients lose residual hearing after implantation. The objective of this study was to determine the mechanisms of EAS-induced hearing loss in an animal model with high-frequency hearing loss. Guinea pigs were exposed to 24 h of noise (12-24 kHz at 116 dB) to induce a high-frequency hearing loss. After recovery, two groups of animals were implanted (n = 6 per group), with one group receiving chronic acoustic and electric stimulation for 10 weeks, and the other group receiving no stimulation during this time frame. A third group (n = 6) was not implanted, but received chronic acoustic stimulation. Auditory brainstem responses were recorded biweekly to monitor changes in hearing. The organ of Corti was immunolabeled with phalloidin, anti-CtBP2, and anti-GluR2 to quantify hair cells, ribbons and post-synaptic receptors. The lateral wall was immunolabeled with phalloidin and lectin to quantify stria vascularis capillary diameters. Bimodal or trimodal diameter distributions were observed; the number and location of peaks were objectively determined using the Aikake Information Criterion and Expectation Maximization algorithm. Noise exposure led to immediate hearing loss at 16-32 kHz for all groups. Cochlear implantation led to additional hearing loss at 4-8 kHz; this hearing loss was negatively and positively correlated with minimum and maximum peaks of the bimodal or trimodal distributions of stria vascularis capillary diameters, respectively. After chronic stimulation, no significant group changes in thresholds were seen; however, elevated thresholds at 1 kHz in implanted, stimulated animals were significantly correlated with decreased presynaptic ribbon and postsynaptic receptor counts. Inner and outer hair cell counts did not differ between groups and

  4. Absent fetal movement response with a blunted cardioacceleratory fetal response to external vibratory acoustic stimulation in a fetus with the Pena-Shokeir syndrome (fetal akinesia and hypokinesia sequence).

    PubMed

    Sherer, D M; Sanko, S R; Metlay, L A; Woods, J R

    1992-01-01

    We present a case that describes a partial fetal response to external vibratory acoustic stimulation in that, although no fetal movements were elicited, a blunted, brief positive cardioacceleratory response was noted. This fetus exhibited features of the Pena-Shokeir syndrome, characterized by skeletal neurogenic atrophy, yet with a normal auditory system at autopsy. This observation may suggest that the prolonged increase in the basal fetal heart noted after fetal vibratory acoustic stimulation is sustained by active fetal movements, absent in this fetus due to joint contractures.

  5. Electrical Activity of the Cerebral Cortex during the Low-Frequency Acoustic Stimulation in Women with Different Characteristics of Alpha Rhythm

    PubMed Central

    Morenko, Alevtyna; Morenko, Olena

    2016-01-01

    Background Human functional capabilities, to a certain extent, depend on an individual's nervous system. The recording of the spontaneous electroencephalogram (EEG) makes it possible to estimate specific features of the nervous system, and in particular the activity of the human brain. Purpose This study is aimed at investigating the brain in women with a high or a low individual α-frequency (ІαF), determined in a quiescent state during low-frequency acoustic stimulation. Methods The study group consisted of 113 right-handed healthy women in the age group 19-21 years. The study group was divided into 2 categories in terms of the average magnitude of ІαF - groups with high (n = 59, IαF ≥10.25 Hz) and low (n = 54, IαF ≤10.25 Hz) values of ІαF. The power and coherence of electrical activity of the cerebral cortex as well as the differences between the groups were evaluated in a quiescent state during low-frequency acoustic stimulation. Results In case of low-frequency acoustic stimulation, a high rate of EEG θ-, β2-power, γ-waves in the cortex, α1-oscillations - in frontal areas were registered in women with a high α-frequency, while the power α2-, α3- and β1-activity became lower in the cortex. Women with a low α-frequency had a decrease of the cerebral cortex α-θ-, α- and β-activity. This was recorded as more generalized, and the expression of γ-waves was more localized. All the participants had increased values of coherence of the EEG frequency components in the cortex. Some overexertion on the right side was detected in the right hemisphere posterior structures. Some local reduction of the coherence of θ-, α1-, α3-oscillations was found in women with a high α-frequency and α1-activity among the study group members with a low α-frequency in the frontal and anterior temporal areas. Conclusion The establishment of common factors in the study group is an important step towards defining clear prognostic criteria for the physiological

  6. Highly efficient Cas9-mediated transcriptional programming

    DOE PAGES

    Chavez, Alejandro; Scheiman, Jonathan; Vora, Suhani; ...

    2015-03-02

    The RNA-guided nuclease Cas9 can be reengineered as a programmable transcription factor. However, modest levels of gene activation have limited potential applications. Here we describe an improved transcriptional regulator through the rational design of a tripartite activator, VP64-p65-Rta (VPR), fused to nuclease-null Cas9. Here, we demonstrate its utility in activating endogenous coding and non-coding genes, targeting several genes simultaneously and stimulating neuronal differentiation of human induced pluripotent stem cells (iPSCs).

  7. [CAS General Standards 2012

    ERIC Educational Resources Information Center

    Council for the Advancement of Standards in Higher Education, 2011

    2011-01-01

    The mission of the Council for the Advancement of Standards in Higher Education (CAS) is to promote the improvement of programs and services to enhance the quality of student learning and development. CAS is a consortium of professional associations who work collaboratively to develop and promulgate standards and guidelines and to encourage…

  8. On the formation of nanostructures on a CdTe surface, stimulated by surface acoustic waves under nanosecond laser irradiation

    SciTech Connect

    Vlasenko, A. I.; Baidullaeva, A.; Veleschuk, V. P. Mozol, P. E.; Boiko, N. I.; Litvin, O. S.

    2015-02-15

    The formation of nanoscale structures in the unirradiated part of a p-CdTe crystal surface irradiated by a nanosecond ruby laser is revealed and investigated. It is shown that their formation is caused by the effect of the long-range action of a laser pulse with an intensity of I = 20 MW/cm{sup 2}. Nanoscale-structure formation is explained by the influence of the pressure gradient of the surface acoustic wave, in particular, within the “vacancy-pump” mechanism on the surface.

  9. Cas1-Cas2 complex formation mediates spacer acquisition during CRISPR-Cas adaptive immunity.

    PubMed

    Nuñez, James K; Kranzusch, Philip J; Noeske, Jonas; Wright, Addison V; Davies, Christopher W; Doudna, Jennifer A

    2014-06-01

    The initial stage of CRISPR-Cas immunity involves the integration of foreign DNA spacer segments into the host genomic CRISPR locus. The nucleases Cas1 and Cas2 are the only proteins conserved among all CRISPR-Cas systems, yet the molecular functions of these proteins during immunity are unknown. Here we show that Cas1 and Cas2 from Escherichia coli form a stable complex that is essential for spacer acquisition and determine the 2.3-Å-resolution crystal structure of the Cas1-Cas2 complex. Mutations that perturb Cas1-Cas2 complex formation disrupt CRISPR DNA recognition and spacer acquisition in vivo. Active site mutants of Cas2, unlike those of Cas1, can still acquire new spacers, thus indicating a nonenzymatic role of Cas2 during immunity. These results reveal the universal roles of Cas1 and Cas2 and suggest a mechanism by which Cas1-Cas2 complexes specify sites of CRISPR spacer integration.

  10. [Trimetazidine (Vastarel 20 mg) and electro-acoustic stimulation in the treatment of tinnitus. Apropos of 64 cases].

    PubMed

    Desaulty, A; Gelaude, A

    1990-01-01

    This open pilot study was carried out with the intent of assessing the pertinence of combining Vastarel 20 mg with electroacoustic stimulation, as opposed to using solely the electroacoustic stimulation method in the management of subjective tinnitus. Enrolled in the study were 64 patients presenting with subjective tinnitus, 50% of which were related to vascular disorders. Following the entry visit (clinical examination, pure-tone audiometry, Metz' test, auditory evoked potentials, CT scans of the internal auditory canal), the patients underwent six 45-minute sessions of electroacoustic stimulation at one-week intervals. Half the patients followed this sole treatment, while the other half was immediately started on Vastarel 20 mg (3 tablets daily) concurrently with the first electroacoustic stimulation session and maintained on this regimen for 3 months. The electroacoustic stimulation (EAS) device used (Tinitop) was operated by emitting a synchronic sound signal mediated by a cask and an electric signal mediated by adhesive electrodes placed in the pretragal area. Results Results were analyzed through history-taking on the 45th and 90th days following the onset of the treatment, subjective improvement of tinnitus being rated from 0% to 100% based on 25% scoring levels (0 = no effect; 100% = complete disappearance of tinnitus spells). At day 45, the proportion of good and very good results (50% improvement or more) was similar (56%), regardless of whether Vastarel 20 mg was or not associated with EAS therapy. On the other hand, the combination of Vastarel 20 mg with masking of tinnitus proved particularly useful in preventing recurrences.(ABSTRACT TRUNCATED AT 250 WORDS)

  11. Cas9 Variants Expand the Target Repertoire in Caenorhabditis elegans.

    PubMed

    Bell, Ryan T; Fu, Becky X H; Fire, Andrew Z

    2016-02-01

    The proliferation of CRISPR/Cas9-based methods in Caenorhabditis elegans has enabled efficient genome editing and precise genomic tethering of Cas9 fusion proteins. Experimental designs using CRISPR/Cas9 are currently limited by the need for a protospacer adjacent motif (PAM) in the target with the sequence NGG. Here we report the characterization of two modified Cas9 proteins in C. elegans that recognize NGA and NGCG PAMs. We found that each variant could stimulate homologous recombination with a donor template at multiple loci and that PAM specificity was comparable to that of wild-type Cas9. To directly compare effectiveness, we used CRISPR/Cas9 genome editing to generate a set of assay strains with a common single-guide RNA (sgRNA) target sequence, but that differ in the juxtaposed PAM (NGG, NGA, or NGCG). In this controlled setting, we determined that the NGA PAM Cas9 variant can be as effective as wild-type Cas9. We similarly edited a genomic target to study the influence of the base following the NGA PAM. Using four strains with four NGAN PAMs differing only at the fourth position and adjacent to the same sgRNA target, we observed that efficient homologous replacement was attainable with any base in the fourth position, with an NGAG PAM being the most effective. In addition to demonstrating the utility of two Cas9 mutants in C. elegans and providing reagents that permit CRISPR/Cas9 experiments with fewer restrictions on potential targets, we established a means to benchmark the efficiency of different Cas9::PAM combinations that avoids variations owing to differences in the sgRNA sequence.

  12. Acoustic neuroma

    MedlinePlus

    Vestibular schwannoma; Tumor - acoustic; Cerebellopontine angle tumor; Angle tumor; Hearing loss - acoustic; Tinnitus - acoustic ... Acoustic neuromas have been linked with the genetic disorder neurofibromatosis type 2 (NF2). Acoustic neuromas are uncommon.

  13. A dynamic pressure view cell for acoustic stimulation of fluids—Micro-bubble generation and fluid movement in porous media

    NASA Astrophysics Data System (ADS)

    Stewart, Robert A.; Shaw, J. M.

    2015-09-01

    The development and baseline operation of an acoustic view cell for observing fluids, and fluid-fluid and fluid-solid interfaces in porous media over the frequency range of 10-5000 Hz is described. This range includes the industrially relevant frequency range 500-5000 Hz that is not covered by existing devices. Pressure waveforms of arbitrary shape are generated in a 17.46 mm ID by 200 mm and 690.5 mm long glass tubes at flow rates up to 200 ml/min using a syringe pump. Peak-to-peak amplitudes exceeding 80 kPa are readily realized at frequencies from 10 to 5000 Hz in bubble free fluids when actuated with 20 Vpp as exemplified using castor oil. At resonant frequencies, peak-to-peak pressure amplitudes exceeding 500 kPa were obtained (castor oil at 2100 Hz when actuated with 20 Vpp). Impacts of vibration on macroscopic liquid-liquid and liquid-vapour interfaces and interface movement are illustrated. Pressure wave transmission and attenuation in a fluid saturated porous medium, randomly packed 250-330 μm spherical silica beads, is also demonstrated. Attenuation differences and frequency shifts in resonant peaks are used to detect the presence and generation of dispersed micro-bubbles (<180 μm diameter), and bubbles within porous media that are not readily visualized. Envisioned applications include assessment of the impacts of vibration on reaction, mass transfer, and flow/flow pattern outcomes. This knowledge will inform laboratory and pilot scale process studies, where nuisance vibrations may affect the interpretation of process outcomes, and large scale or in situ processes in aquifers or hydrocarbon reservoirs where imposed vibration may be deployed to improve aspects of process performance. Future work will include miscible interface observation and quantitative measurements in the bulk and in porous media where the roles of micro-bubbles comprise subjects of special interest.

  14. A dynamic pressure view cell for acoustic stimulation of fluids--Micro-bubble generation and fluid movement in porous media.

    PubMed

    Stewart, Robert A; Shaw, J M

    2015-09-01

    The development and baseline operation of an acoustic view cell for observing fluids, and fluid-fluid and fluid-solid interfaces in porous media over the frequency range of 10-5000 Hz is described. This range includes the industrially relevant frequency range 500-5000 Hz that is not covered by existing devices. Pressure waveforms of arbitrary shape are generated in a 17.46 mm ID by 200 mm and 690.5 mm long glass tubes at flow rates up to 200 ml/min using a syringe pump. Peak-to-peak amplitudes exceeding 80 kPa are readily realized at frequencies from 10 to 5000 Hz in bubble free fluids when actuated with 20 Vpp as exemplified using castor oil. At resonant frequencies, peak-to-peak pressure amplitudes exceeding 500 kPa were obtained (castor oil at 2100 Hz when actuated with 20 Vpp). Impacts of vibration on macroscopic liquid-liquid and liquid-vapour interfaces and interface movement are illustrated. Pressure wave transmission and attenuation in a fluid saturated porous medium, randomly packed 250-330 μm spherical silica beads, is also demonstrated. Attenuation differences and frequency shifts in resonant peaks are used to detect the presence and generation of dispersed micro-bubbles (<180 μm diameter), and bubbles within porous media that are not readily visualized. Envisioned applications include assessment of the impacts of vibration on reaction, mass transfer, and flow/flow pattern outcomes. This knowledge will inform laboratory and pilot scale process studies, where nuisance vibrations may affect the interpretation of process outcomes, and large scale or in situ processes in aquifers or hydrocarbon reservoirs where imposed vibration may be deployed to improve aspects of process performance. Future work will include miscible interface observation and quantitative measurements in the bulk and in porous media where the roles of micro-bubbles comprise subjects of special interest.

  15. The role of Cas8 in type I CRISPR interference.

    PubMed

    Cass, Simon D B; Haas, Karina A; Stoll, Britta; Alkhnbashi, Omer S; Sharma, Kundan; Urlaub, Henning; Backofen, Rolf; Marchfelder, Anita; Bolt, Edward L

    2015-05-05

    CRISPR (clustered regularly interspaced short palindromic repeat) systems provide bacteria and archaea with adaptive immunity to repel invasive genetic elements. Type I systems use 'cascade' [CRISPR-associated (Cas) complex for antiviral defence] ribonucleoprotein complexes to target invader DNA, by base pairing CRISPR RNA (crRNA) to protospacers. Cascade identifies PAMs (protospacer adjacent motifs) on invader DNA, triggering R-loop formation and subsequent DNA degradation by Cas3. Cas8 is a candidate PAM recognition factor in some cascades. We analysed Cas8 homologues from type IB CRISPR systems in archaea Haloferax volcanii (Hvo) and Methanothermobacter thermautotrophicus (Mth). Cas8 was essential for CRISPR interference in Hvo and purified Mth Cas8 protein responded to PAM sequence when binding to nucleic acids. Cas8 interacted physically with Cas5-Cas7-crRNA complex, stimulating binding to PAM containing substrates. Mutation of conserved Cas8 amino acid residues abolished interference in vivo and altered catalytic activity of Cas8 protein in vitro. This is experimental evidence that Cas8 is important for targeting Cascade to invader DNA.

  16. Programmable RNA recognition and cleavage by CRISPR/Cas9.

    PubMed

    O'Connell, Mitchell R; Oakes, Benjamin L; Sternberg, Samuel H; East-Seletsky, Alexandra; Kaplan, Matias; Doudna, Jennifer A

    2014-12-11

    The CRISPR-associated protein Cas9 is an RNA-guided DNA endonuclease that uses RNA-DNA complementarity to identify target sites for sequence-specific double-stranded DNA (dsDNA) cleavage. In its native context, Cas9 acts on DNA substrates exclusively because both binding and catalysis require recognition of a short DNA sequence, known as the protospacer adjacent motif (PAM), next to and on the strand opposite the twenty-nucleotide target site in dsDNA. Cas9 has proven to be a versatile tool for genome engineering and gene regulation in a large range of prokaryotic and eukaryotic cell types, and in whole organisms, but it has been thought to be incapable of targeting RNA. Here we show that Cas9 binds with high affinity to single-stranded RNA (ssRNA) targets matching the Cas9-associated guide RNA sequence when the PAM is presented in trans as a separate DNA oligonucleotide. Furthermore, PAM-presenting oligonucleotides (PAMmers) stimulate site-specific endonucleolytic cleavage of ssRNA targets, similar to PAM-mediated stimulation of Cas9-catalysed DNA cleavage. Using specially designed PAMmers, Cas9 can be specifically directed to bind or cut RNA targets while avoiding corresponding DNA sequences, and we demonstrate that this strategy enables the isolation of a specific endogenous messenger RNA from cells. These results reveal a fundamental connection between PAM binding and substrate selection by Cas9, and highlight the utility of Cas9 for programmable transcript recognition without the need for tags.

  17. Patients with CDH23 mutations and the 1555A>G mitochondrial mutation are good candidates for electric acoustic stimulation (EAS)

    PubMed Central

    Usami, Shin-Ichi; Miyagawa, Maiko; Nishio, Shin-Ya; Moteki, Hideaki; Takumi, Yutaka; Suzuki, Mika; Kitano, Yoko; Iwasaki, Satoshi

    2012-01-01

    Conclusions: CDH23 mutations and the 1555A>G mitochondrial mutation were identified among our series of electric acoustic stimulation (EAS) patients, confirming that these genes were important in hearing loss with involvement of high frequency. Successful hearing preservation as well as good outcomes from EAS indicated that patients with this combination of mutations are good candidates for EAS. Objectives: Screening for gene mutations that possibly cause hearing loss involving high frequency was performed to identify the responsible genes in patients with EAS. In addition to a review of the genetic background of the patients with residual hearing loss, the benefit of EAS for patients with particular gene mutations was evaluated. Methods: Eighteen patients (15 late-onset, 3 early-onset) with residual hearing who had received EAS were included in this study. Genetic analysis was performed to identify GJB2, CDH23, SLC26A4, and the 1555 mitochondrial mutations. Results: Three early-onset patients had CDH23 mutations. One late-onset patient had the 1555 A>G mitochondrial mutation. PMID:22443853

  18. Cas9 Functionally Opens Chromatin

    PubMed Central

    Barkal, Amira A.; Srinivasan, Sharanya; Hashimoto, Tatsunori; Gifford, David K.; Sherwood, Richard I.

    2016-01-01

    Using a nuclease-dead Cas9 mutant, we show that Cas9 reproducibly induces chromatin accessibility at previously inaccessible genomic loci. Cas9 chromatin opening is sufficient to enable adjacent binding and transcriptional activation by the settler transcription factor retinoic acid receptor at previously unbound motifs. Thus, we demonstrate a new use for Cas9 in increasing surrounding chromatin accessibility to alter local transcription factor binding. PMID:27031353

  19. Nucleosome breathing and remodeling constrain CRISPR-Cas9 function

    PubMed Central

    Isaac, R Stefan; Jiang, Fuguo; Doudna, Jennifer A; Lim, Wendell A; Narlikar, Geeta J; Almeida, Ricardo

    2016-01-01

    The CRISPR-Cas9 bacterial surveillance system has become a versatile tool for genome editing and gene regulation in eukaryotic cells, yet how CRISPR-Cas9 contends with the barriers presented by eukaryotic chromatin is poorly understood. Here we investigate how the smallest unit of chromatin, a nucleosome, constrains the activity of the CRISPR-Cas9 system. We find that nucleosomes assembled on native DNA sequences are permissive to Cas9 action. However, the accessibility of nucleosomal DNA to Cas9 is variable over several orders of magnitude depending on dynamic properties of the DNA sequence and the distance of the PAM site from the nucleosome dyad. We further find that chromatin remodeling enzymes stimulate Cas9 activity on nucleosomal templates. Our findings imply that the spontaneous breathing of nucleosomal DNA together with the action of chromatin remodelers allow Cas9 to effectively act on chromatin in vivo. DOI: http://dx.doi.org/10.7554/eLife.13450.001 PMID:27130520

  20. Dynamic changes following combined treatment with gentamicin and ethacrynic acid with and without acoustic stimulation. Cellular uptake and functional correlates.

    PubMed

    Hayashida, T; Hiel, H; Dulon, D; Erre, J P; Guilhaume, A; Aran, J M

    1989-01-01

    Regional selectivity of gentamicin (GM) ototoxicity was studied in guinea pigs (GPs) using electrophysiological, morphological, autoradiographic and immunohistological observations following combined treatment with GM (150 mg/kg i.m.) and ethacrynic acid (EA) (30 mg/kg i.c. or i.v., 1.5 h after GM injection). The GPs were either continuously stimulated every 5 min with a series of 256 clicks (70 dB peSPL, 10/s) during 3 h for monitoring fast changes in VIII nerve compound action potential (CAP) after the EA injection, and thereafter kept in the animal quarters (background noise of 60 dB SPL) (group I), or similarly monitored for only 10 min after the EA injection and thereafter kept in a soundproof room (around 0 dB SPL) (group II). Whenever GM labelling was observed it was localized only in the sensory hair cells. From 3 h after EA injection, the GPs in group I presented threshold elevations in the high-frequency region, which progressed to 60-80 dB at all frequencies at and after 48 h. Parallel to the threshold pattern, GM uptake in outer hair cells (OHCs) was seen with an increasing concentration from apex toward base from 3 to 24 h, while after 48 h almost all OHCs were destroyed and inner hair cells (IHCs) were marked by GM. In group II no changes in CAP thresholds were observed until more than 24 h, although GM was detected in the hair cells from 6 h on. At this early stage, the distribution of GM lacked a clear pattern, particularly without a clear apex-base gradient, and GM deposits were found only around the basal body. However in both groups, in late stage (greater than 24 h), the base-apex gradient was more pronounced and GM was found throughout the cell body, with a marked concentration below the cuticular plate. These results suggest that GM may penetrate hair cells around the basal body and that activating the cells by sound potentiates both GM uptake and its intracellular toxicity.

  1. Low Frequency Acoustics

    DTIC Science & Technology

    2016-06-13

    with NOAA , ONR is providing technical services that will help establish a baseline for assessment of long- term VLF acoustic trends in selected...ABSTRACT unclassified c. THIS PAGE unclassified Standard Form 298 (Rev. 8-98) Prescribed by ANSI Std Z39-18 sponsored by NOAA , was added to the...with NOAA (NMFS) and other parties has dealt with ocean acoustics related to issues stimulated by the Marine Mammal Protection Act. A focal point has

  2. Acoustic Neuroma

    MedlinePlus

    ... search IRSA's site Unique Hits since January 2003 Acoustic Neuroma Click Here for Acoustic Neuroma Practice Guideline ... to microsurgery. One doctor's story of having an acoustic neuroma In August 1991, Dr. Thomas F. Morgan ...

  3. Cullin 5 destabilizes Cas to inhibit Src-dependent cell transformation.

    PubMed

    Teckchandani, Anjali; Laszlo, George S; Simó, Sergi; Shah, Khyati; Pilling, Carissa; Strait, Alexander A; Cooper, Jonathan A

    2014-02-01

    Phosphorylation-dependent protein ubiquitylation and degradation provides an irreversible mechanism to terminate protein kinase signaling. Here, we report that mammary epithelial cells require cullin-5-RING-E3-ubiquitin-ligase complexes (Cul5-CRLs) to prevent transformation by a Src-Cas signaling pathway. Removal of Cul5 stimulates growth-factor-independent growth and migration, membrane dynamics and colony dysmorphogenesis, which are all dependent on the endogenous tyrosine kinase Src. Src is activated in Cul5-deficient cells, but Src activation alone is not sufficient to cause transformation. We found that Cul5 and Src together stimulate degradation of the Src substrate p130Cas (Crk-associated substrate). Phosphorylation stimulates Cas binding to the Cul5-CRL adaptor protein SOCS6 and consequent proteasome-dependent degradation. Cas is necessary for the transformation of Cul5-deficient cells. Either knockdown of SOCS6 or use of a degradation-resistant Cas mutant stimulates membrane ruffling, but not other aspects of transformation. Our results show that endogenous Cul5 suppresses epithelial cell transformation by several pathways, including inhibition of Src-Cas-induced ruffling through SOCS6.

  4. Dual nuclease activity of a Cas2 protein in CRISPR-Cas subtype I-B of Leptospira interrogans.

    PubMed

    Dixit, Bhuvan; Ghosh, Karukriti Kaushik; Fernandes, Gary; Kumar, Pankaj; Gogoi, Prerana; Kumar, Manish

    2016-04-01

    Leptospira interrogans serovar Copenhageni strain Fiocruz L1-130 carries a set of cas genes associated with CRISPR-Cas subtype I-B. Herein, we report for the first time active transcription of a set of cas genes (cas1 to cas8) of L. interrogans where cas4, cas1, cas2 and cas6, cas3, cas8, cas7, cas5 are clustered together in two independent operons. As an initial step toward comprehensive understanding of CRISPR-Cas system in spirochete, the biochemical study of one of the core Leptospira Cas2 proteins (Lep_Cas2) showed nuclease activity on both DNA and RNA in a nonspecific manner. Additionally, unlike other known Cas2 proteins, Lep_Cas2 showed metal-independent RNase activity and preferential activity on RNA over DNA. These results provide insight for understanding Cas2 diversity existing in the prokaryotic adaptive immune system.

  5. [The effects of Mexidol on food conditioning and synaptic fine structure of hippocampal field CA1 in rats exposed to a single acoustic stimulation with ultrasonic components].

    PubMed

    Alekseeva, T G; Loseva, E V; Mering, T A

    2004-01-01

    The effect of exposure of rats to a complex acoustic signal with ultrasonic components on line structure of synapses of the CA1 field of the hippocampus was studied during a course treatment (two weeks) with broad-spectrum antioxidant Mexidol. Under the same conditions, the time course of food conditioning by a conditioned tone stimulus and acquisition of trace conditioned reflex (time interval counting) were studied in the same rat group. Rats non-exposed to stress against the background of Mexidol and without Mexidol treatment served as control. Analysis of fine structure of the vesicle redistribution in CA1 synapses revealed a reduction of the efficacy of synaptic transmission a day after the exposure to the complex acoustic stimulus. We found a negative effect of the complex acoustic stimulus on conditioning by tone and acquisition of time-counting trace reflex by rats. This effect was shown to be normalized by the course Mexidol treatment. The results suggests the expediency of Mexidol application for prevention of cognitive disorders, which are frequent under stress-inducing conditions.

  6. Structure and activity of the Cas3 HD nuclease MJ0384, an effector enzyme of the CRISPR interference

    SciTech Connect

    Beloglazova, Natalia; Petit, Pierre; Flick, Robert; Brown, Greg; Savchenko, Alexei; Yakunin, Alexander F.

    2012-03-15

    Clustered regularly interspaced short palindromic repeats (CRISPRs) and Cas proteins represent an adaptive microbial immunity system against viruses and plasmids. Cas3 proteins have been proposed to play a key role in the CRISPR mechanism through the direct cleavage of invasive DNA. Here, we show that the Cas3 HD domain protein MJ0384 from Methanocaldococcus jannaschii cleaves endonucleolytically and exonucleolytically (3'-5') single-stranded DNAs and RNAs, as well as 3'-flaps, splayed arms, and R-loops. The degradation of branched DNA substrates by MJ0384 is stimulated by the Cas3 helicase MJ0383 and ATP. The crystal structure of MJ0384 revealed the active site with two bound metal cations and together with site-directed mutagenesis suggested a catalytic mechanism. Our studies suggest that the Cas3 HD nucleases working together with the Cas3 helicases can completely degrade invasive DNAs through the combination of endo- and exonuclease activities.

  7. p130Cas over-expression impairs mammary branching morphogenesis in response to estrogen and EGF.

    PubMed

    Camacho Leal, Maria del Pilar; Pincini, Alessandra; Tornillo, Giusy; Fiorito, Elisa; Bisaro, Brigitte; Di Luca, Elisa; Turco, Emilia; Defilippi, Paola; Cabodi, Sara

    2012-01-01

    p130Cas adaptor protein regulates basic processes such as cell cycle control, survival and migration. p130Cas over-expression has been related to mammary gland transformation, however the in vivo consequences of p130Cas over-expression during mammary gland morphogenesis are not known. In ex vivo mammary explants from MMTV-p130Cas transgenic mice, we show that p130Cas impairs the functional interplay between Epidermal Growth Factor Receptor (EGFR) and Estrogen Receptor (ER) during mammary gland development. Indeed, we demonstrate that p130Cas over-expression upon the concomitant stimulation with EGF and estrogen (E2) severely impairs mammary morphogenesis giving rise to enlarged multicellular spherical structures with altered architecture and absence of the central lumen. These filled acinar structures are characterized by increased cell survival and proliferation and by a strong activation of Erk1/2 MAPKs and Akt. Interestingly, antagonizing the ER activity is sufficient to re-establish branching morphogenesis and normal Erk1/2 MAPK activity. Overall, these results indicate that high levels of p130Cas expression profoundly affect mammary morphogenesis by altering epithelial architecture, survival and unbalancing Erk1/2 MAPKs activation in response to growth factors and hormones. These results suggest that alteration of morphogenetic pathways due to p130Cas over-expression might prime mammary epithelium to tumorigenesis.

  8. Acoustic Neuroma

    MedlinePlus

    An acoustic neuroma is a benign tumor that develops on the nerve that connects the ear to the brain. ... can press against the brain, becoming life-threatening. Acoustic neuroma can be difficult to diagnose, because the ...

  9. Specific and rapid effects of acoustic stimulation on the tonotopic distribution of Kv3.1b potassium channels in the adult rat.

    PubMed

    Strumbos, J G; Polley, D B; Kaczmarek, L K

    2010-05-19

    Recent studies have demonstrated that total cellular levels of voltage-gated potassium channel subunits can change on a time scale of minutes in acute slices and cultured neurons, raising the possibility that rapid changes in the abundance of channel proteins contribute to experience-dependent plasticity in vivo. In order to investigate this possibility, we took advantage of the medial nucleus of the trapezoid body (MNTB) sound localization circuit, which contains neurons that precisely phase-lock their action potentials to rapid temporal fluctuations in the acoustic waveform. Previous work has demonstrated that the ability of these neurons to follow high-frequency stimuli depends critically upon whether they express adequate amounts of the potassium channel subunit Kv3.1. To test the hypothesis that net amounts of Kv3.1 protein would be rapidly upregulated when animals are exposed to sounds that require high frequency firing for accurate encoding, we briefly exposed adult rats to acoustic environments that varied according to carrier frequency and amplitude modulation (AM) rate. Using an antibody directed at the cytoplasmic C-terminus of Kv3.1b (the adult splice isoform of Kv3.1), we found that total cellular levels of Kv3.1b protein-as well as the tonotopic distribution of Kv3.1b-labeled cells-was significantly altered following 30 min of exposure to rapidly modulated (400 Hz) sounds relative to slowly modulated (0-40 Hz, 60 Hz) sounds. These results provide direct evidence that net amounts of Kv3.1b protein can change on a time scale of minutes in response to stimulus-driven synaptic activity, permitting auditory neurons to actively adapt their complement of ion channels to changes in the acoustic environment.

  10. Specific and rapid effects of acoustic stimulation on the tonotopic distribution of Kv3.1b potassium channels in the adult rat

    PubMed Central

    Strumbos, John G.; Polley, Daniel B.; Kaczmarek, Leonard K.

    2010-01-01

    Recent studies have demonstrated that total cellular levels of voltage-gated potassium channel subunits can change on a time scale of minutes in acute slices and cultured neurons (Raab-Graham et al., 2006), raising the possibility that rapid changes in the abundance of channel proteins contribute to experience-dependent plasticity in vivo. In order to investigate this possibility, we took advantage of the medial nucleus of the trapezoid body (MNTB) sound localization circuit, which contains neurons that precisely phase-lock their action potentials to rapid temporal fluctuations in the acoustic waveform. Previous work has demonstrated that the ability of these neurons to follow high-frequency stimuli depends critically upon whether they express adequate amounts of the potassium channel subunit Kv3.1. To test the hypothesis that net amounts of Kv3.1 protein would be rapidly upregulated when animals are exposed to sounds that require high frequency firing for accurate encoding, we briefly exposed adult rats to acoustic environments that varied according to carrier frequency and amplitude modulation (AM) rate. Using an antibody directed at the cytoplasmic C-terminus of Kv3.1b (the adult splice isoform of Kv3.1), we found that total cellular levels of Kv3.1b protein – as well as the tonotopic distribution of Kv3.1b-labeled cells – was significantly altered following 30 minutes of exposure to rapidly modulated (400 Hz) sounds relative to slowly modulated (0–40 Hz, 60 Hz) sounds. These results provide direct evidence that net amounts of Kv3.1b protein can change on a time scale of minutes in response to stimulus-driven synaptic activity, permitting auditory neurons to actively adapt their complement of ion channels to changes in the acoustic environment. PMID:20219640

  11. Acoustic Seaglider

    DTIC Science & Technology

    2008-03-07

    a national naval responsibility. Acoustic sensors on mobile, autonomous platforms will enable basic research topics on temporal and spatial...problem and acoustic navigation and communications within the context of distributed autonomous persistent undersea surveillance sensor networks...Acoustic sensors on mobile, autonomous platforms will enable basic research topics on temporal and spatial coherence and the description of ambient

  12. Acoustic seal

    NASA Technical Reports Server (NTRS)

    Steinetz, Bruce M. (Inventor)

    2006-01-01

    The invention relates to a sealing device having an acoustic resonator. The acoustic resonator is adapted to create acoustic waveforms to generate a sealing pressure barrier blocking fluid flow from a high pressure area to a lower pressure area. The sealing device permits noncontacting sealing operation. The sealing device may include a resonant-macrosonic-synthesis (RMS) resonator.

  13. Acoustic Seal

    NASA Technical Reports Server (NTRS)

    Steinetz, Bruce M. (Inventor)

    2006-01-01

    The invention relates to a sealing device having an acoustic resonator. The acoustic resonator is adapted to create acoustic waveforms to generate a sealing pressure barrier blocking fluid flow from a high pressure area to a lower pressure area. The sealing device permits noncontacting sealing operation. The sealing device may include a resonant-macrosonic-synthesis (RMS) resonator.

  14. The radii of SU Cas and TU Cas

    NASA Technical Reports Server (NTRS)

    Niva, G. D.; Schmidt, E. G.

    1980-01-01

    It is possible to obtain the masses of Cepheid variables by several methods involving the pulsation theory. However, these masses are frequently smaller than those indicated by the theory of stellar evolution. The cause of this discrepancy is not fully understood. Since the pulsation theory indicates that there is a relation among the mass, the radius and the period, the discrepancy also manifests itself in the radii of these stars. With this in mind, radius determinations for two Cepheids, SU Cas and TU Cas, were undertaken. It is concluded that because of the agreement between the present radius and the beat radius of TU Cas, the pulsation theory is giving correct information about the radii of beat Cepheids. This implies that the luminosities of short period Cepheids have been overestimated. Thus, the solution to the mass discrepancy should perhaps be sought in the theory of stellar evolution or in the possibility of mass loss.

  15. Childhood Apraxia of Speech (CAS) in two patients with 16p11.2 microdeletion syndrome

    PubMed Central

    Raca, Gordana; Baas, Becky S; Kirmani, Salman; Laffin, Jennifer J; Jackson, Craig A; Strand, Edythe A; Jakielski, Kathy J; Shriberg, Lawrence D

    2013-01-01

    We report clinical findings that extend the phenotype of the ∼550 kb 16p11.2 microdeletion syndrome to include a rare, severe, and persistent pediatric speech sound disorder termed Childhood Apraxia of Speech (CAS). CAS is the speech disorder identified in a multigenerational pedigree (‘KE') in which half of the members have a mutation in FOXP2 that co-segregates with CAS, oromotor apraxia, and low scores on a nonword repetition task. Each of the two patients in the current report completed a 2-h assessment protocol that provided information on their cognitive, language, speech, oral mechanism, motor, and developmental histories and performance. Their histories and standard scores on perceptual and acoustic speech tasks met clinical and research criteria for CAS. Array comparative genomic hybridization analyses identified deletions at chromosome 16p11.2 in each patient. These are the first reported cases with well-characterized CAS in the 16p11.2 syndrome literature and the first report of this microdeletion in CAS genetics research. We discuss implications of findings for issues in both literatures. PMID:22909774

  16. New CRISPR-Cas systems discovered.

    PubMed

    Yang, Hui; Patel, Dinshaw J

    2017-03-01

    In bacteria and archaea, CRISPR-Cas adaptive immune systems utilize RNA-guided endonucleases to defend against invasion by foreign nucleic acids of bacteriophage, virus and plasmid origin. In a recent paper published in Nature, Burstein et al. identified the first Cas9 protein in uncultivated archaea and two novel CRISPR-CasX and CRISPR-CasY systems in uncultivated bacteria by capitalizing on analysis of terabase-scale metagenomic datasets from natural uncultivated organisms.

  17. CAS-Induced Difficulties in Learning Mathematics?

    ERIC Educational Resources Information Center

    Jankvist, Uffe Thomas; Misfeldt, Morten

    2015-01-01

    In recent years computer algebra systems (CAS) have become an integrated part of the upper secondary school mathematics program. Despite the many positive possibilities of CAS, there also seems to be a flip side of the coin in relation to actual difficulties in learning mathematics, not least because a strong dependence on CAS for mathematical…

  18. A Kinase-Independent Function of c-Src Mediates p130Cas Phosphorylation at the Serine-639 Site in Pressure Overloaded Myocardium.

    PubMed

    Palanisamy, Arun P; Suryakumar, Geetha; Panneerselvam, Kavin; Willey, Christopher D; Kuppuswamy, Dhandapani

    2015-12-01

    Early work in pressure overloaded (PO) myocardium shows that integrins mediate focal adhesion complex formation by recruiting the adaptor protein p130Cas (Cas) and nonreceptor tyrosine kinase c-Src. To explore c-Src role in Cas-associated changes during PO, we used a feline right ventricular in vivo PO model and a three-dimensional (3D) collagen-embedded adult cardiomyocyte in vitro model that utilizes a Gly-Arg-Gly-Asp-Ser (RGD) peptide for integrin stimulation. Cas showed slow electrophoretic mobility (band-shifting), recruitment to the cytoskeleton, and tyrosine phosphorylation at 165, 249, and 410 sites in both 48 h PO myocardium and 1 h RGD-stimulated cardiomyocytes. Adenoviral mediated expression of kinase inactive (negative) c-Src mutant with intact scaffold domains (KN-Src) in cardiomyocytes did not block the RGD stimulated changes in Cas. Furthermore, expression of KN-Src or kinase active c-Src mutant with intact scaffold function (A-Src) in two-dimensionally (2D) cultured cardiomyocytes was sufficient to cause Cas band-shifting, although tyrosine phosphorylation required A-Src. These data indicate that c-Src's adaptor function, but not its kinase function, is required for a serine/threonine specific phosphorylation(s) responsible for Cas band-shifting. To explore this possibility, Chinese hamster ovary cells that stably express Cas were infected with either β-gal or KN-Src adenoviruses and used for Cas immunoprecipitation combined with mass spectrometry analysis. In the KN-Src expressing cells, Cas showed phosphorylation at the serine-639 (human numbering) site. A polyclonal antibody raised against phospho-serine-639 detected Cas phosphorylation in 24-48 h PO myocardium. Our studies indicate that c-Src's adaptor function mediates serine-639 phosphorylation of Cas during integrin activation in PO myocardium.

  19. Comparative assessments of CRISPR-Cas nucleases' cleavage efficiency in planta.

    PubMed

    Johnson, Ross A; Gurevich, Vyacheslav; Filler, Shdema; Samach, Aviva; Levy, Avraham A

    2015-01-01

    Custom-designed nucleases can enable precise plant genome editing by catalyzing DNA-breakage at specific targets to stimulate targeted mutagenesis or gene replacement. The CRISPR-Cas system, with its target-specifying RNA molecule to direct the Cas9 nuclease, is a recent addition to existing nucleases that bind and cleave the target through linked protein domains (e.g. TALENs and zinc-finger nucleases). We have conducted a comparative study of these different types of custom-designed nucleases and we have assessed various components of the CRISPR-Cas system. For this purpose, we have adapted our previously reported assay for cleavage-dependent luciferase gene correction in Nicotiana benthamiana leaves (Johnson et al. in Plant Mol Biol 82(3):207-221, 2013). We found that cleavage by CRISPR-Cas was more efficient than cleavage of the same target by TALENs. We also compared the cleavage efficiency of the Streptococcus pyogenes Cas9 protein based on expression using three different Cas9 gene variants. We found significant differences in cleavage efficiency between these variants, with human and Arabidopsis thaliana codon-optimized genes having the highest cleavage efficiencies. We compared the activity of 12 de novo-designed single synthetic guide RNA (sgRNA) constructs, and found their cleavage efficiency varied drastically when using the same Cas9 nuclease. Finally, we show that, for one of the targets tested with our assay, we could induce a germinally-transmitted deletion in a repeat array in A. thaliana. This work emphasizes the efficiency of the CRISPR-Cas system in plants. It also shows that further work is needed to be able to predict the optimal design of sgRNAs or Cas9 variants.

  20. Musical Acoustics

    NASA Astrophysics Data System (ADS)

    Gough, Colin

    This chapter provides an introduction to the physical and psycho-acoustic principles underlying the production and perception of the sounds of musical instruments. The first section introduces generic aspects of musical acoustics and the perception of musical sounds, followed by separate sections on string, wind and percussion instruments.

  1. CRISPR/Cas9 Technologies.

    PubMed

    Williams, Bart O; Warman, Matthew L

    2017-02-23

    The Clustered Regularly Interspaced Palindromic Repeats (CRISPR)/CRISPR-associated protein (Cas) pathway is revolutionizing biological research. Modifications to this primitive prokaryotic immune system now enable scientists to efficiently edit DNA or modulate gene expression in living eukaryotic cells and organisms. Thus, many laboratories can now perform important experiments that previously were considered scientifically risky or too costly. Here, we describe the components of the CRISPR/Cas system that have been engineered for use in eukaryotes. We also explain how this system can be used to genetically modify cell lines and model organisms, or regulate gene expression in order to search for new participants in biological pathways. © 2017 American Society for Bone and Mineral Research.

  2. Genome modification by CRISPR/Cas9.

    PubMed

    Ma, Yuanwu; Zhang, Lianfeng; Huang, Xingxu

    2014-12-01

    Clustered regularly interspaced short palindromic repeats (CRISPR)-CRISPR-associated protein (Cas)9-mediated genome modification enables us to edit the genomes of a variety of organisms rapidly and efficiently. The advantages of the CRISPR-Cas9 system have made it an increasingly popular genetic engineering tool for biological and therapeutic applications. Moreover, CRISPR-Cas9 has been employed to recruit functional domains that repress/activate gene expression or label specific genomic loci in living cells or organisms, in order to explore developmental mechanisms, gene expression regulation, and animal behavior. One major concern about this system is its specificity; although CRISPR-Cas9-mediated off-target mutation has been broadly studied, more efforts are required to further improve the specificity of CRISPR-Cas9. We will also discuss the potential applications of CRISPR-Cas9.

  3. Expanding CRISPR/Cas9 Genome Editing Capacity in Zebrafish Using SaCas9

    PubMed Central

    Feng, Yan; Chen, Cheng; Han, Yuxiang; Chen, Zelin; Lu, Xiaochan; Liang, Fang; Li, Song; Qin, Wei; Lin, Shuo

    2016-01-01

    The type II CRISPR/Cas9 system has been used widely for genome editing in zebrafish. However, the requirement for the 5′-NGG-3′ protospacer-adjacent motif (PAM) of Cas9 from Streptococcus pyogenes (SpCas9) limits its targeting sequences. Here, we report that a Cas9 ortholog from Staphylococcus aureus (SaCas9), and its KKH variant, successfully induced targeted mutagenesis with high frequency in zebrafish. Confirming previous findings, the SpCas9 variant, VQR, can also induce targeted mutations in zebrafish. Bioinformatics analysis of these new Cas targets suggests that the number of available target sites in the zebrafish genome can be greatly expanded. Collectively, the expanded target repertoire of Cas9 in zebrafish should further facilitate the utility of this organism for genetic studies of vertebrate biology. PMID:27317783

  4. Room Acoustics

    NASA Astrophysics Data System (ADS)

    Kuttruff, Heinrich; Mommertz, Eckard

    The traditional task of room acoustics is to create or formulate conditions which ensure the best possible propagation of sound in a room from a sound source to a listener. Thus, objects of room acoustics are in particular assembly halls of all kinds, such as auditoria and lecture halls, conference rooms, theaters, concert halls or churches. Already at this point, it has to be pointed out that these conditions essentially depend on the question if speech or music should be transmitted; in the first case, the criterion for transmission quality is good speech intelligibility, in the other case, however, the success of room-acoustical efforts depends on other factors that cannot be quantified that easily, not least it also depends on the hearing habits of the listeners. In any case, absolutely "good acoustics" of a room do not exist.

  5. Cas6 specificity and CRISPR RNA loading in a complex CRISPR-Cas system.

    PubMed

    Sokolowski, Richard D; Graham, Shirley; White, Malcolm F

    2014-06-01

    CRISPR-Cas is an adaptive prokaryotic immune system, providing protection against viruses and other mobile genetic elements. In type I and type III CRISPR-Cas systems, CRISPR RNA (crRNA) is generated by cleavage of a primary transcript by the Cas6 endonuclease and loaded into multisubunit surveillance/effector complexes, allowing homology-directed detection and cleavage of invading elements. Highly studied CRISPR-Cas systems such as those in Escherichia coli and Pseudomonas aeruginosa have a single Cas6 enzyme that is an integral subunit of the surveillance complex. By contrast, Sulfolobus solfataricus has a complex CRISPR-Cas system with three types of surveillance complexes (Cascade/type I-A, CSM/type III-A and CMR/type III-B), five Cas6 paralogues and two different CRISPR-repeat families (AB and CD). Here, we investigate the kinetic properties of two different Cas6 paralogues from S. solfataricus. The Cas6-1 subtype is specific for CD-family CRISPR repeats, generating crRNA by multiple turnover catalysis whilst Cas6-3 has a broader specificity and also processes a non-coding RNA with a CRISPR repeat-related sequence. Deep sequencing of crRNA in surveillance complexes reveals a biased distribution of spacers derived from AB and CD loci, suggesting functional coupling between Cas6 paralogues and their downstream effector complexes.

  6. CAS as Environments for Implementing Mathematical Microworlds.

    ERIC Educational Resources Information Center

    Alpers, Burkhard

    2002-01-01

    Investigates whether computer algebra systems (CAS) are suitable environments for implementing mathematical microworlds. Recalls what constitutes a microworld and explores how CAS can be used for implementation, stating potentials as well as limitations. Provides as an example the microworld "Formula 1", implemented in Maple Software. (Author/KHR)

  7. Acoustic biosensors

    PubMed Central

    Fogel, Ronen; Seshia, Ashwin A.

    2016-01-01

    Resonant and acoustic wave devices have been researched for several decades for application in the gravimetric sensing of a variety of biological and chemical analytes. These devices operate by coupling the measurand (e.g. analyte adsorption) as a modulation in the physical properties of the acoustic wave (e.g. resonant frequency, acoustic velocity, dissipation) that can then be correlated with the amount of adsorbed analyte. These devices can also be miniaturized with advantages in terms of cost, size and scalability, as well as potential additional features including integration with microfluidics and electronics, scaled sensitivities associated with smaller dimensions and higher operational frequencies, the ability to multiplex detection across arrays of hundreds of devices embedded in a single chip, increased throughput and the ability to interrogate a wider range of modes including within the same device. Additionally, device fabrication is often compatible with semiconductor volume batch manufacturing techniques enabling cost scalability and a high degree of precision and reproducibility in the manufacturing process. Integration with microfluidics handling also enables suitable sample pre-processing/separation/purification/amplification steps that could improve selectivity and the overall signal-to-noise ratio. Three device types are reviewed here: (i) bulk acoustic wave sensors, (ii) surface acoustic wave sensors, and (iii) micro/nano-electromechanical system (MEMS/NEMS) sensors. PMID:27365040

  8. Acoustic biosensors.

    PubMed

    Fogel, Ronen; Limson, Janice; Seshia, Ashwin A

    2016-06-30

    Resonant and acoustic wave devices have been researched for several decades for application in the gravimetric sensing of a variety of biological and chemical analytes. These devices operate by coupling the measurand (e.g. analyte adsorption) as a modulation in the physical properties of the acoustic wave (e.g. resonant frequency, acoustic velocity, dissipation) that can then be correlated with the amount of adsorbed analyte. These devices can also be miniaturized with advantages in terms of cost, size and scalability, as well as potential additional features including integration with microfluidics and electronics, scaled sensitivities associated with smaller dimensions and higher operational frequencies, the ability to multiplex detection across arrays of hundreds of devices embedded in a single chip, increased throughput and the ability to interrogate a wider range of modes including within the same device. Additionally, device fabrication is often compatible with semiconductor volume batch manufacturing techniques enabling cost scalability and a high degree of precision and reproducibility in the manufacturing process. Integration with microfluidics handling also enables suitable sample pre-processing/separation/purification/amplification steps that could improve selectivity and the overall signal-to-noise ratio. Three device types are reviewed here: (i) bulk acoustic wave sensors, (ii) surface acoustic wave sensors, and (iii) micro/nano-electromechanical system (MEMS/NEMS) sensors.

  9. CasA mediates Cas3-catalyzed target degradation during CRISPR RNA-guided interference.

    PubMed

    Hochstrasser, Megan L; Taylor, David W; Bhat, Prashant; Guegler, Chantal K; Sternberg, Samuel H; Nogales, Eva; Doudna, Jennifer A

    2014-05-06

    In bacteria, the clustered regularly interspaced short palindromic repeats (CRISPR)-associated (Cas) DNA-targeting complex Cascade (CRISPR-associated complex for antiviral defense) uses CRISPR RNA (crRNA) guides to bind complementary DNA targets at sites adjacent to a trinucleotide signature sequence called the protospacer adjacent motif (PAM). The Cascade complex then recruits Cas3, a nuclease-helicase that catalyzes unwinding and cleavage of foreign double-stranded DNA (dsDNA) bearing a sequence matching that of the crRNA. Cascade comprises the CasA-E proteins and one crRNA, forming a structure that binds and unwinds dsDNA to form an R loop in which the target strand of the DNA base pairs with the 32-nt RNA guide sequence. Single-particle electron microscopy reconstructions of dsDNA-bound Cascade with and without Cas3 reveal that Cascade positions the PAM-proximal end of the DNA duplex at the CasA subunit and near the site of Cas3 association. The finding that the DNA target and Cas3 colocalize with CasA implicates this subunit in a key target-validation step during DNA interference. We show biochemically that base pairing of the PAM region is unnecessary for target binding but critical for Cas3-mediated degradation. In addition, the L1 loop of CasA, previously implicated in PAM recognition, is essential for Cas3 activation following target binding by Cascade. Together, these data show that the CasA subunit of Cascade functions as an essential partner of Cas3 by recognizing DNA target sites and positioning Cas3 adjacent to the PAM to ensure cleavage.

  10. In vitro enzymology of Cas9.

    PubMed

    Anders, Carolin; Jinek, Martin

    2014-01-01

    Cas9 is a bacterial RNA-guided endonuclease that uses base pairing to recognize and cleave target DNAs with complementarity to the guide RNA. The programmable sequence specificity of Cas9 has been harnessed for genome editing and gene expression control in many organisms. Here, we describe protocols for the heterologous expression and purification of recombinant Cas9 protein and for in vitro transcription of guide RNAs. We describe in vitro reconstitution of the Cas9-guide RNA ribonucleoprotein complex and its use in endonuclease activity assays. The methods outlined here enable mechanistic characterization of the RNA-guided DNA cleavage activity of Cas9 and may assist in further development of the enzyme for genetic engineering applications.

  11. CAS

    SciTech Connect

    Martinez, B.; Pomeroy, G. )

    1989-12-02

    The Security Alarm System is a data acquisition and control system which collects data from intrusion sensors and displays the information in a real-time environment for operators. The Access Control System monitors and controls the movement of personnel with the use of card readers and biometrics hand readers.

  12. Electric-acoustic interactions in the hearing cochlea: single fiber recordings.

    PubMed

    Tillein, J; Hartmann, R; Kral, A

    2015-04-01

    The present study investigates interactions of simultaneous electric and acoustic stimulation in single auditory nerve fibers in normal hearing cats. First, the auditory nerve was accessed with a microelectrode and response areas of single nerve fibers were determined for acoustic stimulation. Second, response thresholds to extracochlear sinusoidal electric stimulation using ball electrodes positioned at the round window were measured. Third, interactions that occurred with combined electric-acoustic stimulation were investigated in two areas: (1) the spectral domain (frequency response areas) and (2) the temporal domain (phase-locking to each stimulus) at moderate stimulus intensities (electric: 6 dB re threshold, acoustic: 20-40 dB re threshold at the characteristic frequency, CF). For fibers responding to both modalities responses to both electric and acoustic stimulation could be clearly identified. CFs, thresholds, and bandwidth (Q10dB) of acoustic responses were not significantly affected by simultaneous electric stimulation. Phase-locking of electric responses decreased in the presence of acoustic stimulation. Indication for electric stimulation of inner hair cells with 125 and 250 Hz were observed. However, these did not disturb the acoustic receptive fields of auditory nerve fibers. There was a trade-off between these responses when the intensities of the stimulation were varied: Relatively more intense stimulation dominated less intense stimulation. The scarcity of interaction between the different stimulus modalities demonstrates the ability of electric-acoustic stimulation to transfer useful information through both stimulation channels at the same time despite cochlear electrophonic effects. Application of 30 Hz electric stimulation resulted in a strong suppression of acoustic activity in the anodic phase of the stimulus. An electric stimulation like this might thus be used to control acoustic responses. This article is part of a Special Issue

  13. Biased allosteric modulation at the CaS receptor engendered by structurally diverse calcimimetics

    PubMed Central

    Cook, A E; Mistry, S N; Gregory, K J; Furness, S G B; Sexton, P M; Scammells, P J; Conigrave, A D; Christopoulos, A; Leach, K

    2015-01-01

    BACKGROUND AND PURPOSE Clinical use of cinacalcet in hyperparathyroidism is complicated by its tendency to induce hypocalcaemia, arising partly from activation of calcium-sensing receptors (CaS receptors) in the thyroid and stimulation of calcitonin release. CaS receptor allosteric modulators that selectively bias signalling towards pathways that mediate desired effects [e.g. parathyroid hormone (PTH) suppression] rather than those mediating undesirable effects (e.g. elevated serum calcitonin), may offer better therapies. EXPERIMENTAL APPROACH We characterized the ligand-biased profile of novel calcimimetics in HEK293 cells stably expressing human CaS receptors, by monitoring intracellular calcium (Ca2+i) mobilization, inositol phosphate (IP)1 accumulation, ERK1/2 phosphorylation (pERK1/2) and receptor expression. KEY RESULTS Phenylalkylamine calcimimetics were biased towards allosteric modulation of Ca2+i mobilization and IP1 accumulation. S,R-calcimimetic B was biased only towards IP1 accumulation. R,R-calcimimetic B and AC-265347 were biased towards IP1 accumulation and pERK1/2. Nor-calcimimetic B was unbiased. In contrast to phenylalkylamines and calcimimetic B analogues, AC-265347 did not promote trafficking of a loss-of-expression, naturally occurring, CaS receptor mutation (G670E). CONCLUSIONS AND IMPLICATIONS The ability of R,R-calcimimetic B and AC-265347 to bias signalling towards pERK1/2 and IP1 accumulation may explain their suppression of PTH levels in vivo at concentrations that have no effect on serum calcitonin levels. The demonstration that AC-265347 promotes CaS receptor receptor signalling, but not trafficking reveals a novel profile of ligand-biased modulation at CaS receptors The identification of allosteric modulators that bias CaS receptor signalling towards distinct intracellular pathways provides an opportunity to develop desirable biased signalling profiles in vivo for mediating selective physiological responses. PMID:25220431

  14. Nonlinear Acoustics

    DTIC Science & Technology

    1974-02-14

    Wester- velt. [60] Streaming. In 1831, Michael Faraday [61] noted that currents of air were set up in the neighborhood of vibrating plates-the first... ducei in the case of a paramettc amy (from Berktay an Leahy 141). C’ "". k•, SEC 10.1 NONLINEAR ACOUSTICS 345 The principal results of their analysis

  15. RXTE Observations of Cas A

    NASA Technical Reports Server (NTRS)

    Rothschild, R. E.; Lingenfelter, R. E.; Heindl, W. A.; Blanco, P. R.; Pelling, M. R.; Gruber, D. E.; Allen, G. E.; Jahoda, K.; Swank, J. H.; Woosley, S. E.; Nomoto, K.; Higdon, J. C.; Dermer, Charles D. (Editor); Strickman, Mark S. (Editor); Kurfess, James D. (Editor)

    1997-01-01

    The exciting detection by the COMPTEL instrument of the 1157 keV Ti-44 line from the supernova remnant Cas A sets important new constraints on supernova dynamics and nucleosynthesis. The Ti-44 decay also produces x-ray lines at 68 and 78 keV, whose flux should be essentially the same as that of the gamma ray line. The revised COMPTEL flux of 4 x l0(exp -5) cm(exp -2)s(exp -1) is very near the sensitivity limit for line detection by the HEXTE instrument on RXTE. We report on the results from two RXTE observations - 20 ks during In Orbit Checkout in January 1996 and 200 ks in April 1996. We also find a strong continuum emission suggesting cosmic ray electron acceleration in the remnant.

  16. Nucleosomes Inhibit Cas9 Endonuclease Activity in Vitro.

    PubMed

    Hinz, John M; Laughery, Marian F; Wyrick, John J

    2015-12-08

    During Cas9 genome editing in eukaryotic cells, the bacterial Cas9 enzyme cleaves DNA targets within chromatin. To understand how chromatin affects Cas9 targeting, we characterized Cas9 activity on nucleosome substrates in vitro. We find that Cas9 endonuclease activity is strongly inhibited when its target site is located within the nucleosome core. In contrast, the nucleosome structure does not affect Cas9 activity at a target site within the adjacent linker DNA. Analysis of target sites that partially overlap with the nucleosome edge indicates that the accessibility of the protospacer-adjacent motif (PAM) is the critical determinant of Cas9 activity on a nucleosome.

  17. Acoustic transducer for acoustic microscopy

    DOEpatents

    Khuri-Yakub, Butrus T.; Chou, Ching H.

    1990-01-01

    A shear acoustic transducer-lens system in which a shear polarized piezoelectric material excites shear polarized waves at one end of a buffer rod having a lens at the other end which excites longitudinal waves in a coupling medium by mode conversion at selected locations on the lens.

  18. Acoustic transducer for acoustic microscopy

    DOEpatents

    Khuri-Yakub, B.T.; Chou, C.H.

    1990-03-20

    A shear acoustic transducer-lens system is described in which a shear polarized piezoelectric material excites shear polarized waves at one end of a buffer rod having a lens at the other end which excites longitudinal waves in a coupling medium by mode conversion at selected locations on the lens. 9 figs.

  19. A newly discovered Bordetella species carries a transcriptionally active CRISPR-Cas with a small Cas9 endonuclease

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The Cas9 endonuclease of the Type II-a clustered regularly interspersed short palindromic repeats (CRISPR), of Streptococcus pyogenes (SpCas9) has been adapted as a widely used tool for genome editing and genome engineering. Herein, we describe a gene encoding a novel Cas9 ortholog (BpsuCas9) and th...

  20. Cas9 specifies functional viral targets during CRISPR-Cas adaptation.

    PubMed

    Heler, Robert; Samai, Poulami; Modell, Joshua W; Weiner, Catherine; Goldberg, Gregory W; Bikard, David; Marraffini, Luciano A

    2015-03-12

    Clustered regularly interspaced short palindromic repeat (CRISPR) loci and their associated (Cas) proteins provide adaptive immunity against viral infection in prokaryotes. Upon infection, short phage sequences known as spacers integrate between CRISPR repeats and are transcribed into small RNA molecules that guide the Cas9 nuclease to the viral targets (protospacers). Streptococcus pyogenes Cas9 cleavage of the viral genome requires the presence of a 5'-NGG-3' protospacer adjacent motif (PAM) sequence immediately downstream of the viral target. It is not known whether and how viral sequences flanked by the correct PAM are chosen as new spacers. Here we show that Cas9 selects functional spacers by recognizing their PAM during spacer acquisition. The replacement of cas9 with alleles that lack the PAM recognition motif or recognize an NGGNG PAM eliminated or changed PAM specificity during spacer acquisition, respectively. Cas9 associates with other proteins of the acquisition machinery (Cas1, Cas2 and Csn2), presumably to provide PAM-specificity to this process. These results establish a new function for Cas9 in the genesis of prokaryotic immunological memory.

  1. [Comparison of differental intracochlear pressures between round window stimulation and ear canal stimulation].

    PubMed

    Wang, Xuelin

    2012-12-01

    Stimulation of the round window (RW) for coupling an implantable hearing system to the cochlea has gained increasing clinical importance. To compare the vibration transfer to the cochlear fluids and partition in response to normal acoustic stimulation and to mechanical stimulation of the RW, we carried out an acoustic-structure coupled finite element analysis using a recently developed finite element (FE) model in our laboratory, which consisted of external ear canal, middle ear and cochlea. Intracochlear pressures were derived during normal forward sound stimulation as well as reverse RW stimulation. A model was utilized to calculate the force required of an actuator at the RW to produce a differential intracochlear pressure that is equivalent to a stimulus produced in normal ear by a given external ear-canal pressure. The current results provided further information to support the optimization of the actuators and adapt existing prostheses for RW stimulation in order to insure sufficient acoustic output.

  2. Phylogeny of Cas9 determines functional exchangeability of dual-RNA and Cas9 among orthologous type II CRISPR-Cas systems

    PubMed Central

    Fonfara, Ines; Le Rhun, Anaïs; Chylinski, Krzysztof; Makarova, Kira S.; Lécrivain, Anne-Laure; Bzdrenga, Janek; Koonin, Eugene V.; Charpentier, Emmanuelle

    2014-01-01

    The CRISPR-Cas-derived RNA-guided Cas9 endonuclease is the key element of an emerging promising technology for genome engineering in a broad range of cells and organisms. The DNA-targeting mechanism of the type II CRISPR-Cas system involves maturation of tracrRNA:crRNA duplex (dual-RNA), which directs Cas9 to cleave invading DNA in a sequence-specific manner, dependent on the presence of a Protospacer Adjacent Motif (PAM) on the target. We show that evolution of dual-RNA and Cas9 in bacteria produced remarkable sequence diversity. We selected eight representatives of phylogenetically defined type II CRISPR-Cas groups to analyze possible coevolution of Cas9 and dual-RNA. We demonstrate that these two components are interchangeable only between closely related type II systems when the PAM sequence is adjusted to the investigated Cas9 protein. Comparison of the taxonomy of bacterial species that harbor type II CRISPR-Cas systems with the Cas9 phylogeny corroborates horizontal transfer of the CRISPR-Cas loci. The reported collection of dual-RNA:Cas9 with associated PAMs expands the possibilities for multiplex genome editing and could provide means to improve the specificity of the RNA-programmable Cas9 tool. PMID:24270795

  3. Acoustic chaos

    SciTech Connect

    Lauterborn, W.; Parlitz, U.; Holzfuss, J.; Billo, A.; Akhatov, I.

    1996-06-01

    Acoustic cavitation, a complex, spatio-temporal dynamical system, is investigated with respect to its chaotic properties. The sound output, the {open_quote}{open_quote}noise{close_quote}{close_quote}, is subjected to time series analysis. The spatial dynamics of the bubble filaments is captured by high speed holographic cinematography and subsequent digital picture processing from the holograms. Theoretical models are put forward for describing the pattern formation. {copyright} {ital 1996 American Institute of Physics.}

  4. Medical Acoustics

    NASA Astrophysics Data System (ADS)

    Beach, Kirk W.; Dunmire, Barbrina

    Medical acoustics can be subdivided into diagnostics and therapy. Diagnostics are further separated into auditory and ultrasonic methods, and both employ low amplitudes. Therapy (excluding medical advice) uses ultrasound for heating, cooking, permeablizing, activating and fracturing tissues and structures within the body, usually at much higher amplitudes than in diagnostics. Because ultrasound is a wave, linear wave physics are generally applicable, but recently nonlinear effects have become more important, even in low-intensity diagnostic applications.

  5. CRISPR-Cas: biology, mechanisms and relevance

    PubMed Central

    Hille, Frank

    2016-01-01

    Prokaryotes have evolved several defence mechanisms to protect themselves from viral predators. Clustered regularly interspaced short palindromic repeats (CRISPR) and their associated proteins (Cas) display a prokaryotic adaptive immune system that memorizes previous infections by integrating short sequences of invading genomes—termed spacers—into the CRISPR locus. The spacers interspaced with repeats are expressed as small guide CRISPR RNAs (crRNAs) that are employed by Cas proteins to target invaders sequence-specifically upon a reoccurring infection. The ability of the minimal CRISPR-Cas9 system to target DNA sequences using programmable RNAs has opened new avenues in genome editing in a broad range of cells and organisms with high potential in therapeutical applications. While numerous scientific studies have shed light on the biochemical processes behind CRISPR-Cas systems, several aspects of the immunity steps, however, still lack sufficient understanding. This review summarizes major discoveries in the CRISPR-Cas field, discusses the role of CRISPR-Cas in prokaryotic immunity and other physiological properties, and describes applications of the system as a DNA editing technology and antimicrobial agent. This article is part of the themed issue ‘The new bacteriology’. PMID:27672148

  6. Acoustic dose and acoustic dose-rate.

    PubMed

    Duck, Francis

    2009-10-01

    Acoustic dose is defined as the energy deposited by absorption of an acoustic wave per unit mass of the medium supporting the wave. Expressions for acoustic dose and acoustic dose-rate are given for plane-wave conditions, including temporal and frequency dependencies of energy deposition. The relationship between the acoustic dose-rate and the resulting temperature increase is explored, as is the relationship between acoustic dose-rate and radiation force. Energy transfer from the wave to the medium by means of acoustic cavitation is considered, and an approach is proposed in principle that could allow cavitation to be included within the proposed definitions of acoustic dose and acoustic dose-rate.

  7. Inhibition of CRISPR/Cas9-Mediated Genome Engineering by a Type I Interferon-Induced Reduction in Guide RNA Expression.

    PubMed

    Machitani, Mitsuhiro; Sakurai, Fuminori; Wakabayashi, Keisaku; Nakatani, Kosuke; Takayama, Kazuo; Tachibana, Masashi; Mizuguchi, Hiroyuki

    2017-01-01

    Clustered regularly interspaced short palindromic repeat (CRISPR)/Cas9-mediated genome engineering technology is a powerful tool for generation of cells and animals with engineered mutations in their genomes. In order to introduce the CRISPR/Cas9 system into target cells, nonviral and viral vectors are often used; however, such vectors trigger innate immune responses associated with production of type I interferons (IFNs). We have recently demonstrated that type I IFNs inhibit short-hairpin RNA-mediated gene silencing, which led us to hypothesize that type I IFNs may also inhibit CRISPR/Cas9-mediated genome mutagenesis. Here we investigated this hypothesis. A single-strand annealing assay using a reporter plasmid demonstrated that CRISPR/Cas9-mediated cleavage efficiencies of the target double-stranded DNA were significantly reduced by IFNα. A mismatch recognition nuclease-dependent genotyping assay also demonstrated that IFNα reduced insertion or deletion (indel) mutation levels by approximately half. Treatment with IFNα did not alter Cas9 protein expression levels, whereas the copy numbers of guide RNA (gRNA) were significantly reduced by IFNα stimulation. These results indicate that type I IFNs significantly reduce gRNA expression levels following introduction of the CRISPR/Cas9 system in the cells, leading to a reduction in the efficiencies of CRISPR/Cas9-mediated genome mutagenesis. Our findings provide important clues for the achievement of efficient genome engineering using the CRISPR/Cas9 system.

  8. Priming in the Type I-F CRISPR-Cas system triggers strand-independent spacer acquisition, bi-directionally from the primed protospacer.

    PubMed

    Richter, Corinna; Dy, Ron L; McKenzie, Rebecca E; Watson, Bridget N J; Taylor, Corinda; Chang, James T; McNeil, Matthew B; Staals, Raymond H J; Fineran, Peter C

    2014-07-01

    Clustered regularly interspaced short palindromic repeats (CRISPR), in combination with CRISPR associated (cas) genes, constitute CRISPR-Cas bacterial adaptive immune systems. To generate immunity, these systems acquire short sequences of nucleic acids from foreign invaders and incorporate these into their CRISPR arrays as spacers. This adaptation process is the least characterized step in CRISPR-Cas immunity. Here, we used Pectobacterium atrosepticum to investigate adaptation in Type I-F CRISPR-Cas systems. Pre-existing spacers that matched plasmids stimulated hyperactive primed acquisition and resulted in the incorporation of up to nine new spacers across all three native CRISPR arrays. Endogenous expression of the cas genes was sufficient, yet required, for priming. The new spacers inhibited conjugation and transformation, and interference was enhanced with increasing numbers of new spacers. We analyzed ∼ 350 new spacers acquired in priming events and identified a 5'-protospacer-GG-3' protospacer adjacent motif. In contrast to priming in Type I-E systems, new spacers matched either plasmid strand and a biased distribution, including clustering near the primed protospacer, suggested a bi-directional translocation model for the Cas1:Cas2-3 adaptation machinery. Taken together these results indicate priming adaptation occurs in different CRISPR-Cas systems, that it can be highly active in wild-type strains and that the underlying mechanisms vary.

  9. Acoustic Tooth Cleaner

    NASA Technical Reports Server (NTRS)

    Heyman, J. S.

    1984-01-01

    Acoustically-energized water jet aids in plaque breakdown. Acoustic Wand includes acoustic transducer 1/4 wave plate, and tapered cone. Together elements energize solution of water containing mild abrasive injected into mouth to help prevent calculous buildup.

  10. Investigation of brightness changes of MZ Cas and TZ Cas in B- and V-light

    NASA Technical Reports Server (NTRS)

    Lukatskaya, F. I.; Kheylo, E. S.

    1973-01-01

    The results are presented concerning statistical processing of two-color observations of MZ Cas and TZ Cas. Light histograms, dispersion and statistical amplitudes are given. Light variations of the variables are represented by normal stochastic processes. Observational data are tabulated.

  11. Putting the CAS Standards to Work. Training Manual for the CAS Self Assessment Guides.

    ERIC Educational Resources Information Center

    Yerian, Jean M.; Miller, Theodore K., Ed.

    These 18 self-assessment guides and training manual from the Council for the Advancement of Standards (CAS) for Student Services/Development Programs translate the CAS Standards and Guidelines of 1986 into a format for self-study purposes. These self-study guides allow an institution to assure compliance with minimally-acceptable practice, gain an…

  12. Overview of CRISPR-Cas9 Biology.

    PubMed

    Ratner, Hannah K; Sampson, Timothy R; Weiss, David S

    2016-12-01

    Prokaryotes use diverse strategies to improve fitness in the face of different environmental threats and stresses, including those posed by mobile genetic elements (e.g., bacteriophages and plasmids). To defend against these elements, many bacteria and archaea use elegant, RNA-directed, nucleic acid-targeting adaptive restriction machineries called CRISPR -: Cas (CRISPR-associated) systems. While providing an effective defense against foreign genetic elements, these systems have also been observed to play critical roles in regulating bacterial physiology during environmental stress. Increasingly, CRISPR-Cas systems, in particular the Type II systems containing the Cas9 endonuclease, have been exploited for their ability to bind desired nucleic acid sequences, as well as direct sequence-specific cleavage of their targets. Cas9-mediated genome engineering is transcending biological research as a versatile and portable platform for manipulating genetic content in myriad systems. Here, we present a systematic overview of CRISPR-Cas history and biology, highlighting the revolutionary tools derived from these systems, which greatly expand the molecular biologists' toolkit.

  13. Acoustic iridescence.

    PubMed

    Cox, Trevor J

    2011-03-01

    An investigation has been undertaken into acoustic iridescence, exploring how a device can be constructed which alter sound waves, in a similar way to structures in nature that act on light to produce optical iridescence. The main construction had many thin perforated sheets spaced half a wavelength apart for a specified design frequency. The sheets create the necessary impedance discontinuities to create backscattered waves, which then interfere to create strongly reflected sound at certain frequencies. Predictions and measurements show a set of harmonics, evenly spaced in frequency, for which sound is reflected strongly. And the frequency of these harmonics increases as the angle of observation gets larger, mimicking the iridescence seen in natural optical systems. Similar to optical systems, the reflections become weaker for oblique angles of reflection. A second construction was briefly examined which exploited a metamaterial made from elements and inclusions which were much smaller than the wavelength. Boundary element method predictions confirmed the potential for creating acoustic iridescence from layers of such a material.

  14. Acoustic transducer

    DOEpatents

    Drumheller, D.S.

    1997-12-30

    An acoustic transducer is described comprising a one-piece hollow mandrel into the outer surface of which is formed a recess with sides perpendicular to the central axis of the mandrel and separated by a first distance and with a bottom parallel to the central axis and within which recess are a plurality of washer-shaped discs of a piezoelectric material and at least one disc of a temperature-compensating material with the discs being captured between the sides of the recess in a pre-stressed interference fit, typically at 2,000 psi of compressive stress. The transducer also includes a power supply and means to connect to a measurement device. The transducer is intended to be used for telemetry between a measurement device located downhole in an oil or gas well and the surface. The transducer is of an construction that is stronger with fewer joints that could leak fluids into the recess holding the piezoelectric elements than is found in previous acoustic transducers. 4 figs.

  15. Acoustic transducer

    DOEpatents

    Drumheller, Douglas S.

    1997-01-01

    An acoustic transducer comprising a one-piece hollow mandrel into the outer surface of which is formed a recess with sides perpendicular to the central axis of the mandrel and separated by a first distance and with a bottom parallel to the central axis and within which recess are a plurality of washer-shaped discs of a piezoelectric material and at least one disc of a temperature-compensating material with the discs being captured between the sides of the recess in a pre-stressed interference fit, typically at 2000 psi of compressive stress. The transducer also includes a power supply and means to connect to a measurement device. The transducer is intended to be used for telemetry between a measurement device located downhole in an oil or gas well and the surface. The transducer is of an construction that is stronger with fewer joints that could leak fluids into the recess holding the piezoelectric elements than is found in previous acoustic transducers.

  16. Target structures for cochlear infrared neural stimulation

    PubMed Central

    Young, Hunter K.; Tan, Xiaodong; Xia, Nan; Richter, Claus-Peter

    2015-01-01

    Abstract. Infrared neural stimulation (INS) is a method to depolarize neurons with infrared light. While consensus exists that heating of the target structure is essential, subsequent steps that result in the generation of an action potential are controversially discussed in the literature. The question of whether cochlear INS is an acoustic event has not been clarified. Results have been published that could be explained solely by an acoustic event. However, data exist that do not support an acoustical stimulus as the dominant factor in cochlear INS. We review the different findings that have been suggested for the mechanism of INS. Furthermore, we present the data that clarify the role of an acoustical event in cochlear INS. Masking experiments have been performed in hearing, hearing impaired, and severely hearing impaired animals. In normal hearing animals, the laser response could be masked by the acoustic stimulus. Once thresholds to acoustic stimuli were elevated, the ability to acoustically mask the INS response gradually disappeared. Thresholds for acoustic stimuli were significantly elevated in animals with compromised cochlear function, while the thresholds for optical stimulation remained largely unchanged. The results suggest that the direct interaction between the radiation and the target structure dominates cochlear INS. PMID:26158006

  17. Sacroillite tuberculeuse: à propos de deux cas

    PubMed Central

    Diallo, Ismaël; Zabsonré, Joëlle Tiendrébéogo; Kambou, Bénilde Marie Ange Tiemtoré; Sondo, Apoline Kongnimissom; Sagna, Yempabou; Ouédraogo, Dieu-Donné

    2016-01-01

    La sacroiliite tuberculeuse est rare et de diagnostic difficile. Les auteurs rapportent deux cas. Il s'agissait dans le premier cas d'une patiente de 40 ans ayant une infection à VIH ; le diagnostic a été histologique après une biopsie chirurgicale. Le second cas a concerné un patient de 25 ans vivant en milieu carcéral chez qui le diagnostic a été établi sur la base des arguments cliniques, biologiques, radiologiques et l'efficacité du traitement ; l'intradermoréaction à la tuberculine était phlycténulaire. Le scanner a été indispensable au diagnostic lésionnel en montrant une érosion des berges et des abcès des parties molles. Le traitement a été médical et a fait appel aux antituberculeux. PMID:28292032

  18. Actin polymerization-dependent activation of Cas-L promotes immunological synapse stability

    PubMed Central

    Santos, Luís C; Blair, David A; Kumari, Sudha; Cammer, Michael; Iskratsch, Thomas; Herbin, Olivier; Alexandropoulos, Konstantina; Dustin, Michael L; Sheetz, Michael P

    2016-01-01

    The immunological synapse formed between a T-cell and an antigen-presenting cell is important for cell–cell communication during T-cell-mediated immune responses. Immunological synapse formation begins with stimulation of the T-cell receptor (TCR). TCR microclusters are assembled and transported to the center of the immunological synapse in an actin polymerization-dependent process. However, the physical link between TCR and actin remains elusive. Here we show that lymphocyte-specific Crk-associated substrate (Cas-L), a member of a force sensing protein family, is required for transport of TCR microclusters and for establishing synapse stability. We found that Cas-L is phosphorylated at TCR microclusters in an actin polymerization-dependent fashion. Furthermore, Cas-L participates in a positive feedback loop leading to amplification of Ca2+ signaling, inside–out integrin activation, and actomyosin contraction. We propose a new role for Cas-L in T-cell activation as a mechanical transducer linking TCR microclusters to the underlying actin network and coordinating multiple actin-dependent structures in the immunological synapse. Our studies highlight the importance of mechanotransduction processes in T-cell-mediated immune responses. PMID:27359298

  19. Generation of site-specific mutant mice using the CRISPR/Cas9 system.

    PubMed

    Min, Bai; Qi, Li; Yanjiao, Shao; Yuanhua, Huang; Dali, Li; Yanlin, Ma

    2015-10-01

    The CRISPR/Cas9 system is a recently developed important technology for genome editing in cellular and animal models. Here we established a CRISPR/Cas9-based system of generating site-specific mutant mice using DNA double-strand breaks (DSBs) induced homologous recombination (HR)-dependent or independent repair mechanism. Through co-microinjection of Cas9 mRNA and single-guide RNA (sgRNA) targeting genomic DNA sequence corresponding to enzyme activity of lysine (K)-specific demethylase 2b (Kdm2b), both a frame-shifted Kdm2b null mutant and a Kdm2b enzyme activity disrupted mouse strain were obtained simultaneously. Moreover, sgRNA targeting flavin containing monooxygenases3 (Fmo3) gene and the corresponding single strand oligonucleotides (ssODN) donor template with point mutation were co-injected into the male pronucleus of one-cell mouse embryos stimulated HR-mediated repair mechanism. Genomic sequence analysis of F0 mice showed that frame-shifted Fmo3 knockout mouse and site-specific Fmo3 knock-in mouse with single base substitution were successfully generated, and these mutations could be stably transmitted to the next generation. Therefore, we successfully generated mouse strains containing site-specific mutations through HR-dependent and -independent DSB repair using the CRISPR/Cas9 system.

  20. Harnessing the CRISPR/Cas9 system to disrupt latent HIV-1 provirus.

    PubMed

    Ebina, Hirotaka; Misawa, Naoko; Kanemura, Yuka; Koyanagi, Yoshio

    2013-01-01

    Even though highly active anti-retroviral therapy is able to keep HIV-1 replication under control, the virus can lie in a dormant state within the host genome, known as a latent reservoir, and poses a threat to re-emerge at any time. However, novel technologies aimed at disrupting HIV-1 provirus may be capable of eradicating viral genomes from infected individuals. In this study, we showed the potential of the CRISPR/Cas9 system to edit the HIV-1 genome and block its expression. When LTR-targeting CRISPR/Cas9 components were transfected into HIV-1 LTR expression-dormant and -inducible T cells, a significant loss of LTR-driven expression was observed after stimulation. Sequence analysis confirmed that this CRISPR/Cas9 system efficiently cleaved and mutated LTR target sites. More importantly, this system was also able to remove internal viral genes from the host cell chromosome. Our results suggest that the CRISPR/Cas9 system may be a useful tool for curing HIV-1 infection.

  1. A new age in functional genomics using CRISPR/Cas9 in arrayed library screening

    PubMed Central

    Agrotis, Alexander; Ketteler, Robin

    2015-01-01

    CRISPR technology has rapidly changed the face of biological research, such that precise genome editing has now become routine for many labs within several years of its initial development. What makes CRISPR/Cas9 so revolutionary is the ability to target a protein (Cas9) to an exact genomic locus, through designing a specific short complementary nucleotide sequence, that together with a common scaffold sequence, constitute the guide RNA bridging the protein and the DNA. Wild-type Cas9 cleaves both DNA strands at its target sequence, but this protein can also be modified to exert many other functions. For instance, by attaching an activation domain to catalytically inactive Cas9 and targeting a promoter region, it is possible to stimulate the expression of a specific endogenous gene. In principle, any genomic region can be targeted, and recent efforts have successfully generated pooled guide RNA libraries for coding and regulatory regions of human, mouse and Drosophila genomes with high coverage, thus facilitating functional phenotypic screening. In this review, we will highlight recent developments in the area of CRISPR-based functional genomics and discuss potential future directions, with a special focus on mammalian cell systems and arrayed library screening. PMID:26442115

  2. A new age in functional genomics using CRISPR/Cas9 in arrayed library screening.

    PubMed

    Agrotis, Alexander; Ketteler, Robin

    2015-01-01

    CRISPR technology has rapidly changed the face of biological research, such that precise genome editing has now become routine for many labs within several years of its initial development. What makes CRISPR/Cas9 so revolutionary is the ability to target a protein (Cas9) to an exact genomic locus, through designing a specific short complementary nucleotide sequence, that together with a common scaffold sequence, constitute the guide RNA bridging the protein and the DNA. Wild-type Cas9 cleaves both DNA strands at its target sequence, but this protein can also be modified to exert many other functions. For instance, by attaching an activation domain to catalytically inactive Cas9 and targeting a promoter region, it is possible to stimulate the expression of a specific endogenous gene. In principle, any genomic region can be targeted, and recent efforts have successfully generated pooled guide RNA libraries for coding and regulatory regions of human, mouse and Drosophila genomes with high coverage, thus facilitating functional phenotypic screening. In this review, we will highlight recent developments in the area of CRISPR-based functional genomics and discuss potential future directions, with a special focus on mammalian cell systems and arrayed library screening.

  3. Evolution and classification of the CRISPR-Cas systems

    PubMed Central

    S. Makarova, Kira; H. Haft, Daniel; Barrangou, Rodolphe; J. J. Brouns, Stan; Charpentier, Emmanuelle; Horvath, Philippe; Moineau, Sylvain; J. M. Mojica, Francisco; I. Wolf, Yuri; Yakunin, Alexander F.; van der Oost, John; V. Koonin, Eugene

    2012-01-01

    The CRISPR–Cas (clustered regularly interspaced short palindromic repeats–CRISPR-associated proteins) modules are adaptive immunity systems that are present in many archaea and bacteria. These defence systems are encoded by operons that have an extraordinarily diverse architecture and a high rate of evolution for both the cas genes and the unique spacer content. Here, we provide an updated analysis of the evolutionary relationships between CRISPR–Cas systems and Cas proteins. Three major types of CRISPR–Cas system are delineated, with a further division into several subtypes and a few chimeric variants. Given the complexity of the genomic architectures and the extremely dynamic evolution of the CRISPR–Cas systems, a unified classification of these systems should be based on multiple criteria. Accordingly, we propose a `polythetic' classification that integrates the phylogenies of the most common cas genes, the sequence and organization of the CRISPR repeats and the architecture of the CRISPR–cas loci. PMID:21552286

  4. SnapShot: Class 1 CRISPR-Cas Systems.

    PubMed

    Makarova, Kira S; Zhang, Feng; Koonin, Eugene V

    2017-02-23

    Class 1 CRISPR-Cas systems are characterized by effector modules consisting of multiple subunits. Class 1 systems comprise about 90% of all CRISPR-Cas loci identified in bacteria and archaea and can target both DNA and RNA.

  5. Caloric stimulation

    MedlinePlus

    Caloric test; Bithermal caloric testing; Cold water calorics; Warm water calorics; Air caloric testing ... your acoustic nerve by delivering cold or warm water or air into your ear canal. When cold ...

  6. CRISPR-Cas immunity in prokaryotes.

    PubMed

    Marraffini, Luciano A

    2015-10-01

    Prokaryotic organisms are threatened by a large array of viruses and have developed numerous defence strategies. Among these, only clustered, regularly interspaced short palindromic repeat (CRISPR)-Cas systems provide adaptive immunity against foreign elements. Upon viral injection, a small sequence of the viral genome, known as a spacer, is integrated into the CRISPR locus to immunize the host cell. Spacers are transcribed into small RNA guides that direct the cleavage of the viral DNA by Cas nucleases. Immunization through spacer acquisition enables a unique form of evolution whereby a population not only rapidly acquires resistance to its predators but also passes this resistance mechanism vertically to its progeny.

  7. Acoustic cryocooler

    DOEpatents

    Swift, Gregory W.; Martin, Richard A.; Radenbaugh, Ray

    1990-01-01

    An acoustic cryocooler with no moving parts is formed from a thermoacoustic driver (TAD) driving a pulse tube refrigerator (PTR) through a standing wave tube. Thermoacoustic elements in the TAD are spaced apart a distance effective to accommodate the increased thermal penetration length arising from the relatively low TAD operating frequency in the range of 15-60 Hz. At these low operating frequencies, a long tube is required to support the standing wave. The tube may be coiled to reduce the overall length of the cryocooler. One or two PTR's are located on the standing wave tube adjacent antinodes in the standing wave to be driven by the standing wave pressure oscillations. It is predicted that a heat input of 1000 W at 1000 K will maintian a cooling load of 5 W at 80 K.

  8. Acoustic transducer

    DOEpatents

    Drumheller, Douglas S.

    2000-01-01

    An active acoustic transducer tool for use down-hole applications. The tool includes a single cylindrical mandrel including a shoulder defining the boundary of a narrowed portion over which is placed a sandwich-style piezoelectric tranducer assembly. The piezoelectric transducer assembly is prestressed by being placed in a thermal interference fit between the shoulder of the mandrel and the base of an anvil which is likewise positioned over the narrower portion of the mandrel. In the preferred embodiment, assembly of the tool is accomplished using a hydraulic jack to stretch the mandrel prior to emplacement of the cylindrical sandwich-style piezoelectric transducer assembly and anvil. After those elements are positioned and secured, the stretched mandrel is allowed to return substantially to its original (pre-stretch) dimensions with the result that the piezoelectric transducer elements are compressed between the anvil and the shoulder of the mandrel.

  9. Acoustic telemetry.

    SciTech Connect

    Drumheller, Douglas Schaeffer; Kuszmaul, Scott S.

    2003-08-01

    Broadcasting messages through the earth is a daunting task. Indeed, broadcasting a normal telephone conversion through the earth by wireless means is impossible with todays technology. Most of us don't care, but some do. Industries that drill into the earth need wireless communication to broadcast navigation parameters. This allows them to steer their drill bits. They also need information about the natural formation that they are drilling. Measurements of parameters such as pressure, temperature, and gamma radiation levels can tell them if they have found a valuable resource such as a geothermal reservoir or a stratum bearing natural gas. Wireless communication methods are available to the drilling industry. Information is broadcast via either pressure waves in the drilling fluid or electromagnetic waves in the earth and well tubing. Data transmission can only travel one way at rates around a few baud. Given that normal Internet telephone modems operate near 20,000 baud, these data rates are truly very slow. Moreover, communication is often interrupted or permanently blocked by drilling conditions or natural formation properties. Here we describe a tool that communicates with stress waves traveling through the steel drill pipe and production tubing in the well. It's based on an old idea called Acoustic Telemetry. But what we present here is more than an idea. This tool exists, it's drilled several wells, and it works. Currently, it's the first and only acoustic telemetry tool that can withstand the drilling environment. It broadcasts one way over a limited range at much faster rates than existing methods, but we also know how build a system that can communicate both up and down wells of indefinite length.

  10. Boosting plant immunity with CRISPR/Cas.

    PubMed

    Chaparro-Garcia, Angela; Kamoun, Sophien; Nekrasov, Vladimir

    2015-11-19

    CRISPR/Cas has recently been transferred to plants to make them resistant to geminiviruses, a damaging family of DNA viruses. We discuss the potential and the limitations of this method.See related Research: http://www.genomebiology.com/2015/16/1/238.

  11. Using the CAS Standards in Assessment Projects

    ERIC Educational Resources Information Center

    Dean, Laura A.

    2013-01-01

    This chapter provides an overview of the use of professional standards of practice in assessment and of the Council for the Advancement of Standards in Higher Education (CAS). It outlines a model for conducting program self-studies and discusses the importance of implementing change based on assessment results.

  12. Effects of Using a Computer Algebra System (CAS) on Junior College Students' Attitudes towards CAS and Achievement in Mathematics

    ERIC Educational Resources Information Center

    Leng, Ng Wee; Choo, Kwee Tiow; Soon, Lau Hock; Yi-Huak, Koh; Sun, Yap Yew

    2005-01-01

    This study examines the effects of using Texas Instruments' Voyage 200 calculator (V200), a graphing calculator with a built-in computer algebra system (CAS), on attitudes towards CAS and achievement in mathematics of junior college students (17 year olds). Students' attitudes towards CAS were examined using a 40-item Likert-type instrument…

  13. Structural plasticity and in vivo activity of Cas1 from the type I-F CRISPR-Cas system.

    PubMed

    Wilkinson, Max E; Nakatani, Yoshio; Staals, Raymond H J; Kieper, Sebastian N; Opel-Reading, Helen K; McKenzie, Rebecca E; Fineran, Peter C; Krause, Kurt L

    2016-04-15

    CRISPR-Cas systems are adaptive immune systems in prokaryotes that provide protection against viruses and other foreign DNA. In the adaptation stage, foreign DNA is integrated into CRISPR (clustered regularly interspaced short palindromic repeat) arrays as new spacers. These spacers are used in the interference stage to guide effector CRISPR associated (Cas) protein(s) to target complementary foreign invading DNA. Cas1 is the integrase enzyme that is central to the catalysis of spacer integration. There are many diverse types of CRISPR-Cas systems, including type I-F systems, which are typified by a unique Cas1-Cas2-3 adaptation complex. In the present study we characterize the Cas1 protein of the potato phytopathogen Pectobacterium atrosepticum, an important model organism for understanding spacer acquisition in type I-F CRISPR-Cas systems. We demonstrate by mutagenesis that Cas1 is essential for adaptation in vivo and requires a conserved aspartic acid residue. By X-ray crystallography, we show that although P. atrosepticum Cas1 adopts a fold conserved among other Cas1 proteins, it possesses remarkable asymmetry as a result of structural plasticity. In particular, we resolve for the first time a flexible, asymmetric loop that may be unique to type I-F Cas1 proteins, and we discuss the implications of these structural features for DNA binding and enzymatic activity.

  14. CasHRA (Cas9-facilitated Homologous Recombination Assembly) method of constructing megabase-sized DNA

    PubMed Central

    Zhou, Jianting; Wu, Ronghai; Xue, Xiaoli; Qin, Zhongjun

    2016-01-01

    Current DNA assembly methods for preparing highly purified linear subassemblies require complex and time-consuming in vitro manipulations that hinder their ability to construct megabase-sized DNAs (e.g. synthetic genomes). We have developed a new method designated ‘CasHRA (Cas9-facilitated Homologous Recombination Assembly)’ that directly uses large circular DNAs in a one-step in vivo assembly process. The large circular DNAs are co-introduced into Saccharomyces cerevisiae by protoplast fusion, and they are cleaved by RNA-guided Cas9 nuclease to release the linear DNA segments for subsequent assembly by the endogenous homologous recombination system. The CasHRA method allows efficient assembly of multiple large DNA segments in vivo; thus, this approach should be useful in the last stage of genome construction. As a proof of concept, we combined CasHRA with an upstream assembly method (Gibson procedure of genome assembly) and successfully constructed a 1.03 Mb MGE-syn1.0 (Minimal Genome of Escherichia coli) that contained 449 essential genes and 267 important growth genes. We expect that CasHRA will be widely used in megabase-sized genome constructions. PMID:27220470

  15. A critical role for p130Cas in the progression of pulmonary hypertension in humans and rodents

    PubMed Central

    Tu, Ly; De Man, Frances; Girerd, Barbara; Huertas, Alice; Chaumais, Marie-Camille; Lecerf, Florence; François, Charlène; Perros, Frédéric; Dorfmüller, Peter; Fadel, Elie; Montani, David; Eddahibi, Saadia; Humbert, Marc; Guignabert, Christophe

    2012-01-01

    Rationale Pulmonary arterial hypertension (PAH) is a progressive and fatal disease characterized by pulmonary arterial muscularization due to excessive pulmonary vascular cell proliferation and migration, a phenotype dependent upon growth factors and activation of receptor tyrosine kinases (RTKs). p130Cas is an adaptor protein involved in several cellular signaling pathways that control cell migration, proliferation and survival. Objectives We hypothesized that in experimental and human PAH p130Cas signaling is over-activated, thereby facilitating the intracellular transmission of signal induced by fibroblast growth factor (FGF)-2, epidermal growth factor (EGF), and platelet-derived growth factor (PDGF). Measurements and Main Results In PAH patients, levels of p130Cas protein and/or activity are higher in the serum, in walls of distal pulmonary arteries, in cultured smooth muscle (PA-SMCs) and pulmonary endothelial cells (P-ECs) than controls. These abnormalities in the p130Cas signaling were also found to be in the chronically hypoxic mice and monocrotaline-injected rats as models of human PAH. We next obtained evidence for convergence and amplification of the growth-stimulating effect of EGF, FGF2 and PDGF signaling pathways via p130Cas signaling pathway. Finally, we found that daily treatment with each of the EGF-R inhibitor gefitinib, the FGF-R inhibitor dovitinib and the PDGF-R inhibitor imatinib started 2 weeks after a subcutaneous monocrotaline injection substantially attenuate the abnormal increase in p130cas and ERK1/2 activation and regress established PH. Conclusions Our findings demonstrate that p130Cas signaling plays a critical role in experimental and iPAH by modulating pulmonary vascular cell migration, proliferation and by acting as an amplifier of RTKs downstream signals. PMID:22798315

  16. Controlling UCAVs by JTACs in CAS missions

    NASA Astrophysics Data System (ADS)

    Kumaş, A. E.

    2014-06-01

    By means of evolving technology, capabilities of UAVs (Unmanned Aerial Vehicle)s are increasing rapidly. This development provides UAVs to be used in many different areas. One of these areas is CAS (Close Air Support) mission. UAVs have several advantages compared to manned aircraft, however there are also some problematic areas. The remote controlling of these vehicles from thousands of nautical miles away via satellite may lead to various problems both ethical and tactical aspects. Therefore, CAS missions require a good level of ALI (Air-Land Integration), a high SA (situational awareness) and precision engagement. In fact, there is an aware friendly element in the target area in CAS missions, unlike the other UAV operations. This element is an Airman called JTAC (Joint Terminal Attack Controller). Unlike the JTAC, UAV operators are too far away from target area and use the limited FOV (Field of View) provided by camera and some other sensor data. In this study, target area situational awareness of a UAV operator and a JTAC, in a high-risk mission for friendly ground forces and civilians such as CAS, are compared. As a result of this comparison, answer to the question who should control the UCAV (Unmanned Combat Aerial Vehicle) in which circumstances is sought. A literature review is made in UAV and CAS fields and recent air operations are examined. The control of UCAV by the JTAC is assessed by SWOT analysis and as a result it is deduced that both control methods can be used in different situations within the framework of the ROE (Rules Of Engagement) is reached.

  17. Targeted Mutagenesis, Precise Gene Editing, and Site-Specific Gene Insertion in Maize Using Cas9 and Guide RNA.

    PubMed

    Svitashev, Sergei; Young, Joshua K; Schwartz, Christine; Gao, Huirong; Falco, S Carl; Cigan, A Mark

    2015-10-01

    Targeted mutagenesis, editing of endogenous maize (Zea mays) genes, and site-specific insertion of a trait gene using clustered regularly interspaced short palindromic repeats (CRISPR)-associated (Cas)-guide RNA technology are reported in maize. DNA vectors expressing maize codon-optimized Streptococcus pyogenes Cas9 endonuclease and single guide RNAs were cointroduced with or without DNA repair templates into maize immature embryos by biolistic transformation targeting five different genomic regions: upstream of the liguleless1 (LIG1) gene, male fertility genes (Ms26 and Ms45), and acetolactate synthase (ALS) genes (ALS1 and ALS2). Mutations were subsequently identified at all sites targeted, and plants containing biallelic multiplex mutations at LIG1, Ms26, and Ms45 were recovered. Biolistic delivery of guide RNAs (as RNA molecules) directly into immature embryo cells containing preintegrated Cas9 also resulted in targeted mutations. Editing the ALS2 gene using either single-stranded oligonucleotides or double-stranded DNA vectors as repair templates yielded chlorsulfuron-resistant plants. Double-strand breaks generated by RNA-guided Cas9 endonuclease also stimulated insertion of a trait gene at a site near LIG1 by homology-directed repair. Progeny showed expected Mendelian segregation of mutations, edits, and targeted gene insertions. The examples reported in this study demonstrate the utility of Cas9-guide RNA technology as a plant genome editing tool to enhance plant breeding and crop research needed to meet growing agriculture demands of the future.

  18. In vivo genome editing using Staphylococcus aureus Cas9

    PubMed Central

    Ran, F. Ann; Cong, Le; Yan, Winston X.; Scott, David A.; Gootenberg, Jonathan S.; Kriz, Andrea J.; Zetsche, Bernd; Shalem, Ophir; Wu, Xuebing; Makarova, Kira S.; Koonin, Eugene; Sharp, Phillip A.; Zhang, Feng

    2015-01-01

    The RNA-guided endonuclease Cas9 has emerged as a versatile genome-editing platform. However, the size of the commonly used Cas9 from Streptococcus pyogenes (SpCas9) limits its utility for basic research and therapeutic applications that employ the highly versatile adeno-associated virus (AAV) delivery vehicle. Here, we characterize six smaller Cas9 orthologs and show that Cas9 from Staphylococcus aureus (SaCas9) can edit the genome with efficiencies similar to those of SpCas9, while being >1kb shorter. We packaged SaCas9 and its sgRNA expression cassette into a single AAV vector and targeted the cholesterol regulatory gene Pcsk9 in the mouse liver. Within one week of injection, we observed >40% gene modification, accompanied by significant reductions in serum Pcsk9 and total cholesterol levels. We further demonstrate the power of using BLESS to assess the genome-wide targeting specificity of SaCas9 and SpCas9, and show that SaCas9 can mediate genome editing in vivo with high specificity. PMID:25830891

  19. Structure and Engineering of Francisella novicida Cas9

    PubMed Central

    Hirano, Hisato; Gootenberg, Jonathan S.; Horii, Takuro; Abudayyeh, Omar O.; Kimura, Mika; Hsu, Patrick D.; Nakane, Takanori; Ishitani, Ryuichiro; Hatada, Izuho; Zhang, Feng; Nishimasu, Hiroshi; Nureki, Osamu

    2016-01-01

    Summary The RNA-guided endonuclease Cas9 cleaves double-stranded DNA targets complementary to the guide RNA, and has been applied to programmable genome editing. Cas9-mediated cleavage requires a protospacer adjacent motif (PAM) juxtaposed with the DNA target sequence, thus constricting the range of targetable sites. Here, we report the 1.7 Å resolution crystal structures of Cas9 from Francisella novicida (FnCas9), one of the largest Cas9 orthologs, in complex with a guide RNA and its PAM-containing DNA targets. A structural comparison of FnCas9 with other Cas9 orthologs revealed striking conserved and divergent features among distantly related CRISPR-Cas9 systems. We found that FnCas9 recognizes the 5′-NGG-3′ PAM, and used the structural information to create a variant that can recognize the more relaxed 5′-YG-3′ PAM. Furthermore, we demonstrated that pre-assembled FnCas9 ribonucleoprotein complexes can be microinjected into mouse zygotes to edit endogenous sites with the 5′-YG-3′ PAMs, thus expanding the target space of the CRISPR-Cas9 toolbox. PMID:26875867

  20. Acoustic source for generating an acoustic beam

    DOEpatents

    Vu, Cung Khac; Sinha, Dipen N.; Pantea, Cristian

    2016-05-31

    An acoustic source for generating an acoustic beam includes a housing; a plurality of spaced apart piezo-electric layers disposed within the housing; and a non-linear medium filling between the plurality of layers. Each of the plurality of piezoelectric layers is configured to generate an acoustic wave. The non-linear medium and the plurality of piezo-electric material layers have a matching impedance so as to enhance a transmission of the acoustic wave generated by each of plurality of layers through the remaining plurality of layers.

  1. Canonical Acoustics and Its Application to Surface Acoustic Wave on Acoustic Metamaterials

    NASA Astrophysics Data System (ADS)

    Shen, Jian Qi

    2016-08-01

    In a conventional formalism of acoustics, acoustic pressure p and velocity field u are used for characterizing acoustic waves propagating inside elastic/acoustic materials. We shall treat some fundamental problems relevant to acoustic wave propagation alternatively by using canonical acoustics (a more concise and compact formalism of acoustic dynamics), in which an acoustic scalar potential and an acoustic vector potential (Φ ,V), instead of the conventional acoustic field quantities such as acoustic pressure and velocity field (p,u) for characterizing acoustic waves, have been defined as the fundamental variables. The canonical formalism of the acoustic energy-momentum tensor is derived in terms of the acoustic potentials. Both the acoustic Hamiltonian density and the acoustic Lagrangian density have been defined, and based on this formulation, the acoustic wave quantization in a fluid is also developed. Such a formalism of acoustic potentials is employed to the problem of negative-mass-density assisted surface acoustic wave that is a highly localized surface bound state (an eigenstate of the acoustic wave equations). Since such a surface acoustic wave can be strongly confined to an interface between an acoustic metamaterial (e.g., fluid-solid composite structures with a negative dynamical mass density) and an ordinary material (with a positive mass density), it will give rise to an effect of acoustic field enhancement on the acoustic interface, and would have potential applications in acoustic device design for acoustic wave control.

  2. What Is an Acoustic Neuroma

    MedlinePlus

    ... ANAUSA.org Connect with us! What is an Acoustic Neuroma? Each heading slides to reveal information. Important ... Acoustic Neuroma Important Points To Know About an Acoustic Neuroma An acoustic neuroma, also called a vestibular ...

  3. Acoustic (loudspeaker) facial EMG monitoring: II. Use of evoked EMG activity during acoustic neuroma resection.

    PubMed

    Prass, R L; Kinney, S E; Hardy, R W; Hahn, J F; Lüders, H

    1987-12-01

    Facial electromyographic (EMG) activity was continuously monitored via loudspeaker during eleven translabyrinthine and nine suboccipital consecutive unselected acoustic neuroma resections. Ipsilateral facial EMG activity was synchronously recorded on the audio channels of operative videotapes, which were retrospectively reviewed in order to allow detailed evaluation of the potential benefit of various acoustic EMG patterns in the performance of specific aspects of acoustic neuroma resection. The use of evoked facial EMG activity was classified and described. Direct local mechanical (surgical) stimulation and direct electrical stimulation were of benefit in the localization and/or delineation of the facial nerve contour. Burst and train acoustic patterns of EMG activity appeared to indicate surgical trauma to the facial nerve that would not have been appreciated otherwise. Early results of postoperative facial function of monitored patients are presented, and the possible value of burst and train acoustic EMG activity patterns in the intraoperative assessment of facial nerve function is discussed. Acoustic facial EMG monitoring appears to provide a potentially powerful surgical tool for delineation of the facial nerve contour, the ongoing use of which may lead to continued improvement in facial nerve function preservation through modification of dissection strategy.

  4. Symptoms of Acoustic Neuroma

    MedlinePlus

    ... Watch and Wait Radiation Microsurgery Acoustic Neuroma Decision Tree Questions for Your Physician Questions to Ask Yourself ... Watch and Wait Radiation Microsurgery Acoustic Neuroma Decision Tree Questions for Your Physician Questions to Ask Yourself ...

  5. NPL closes acoustics department

    NASA Astrophysics Data System (ADS)

    Extance, Andy

    2016-11-01

    The UK's National Physical Laboratory (NPL) has withdrawn funding for its acoustics, polymer and thermoelectrics groups, triggering concern among airborne acoustics specialists that the move could undermine the country's noise-management policies.

  6. Identifying the Acoustic Neuroma

    MedlinePlus

    ... Watch and Wait Radiation Microsurgery Acoustic Neuroma Decision Tree Questions for Your Physician Questions to Ask Yourself ... Watch and Wait Radiation Microsurgery Acoustic Neuroma Decision Tree Questions for Your Physician Questions to Ask Yourself ...

  7. Acoustic emission frequency discrimination

    NASA Technical Reports Server (NTRS)

    Sugg, Frank E. (Inventor); Graham, Lloyd J. (Inventor)

    1988-01-01

    In acoustic emission nondestructive testing, broadband frequency noise is distinguished from narrow banded acoustic emission signals, since the latter are valid events indicative of structural flaws in the material being examined. This is accomplished by separating out those signals which contain frequency components both within and beyond (either above or below) the range of valid acoustic emission events. Application to acoustic emission monitoring during nondestructive bond verification and proof loading of undensified tiles on the Space Shuttle Orbiter is considered.

  8. Deep Water Ocean Acoustics

    DTIC Science & Technology

    2015-07-17

    under-ice scattering , bathymetric diffraction and the application of the ocean acoustic Parabolic Equation to infrasound. 2. Tasks a. Task 1...QSR-14C0172-Ocean Acoustics -063015 Figure 10. Estimated reflection coefficient as a function of frequency by taking the difference of downgoing and...OASIS, INC. 1 Report No. QSR-14C0172-Ocean Acoustics -063015 Quarterly Progress Report Technical and Financial Deep Water Ocean Acoustics

  9. Deep Water Ocean Acoustics

    DTIC Science & Technology

    2015-10-19

    OASIS, INC. 1 Report No. QSR-14C0172-Ocean Acoustics-093015 Quarterly Progress Report Technical and Financial Deep Water Ocean Acoustics...number. 1. REPORT DATE OCT 2015 2. REPORT TYPE 3. DATES COVERED 01-07-2015 to 30-09-2015 4. TITLE AND SUBTITLE Deep Water Ocean Acoustics...understanding of the impact of the ocean and seafloor environmental variability on deep- water (long-range) ocean acoustic propagation and to develop

  10. Shallow Water Acoustics Studies

    DTIC Science & Technology

    2015-09-30

    1 DISTRIBUTION STATEMENT A. Approved for public release; distribution is unlimited. Shallow Water Acoustics Studies James F. Lynch MS #12...N00014-14-1-0040 http://acoustics.whoi.edu/sw06/ LONG TERM GOALS The long term goals of our shallow water acoustics work are to: 1) understand the...nature of low frequency (10-1500 Hz) acoustic propagation, scattering and noise in shallow water when strong oceanic variability is present in the

  11. Coding Acoustic Metasurfaces.

    PubMed

    Xie, Boyang; Tang, Kun; Cheng, Hua; Liu, Zhengyou; Chen, Shuqi; Tian, Jianguo

    2017-02-01

    Coding acoustic metasurfaces can combine simple logical bits to acquire sophisticated functions in wave control. The acoustic logical bits can achieve a phase difference of exactly π and a perfect match of the amplitudes for the transmitted waves. By programming the coding sequences, acoustic metasurfaces with various functions, including creating peculiar antenna patterns and waves focusing, have been demonstrated.

  12. Tutorial on architectural acoustics

    NASA Astrophysics Data System (ADS)

    Shaw, Neil; Talaske, Rick; Bistafa, Sylvio

    2002-11-01

    This tutorial is intended to provide an overview of current knowledge and practice in architectural acoustics. Topics covered will include basic concepts and history, acoustics of small rooms (small rooms for speech such as classrooms and meeting rooms, music studios, small critical listening spaces such as home theatres) and the acoustics of large rooms (larger assembly halls, auditoria, and performance halls).

  13. Protein engineering of Cas9 for enhanced function.

    PubMed

    Oakes, Benjamin L; Nadler, Dana C; Savage, David F

    2014-01-01

    CRISPR/Cas systems act to protect the cell from invading nucleic acids in many bacteria and archaea. The bacterial immune protein Cas9 is a component of one of these CRISPR/Cas systems and has recently been adapted as a tool for genome editing. Cas9 is easily targeted to bind and cleave a DNA sequence via a complementary RNA; this straightforward programmability has gained Cas9 rapid acceptance in the field of genetic engineering. While this technology has developed quickly, a number of challenges regarding Cas9 specificity, efficiency, fusion protein function, and spatiotemporal control within the cell remain. In this work, we develop a platform for constructing novel proteins to address these open questions. We demonstrate methods to either screen or select active Cas9 mutants and use the screening technique to isolate functional Cas9 variants with a heterologous PDZ domain inserted within the protein. As a proof of concept, these methods lay the groundwork for the future construction of diverse Cas9 proteins. Straightforward and accessible techniques for genetic editing are helping to elucidate biology in new and exciting ways; a platform to engineer new functionalities into Cas9 will help forge the next generation of genome-modifying tools.

  14. Inhibition of CRISPR-Cas9 with Bacteriophage Proteins.

    PubMed

    Rauch, Benjamin J; Silvis, Melanie R; Hultquist, Judd F; Waters, Christopher S; McGregor, Michael J; Krogan, Nevan J; Bondy-Denomy, Joseph

    2017-01-12

    Bacterial CRISPR-Cas systems utilize sequence-specific RNA-guided nucleases to defend against bacteriophage infection. As a countermeasure, numerous phages are known that produce proteins to block the function of class 1 CRISPR-Cas systems. However, currently no proteins are known to inhibit the widely used class 2 CRISPR-Cas9 system. To find these inhibitors, we searched cas9-containing bacterial genomes for the co-existence of a CRISPR spacer and its target, a potential indicator for CRISPR inhibition. This analysis led to the discovery of four unique type II-A CRISPR-Cas9 inhibitor proteins encoded by Listeria monocytogenes prophages. More than half of L. monocytogenes strains with cas9 contain at least one prophage-encoded inhibitor, suggesting widespread CRISPR-Cas9 inactivation. Two of these inhibitors also blocked the widely used Streptococcus pyogenes Cas9 when assayed in Escherichia coli and human cells. These natural Cas9-specific "anti-CRISPRs" present tools that can be used to regulate the genome engineering activities of CRISPR-Cas9.

  15. Precision Targeted Mutagenesis via Cas9 Paired Nickases in Rice

    PubMed Central

    Mikami, Masafumi; Toki, Seiichi; Endo, Masaki

    2016-01-01

    Recent reports of CRISPR- (clustered regularly interspaced short palindromic repeats)/Cas9 (CRISPR-associated protein 9) mediated heritable mutagenesis in plants highlight the need for accuracy of the mutagenesis directed by this system. Off-target mutations are an important issue when considering functional gene analysis, as well as the molecular breeding of crop plants with large genome size, i.e. with many duplicated genes, and where the whole-genome sequence is still lacking. In mammals, off-target mutations can be suppressed by using Cas9 paired nickases together with paired guide RNAs (gRNAs). However, the performance of Cas9 paired nickases has not yet been fully assessed in plants. Here, we analyzed on- and off-target mutation frequency in rice calli and regenerated plants using Cas9 nuclease or Cas9 nickase with paired gRNAs. When Cas9 paired nickases were used, off-target mutations were fully suppressed in rice calli and regenerated plants. However, on-target mutation frequency also decreased compared with that induced by the Cas9 paired nucleases system. Since the gRNA sequence determines specific binding of Cas9 protein–gRNA ribonucleoproteins at the targeted sequence, the on-target mutation frequency of Cas9 paired nickases depends on the design of paired gRNAs. Our results suggest that a combination of gRNAs that can induce mutations at high efficiency with Cas9 nuclease should be used together with Cas9 nickase. Furthermore, we confirmed that a combination of gRNAs containing a one nucleotide (1 nt) mismatch toward the target sequence could not induce mutations when expressed with Cas9 nickase. Our results clearly show the effectiveness of Cas9 paired nickases in delivering on-target specific mutations. PMID:26936792

  16. Annotation and Classification of CRISPR-Cas Systems.

    PubMed

    Makarova, Kira S; Koonin, Eugene V

    2015-01-01

    The clustered regularly interspaced short palindromic repeats (CRISPR)-Cas (CRISPR-associated proteins) is a prokaryotic adaptive immune system that is represented in most archaea and many bacteria. Among the currently known prokaryotic defense systems, the CRISPR-Cas genomic loci show unprecedented complexity and diversity. Classification of CRISPR-Cas variants that would capture their evolutionary relationships to the maximum possible extent is essential for comparative genomic and functional characterization of this theoretically and practically important system of adaptive immunity. To this end, a multipronged approach has been developed that combines phylogenetic analysis of the conserved Cas proteins with comparison of gene repertoires and arrangements in CRISPR-Cas loci. This approach led to the current classification of CRISPR-Cas systems into three distinct types and ten subtypes for each of which signature genes have been identified. Comparative genomic analysis of the CRISPR-Cas systems in new archaeal and bacterial genomes performed over the 3 years elapsed since the development of this classification makes it clear that new types and subtypes of CRISPR-Cas need to be introduced. Moreover, this classification system captures only part of the complexity of CRISPR-Cas organization and evolution, due to the intrinsic modularity and evolutionary mobility of these immunity systems, resulting in numerous recombinant variants. Moreover, most of the cas genes evolve rapidly, complicating the family assignment for many Cas proteins and the use of family profiles for the recognition of CRISPR-Cas subtype signatures. Further progress in the comparative analysis of CRISPR-Cas systems requires integration of the most sensitive sequence comparison tools, protein structure comparison, and refined approaches for comparison of gene neighborhoods.

  17. Indoor acoustic gain design

    NASA Astrophysics Data System (ADS)

    Concha-Abarca, Justo Andres

    2002-11-01

    The design of sound reinforcement systems includes many variables and usually some of these variables are discussed. There are criteria to optimize the performance of the sound reinforcement systems under indoor conditions. The equivalent acoustic distance, the necessary acoustic gain, and the potential acoustic gain are parameters which must be adjusted with respect to the loudspeaker array, electric power and directionality of loudspeakers, the room acoustics conditions, the distance and distribution of the audience, and the type of the original sources. The design and installation of front of the house and monitoring systems have individual criteria. This article is about this criteria and it proposes general considerations for the indoor acoustic gain design.

  18. CRISPR/Cas9-mediated gene editing in human zygotes using Cas9 protein.

    PubMed

    Tang, Lichun; Zeng, Yanting; Du, Hongzi; Gong, Mengmeng; Peng, Jin; Zhang, Buxi; Lei, Ming; Zhao, Fang; Wang, Weihua; Li, Xiaowei; Liu, Jianqiao

    2017-03-01

    Previous works using human tripronuclear zygotes suggested that the clustered regularly interspaced short palindromic repeat (CRISPR)/Cas9 system could be a tool in correcting disease-causing mutations. However, whether this system was applicable in normal human (dual pronuclear, 2PN) zygotes was unclear. Here we demonstrate that CRISPR/Cas9 is also effective as a gene-editing tool in human 2PN zygotes. By injection of Cas9 protein complexed with the appropriate sgRNAs and homology donors into one-cell human embryos, we demonstrated efficient homologous recombination-mediated correction of point mutations in HBB and G6PD. However, our results also reveal limitations of this correction procedure and highlight the need for further research.

  19. Guide RNA functional modules direct Cas9 activity and orthogonality.

    PubMed

    Briner, Alexandra E; Donohoue, Paul D; Gomaa, Ahmed A; Selle, Kurt; Slorach, Euan M; Nye, Christopher H; Haurwitz, Rachel E; Beisel, Chase L; May, Andrew P; Barrangou, Rodolphe

    2014-10-23

    The RNA-guided Cas9 endonuclease specifically targets and cleaves DNA in a sequence-dependent manner and has been widely used for programmable genome editing. Cas9 activity is dependent on interactions with guide RNAs, and evolutionarily divergent Cas9 nucleases have been shown to work orthogonally. However, the molecular basis of selective Cas9:guide-RNA interactions is poorly understood. Here, we identify and characterize six conserved modules within native crRNA:tracrRNA duplexes and single guide RNAs (sgRNAs) that direct Cas9 endonuclease activity. We show the bulge and nexus are necessary for DNA cleavage and demonstrate that the nexus and hairpins are instrumental in defining orthogonality between systems. In contrast, the crRNA:tracrRNA complementary region can be modified or partially removed. Collectively, our results establish guide RNA features that drive DNA targeting by Cas9 and open new design and engineering avenues for CRISPR technologies.

  20. Advances in therapeutic CRISPR/Cas9 genome editing.

    PubMed

    Savić, Nataša; Schwank, Gerald

    2016-02-01

    Targeted nucleases are widely used as tools for genome editing. Two years ago the clustered regularly interspaced short palindromic repeat (CRISPR)-associated Cas9 nuclease was used for the first time, and since then has largely revolutionized the field. The tremendous success of the CRISPR/Cas9 genome editing tool is powered by the ease design principle of the guide RNA that targets Cas9 to the desired DNA locus, and by the high specificity and efficiency of CRISPR/Cas9-generated DNA breaks. Several studies recently used CRISPR/Cas9 to successfully modulate disease-causing alleles in vivo in animal models and ex vivo in somatic and induced pluripotent stem cells, raising hope for therapeutic genome editing in the clinics. In this review, we will summarize and discuss such preclinical CRISPR/Cas9 gene therapy reports.

  1. Harnessing CRISPR-Cas9 immunity for genetic engineering.

    PubMed

    Charpentier, Emmanuelle; Marraffini, Luciano A

    2014-06-01

    CRISPR-Cas encodes an adaptive immune system that defends prokaryotes against infectious viruses and plasmids. Immunity is mediated by Cas nucleases, which use small RNA guides (the crRNAs) to specify a cleavage site within the genome of invading nucleic acids. In type II CRISPR-Cas systems, the DNA-cleaving activity is performed by a single enzyme Cas9 guided by an RNA duplex. Using synthetic single RNA guides, Cas9 can be reprogrammed to create specific double-stranded DNA breaks in the genomes of a variety of organisms, ranging from human cells to bacteria, and thus constitutes a powerful tool for genetic engineering. Here we describe recent advancements in our understanding of type II CRISPR-Cas immunity and how these studies led to revolutionary genome editing applications.

  2. Characterization and Evolution of Salmonella CRISPR-Cas Systems

    DTIC Science & Technology

    2014-01-01

    SECURITY CLASSIFICATION OF: Prokaryotic CRISPR -Cas (clustered regularly interspaced short palindromic repeats and CRISPR -associated genes) systems provide...adaptive immunity from invasive genetic elements and encompass three essential features: (i) cas genes, (ii) a CRISPR array composed of spacers and...direct repeats and (iii) an AT-rich leader sequence upstream of the array. We performed in- depth sequence analysis of the CRISPR -Cas systems in .600

  3. Control of gene expression by CRISPR-Cas systems.

    PubMed

    Bikard, David; Marraffini, Luciano A

    2013-01-01

    Clustered regularly interspaced short palindromic repeats (CRISPR) loci and their associated cas (CRISPR-associated) genes provide adaptive immunity against viruses (phages) and other mobile genetic elements in bacteria and archaea. While most of the early work has largely been dominated by examples of CRISPR-Cas systems directing the cleavage of phage or plasmid DNA, recent studies have revealed a more complex landscape where CRISPR-Cas loci might be involved in gene regulation. In this review, we summarize the role of these loci in the regulation of gene expression as well as the recent development of synthetic gene regulation using engineered CRISPR-Cas systems.

  4. Ectopia cordis thoracique sporadique: description clinique d'un cas

    PubMed Central

    Lubala, Toni Kasole; Mutombo, Augustin Mulangu; Katamea, Tina; Lubala, Nina; Munkana, Arthur Ndundula; Kabuya, Maguy Sangaji; Monga, Joséphine Kalenga; Luboya, Oscar Numbi

    2012-01-01

    Nous décrivons un cas d'ectopia cordis, une malformation cardiaque congénitale extrêmement rare dans laquelle le coeur est partiellement ou complètement situé en dehors des limites de la cage thoracique. Dans le cas que nous décrivons, elle est thoracique et isolée. Ce cas a été diagnostiqué en salle de naissance au Katanga, au sud de la République Démocratique du Congo. Il s'agit du premier cas documenté chez un nouveau-né Congolais. PMID:23346276

  5. CRISPR-Cas9-guided Genome Engineering in C. elegans

    PubMed Central

    Kim, Hyun-Min; Colaiácovo, Monica P.

    2016-01-01

    The CRISPR (clustered regularly interspaced short palindromic repeats)-Cas (CRISPR-associated) system is successfully being used for efficient and targeted genome editing in various organisms including the nematode C. elegans. Recent studies developed various CRISPR-Cas9 approaches to enhance genome engineering via two major DNA double-strand break repair pathways: non-homologous end joining and homologous recombination. Here we describe a protocol for Cas9-mediated C. elegans genome editing together with single guide RNA (sgRNA) and repair template cloning and injection methods required for delivering Cas9, sgRNAs and repair template DNA into the C. elegans germline. PMID:27366893

  6. Calibrated Ancillary System (CAS) user's guide, volume 1

    NASA Technical Reports Server (NTRS)

    1986-01-01

    The Calibrated Ancillary System (CAS) provides real-time calibrated parameters from the orbiter downlink (ancillary data) to the Goddard Space Flight Center (GSFC). This user's guide contains the introduction to the equipment, operation, general procedures, and specific procedures of the CAS. Volume 1 includes a general overview of the CAS relationships with other equipment, physical design, and hardware and software subsystems. In addition, a description of the user levels and tasks, an introduction to CAS operation, and an outline of general operating procedures are included.

  7. Foreign DNA capture during CRISPR–Cas adaptive immunity

    PubMed Central

    Nuñez, James K.; Harrington, Lucas B.; Kranzusch, Philip J.; Engelman, Alan N.; Doudna, Jennifer A.

    2015-01-01

    Bacteria and archaea generate adaptive immunity against phages and plasmids by integrating foreign DNA of specific 30–40 base pair (bp) lengths into clustered regularly interspaced short palindromic repeats (CRISPR) loci as spacer segments1–6. The universally conserved Cas1–Cas2 integrase complex catalyzes spacer acquisition using a direct nucleophilic integration mechanism similar to retroviral integrases and transposases7–13. How the Cas1–Cas2 complex selects foreign DNA substrates for integration remains unknown. Here we present X-ray crystal structures of the Escherichia coli Cas1–Cas2 complex bound to cognate 33 nucleotide (nt) protospacer DNA substrates. The protein complex creates a curved binding surface spanning the length of the DNA and splays the ends of the protospacer to allow each terminal nucleophilic 3′–OH to enter a channel leading into the Cas1 active sites. Phosphodiester backbone interactions between the protospacer and the proteins explain the sequence-nonspecific substrate selection observed in vivo2–4. Our results uncover the structural basis for foreign DNA capture and the mechanism by which Cas1–Cas2 functions as a molecular ruler to dictate the sequence architecture of CRISPR loci. PMID:26503043

  8. Foreign DNA capture during CRISPR-Cas adaptive immunity.

    PubMed

    Nuñez, James K; Harrington, Lucas B; Kranzusch, Philip J; Engelman, Alan N; Doudna, Jennifer A

    2015-11-26

    Bacteria and archaea generate adaptive immunity against phages and plasmids by integrating foreign DNA of specific 30-40-base-pair lengths into clustered regularly interspaced short palindromic repeat (CRISPR) loci as spacer segments. The universally conserved Cas1-Cas2 integrase complex catalyses spacer acquisition using a direct nucleophilic integration mechanism similar to retroviral integrases and transposases. How the Cas1-Cas2 complex selects foreign DNA substrates for integration remains unknown. Here we present X-ray crystal structures of the Escherichia coli Cas1-Cas2 complex bound to cognate 33-nucleotide protospacer DNA substrates. The protein complex creates a curved binding surface spanning the length of the DNA and splays the ends of the protospacer to allow each terminal nucleophilic 3'-OH to enter a channel leading into the Cas1 active sites. Phosphodiester backbone interactions between the protospacer and the proteins explain the sequence-nonspecific substrate selection observed in vivo. Our results uncover the structural basis for foreign DNA capture and the mechanism by which Cas1-Cas2 functions as a molecular ruler to dictate the sequence architecture of CRISPR loci.

  9. Strongly driven ion acoustic waves in laser produced plasmas

    SciTech Connect

    Baldis, H.A.; Labaune, C.; Renard, N.

    1994-09-20

    This paper present an experimental study of ion acoustic waves with wavenumbers corresponding to stimulated Brillouin scattering. Time resolved Thomson scattering in frequency and wavenumber space, has permitted to observe the dispersion relation of the waves as a function of the laser intensity. Apart from observing ion acoustic waves associated with a strong second component is observed at laser intensities above 10{sup 13}Wcm{sup {minus}2}.

  10. Electrical Stimulation as an Aid to Speechreading.

    ERIC Educational Resources Information Center

    Tyler, Richard S.; And Others

    1988-01-01

    This paper, discussing use of electrical stimulation by postlingually deafened adults to supplement speechreading, focuses on: information conveyed by vision, acoustic information needed to resolve visual confusions, basic psychophysical abilities of cochlear implant patients, auditory-alone and audiovisual perception by cochlear-implant patients,…

  11. AST Launch Vehicle Acoustics

    NASA Technical Reports Server (NTRS)

    Houston, Janice; Counter, D.; Giacomoni, D.

    2015-01-01

    The liftoff phase induces acoustic loading over a broad frequency range for a launch vehicle. These external acoustic environments are then used in the prediction of internal vibration responses of the vehicle and components which result in the qualification levels. Thus, predicting these liftoff acoustic (LOA) environments is critical to the design requirements of any launch vehicle. If there is a significant amount of uncertainty in the predictions or if acoustic mitigation options must be implemented, a subscale acoustic test is a feasible pre-launch test option to verify the LOA environments. The NASA Space Launch System (SLS) program initiated the Scale Model Acoustic Test (SMAT) to verify the predicted SLS LOA environments and to determine the acoustic reduction with an above deck water sound suppression system. The SMAT was conducted at Marshall Space Flight Center and the test article included a 5% scale SLS vehicle model, tower and Mobile Launcher. Acoustic and pressure data were measured by approximately 250 instruments. The SMAT liftoff acoustic results are presented, findings are discussed and a comparison is shown to the Ares I Scale Model Acoustic Test (ASMAT) results.

  12. Tenth anniversary of CAS ONLINE service : What CAS services should be in the new era of chemical information

    NASA Astrophysics Data System (ADS)

    Kostakos, Charles N.

    Chemical Abstracts Service celebrated 10th anniversary of CAS online information service in 1990. A speech given on the occasion reviewed history of the CAS ONLINE, in relation to its most important benefits for scientists and engineers. The development of STN international, the network through which CAS ONLINE is accessible around the world, was also discussed in the speech. The CAS ONLINE now contains a wide variety of files relating to chemical field including CA file, Registry file. CA previews,. CASREACT, CIN. MARPAT, etc for supplying chemical information worldwide.

  13. Acoustic Translation of an Acoustically Levitated Sample

    NASA Technical Reports Server (NTRS)

    Barmatz, M. B.; Allen, J. L.

    1986-01-01

    Acoustic-levitation apparatus uses only one acoustic mode to move sample from one region of chamber to another. Sample heated and cooled quickly by translation between hot and cold regions of levitation chamber. Levitated sample is raised into furnace region by raising plunger. Frequency of sound produced by transducers adjusted by feedback system to maintain (102) resonant mode, which levitates sample midway between transducers and plunger regardless of plunger position.

  14. Automatic detection of unattended changes in room acoustics.

    PubMed

    Frey, Johannes Daniel; Wendt, Mike; Jacobsen, Thomas

    2015-01-01

    Previous research has shown that the human auditory system continuously monitors its acoustic environment, detecting a variety of irregularities (e.g., deviance from prior stimulation regularity in pitch, loudness, duration, and (perceived) sound source location). Detection of irregularities can be inferred from a component of the event-related brain potential (ERP), referred to as the mismatch negativity (MMN), even in conditions in which participants are instructed to ignore the auditory stimulation. The current study extends previous findings by demonstrating that auditory irregularities brought about by a change in room acoustics elicit a MMN in a passive oddball protocol (acoustic stimuli with differing room acoustics, that were otherwise identical, were employed as standard and deviant stimuli), in which participants watched a fiction movie (silent with subtitles). While the majority of participants reported no awareness for any changes in the auditory stimulation, only one out of 14 participants reported to have become aware of changing room acoustics or sound source location. Together, these findings suggest automatic monitoring of room acoustics.

  15. Acoustic Immittance, Absorbance, and Reflectance in the Human Ear Canal

    PubMed Central

    Rosowski, John J.; Wilber, Laura Ann

    2015-01-01

    Ear canal measurements of acoustic immittance (a term that groups impedance and its inverse, admittance) and the related quantities of acoustic reflectance and power absorbance have been used to assess auditory function and aid in the differential diagnosis of conductive hearing loss for over 50 years. The change in such quantities after stimulation of the acoustic reflex also has been used in diagnosis. In this article, we define these quantities, describe how they are commonly measured, and discuss appropriate calibration procedures and standards necessary for accurate immittance/reflectance measurements. PMID:27516708

  16. New CRISPR-Cas systems from uncultivated microbes.

    PubMed

    Burstein, David; Harrington, Lucas B; Strutt, Steven C; Probst, Alexander J; Anantharaman, Karthik; Thomas, Brian C; Doudna, Jennifer A; Banfield, Jillian F

    2017-02-09

    CRISPR-Cas systems provide microbes with adaptive immunity by employing short DNA sequences, termed spacers, that guide Cas proteins to cleave foreign DNA. Class 2 CRISPR-Cas systems are streamlined versions, in which a single RNA-bound Cas protein recognizes and cleaves target sequences. The programmable nature of these minimal systems has enabled researchers to repurpose them into a versatile technology that is broadly revolutionizing biological and clinical research. However, current CRISPR-Cas technologies are based solely on systems from isolated bacteria, leaving the vast majority of enzymes from organisms that have not been cultured untapped. Metagenomics, the sequencing of DNA extracted directly from natural microbial communities, provides access to the genetic material of a huge array of uncultivated organisms. Here, using genome-resolved metagenomics, we identify a number of CRISPR-Cas systems, including the first reported Cas9 in the archaeal domain of life, to our knowledge. This divergent Cas9 protein was found in little-studied nanoarchaea as part of an active CRISPR-Cas system. In bacteria, we discovered two previously unknown systems, CRISPR-CasX and CRISPR-CasY, which are among the most compact systems yet discovered. Notably, all required functional components were identified by metagenomics, enabling validation of robust in vivo RNA-guided DNA interference activity in Escherichia coli. Interrogation of environmental microbial communities combined with in vivo experiments allows us to access an unprecedented diversity of genomes, the content of which will expand the repertoire of microbe-based biotechnologies.

  17. New CRISPR–Cas systems from uncultivated microbes

    NASA Astrophysics Data System (ADS)

    Burstein, David; Harrington, Lucas B.; Strutt, Steven C.; Probst, Alexander J.; Anantharaman, Karthik; Thomas, Brian C.; Doudna, Jennifer A.; Banfield, Jillian F.

    2016-12-01

    CRISPR–Cas systems provide microbes with adaptive immunity by employing short DNA sequences, termed spacers, that guide Cas proteins to cleave foreign DNA. Class 2 CRISPR–Cas systems are streamlined versions, in which a single RNA-bound Cas protein recognizes and cleaves target sequences. The programmable nature of these minimal systems has enabled researchers to repurpose them into a versatile technology that is broadly revolutionizing biological and clinical research. However, current CRISPR–Cas technologies are based solely on systems from isolated bacteria, leaving the vast majority of enzymes from organisms that have not been cultured untapped. Metagenomics, the sequencing of DNA extracted directly from natural microbial communities, provides access to the genetic material of a huge array of uncultivated organisms. Here, using genome-resolved metagenomics, we identify a number of CRISPR–Cas systems, including the first reported Cas9 in the archaeal domain of life, to our knowledge. This divergent Cas9 protein was found in little-studied nanoarchaea as part of an active CRISPR–Cas system. In bacteria, we discovered two previously unknown systems, CRISPR–CasX and CRISPR–CasY, which are among the most compact systems yet discovered. Notably, all required functional components were identified by metagenomics, enabling validation of robust in vivo RNA-guided DNA interference activity in Escherichia coli. Interrogation of environmental microbial communities combined with in vivo experiments allows us to access an unprecedented diversity of genomes, the content of which will expand the repertoire of microbe-based biotechnologies.

  18. Recent Advances in Genome Editing Using CRISPR/Cas9

    PubMed Central

    Ding, Yuduan; Li, Hong; Chen, Ling-Ling; Xie, Kabin

    2016-01-01

    The CRISPR (clustered regularly interspaced short palindromic repeat)-Cas9 (CRISPR-associated nuclease 9) system is a versatile tool for genome engineering that uses a guide RNA (gRNA) to target Cas9 to a specific sequence. This simple RNA-guided genome-editing technology has become a revolutionary tool in biology and has many innovative applications in different fields. In this review, we briefly introduce the Cas9-mediated genome-editing method, summarize the recent advances in CRISPR/Cas9 technology, and discuss their implications for plant research. To date, targeted gene knockout using the Cas9/gRNA system has been established in many plant species, and the targeting efficiency and capacity of Cas9 has been improved by optimizing its expression and that of its gRNA. The CRISPR/Cas9 system can also be used for sequence-specific mutagenesis/integration and transcriptional control of target genes. We also discuss off-target effects and the constraint that the protospacer-adjacent motif (PAM) puts on CRISPR/Cas9 genome engineering. To address these problems, a number of bioinformatic tools are available to help design specific gRNAs, and new Cas9 variants and orthologs with high fidelity and alternative PAM specificities have been engineered. Owing to these recent efforts, the CRISPR/Cas9 system is becoming a revolutionary and flexible tool for genome engineering. Adoption of the CRISPR/Cas9 technology in plant research would enable the investigation of plant biology at an unprecedented depth and create innovative applications in precise crop breeding. PMID:27252719

  19. Nearfield Acoustical Holography

    NASA Astrophysics Data System (ADS)

    Hayek, Sabih I.

    Nearfield acoustical holography (NAH) is a method by which a set of acoustic pressure measurements at points located on a specific surface (called a hologram) can be used to image sources on vibrating surfaces on the acoustic field in three-dimensional space. NAH data are processed to take advantage of the evanescent wavefield to image sources that are separated less that one-eighth of a wavelength.

  20. Deep Water Acoustics

    DTIC Science & Technology

    2016-06-28

    Estimates of basin-wide sound speed ( temperature ) fields obtained by the combination of acoustic, altimetry, and other data types with ocean...of acoustic coherence at long ranges in the ocean. Estimates of basin-wide sound speed ( temperature ) fields obtained by the combination of acoustic...index.html Award Number N00014-13-1-0053 LONG-TERM GOALS The ultimate limitations to the performance of long-range sonar are due to ocean sound speed

  1. Acoustic Communications (ACOMMS) ATD

    DTIC Science & Technology

    2016-06-14

    Acoustic Communications (ACOMMS) ATD Tam Nguyen 2531 Jefferson Davis Hwy Arlington, VA 22242 phone: (703) 604-6013 ext 520 fax: (703) 604-6056...email: NguyenTL@navsea.navy.mil Award # N0001499PD30007 LONG-TERM GOALS The goal of the recently completed Acoustic Communications Advanced...Technology Demonstration program (ACOMMS ATD) was to demonstrate long range and moderate data rate underwater acoustic communications between a submarine

  2. Deep Water Ocean Acoustics

    DTIC Science & Technology

    2016-04-30

    OASIS, INC. 1 Report No. QSR-14C0172-Ocean Acoustics-043016 Quarterly Progress Report Technical and Financial Deep Water Ocean Acoustics...understanding of the impact of the ocean and seafloor environmental variability on deep- water (long-range) ocean acoustic propagation and to...improve our understanding. During the past few years, the physics effects studied have been three-dimensional propagation on global scales, deep water

  3. Efficient chromosomal gene modification with CRISPR/cas9 and PCR-based homologous recombination donors in cultured Drosophila cells.

    PubMed

    Böttcher, Romy; Hollmann, Manuel; Merk, Karin; Nitschko, Volker; Obermaier, Christina; Philippou-Massier, Julia; Wieland, Isabella; Gaul, Ulrike; Förstemann, Klaus

    2014-06-01

    The ability to edit the genome is essential for many state-of-the-art experimental paradigms. Since DNA breaks stimulate repair, they can be exploited to target site-specific integration. The clustered, regularly interspaced, short palindromic repeats (CRISPR)/cas9 system from Streptococcus pyogenes has been harnessed into an efficient and programmable nuclease for eukaryotic cells. We thus combined DNA cleavage by cas9, the generation of homologous recombination donors by polymerase chain reaction (PCR) and transient depletion of the non-homologous end joining factor lig4. Using cultured Drosophila melanogaster S2-cells and the phosphoglycerate kinase gene as a model, we reached targeted integration frequencies of up to 50% in drug-selected cell populations. Homology arms as short as 29 nt appended to the PCR primer resulted in detectable integration, slightly longer extensions are beneficial. We confirmed established rules for S. pyogenes cas9 sgRNA design and demonstrate that the complementarity region allows length variation and 5'-extensions. This enables generation of U6-promoter fusion templates by overlap-extension PCR with a standardized protocol. We present a series of PCR template vectors for C-terminal protein tagging and clonal Drosophila S2 cell lines with stable expression of a myc-tagged cas9 protein. The system can be used for epitope tagging or reporter gene knock-ins in an experimental setup that can in principle be fully automated.

  4. Acoustic dispersive prism

    NASA Astrophysics Data System (ADS)

    Esfahlani, Hussein; Karkar, Sami; Lissek, Herve; Mosig, Juan R.

    2016-01-01

    The optical dispersive prism is a well-studied element, which allows separating white light into its constituent spectral colors, and stands in nature as water droplets. In analogy to this definition, the acoustic dispersive prism should be an acoustic device with capability of splitting a broadband acoustic wave into its constituent Fourier components. However, due to the acoustical nature of materials as well as the design and fabrication difficulties, there is neither any natural acoustic counterpart of the optical prism, nor any artificial design reported so far exhibiting an equivalent acoustic behaviour. Here, based on exotic properties of the acoustic transmission-line metamaterials and exploiting unique physical behaviour of acoustic leaky-wave radiation, we report the first acoustic dispersive prism, effective within the audible frequency range 800 Hz–1300 Hz. The dispersive nature, and consequently the frequency-dependent refractive index of the metamaterial are exploited to split the sound waves towards different and frequency-dependent directions. Meanwhile, the leaky-wave nature of the structure facilitates the sound wave radiation into the ambient medium.

  5. Acoustic dispersive prism.

    PubMed

    Esfahlani, Hussein; Karkar, Sami; Lissek, Herve; Mosig, Juan R

    2016-01-07

    The optical dispersive prism is a well-studied element, which allows separating white light into its constituent spectral colors, and stands in nature as water droplets. In analogy to this definition, the acoustic dispersive prism should be an acoustic device with capability of splitting a broadband acoustic wave into its constituent Fourier components. However, due to the acoustical nature of materials as well as the design and fabrication difficulties, there is neither any natural acoustic counterpart of the optical prism, nor any artificial design reported so far exhibiting an equivalent acoustic behaviour. Here, based on exotic properties of the acoustic transmission-line metamaterials and exploiting unique physical behaviour of acoustic leaky-wave radiation, we report the first acoustic dispersive prism, effective within the audible frequency range 800 Hz-1300 Hz. The dispersive nature, and consequently the frequency-dependent refractive index of the metamaterial are exploited to split the sound waves towards different and frequency-dependent directions. Meanwhile, the leaky-wave nature of the structure facilitates the sound wave radiation into the ambient medium.

  6. Low frequency acoustic microscope

    DOEpatents

    Khuri-Yakub, Butrus T.

    1986-11-04

    A scanning acoustic microscope is disclosed for the detection and location of near surface flaws, inclusions or voids in a solid sample material. A focused beam of acoustic energy is directed at the sample with its focal plane at the subsurface flaw, inclusion or void location. The sample is scanned with the beam. Detected acoustic energy specularly reflected and mode converted at the surface of the sample and acoustic energy reflected by subsurface flaws, inclusions or voids at the focal plane are used for generating an interference signal which is processed and forms a signal indicative of the subsurface flaws, inclusions or voids.

  7. Acoustic dispersive prism

    PubMed Central

    Esfahlani, Hussein; Karkar, Sami; Lissek, Herve; Mosig, Juan R.

    2016-01-01

    The optical dispersive prism is a well-studied element, which allows separating white light into its constituent spectral colors, and stands in nature as water droplets. In analogy to this definition, the acoustic dispersive prism should be an acoustic device with capability of splitting a broadband acoustic wave into its constituent Fourier components. However, due to the acoustical nature of materials as well as the design and fabrication difficulties, there is neither any natural acoustic counterpart of the optical prism, nor any artificial design reported so far exhibiting an equivalent acoustic behaviour. Here, based on exotic properties of the acoustic transmission-line metamaterials and exploiting unique physical behaviour of acoustic leaky-wave radiation, we report the first acoustic dispersive prism, effective within the audible frequency range 800 Hz–1300 Hz. The dispersive nature, and consequently the frequency-dependent refractive index of the metamaterial are exploited to split the sound waves towards different and frequency-dependent directions. Meanwhile, the leaky-wave nature of the structure facilitates the sound wave radiation into the ambient medium. PMID:26739504

  8. Expanding the CRISPR Toolbox: Targeting RNA with Cas13b.

    PubMed

    Barrangou, Rodolphe; Gersbach, Charles A

    2017-02-16

    In this issue of Molecular Cell, Smargon et al. (2017) unearth Cas13b from type VI-B CRISPR-Cas immune systems and characterize its RNA-guided, RNA-targeting activity, including regulation by the novel co-factors Csx27 and Csx28, as well as non-specific collateral RNA damage.

  9. Using CAS to Solve a Mathematics Task: A Deconstruction

    ERIC Educational Resources Information Center

    Berger, Margot

    2010-01-01

    I investigate how and whether a heterogeneous group of first-year university mathematics students in South Africa harness the potential power of a computer algebra system (CAS) when doing a specific mathematics task. In order to do this, I develop a framework for deconstructing a mathematics task requiring the use of CAS, into its primary…

  10. Calibrated Ancillary System (CAS) user's guide, volume 2

    NASA Technical Reports Server (NTRS)

    1986-01-01

    The Calibrated Ancillary System (CAS) provides real-time calibrated parameters from the orbiter downlink (ancillary data) to the Goddard Space Flight Center (GSFC). This user's guide contains the introduction to the equipment, operation, general procedures, and specific procedures of CAS. Volume 2 describes the central status and control (CSAC) procedures, supervisor procedures, and logging procedures.

  11. Calibrated Ancillary System (CAS) user's guide, volume 3

    NASA Technical Reports Server (NTRS)

    1986-01-01

    The Calibrated Ancillary System (CAS) provides real-time calibrated parameters from the orbiter downlink (ancillary data) to the Goddard Space Flight Center (GSFC). This user's guide contains the introduction to the equipment, operation, general procedures, and specific procedures of the CAS. Volume 3 describes logging and delogging procedures, real-time procedures, and error messages.

  12. Calibrated Ancillary System (CAS) user's guide, volume 8

    NASA Technical Reports Server (NTRS)

    1986-01-01

    The Calibrated Ancillary System (CAS) provides real-time calibrated parameters from the orbiter downlink (ancillary data) to the Goddard Space Flight Center (GSFC). This user's guide contains the introduction to the equipment, operation, general procedures, and specific procedures of CAS. Volume 8 describes procedures for invoking checkout software, file maintenance procedures, system manager procedures.

  13. Transformation of OODT CAS to Perform Larger Tasks

    NASA Technical Reports Server (NTRS)

    Mattmann, Chris; Freeborn, Dana; Crichton, Daniel; Hughes, John; Ramirez, Paul; Hardman, Sean; Woollard, David; Kelly, Sean

    2008-01-01

    A computer program denoted OODT CAS has been transformed to enable performance of larger tasks that involve greatly increased data volumes and increasingly intensive processing of data on heterogeneous, geographically dispersed computers. Prior to the transformation, OODT CAS (also alternatively denoted, simply, 'CAS') [wherein 'OODT' signifies 'Object-Oriented Data Technology' and 'CAS' signifies 'Catalog and Archive Service'] was a proven software component used to manage scientific data from spaceflight missions. In the transformation, CAS was split into two separate components representing its canonical capabilities: file management and workflow management. In addition, CAS was augmented by addition of a resource-management component. This third component enables CAS to manage heterogeneous computing by use of diverse resources, including high-performance clusters of computers, commodity computing hardware, and grid computing infrastructures. CAS is now more easily maintainable, evolvable, and reusable. These components can be used separately or, taking advantage of synergies, can be used together. Other elements of the transformation included addition of a separate Web presentation layer that supports distribution of data products via Really Simple Syndication (RSS) feeds, and provision for full Resource Description Framework (RDF) exports of metadata.

  14. Optimization of genome editing through CRISPR-Cas9 engineering.

    PubMed

    Zhang, Jian-Hua; Adikaram, Poorni; Pandey, Mritunjay; Genis, Allison; Simonds, William F

    2016-04-01

    CRISPR (Clustered Regularly-Interspaced Short Palindromic Repeats)-Cas9 (CRISPR associated protein 9) has rapidly become the most promising genome editing tool with great potential to revolutionize medicine. Through guidance of a 20 nucleotide RNA (gRNA), CRISPR-Cas9 finds and cuts target protospacer DNA precisely 3 base pairs upstream of a PAM (Protospacer Adjacent Motif). The broken DNA ends are repaired by either NHEJ (Non-Homologous End Joining) resulting in small indels, or by HDR (Homology Directed Repair) for precise gene or nucleotide replacement. Theoretically, CRISPR-Cas9 could be used to modify any genomic sequences, thereby providing a simple, easy, and cost effective means of genome wide gene editing. However, the off-target activity of CRISPR-Cas9 that cuts DNA sites with imperfect matches with gRNA have been of significant concern because clinical applications require 100% accuracy. Additionally, CRISPR-Cas9 has unpredictable efficiency among different DNA target sites and the PAM requirements greatly restrict its genome editing frequency. A large number of efforts have been made to address these impeding issues, but much more is needed to fully realize the medical potential of CRISPR-Cas9. In this article, we summarize the existing problems and current advances of the CRISPR-Cas9 technology and provide perspectives for the ultimate perfection of Cas9-mediated genome editing.

  15. Reaction to Indispensable Manual Calculation Skills in a CAS Environment.

    ERIC Educational Resources Information Center

    Monaghan, John

    2001-01-01

    Reacts to an article published in a previous issue of this journal on the effects of graphing calculators and computer algebra systems (CAS) on students' manual calculation and algebraic manipulation skills. Considers the contribution made by Jean-Baptiste Lagrange to thinking about the role of CAS in teaching algebra. (ASK)

  16. 48 CFR 9903.201-2 - Types of CAS coverage.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ...) Receive a single CAS-covered contract award of $50 million or more; or (2) Received $50 million or more in... business unit receives a single CAS-covered contract award of $50 million or more, that contract must be... institution that operate as independent organizational entities under the auspices of the parent...

  17. From Calculus to Dynamical Systems through DGS and CAS

    ERIC Educational Resources Information Center

    García, Jeanett López; Zamudio, Jorge Javier Jiménez

    2015-01-01

    Several factors have motivated the use of CAS or DGS in the teaching-learning process, such as: the development of new technologies, the availability of computers, and the widespread use of the Internet, among others. Even more, the trend to include CAS and DGS in the curricula of some undergraduate studies has resulted in the instruction of the…

  18. Teaching Undergraduate Mathematics Using CAS Technology: Issues and Prospects

    ERIC Educational Resources Information Center

    Tobin, Patrick C.; Weiss, Vida

    2016-01-01

    The use of handheld CAS technology in undergraduate mathematics courses in Australia is paradoxically shrinking under sustained disapproval or disdain from the professional mathematics community. Mathematics education specialists argue with their mathematics colleagues over a range of issues in course development and this use of CAS or even…

  19. CRISPR-Cas Technologies and Applications in Food Bacteria.

    PubMed

    Stout, Emily; Klaenhammer, Todd; Barrangou, Rodolphe

    2017-02-28

    Clustered regularly interspaced short palindromic repeats (CRISPRs) and CRISPR-associated (Cas) proteins form adaptive immune systems that occur in many bacteria and most archaea. In addition to protecting bacteria from phages and other invasive mobile genetic elements, CRISPR-Cas molecular machines can be repurposed as tool kits for applications relevant to the food industry. A primary concern of the food industry has long been the proper management of food-related bacteria, with a focus on both enhancing the outcomes of beneficial microorganisms such as starter cultures and probiotics and limiting the presence of detrimental organisms such as pathogens and spoilage microorganisms. This review introduces CRISPR-Cas as a novel set of technologies to manage food bacteria and offers insights into CRISPR-Cas biology. It primarily focuses on the applications of CRISPR-Cas systems and tools in starter cultures and probiotics, encompassing strain-typing, phage resistance, plasmid vaccination, genome editing, and antimicrobial activity.

  20. Cas9-mediated targeting of viral RNA in eukaryotic cells.

    PubMed

    Price, Aryn A; Sampson, Timothy R; Ratner, Hannah K; Grakoui, Arash; Weiss, David S

    2015-05-12

    Clustered, regularly interspaced, short palindromic repeats-CRISPR associated (CRISPR-Cas) systems are prokaryotic RNA-directed endonuclease machineries that act as an adaptive immune system against foreign genetic elements. Using small CRISPR RNAs that provide specificity, Cas proteins recognize and degrade nucleic acids. Our previous work demonstrated that the Cas9 endonuclease from Francisella novicida (FnCas9) is capable of targeting endogenous bacterial RNA. Here, we show that FnCas9 can be directed by an engineered RNA-targeting guide RNA to target and inhibit a human +ssRNA virus, hepatitis C virus, within eukaryotic cells. This work reveals a versatile and portable RNA-targeting system that can effectively function in eukaryotic cells and be programmed as an antiviral defense.

  1. Cas9-mediated targeting of viral RNA in eukaryotic cells

    PubMed Central

    Price, Aryn A.; Sampson, Timothy R.; Ratner, Hannah K.; Grakoui, Arash; Weiss, David S.

    2015-01-01

    Clustered, regularly interspaced, short palindromic repeats–CRISPR associated (CRISPR-Cas) systems are prokaryotic RNA-directed endonuclease machineries that act as an adaptive immune system against foreign genetic elements. Using small CRISPR RNAs that provide specificity, Cas proteins recognize and degrade nucleic acids. Our previous work demonstrated that the Cas9 endonuclease from Francisella novicida (FnCas9) is capable of targeting endogenous bacterial RNA. Here, we show that FnCas9 can be directed by an engineered RNA-targeting guide RNA to target and inhibit a human +ssRNA virus, hepatitis C virus, within eukaryotic cells. This work reveals a versatile and portable RNA-targeting system that can effectively function in eukaryotic cells and be programmed as an antiviral defense. PMID:25918406

  2. Diversity and evolution of class 2 CRISPR-Cas systems.

    PubMed

    Shmakov, Sergey; Smargon, Aaron; Scott, David; Cox, David; Pyzocha, Neena; Yan, Winston; Abudayyeh, Omar O; Gootenberg, Jonathan S; Makarova, Kira S; Wolf, Yuri I; Severinov, Konstantin; Zhang, Feng; Koonin, Eugene V

    2017-03-01

    Class 2 CRISPR-Cas systems are characterized by effector modules that consist of a single multidomain protein, such as Cas9 or Cpf1. We designed a computational pipeline for the discovery of novel class 2 variants and used it to identify six new CRISPR-Cas subtypes. The diverse properties of these new systems provide potential for the development of versatile tools for genome editing and regulation. In this Analysis article, we present a comprehensive census of class 2 types and class 2 subtypes in complete and draft bacterial and archaeal genomes, outline evolutionary scenarios for the independent origin of different class 2 CRISPR-Cas systems from mobile genetic elements, and propose an amended classification and nomenclature of CRISPR-Cas.

  3. Guide RNA engineering for versatile Cas9 functionality

    PubMed Central

    Nowak, Chance M.; Lawson, Seth; Zerez, Megan; Bleris, Leonidas

    2016-01-01

    The Clustered Regularly Interspaced Short Palindromic Repeats system allows a single guide RNA (sgRNA) to direct a protein with combined helicase and nuclease activity to the DNA. Streptococcus pyogenes Cas9 (SpCas9), a CRISPR-associated protein, has revolutionized our ability to probe and edit the human genome in vitro and in vivo. Arguably, the true modularity of the Cas9 platform is conferred through the ease of sgRNA programmability as well as the degree of modifications the sgRNA can tolerate without compromising its association with SpCas9 and function. In this review, we focus on the properties and recent engineering advances of the sgRNA component in Cas9-mediated genome targeting. PMID:27733506

  4. Implementing the CAS Standards: The Implementation of the CAS Standards in Student Affairs as a Comprehensive Assessment Approach

    ERIC Educational Resources Information Center

    Dorman, Jesse A.

    2012-01-01

    The increasing use of the CAS standards as a comprehensive assessment approach in divisions of student affairs necessitates a more in-depth understanding of how the CAS standards are being implemented in these settings. In response to increasing calls for improvement, accountability and professionalism in student affairs (Bresciani, 2006; Cooper…

  5. Combined Electric and Contralateral Acoustic Hearing: Word and Sentence Recognition with Bimodal Hearing

    ERIC Educational Resources Information Center

    Gifford, Rene H.; Dorman, Michael F.; McKarns, Sharon A.; Spahr, Anthony J.

    2007-01-01

    Purpose: The authors assessed whether (a) a full-insertion cochlear implant would provide a higher level of speech understanding than bilateral low-frequency acoustic hearing, (b) contralateral acoustic hearing would add to the speech understanding provided by the implant, and (c) the level of performance achieved with electric stimulation plus…

  6. Microbial-Induced Heterogeneity in the Acoustic Properties of Porous Media

    EPA Science Inventory

    Acoustic wave data were acquired over a two-dimensional region of a microbial-stimulated sand column and an unstimulated sand column to assess the spatiotemporal changes in a porous medium caused by microbial growth and biofilm formation. The acoustic signals from the unstimulate...

  7. Interference activity of a minimal Type I CRISPR–Cas system from Shewanella putrefaciens

    PubMed Central

    Dwarakanath, Srivatsa; Brenzinger, Susanne; Gleditzsch, Daniel; Plagens, André; Klingl, Andreas; Thormann, Kai; Randau, Lennart

    2015-01-01

    Type I CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats)–Cas (CRISPR-associated) systems exist in bacterial and archaeal organisms and provide immunity against foreign DNA. The Cas protein content of the DNA interference complexes (termed Cascade) varies between different CRISPR-Cas subtypes. A minimal variant of the Type I-F system was identified in proteobacterial species including Shewanella putrefaciens CN-32. This variant lacks a large subunit (Csy1), Csy2 and Csy3 and contains two unclassified cas genes. The genome of S. putrefaciens CN-32 contains only five Cas proteins (Cas1, Cas3, Cas6f, Cas1821 and Cas1822) and a single CRISPR array with 81 spacers. RNA-Seq analyses revealed the transcription of this array and the maturation of crRNAs (CRISPR RNAs). Interference assays based on plasmid conjugation demonstrated that this CRISPR-Cas system is active in vivo and that activity is dependent on the recognition of the dinucleotide GG PAM (Protospacer Adjacent Motif) sequence and crRNA abundance. The deletion of cas1821 and cas1822 reduced the cellular crRNA pool. Recombinant Cas1821 was shown to form helical filaments bound to RNA molecules, which suggests its role as the Cascade backbone protein. A Cascade complex was isolated which contained multiple Cas1821 copies, Cas1822, Cas6f and mature crRNAs. PMID:26350210

  8. The Acoustical Environment.

    ERIC Educational Resources Information Center

    Smith, Melissa

    Asserting that without an adequate acoustical environment, learning activities can be hindered, this paper reviews the literature on classroom acoustics, particularly noise, reverberation, signal-to-noise ratio, task performance, and recommendations for improvement. Through this review, the paper seeks to determine whether portable classrooms…

  9. Cystic acoustic schwannomas.

    PubMed

    Lunardi, P; Missori, P; Mastronardi, L; Fortuna, A

    1991-01-01

    Three cases with large space-occupying cysts in the cerebellopontine angle are reported. CT and MRI findings were not typical for acoustic schwannomas but at operation, besides the large cysts, small acoustic schwannomas could be detected and removed. The clinical and neuroradiological features of this unusual variety and the CT and MRI differential diagnosis of cerebellopontine angle lesions are discussed.

  10. Pilomatricome: étude de 22 cas

    PubMed Central

    Nasreddine, Fatima Zahra; Hali, Fouzia; Chiheb, Soumiya

    2016-01-01

    Le pilomatricome est une tumeur cutanée fréquente et bénigne du follicule pileux chez l'enfant. C'est une tumeur annexielle souvent méconnue et confondue avec d'autres lésions cutanées. Les localisations habituelles sont la tête et le cou. Le but de ce travail est de rapporter une série de 22 cas comportant des formes inhabituelles colligées au service de dermatologie sur une période allant de Janvier 2006 jusqu'au Mai 2015. L’étude a concerné 16 femmes et 6 hommes. La moyenne d’âge était de 23,3 ans (4-80 ans). La localisation cervico faciale a été observée dans 12 cas, 2 patients avaient des localisations multiples, un garçon de 4ans avait une localisation au niveau fronto-temporal et une fillette de 14 ans avait une localisation au niveau du visage et de l'avant-bras, et un patient de 48 ans avait une localisation sous unguéale. L'aspect clinique était typique dans tous les cas avec des nodules sous cutanés de consistance pierreuse. Tous les patients ont bénéficié d'une exérèse des nodules sous anesthésie locale. L’étude histologique était en faveur d'un épithélioma momifié de Malherbe d'exérèse complète sans signes de malignité. Aucun patient n'a présenté de rechute. L'originalité de notre étude réside dans la présence de localisations exceptionnelles au niveau latéro-vertébral, des membres et sous-unguéale, l’âge de survenue inhabituel à 80 ans et la présence de localisations multiples signalées chez 2 enfants. PMID:27516819

  11. Acoustic Remote Sensing

    NASA Astrophysics Data System (ADS)

    Dowling, David R.; Sabra, Karim G.

    2015-01-01

    Acoustic waves carry information about their source and collect information about their environment as they propagate. This article reviews how these information-carrying and -collecting features of acoustic waves that travel through fluids can be exploited for remote sensing. In nearly all cases, modern acoustic remote sensing involves array-recorded sounds and array signal processing to recover multidimensional results. The application realm for acoustic remote sensing spans an impressive range of signal frequencies (10-2 to 107 Hz) and distances (10-2 to 107 m) and involves biomedical ultrasound imaging, nondestructive evaluation, oil and gas exploration, military systems, and Nuclear Test Ban Treaty monitoring. In the past two decades, approaches have been developed to robustly localize remote sources; remove noise and multipath distortion from recorded signals; and determine the acoustic characteristics of the environment through which the sound waves have traveled, even when the recorded sounds originate from uncooperative sources or are merely ambient noise.

  12. Acoustic suspension system

    NASA Technical Reports Server (NTRS)

    Lee, M. C.; Wang, T. G. (Inventor)

    1983-01-01

    An acoustic levitation system is described, with single acoustic source and a small reflector to stably levitate a small object while the object is processed as by coating or heating it. The system includes a concave acoustic source which has locations on opposite sides of its axis that vibrate towards and away from a focal point to generate a converging acoustic field. A small reflector is located near the focal point, and preferably slightly beyond it, to create an intense acoustic field that stably supports a small object near the reflector. The reflector is located about one-half wavelength from the focal point and is concavely curved to a radius of curvature (L) of about one-half the wavelength, to stably support an object one-quarter wavelength (N) from the reflector.

  13. Virtual acoustics displays

    NASA Technical Reports Server (NTRS)

    Wenzel, Elizabeth M.; Fisher, Scott S.; Stone, Philip K.; Foster, Scott H.

    1991-01-01

    The real time acoustic display capabilities are described which were developed for the Virtual Environment Workstation (VIEW) Project at NASA-Ames. The acoustic display is capable of generating localized acoustic cues in real time over headphones. An auditory symbology, a related collection of representational auditory 'objects' or 'icons', can be designed using ACE (Auditory Cue Editor), which links both discrete and continuously varying acoustic parameters with information or events in the display. During a given display scenario, the symbology can be dynamically coordinated in real time with 3-D visual objects, speech, and gestural displays. The types of displays feasible with the system range from simple warnings and alarms to the acoustic representation of multidimensional data or events.

  14. Cochlear bionic acoustic metamaterials

    NASA Astrophysics Data System (ADS)

    Ma, Fuyin; Wu, Jiu Hui; Huang, Meng; Fu, Gang; Bai, Changan

    2014-11-01

    A design of bionic acoustic metamaterial and acoustic functional devices was proposed by employing the mammalian cochlear as a prototype. First, combined with the experimental data in previous literatures, it is pointed out that the cochlear hair cells and stereocilia cluster are a kind of natural biological acoustic metamaterials with the negative stiffness characteristics. Then, to design the acoustic functional devices conveniently in engineering application, a simplified parametric helical structure was proposed to replace actual irregular cochlea for bionic design, and based on the computational results of such a bionic parametric helical structure, it is suggested that the overall cochlear is a local resonant system with the negative dynamic effective mass characteristics. There are many potential applications in the bandboard energy recovery device, cochlear implant, and acoustic black hole.

  15. Acoustic integrated extinction

    PubMed Central

    Norris, Andrew N.

    2015-01-01

    The integrated extinction (IE) is defined as the integral of the scattering cross section as a function of wavelength. Sohl et al. (2007 J. Acoust. Soc. Am. 122, 3206–3210. (doi:10.1121/1.2801546)) derived an IE expression for acoustic scattering that is causal, i.e. the scattered wavefront in the forward direction arrives later than the incident plane wave in the background medium. The IE formula was based on electromagnetic results, for which scattering is causal by default. Here, we derive a formula for the acoustic IE that is valid for causal and non-causal scattering. The general result is expressed as an integral of the time-dependent forward scattering function. The IE reduces to a finite integral for scatterers with zero long-wavelength monopole and dipole amplitudes. Implications for acoustic cloaking are discussed and a new metric is proposed for broadband acoustic transparency. PMID:27547100

  16. Direct Field Acoustic Testing

    NASA Technical Reports Server (NTRS)

    Larkin, Paul; Goldstein, Bob

    2008-01-01

    This paper presents an update to the methods and procedures used in Direct Field Acoustic Testing (DFAT). The paper will discuss some of the recent techniques and developments that are currently being used and the future publication of a reference standard. Acoustic testing using commercial sound system components is becoming a popular and cost effective way of generating a required acoustic test environment both in and out of a reverberant chamber. This paper will present the DFAT test method, the usual setup and procedure and the development and use of a closed-loop, narrow-band control system. Narrow-band control of the acoustic PSD allows all standard techniques and procedures currently used in random control to be applied to acoustics and some examples are given. The paper will conclude with a summary of the development of a standard practice guideline that is hoped to be available in the first quarter of next year.

  17. Virtual acoustics displays

    NASA Astrophysics Data System (ADS)

    Wenzel, Elizabeth M.; Fisher, Scott S.; Stone, Philip K.; Foster, Scott H.

    1991-03-01

    The real time acoustic display capabilities are described which were developed for the Virtual Environment Workstation (VIEW) Project at NASA-Ames. The acoustic display is capable of generating localized acoustic cues in real time over headphones. An auditory symbology, a related collection of representational auditory 'objects' or 'icons', can be designed using ACE (Auditory Cue Editor), which links both discrete and continuously varying acoustic parameters with information or events in the display. During a given display scenario, the symbology can be dynamically coordinated in real time with 3-D visual objects, speech, and gestural displays. The types of displays feasible with the system range from simple warnings and alarms to the acoustic representation of multidimensional data or events.

  18. Crystal Structure of Streptococcus pyogenes Cas1 and Its Interaction with Csn2 in the Type II CRISPR-Cas System.

    PubMed

    Ka, Donghyun; Lee, Hasup; Jung, Yi-Deun; Kim, Kyunggon; Seok, Chaok; Suh, Nayoung; Bae, Euiyoung

    2016-01-05

    CRISPRs and Cas proteins constitute an RNA-guided microbial immune system against invading nucleic acids. Cas1 is a universal Cas protein found in all three types of CRISPR-Cas systems, and its role is implicated in new spacer acquisition during CRISPR-mediated adaptive immunity. Here, we report the crystal structure of Streptococcus pyogenes Cas1 (SpCas1) in a type II CRISPR-Cas system and characterize its interaction with S. pyogenes Csn2 (SpCsn2). The SpCas1 structure reveals a unique conformational state distinct from type I Cas1 structures, resulting in a more extensive dimerization interface, a more globular overall structure, and a disruption of potential metal-binding sites for catalysis. We demonstrate that SpCas1 directly interacts with SpCsn2, and identify the binding interface and key residues for Cas complex formation. These results provide structural information for a type II Cas1 protein, and lay a foundation for studying multiprotein Cas complexes functioning in type II CRISPR-Cas systems.

  19. CRISPR/Cas9 Based Genome Editing of Penicillium chrysogenum.

    PubMed

    Pohl, C; Kiel, J A K W; Driessen, A J M; Bovenberg, R A L; Nygård, Y

    2016-07-15

    CRISPR/Cas9 based systems have emerged as versatile platforms for precision genome editing in a wide range of organisms. Here we have developed powerful CRISPR/Cas9 tools for marker-based and marker-free genome modifications in Penicillium chrysogenum, a model filamentous fungus and industrially relevant cell factory. The developed CRISPR/Cas9 toolbox is highly flexible and allows editing of new targets with minimal cloning efforts. The Cas9 protein and the sgRNA can be either delivered during transformation, as preassembled CRISPR-Cas9 ribonucleoproteins (RNPs) or expressed from an AMA1 based plasmid within the cell. The direct delivery of the Cas9 protein with in vitro synthesized sgRNA to the cells allows for a transient method for genome engineering that may rapidly be applicable for other filamentous fungi. The expression of Cas9 from an AMA1 based vector was shown to be highly efficient for marker-free gene deletions.

  20. HPCCP/CAS Workshop Proceedings 1998

    NASA Technical Reports Server (NTRS)

    Schulbach, Catherine; Mata, Ellen (Editor); Schulbach, Catherine (Editor)

    1999-01-01

    This publication is a collection of extended abstracts of presentations given at the HPCCP/CAS (High Performance Computing and Communications Program/Computational Aerosciences Project) Workshop held on August 24-26, 1998, at NASA Ames Research Center, Moffett Field, California. The objective of the Workshop was to bring together the aerospace high performance computing community, consisting of airframe and propulsion companies, independent software vendors, university researchers, and government scientists and engineers. The Workshop was sponsored by the HPCCP Office at NASA Ames Research Center. The Workshop consisted of over 40 presentations, including an overview of NASA's High Performance Computing and Communications Program and the Computational Aerosciences Project; ten sessions of papers representative of the high performance computing research conducted within the Program by the aerospace industry, academia, NASA, and other government laboratories; two panel sessions; and a special presentation by Mr. James Bailey.

  1. Adaptation in CRISPR-Cas Systems.

    PubMed

    Sternberg, Samuel H; Richter, Hagen; Charpentier, Emmanuelle; Qimron, Udi

    2016-03-17

    Clustered regularly interspaced short palindromic repeats (CRISPR) and CRISPR-associated (Cas) proteins constitute an adaptive immune system in prokaryotes. The system preserves memories of prior infections by integrating short segments of foreign DNA, termed spacers, into the CRISPR array in a process termed adaptation. During the past 3 years, significant progress has been made on the genetic requirements and molecular mechanisms of adaptation. Here we review these recent advances, with a focus on the experimental approaches that have been developed, the insights they generated, and a proposed mechanism for self- versus non-self-discrimination during the process of spacer selection. We further describe the regulation of adaptation and the protein players involved in this fascinating process that allows bacteria and archaea to harbor adaptive immunity.

  2. Optogenetic stimulation of the auditory pathway

    PubMed Central

    Hernandez, Victor H.; Gehrt, Anna; Reuter, Kirsten; Jing, Zhizi; Jeschke, Marcus; Mendoza Schulz, Alejandro; Hoch, Gerhard; Bartels, Matthias; Vogt, Gerhard; Garnham, Carolyn W.; Yawo, Hiromu; Fukazawa, Yugo; Augustine, George J.; Bamberg, Ernst; Kügler, Sebastian; Salditt, Tim; de Hoz, Livia; Strenzke, Nicola; Moser, Tobias

    2014-01-01

    Auditory prostheses can partially restore speech comprehension when hearing fails. Sound coding with current prostheses is based on electrical stimulation of auditory neurons and has limited frequency resolution due to broad current spread within the cochlea. In contrast, optical stimulation can be spatially confined, which may improve frequency resolution. Here, we used animal models to characterize optogenetic stimulation, which is the optical stimulation of neurons genetically engineered to express the light-gated ion channel channelrhodopsin-2 (ChR2). Optogenetic stimulation of spiral ganglion neurons (SGNs) activated the auditory pathway, as demonstrated by recordings of single neuron and neuronal population responses. Furthermore, optogenetic stimulation of SGNs restored auditory activity in deaf mice. Approximation of the spatial spread of cochlear excitation by recording local field potentials (LFPs) in the inferior colliculus in response to suprathreshold optical, acoustic, and electrical stimuli indicated that optogenetic stimulation achieves better frequency resolution than monopolar electrical stimulation. Virus-mediated expression of a ChR2 variant with greater light sensitivity in SGNs reduced the amount of light required for responses and allowed neuronal spiking following stimulation up to 60 Hz. Our study demonstrates a strategy for optogenetic stimulation of the auditory pathway in rodents and lays the groundwork for future applications of cochlear optogenetics in auditory research and prosthetics. PMID:24509078

  3. Tumeur de Frantz: deux nouveaux cas

    PubMed Central

    Bellarbi, Salma; Sina, Mohamed; Jahid, Ahmed; Zouaidia, Fouad; Bernoussi, Zakia; Mahassini, Najat

    2013-01-01

    A travers cet article, nous détaillons les caractéristiques clinico-pathologiques et discutons l'histogenèse de la tumeur de Frantz. Deux patients opérés pour tumeur de Frantz. Ils ont eu un traitement chirurgical seul. L'étude morphologique était couplée à un examen immuno-histochimique (IHC) utilisant les anticorps anti CD10, anti- vimentine, anti-énolase neuronale spécifique (NSE), anti-synaptophysine, anti-chromogranine A et anti-cytokératine. Un immuno-marquage à l'anti-oestrogène et l'anti-progestérone a été réalisé dans un cas. Il s'agissait d'une femme âgée de 45ans et d'un garçon de 12 ans. Les aspects échographiques et scannographiques étaient non spécifiques. Une exérèse chirurgicale complète a été réalisée dans les deux cas. L'analyse histologique évoquait une tumeur de Frantz. Le diagnostic a été retenu après étude immuno-histohimique. L'évolution était favorable sans récidive avec respectivement un recul de 18 et 16 mois. La tumeur de Frantz est une entité rare. Son diagnostic repose sur l'examen anatomopathologique complété par l'étude immuno-histochimique. Son pronostic est excellent après résection chirurgicale. PMID:23503717

  4. Brain Stimulation Therapies

    MedlinePlus

    ... Magnetic Seizure Therapy Deep Brain Stimulation Additional Resources Brain Stimulation Therapies Overview Brain stimulation therapies can play ... for a shorter recovery time than ECT Deep Brain Stimulation Deep brain stimulation (DBS) was first developed ...

  5. CRISPR-Cas9-Mediated Genome Editing in Leishmania donovani

    PubMed Central

    Zhang, Wen-Wei

    2015-01-01

    ABSTRACT The prokaryotic CRISPR (clustered regularly interspaced short palindromic repeat)-Cas9, an RNA-guided endonuclease, has been shown to mediate efficient genome editing in a wide variety of organisms. In the present study, the CRISPR-Cas9 system has been adapted to Leishmania donovani, a protozoan parasite that causes fatal human visceral leishmaniasis. We introduced the Cas9 nuclease into L. donovani and generated guide RNA (gRNA) expression vectors by using the L. donovani rRNA promoter and the hepatitis delta virus (HDV) ribozyme. It is demonstrated within that L. donovani mainly used homology-directed repair (HDR) and microhomology-mediated end joining (MMEJ) to repair the Cas9 nuclease-created double-strand DNA break (DSB). The nonhomologous end-joining (NHEJ) pathway appears to be absent in L. donovani. With this CRISPR-Cas9 system, it was possible to generate knockouts without selection by insertion of an oligonucleotide donor with stop codons and 25-nucleotide homology arms into the Cas9 cleavage site. Likewise, we disrupted and precisely tagged endogenous genes by inserting a bleomycin drug selection marker and GFP gene into the Cas9 cleavage site. With the use of Hammerhead and HDV ribozymes, a double-gRNA expression vector that further improved gene-targeting efficiency was developed, and it was used to make precise deletion of the 3-kb miltefosine transporter gene (LdMT). In addition, this study identified a novel single point mutation caused by CRISPR-Cas9 in LdMT (M381T) that led to miltefosine resistance, a concern for the only available oral antileishmanial drug. Together, these results demonstrate that the CRISPR-Cas9 system represents an effective genome engineering tool for L. donovani. PMID:26199327

  6. Characterization and evolution of Salmonella CRISPR-Cas systems.

    PubMed

    Shariat, Nikki; Timme, Ruth E; Pettengill, James B; Barrangou, Rodolphe; Dudley, Edward G

    2015-02-01

    Prokaryotic CRISPR-Cas (clustered regularly interspaced short palindromic repeats and CRISPR-associated genes) systems provide adaptive immunity from invasive genetic elements and encompass three essential features: (i) cas genes, (ii) a CRISPR array composed of spacers and direct repeats and (iii) an AT-rich leader sequence upstream of the array. We performed in-depth sequence analysis of the CRISPR-Cas systems in >600 Salmonella, representing four clinically prevalent serovars. Each CRISPR-Cas feature is extremely conserved in the Salmonella, and the CRISPR1 locus is more highly conserved than CRISPR2. Array composition is serovar-specific, although no convincing evidence of recent spacer acquisition against exogenous nucleic acids exists. Only 12% of spacers match phage and plasmid sequences and self-targeting spacers are associated with direct repeat variants. High nucleotide identity (>99.9%) exists across the cas operon among isolates of a single serovar and in some cases this conservation extends across divergent serovars. These observations reflect historical CRISPR-Cas immune activity, showing that this locus has ceased undergoing adaptive events. Intriguingly, the high level of conservation across divergent serovars shows that the genetic integrity of these inactive loci is maintained over time, contrasting with the canonical view that inactive CRISPR loci degenerate over time. This thorough characterization of Salmonella CRISPR-Cas systems presents new insights into Salmonella CRISPR evolution, particularly with respect to cas gene conservation, leader sequences, organization of direct repeats and protospacer matches. Collectively, our data suggest that Salmonella CRISPR-Cas systems are no longer immunogenic; rather, their impressive conservation indicates they may have an alternative function in Salmonella.

  7. Characterization and evolution of Salmonella CRISPR-Cas systems.

    PubMed

    Shariat, Nikki; Timme, Ruth E; Pettengill, James B; Barrangou, Rodolphe; Dudley, Edward G

    2015-02-01

    Prokaryotic CRISPR-Cas (clustered regularly interspaced short palindromic repeats and CRISPR-associated genes) systems provide adaptive immunity from invasive genetic elements and encompass three essential features: (i) cas genes, (ii) a CRISPR array composed of spacers and direct repeats and (iii) an AT-rich leader sequence upstream of the array. We performed in-depth sequence analysis of the CRISPR-Cas systems in >600 Salmonella, representing four clinically prevalent serovars. Each CRISPR-Cas feature is extremely conserved in the Salmonella, and the CRISPR1 locus is more highly conserved than CRISPR2. Array composition is serovar-specific, although no convincing evidence of recent spacer acquisition against exogenous nucleic acids exists. Only 12 % of spacers match phage and plasmid sequences and self-targeting spacers are associated with direct repeat variants. High nucleotide identity (>99.9 %) exists across the cas operon among isolates of a single serovar and in some cases this conservation extends across divergent serovars. These observations reflect historical CRISPR-Cas immune activity, showing that this locus has ceased undergoing adaptive events. Intriguingly, the high level of conservation across divergent serovars shows that the genetic integrity of these inactive loci is maintained over time, contrasting with the canonical view that inactive CRISPR loci degenerate over time. This thorough characterization of Salmonella CRISPR-Cas systems presents new insights into Salmonella CRISPR evolution, particularly with respect to cas gene conservation, leader sequences, organization of direct repeats and protospacer matches. Collectively, our data suggest that Salmonella CRISPR-Cas systems are no longer immunogenic; rather, their impressive conservation indicates they may have an alternative function in Salmonella.

  8. 205 PRODUCTION OF Cas9-EXPRESSING CATTLE USING DNA TRANSPOSON.

    PubMed

    Hahn, S-E; Yum, S-Y; Lee, S-J; Lee, C-I; Kim, H-S; Kim, H-J; Choi, W-J; Lee, J-H; Jang, G

    2016-01-01

    A genome-editing technology, CRISPR/Cas9 system is proved to be a powerful tool for knockout and knock-in in various species. When 2 components [Cas9 and single guide (sg) RNA] are delivered into cells or embryos, the events of gene editing occur. Because Cas9 is essential for every gene editing based on the CRISPR/Cas9 system, some studies reported that efficiency of gene editing would be increased as Cas9 was integrated into cells or animals. Accordingly, if the Cas9-expressing cattle is born, it would be broadly used for gene editing in cattle. For this study, the Cas9 and RFP genes were cloned into the PiggyBac transposon system. PiggyBac-Cas9-RFP and transposase were microinjected into 1436 IVF embryos and 241 blastocysts were formed. Blastocysts with RFP expression accounted for 14.1% of total formed blastocysts. Five blastocysts were selected and transferred into 5 recipient cow (1 embryo per recipient). After gestation periods, 4 transgenic cattle were delivered without any veterinary assistance. From transgenic cattle, ear skin tissue was collected for primary culture. On those primary cells, sgRNA in DNA form for various genes such as PRNP, RB1, and BLG were transfected with 2μg of sgRNA per 5×10(5) cells using electroporation. As expected, every group of each sgRNA delivered was confirmed to be mutated by T7E1 assay. The data demonstrated that, for the first time, transgenic cattle with Cas9 expression were born, grown up to date (age=5 months) and will be a valuable resource for genome editing in cattle.

  9. Cas9 gRNA engineering for genome editing, activation and repression.

    PubMed

    Kiani, Samira; Chavez, Alejandro; Tuttle, Marcelle; Hall, Richard N; Chari, Raj; Ter-Ovanesyan, Dmitry; Qian, Jason; Pruitt, Benjamin W; Beal, Jacob; Vora, Suhani; Buchthal, Joanna; Kowal, Emma J K; Ebrahimkhani, Mohammad R; Collins, James J; Weiss, Ron; Church, George

    2015-11-01

    We demonstrate that by altering the length of Cas9-associated guide RNA (gRNA) we were able to control Cas9 nuclease activity and simultaneously perform genome editing and transcriptional regulation with a single Cas9 protein. We exploited these principles to engineer mammalian synthetic circuits with combined transcriptional regulation and kill functions governed by a single multifunctional Cas9 protein.

  10. Cas9 gRNA engineering for genome editing, activation and repression

    SciTech Connect

    Kiani, Samira; Chavez, Alejandro; Tuttle, Marcelle; Hall, Richard N.; Chari, Raj; Ter-Ovanesyan, Dmitry; Qian, Jason; Pruitt, Benjamin W.; Beal, Jacob; Vora, Suhani; Buchthal, Joanna; Kowal, Emma J. K.; Ebrahimkhani, Mohammad R.; Collins, James J.; Weiss, Ron; Church, George

    2015-09-07

    Here we demonstrate that by altering the length of Cas9-associated guide RNA(gRNA) we were able to control Cas9 nuclease activity and simultaneously perform genome editing and transcriptional regulation with a single Cas9 protein. We exploited these principles to engineer mammalian synthetic circuits with combined transcriptional regulation and kill functions governed by a single multifunctional Cas9 protein.

  11. Grossesse intra murale à propos d'un cas

    PubMed Central

    de Tové, Kofi-Mensa Savi; Salifou, Kabibou; Imorou, Rachidi Sidi; Biaou, Olivier; Boco, Vicentia

    2015-01-01

    La grossesse intra-murale est la variété la plus rare de grossesse extra-utérine. Il s'agit de la localisation de l’œuf dans l’épaisseur du myomètre. En cas de retard diagnostic, l’évolution peut être catastrophique avec rupture utérine et hémorragie cataclysmique. L’échographie permet dans certains cas un diagnostic pré opératoire. Les auteurs rapportent un cas survenu chez une patiente aux antécédents de curetage. PMID:26448812

  12. Orbital period determination in an eclipsing dwarf nova HT Cas

    NASA Astrophysics Data System (ADS)

    Bąkowska, Karolina; Olech, Arkadiusz

    2014-09-01

    HT Cassiopeiae was discovered over seventy years ago (Hoffmeister 1943). Unfortunately, for 35 years this object did not receive any attention, until the eclipses of HT Cas were observed by Bond. After a first analysis, Patterson (1981) called HT Cas "a Rosetta stone among dwarf novae". Since then, the literature on this star is still growing, reaching several dozens of publications. We present an orbital period determination of HT Cas during the November 2010 super-outburst, but also during a longer time span, to check its stability.

  13. Acoustic mapping velocimetry

    NASA Astrophysics Data System (ADS)

    Muste, M.; Baranya, S.; Tsubaki, R.; Kim, D.; Ho, H.; Tsai, H.; Law, D.

    2016-05-01

    Knowledge of sediment dynamics in rivers is of great importance for various practical purposes. Despite its high relevance in riverine environment processes, the monitoring of sediment rates remains a major and challenging task for both suspended and bed load estimation. While the measurement of suspended load is currently an active area of testing with nonintrusive technologies (optical and acoustic), bed load measurement does not mark a similar progress. This paper describes an innovative combination of measurement techniques and analysis protocols that establishes the proof-of-concept for a promising technique, labeled herein Acoustic Mapping Velocimetry (AMV). The technique estimates bed load rates in rivers developing bed forms using a nonintrusive measurements approach. The raw information for AMV is collected with acoustic multibeam technology that in turn provides maps of the bathymetry over longitudinal swaths. As long as the acoustic maps can be acquired relatively quickly and the repetition rate for the mapping is commensurate with the movement of the bed forms, successive acoustic maps capture the progression of the bed form movement. Two-dimensional velocity maps associated with the bed form migration are obtained by implementing algorithms typically used in particle image velocimetry to acoustic maps converted in gray-level images. Furthermore, use of the obtained acoustic and velocity maps in conjunction with analytical formulations (e.g., Exner equation) enables estimation of multidirectional bed load rates over the whole imaged area. This paper presents a validation study of the AMV technique using a set of laboratory experiments.

  14. Acoustic cooling engine

    DOEpatents

    Hofler, Thomas J.; Wheatley, John C.; Swift, Gregory W.; Migliori, Albert

    1988-01-01

    An acoustic cooling engine with improved thermal performance and reduced internal losses comprises a compressible fluid contained in a resonant pressure vessel. The fluid has a substantial thermal expansion coefficient and is capable of supporting an acoustic standing wave. A thermodynamic element has first and second ends and is located in the resonant pressure vessel in thermal communication with the fluid. The thermal response of the thermodynamic element to the acoustic standing wave pumps heat from the second end to the first end. The thermodynamic element permits substantial flow of the fluid through the thermodynamic element. An acoustic driver cyclically drives the fluid with an acoustic standing wave. The driver is at a location of maximum acoustic impedance in the resonant pressure vessel and proximate the first end of the thermodynamic element. A hot heat exchanger is adjacent to and in thermal communication with the first end of the thermodynamic element. The hot heat exchanger conducts heat from the first end to portions of the resonant pressure vessel proximate the hot heat exchanger. The hot heat exchanger permits substantial flow of the fluid through the hot heat exchanger. The resonant pressure vessel can include a housing less than one quarter wavelength in length coupled to a reservoir. The housing can include a reduced diameter portion communicating with the reservoir. The frequency of the acoustic driver can be continuously controlled so as to maintain resonance.

  15. Acoustic sniper localization system

    NASA Astrophysics Data System (ADS)

    Prado, Gervasio; Dhaliwal, Hardave; Martel, Philip O.

    1997-02-01

    Technologies for sniper localization have received increased attention in recent months as American forces have been deployed to various trouble spots around the world. Among the technologies considered for this task acoustics is a natural choice for various reasons. The acoustic signatures of gunshots are loud and distinctive, making them easy to detect even in high noise background environments. Acoustics provides a passive sensing technology with excellent range and non line of sight capabilities. Last but not least, an acoustic sniper location system can be built at a low cost with off the shelf components. Despite its many advantages, the performance of acoustic sensors can degrade under adverse propagation conditions. Localization accuracy, although good, is usually not accurate enough to pinpoint a sniper's location in some scenarios (for example which widow in a building or behind which tree in a grove). For these more demanding missions, the acoustic sensor can be used in conjunction with an infra red imaging system that detects the muzzle blast of the gun. The acoustic system can be used to cue the pointing system of the IR camera in the direction of the shot's source.

  16. Study of Eclipsing Binary and Multiple Systems in OB Associations IV: Cas OB6 Member DN Cas

    NASA Astrophysics Data System (ADS)

    Bakış, V.; Bakış, H.; Bilir, S.; Eker, Z.

    2016-09-01

    An early-type, massive, short-period (Porb=2d.310951) eclipsing spectroscopic binary DN Cas has been re-visited with new spectral and photometric data. The masses and radii of the components have been obtained as M1=19.04± 0.07 M⊙, M2=13.73± 0.05 M⊙ and R1=7.22± 0.06 R⊙, R2=5.79± 0.06 R⊙, respectively. Both components present synchronous rotation (Vrot1=160 km s-1, Vrot2=130 km s-1) with their orbit. Orbital period analysis yielded a physically bound additional component in the system with a minimum mass of M3=0.88 M⊙ orbiting in an eccentric orbit (e = 0.37 ± 0.2) with an orbital period of P 12 = 42 ± 9 yr. High precision absolute parameters of the system allowed us to derive a distance to DN Cas as 1.7 ± 0.2 kpc which locates the system within the borders of the Cas OB6 association (d = 1.8 kpc). The space velocities and the age of DN Cas are in agreement with those of Cas OB6. The age of DN Cas (τ = 3-5 Myr) is found to be 1-2 Myr older than the embedded clusters (IC 1795, IC 1805, and IC 1848) in the Cas OB6 association, which implies a sequential star formation in the association.

  17. Integrase-mediated spacer acquisition during CRISPR-Cas adaptive immunity.

    PubMed

    Nuñez, James K; Lee, Amy S Y; Engelman, Alan; Doudna, Jennifer A

    2015-03-12

    Bacteria and archaea insert spacer sequences acquired from foreign DNAs into CRISPR loci to generate immunological memory. The Escherichia coli Cas1-Cas2 complex mediates spacer acquisition in vivo, but the molecular mechanism of this process is unknown. Here we show that the purified Cas1-Cas2 complex integrates oligonucleotide DNA substrates into acceptor DNA to yield products similar to those generated by retroviral integrases and transposases. Cas1 is the catalytic subunit and Cas2 substantially increases integration activity. Protospacer DNA with free 3'-OH ends and supercoiled target DNA are required, and integration occurs preferentially at the ends of CRISPR repeats and at sequences adjacent to cruciform structures abutting AT-rich regions, similar to the CRISPR leader sequence. Our results demonstrate the Cas1-Cas2 complex to be the minimal machinery that catalyses spacer DNA acquisition and explain the significance of CRISPR repeats in providing sequence and structural specificity for Cas1-Cas2-mediated adaptive immunity.

  18. The room acoustic rendering equation.

    PubMed

    Siltanen, Samuel; Lokki, Tapio; Kiminki, Sami; Savioja, Lauri

    2007-09-01

    An integral equation generalizing a variety of known geometrical room acoustics modeling algorithms is presented. The formulation of the room acoustic rendering equation is adopted from computer graphics. Based on the room acoustic rendering equation, an acoustic radiance transfer method, which can handle both diffuse and nondiffuse reflections, is derived. In a case study, the method is used to predict several acoustic parameters of a room model. The results are compared to measured data of the actual room and to the results given by other acoustics prediction software. It is concluded that the method can predict most acoustic parameters reliably and provides results as accurate as current commercial room acoustic prediction software. Although the presented acoustic radiance transfer method relies on geometrical acoustics, it can be extended to model diffraction and transmission through materials in future.

  19. PRSEUS Acoustic Panel Fabrication

    NASA Technical Reports Server (NTRS)

    Nicolette, Velicki; Yovanof, Nicolette P.; Baraja, Jaime; Mathur, Gopal; Thrash, Patrick; Pickell, Robert

    2011-01-01

    This report describes the development of a novel structural concept, Pultruded Rod Stitched Efficient Unitized Structure (PRSEUS), that addresses the demanding fuselage loading requirements for the Hybrid Wing or Blended Wing Body (BWB) airplane configuration with regards to acoustic response. A PRSEUS panel was designed and fabricated and provided to NASA-LaRC for acoustic response testing in the Structural Acoustics Loads and Transmission (SALT) facility). Preliminary assessments of the sound transmission characteristics of a PRSEUS panel subjected to a representative Hybrid Wing Body (HWB) operating environment were completed for the NASA Environmentally Responsible Aviation (ERA) Program.

  20. Acoustic well cleaner

    DOEpatents

    Maki, Jr., Voldi E.; Sharma, Mukul M.

    1997-01-21

    A method and apparatus are disclosed for cleaning the wellbore and the near wellbore region. A sonde is provided which is adapted to be lowered into a borehole and which includes a plurality of acoustic transducers arranged around the sonde. Electrical power provided by a cable is converted to acoustic energy. The high intensity acoustic energy directed to the borehole wall and into the near wellbore region, redissolves or resuspends the material which is reducing the permeability of the formation and/or restricting flow in the wellbore.

  1. Acoustical heat pumping engine

    DOEpatents

    Wheatley, John C.; Swift, Gregory W.; Migliori, Albert

    1983-08-16

    The disclosure is directed to an acoustical heat pumping engine without moving seals. A tubular housing holds a compressible fluid capable of supporting an acoustical standing wave. An acoustical driver is disposed at one end of the housing and the other end is capped. A second thermodynamic medium is disposed in the housing near to but spaced from the capped end. Heat is pumped along the second thermodynamic medium toward the capped end as a consequence both of the pressure oscillation due to the driver and imperfect thermal contact between the fluid and the second thermodynamic medium.

  2. Acoustical heat pumping engine

    DOEpatents

    Wheatley, J.C.; Swift, G.W.; Migliori, A.

    1983-08-16

    The disclosure is directed to an acoustical heat pumping engine without moving seals. A tubular housing holds a compressible fluid capable of supporting an acoustical standing wave. An acoustical driver is disposed at one end of the housing and the other end is capped. A second thermodynamic medium is disposed in the housing near to but spaced from the capped end. Heat is pumped along the second thermodynamic medium toward the capped end as a consequence both of the pressure oscillation due to the driver and imperfect thermal contact between the fluid and the second thermodynamic medium. 2 figs.

  3. Application of CRISPR/Cas9 for biomedical discoveries.

    PubMed

    Riordan, Sean M; Heruth, Daniel P; Zhang, Li Q; Ye, Shui Qing

    2015-01-01

    The Clustered Regions of Interspersed Palindromic Repeats-Cas9 (CRISPR/Cas9), a viral defense system found in bacteria and archaea, has emerged as a tour de force genome editing tool. The CRISPR/Cas9 system is much easier to customize and optimize because the site selection for DNA cleavage is guided by a short sequence of RNA rather than an engineered protein as in the systems of zinc finger nucleases (ZFN), transcription activator-like effector nucleases (TALEN), and meganucleases. Although it still suffers from some off-target effects, the CRISPR/Cas9 system has been broadly and successfully applied for biomedical discoveries in a number of areas. In this review, we present a brief history and development of the CRISPR system and focus on the application of this genome editing technology for biomedical discoveries. We then present concise concluding remarks and future directions for this fast moving field.

  4. Editing plant genomes with CRISPR/Cas9.

    PubMed

    Belhaj, Khaoula; Chaparro-Garcia, Angela; Kamoun, Sophien; Patron, Nicola J; Nekrasov, Vladimir

    2015-04-01

    CRISPR/Cas9 is a rapidly developing genome editing technology that has been successfully applied in many organisms, including model and crop plants. Cas9, an RNA-guided DNA endonuclease, can be targeted to specific genomic sequences by engineering a separately encoded guide RNA with which it forms a complex. As only a short RNA sequence must be synthesized to confer recognition of a new target, CRISPR/Cas9 is a relatively cheap and easy to implement technology that has proven to be extremely versatile. Remarkably, in some plant species, homozygous knockout mutants can be produced in a single generation. Together with other sequence-specific nucleases, CRISPR/Cas9 is a game-changing technology that is poised to revolutionise basic research and plant breeding.

  5. Application of CRISPR/Cas9 to Autophagy Research.

    PubMed

    O'Prey, J; Sakamaki, J; Baudot, A D; New, M; Van Acker, T; Tooze, S A; Long, J S; Ryan, K M

    2017-01-01

    The ability to efficiently modulate autophagy activity is paramount in the study of the field. Conventional broad-range autophagy inhibitors and genetic manipulation using RNA interference (RNAi), although widely used in autophagy research, are often limited in specificity or efficacy. In this chapter, we address the problems of conventional autophagy-modulating tools by exploring the use of three different CRISPR/Cas9 systems to abrogate autophagy in numerous human and mouse cell lines. The first system generates cell lines constitutively deleted of ATG5 or ATG7 whereas the second and third systems express a Tet-On inducible-Cas9 that enables regulated deletion of ATG5 or ATG7. We observed the efficiency of autophagy inhibition using the CRISPR/Cas9 strategy to surpass that of RNAi, and successfully generated cells with complete and sustained autophagy disruption through the CRISPR/Cas9 technology.

  6. CRISPR-Cas systems: Prokaryotes upgrade to adaptive immunity.

    PubMed

    Barrangou, Rodolphe; Marraffini, Luciano A

    2014-04-24

    Clustered regularly interspaced short palindromic repeats (CRISPR), and associated proteins (Cas) comprise the CRISPR-Cas system, which confers adaptive immunity against exogenic elements in many bacteria and most archaea. CRISPR-mediated immunization occurs through the uptake of DNA from invasive genetic elements such as plasmids and viruses, followed by its integration into CRISPR loci. These loci are subsequently transcribed and processed into small interfering RNAs that guide nucleases for specific cleavage of complementary sequences. Conceptually, CRISPR-Cas shares functional features with the mammalian adaptive immune system, while also exhibiting characteristics of Lamarckian evolution. Because immune markers spliced from exogenous agents are integrated iteratively in CRISPR loci, they constitute a genetic record of vaccination events and reflect environmental conditions and changes over time. Cas endonucleases, which can be reprogrammed by small guide RNAs have shown unprecedented potential and flexibility for genome editing and can be repurposed for numerous DNA targeting applications including transcriptional control.

  7. 48 CFR 9903.201-1 - CAS applicability.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... following categories of contracts and subcontracts are exempt from all CAS requirements: (1) Sealed bid... subcontracts awarded on the basis of adequate price competition without submission of cost or pricing data....

  8. Engineering the Caenorhabditis elegans genome with CRISPR/Cas9.

    PubMed

    Waaijers, Selma; Boxem, Mike

    2014-08-01

    The development in early 2013 of CRISPR/Cas9-based genome engineering promises to dramatically advance our ability to alter the genomes of model systems at will. A single, easily produced targeting RNA guides the Cas9 endonuclease to a specific DNA sequence where it creates a double strand break. Imprecise repair of the break can yield mutations, while homologous recombination with a repair template can be used to effect specific changes to the genome. The tremendous potential of this system led several groups to independently adapt it for use in Caenorhabditiselegans, where it was successfully used to generate mutations and to create tailored genome changes through homologous recombination. Here, we review the different approaches taken to adapt CRISPR/Cas9 for C. elegans, and provide practical guidelines for CRISPR/Cas9-based genome engineering.

  9. 48 CFR 970.3002-1 - CAS applicability.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... SUPPLEMENTARY REGULATIONS DOE MANAGEMENT AND OPERATING CONTRACTS Cost Accounting Standards Administration 970.3002-1 CAS applicability. The provisions of 48 CFR part 30 and 48 CFR chapter 99 (FAR Appendix)...

  10. The structural biology of CRISPR-Cas systems.

    PubMed

    Jiang, Fuguo; Doudna, Jennifer A

    2015-02-01

    Prokaryotic CRISPR-Cas genomic loci encode RNA-mediated adaptive immune systems that bear some functional similarities with eukaryotic RNA interference. Acquired and heritable immunity against bacteriophage and plasmids begins with integration of ∼30 base pair foreign DNA sequences into the host genome. CRISPR-derived transcripts assemble with CRISPR-associated (Cas) proteins to target complementary nucleic acids for degradation. Here we review recent advances in the structural biology of these targeting complexes, with a focus on structural studies of the multisubunit Type I CRISPR RNA-guided surveillance and the Cas9 DNA endonuclease found in Type II CRISPR-Cas systems. These complexes have distinct structures that are each capable of site-specific double-stranded DNA binding and local helix unwinding.

  11. Kinetic Enhancement of Raman Backscatter, and Electron Acoustic Thomson Scatter

    SciTech Connect

    Strozzi, D J; Williams, E A; Langdon, A B; Bers, A

    2006-09-01

    1-D Eulerian Vlasov-Maxwell simulations are presented which show kinetic enhancement of stimulated Raman backscatter (SRBS) due to electron trapping in regimes of heavy linear Landau damping. The conventional Raman Langmuir wave is transformed into a set of beam acoustic modes [L. Yin et al., Phys. Rev. E 73, 025401 (2006)]. For the first time, a low phase velocity electron acoustic wave (EAW) is seen developing from the self-consistent Raman physics. Backscatter of the pump laser off the EAW fluctuations is reported and referred to as electron acoustic Thomson scatter. This light is similar in wavelength to, although much lower in amplitude than, the reflected light between the pump and SRBS wavelengths observed in single hot spot experiments, and previously interpreted as stimulated electron acoustic scatter [D. S. Montgomery et al., Phys. Rev. Lett. 87, 155001 (2001)]. The EAW observed in our simulations is strongest well below the phase-matched frequency for electron acoustic scatter, and therefore the EAW is not produced by it. The beating of different beam acoustic modes is proposed as the EAW excitation mechanism, and is called beam acoustic decay. Supporting evidence for this process, including bispectral analysis, is presented. The linear electrostatic modes, found by projecting the numerical distribution function onto a Gauss-Hermite basis, include beam acoustic modes (some of which are unstable even without parametric coupling to light waves) and a strongly-damped EAW similar to the observed one. This linear EAW results from non-Maxwellian features in the electron distribution, rather than nonlinearity due to electron trapping.

  12. Stimulated Brillouin scatter in a magnetized ionospheric plasma.

    PubMed

    Bernhardt, P A; Selcher, C A; Lehmberg, R H; Rodriguez, S P; Thomason, J F; Groves, K M; McCarrick, M J; Frazer, G J

    2010-04-23

    High power electromagnetic waves transmitted from the HAARP facility in Alaska can excite low-frequency electrostatic waves by magnetized stimulated Brillouin scatter. Either an ion-acoustic wave with a frequency less than the ion cyclotron frequency (f(CI)) or an electrostatic ion cyclotron (EIC) wave just above f(CI) can be produced. The coupled equations describing the magnetized stimulated Brillouin scatter instability show that the production of both ion-acoustic and EIC waves is strongly influenced by the wave propagation relative to the background magnetic field. Experimental observations of stimulated electromagnetic emissions using the HAARP transmitter have confirmed that only ion-acoustic waves are excited for propagation along the magnetic zenith and that EIC waves can only be detected with oblique propagation angles. The ion composition can be obtained from the measured EIC frequency.

  13. Stimulated Brillouin Scatter in a Magnetized Ionospheric Plasma

    SciTech Connect

    Bernhardt, P. A.; Selcher, C. A.; Lehmberg, R. H.; Rodriguez, S. P.; Thomason, J. F.; Groves, K. M.; McCarrick, M. J.; Frazer, G. J.

    2010-04-23

    High power electromagnetic waves transmitted from the HAARP facility in Alaska can excite low-frequency electrostatic waves by magnetized stimulated Brillouin scatter. Either an ion-acoustic wave with a frequency less than the ion cyclotron frequency (f{sub CI}) or an electrostatic ion cyclotron (EIC) wave just above f{sub CI} can be produced. The coupled equations describing the magnetized stimulated Brillouin scatter instability show that the production of both ion-acoustic and EIC waves is strongly influenced by the wave propagation relative to the background magnetic field. Experimental observations of stimulated electromagnetic emissions using the HAARP transmitter have confirmed that only ion-acoustic waves are excited for propagation along the magnetic zenith and that EIC waves can only be detected with oblique propagation angles. The ion composition can be obtained from the measured EIC frequency.

  14. Acoustic imaging system

    DOEpatents

    Smith, Richard W.

    1979-01-01

    An acoustic imaging system for displaying an object viewed by a moving array of transducers as the array is pivoted about a fixed point within a given plane. A plurality of transducers are fixedly positioned and equally spaced within a laterally extending array and operatively directed to transmit and receive acoustic signals along substantially parallel transmission paths. The transducers are sequentially activated along the array to transmit and receive acoustic signals according to a preestablished sequence. Means are provided for generating output voltages for each reception of an acoustic signal, corresponding to the coordinate position of the object viewed as the array is pivoted. Receptions from each of the transducers are presented on the same display at coordinates corresponding to the actual position of the object viewed to form a plane view of the object scanned.

  15. Compact acoustic refrigerator

    SciTech Connect

    Bennett, G.A.

    1991-12-31

    This invention is comprised of a compact acoustic refrigeration system that actively cools components, e.g., electrical circuits, in a borehole environment. An acoustic engine includes first thermodynamic elements for generating a standing acoustic wave in a selected medium. An acoustic refrigerator includes second thermodynamic elements located in the standing wave for generating a relatively cold temperature at a first end of the second thermodynamic elements and a relatively hot temperature at a second end of the second thermodynamic elements. A resonator volume cooperates with the first and second thermodynamic elements to support the standing wave. To accommodate the high heat fluxes required for heat transfer to/from the first and second thermodynamic elements, first heat pipes transfer heat from the heat load to the second thermodynamic elements and second heat pipes transfer heat from first and second thermodynamic elements to the borehole environment.

  16. Acoustic borehole logging

    SciTech Connect

    Medlin, W.L.; Manzi, S.J.

    1990-10-09

    This patent describes an acoustic borehole logging method. It comprises traversing a borehole with a borehole logging tool containing a transmitter of acoustic energy having a free-field frequency spectrum with at least one characteristic resonant frequency of vibration and spaced-apart receiver, repeatedly exciting the transmitter with a swept frequency tone burst of a duration sufficiently greater than the travel time of acoustic energy between the transmitter and the receiver to allow borehole cavity resonances to be established within the borehole cavity formed between the borehole logging tool and the borehole wall, detecting acoustic energy amplitude modulated by the borehole cavity resonances with the spaced-apart receiver, and recording an amplitude verses frequency output of the receiver in correlation with depth as a log of the borehole frequency spectrum representative of the subsurface formation comprising the borehole wall.

  17. Acoustic imaging system

    NASA Technical Reports Server (NTRS)

    Kendall, J. M., Jr.

    1977-01-01

    Tool detects noise sources by scanning sound "scene" and displaying relative location of noise-producing elements in area. System consists of ellipsoidal acoustic mirror and microphone and a display device.

  18. Compact acoustic refrigerator

    DOEpatents

    Bennett, G.A.

    1992-11-24

    A compact acoustic refrigeration system actively cools components, e.g., electrical circuits, in a borehole environment. An acoustic engine includes first thermodynamic elements for generating a standing acoustic wave in a selected medium. An acoustic refrigerator includes second thermodynamic elements located in the standing wave for generating a relatively cold temperature at a first end of the second thermodynamic elements and a relatively hot temperature at a second end of the second thermodynamic elements. A resonator volume cooperates with the first and second thermodynamic elements to support the standing wave. To accommodate the high heat fluxes required for heat transfer to/from the first and second thermodynamic elements, first heat pipes transfer heat from the heat load to the second thermodynamic elements and second heat pipes transfer heat from first and second thermodynamic elements to the borehole environment. 18 figs.

  19. Compact acoustic refrigerator

    DOEpatents

    Bennett, Gloria A.

    1992-01-01

    A compact acoustic refrigeration system actively cools components, e.g., electrical circuits (22), in a borehole environment. An acoustic engine (12, 14) includes first thermodynamic elements (12) for generating a standing acoustic wave in a selected medium. An acoustic refrigerator (16, 26, 28) includes second thermodynamic elements (16) located in the standing wave for generating a relatively cold temperature at a first end of the second thermodynamic elements (16) and a relatively hot temperature at a second end of the second thermodynamic elements (16). A resonator volume (18) cooperates with the first and second thermodynamic elements (12, 16) to support the standing wave. To accommodate the high heat fluxes required for heat transfer to/from the first and second thermodynamic elements (12, 16), first heat pipes (24, 26) transfer heat from the heat load (22) to the second thermodynamic elements (16) and second heat pipes (28, 32) transfer heat from first and second thermodynamic elements (12, 16) to the borehole environment.

  20. Acoustic bubble traps

    NASA Astrophysics Data System (ADS)

    Geisler, Reinhard; Kurz, Thomas; Lauterborn, Werner

    2000-07-01

    A small, oscillating bubble in a liquid can be trapped in the antinode of an acoustic standing wave field. Bubble stability is required for the study of single bubble sonoluminescence (SBSL). The properties of the acoustic resonator are essential for the stable trapping of sonoluminescing bubbles. Resonators can be chosen according to the intended application: size and geometry can be varied in a wide range. In this work, the acoustic responses of different resonators were measured by means of holographic interferometry, hydrophones and a laser vibrometer. Also, high-speed photography was used to observe the bubble dynamics. Several single, stable sonoluminescent bubbles were trapped simultaneously within an acoustic resonator in the pressure antinodes of a higher harmonic mode (few bubble sonoluminescence, FBSL).

  1. Department of Cybernetic Acoustics

    NASA Astrophysics Data System (ADS)

    The development of the theory, instrumentation and applications of methods and systems for the measurement, analysis, processing and synthesis of acoustic signals within the audio frequency range, particularly of the speech signal and the vibro-acoustic signal emitted by technical and industrial equipments treated as noise and vibration sources was discussed. The research work, both theoretical and experimental, aims at applications in various branches of science, and medicine, such as: acoustical diagnostics and phoniatric rehabilitation of pathological and postoperative states of the speech organ; bilateral ""man-machine'' speech communication based on the analysis, recognition and synthesis of the speech signal; vibro-acoustical diagnostics and continuous monitoring of the state of machines, technical equipments and technological processes.

  2. Basic Linear Acoustics

    NASA Astrophysics Data System (ADS)

    Pierce, Alan D.

    This chapter deals with the physical and mathematical aspects of sound when the disturbances are, in some sense, small. Acoustics is usually concerned with small-amplitude phenomena, and consequently a linear description is usually acoustics applicable. Disturbances are governed by the properties of the medium in which they occur, and the governing equations are the equations of continuum mechanics, which apply equally to gases, liquids, and solids. These include the mass, momentum, and energy equations, as well as thermodynamic principles. The viscosity and thermal conduction enter into the versions of these equations that apply to fluids. Fluids of typical great interest are air and sea water, and consequently this chapter includes a summary of their relevant acoustic properties. The foundation is also laid for the consideration of acoustic waves in elastic solids, suspensions, bubbly liquids, and porous media.

  3. Acoustics lecturing in Mexico

    NASA Astrophysics Data System (ADS)

    Beristain, Sergio

    2002-11-01

    Some thirty years ago acoustics lecturing started in Mexico at the National Polytechnic Institute in Mexico City, as part of the Bachelor of Science degree in Communications and Electronics Engineering curricula, including the widest program on this field in the whole country. This program has been producing acoustics specialists ever since. Nowadays many universities and superior education institutions around the country are teaching students at the B.Sc. level and postgraduate level many topics related to acoustics, such as Architectural Acoustics, Seismology, Mechanical Vibrations, Noise Control, Audio, Audiology, Music, etc. Also many institutions have started research programs in related fields, with participation of medical doctors, psychologists, musicians, engineers, etc. Details will be given on particular topics and development.

  4. Acoustic Neuroma Association

    MedlinePlus

    ... this sponsor... Platinum Sponsor More from this sponsor... Gold Sponsor University of Colorado Acoustic Neuroma Program Rocky Mountain Gamma Knife Center More from this sponsor... Gold Sponsor NYU Langone Medical Center Departments of Neurosurgery ...

  5. Stimulated Brillouin scattering enhancement in silicon inverse opal waveguides

    NASA Astrophysics Data System (ADS)

    Smith, M. J. A.; Wolff, C.; de Sterke, C. M.; Lapine, M.; Kuhlmey, B. T.; Poulton, C. G.

    2016-10-01

    Silicon is an ideal material for on-chip applications, however its poor acoustic properties limit its performance for important optoacoustic applications, particularly for Stimulated Brillouin Scattering (SBS). We theoretically show that silicon inverse opals exhibit a strongly improved acoustic performance that enhances the bulk SBS gain coefficient by more than two orders of magnitude. We also design a waveguide that incorporates silicon inverse opals and which has SBS gain values that are comparable with chalcogenide glass waveguides. This research opens new directions for opto-acoustic applications in on-chip material systems.

  6. Wavefront modulation and subwavelength diffractive acoustics with an acoustic metasurface

    NASA Astrophysics Data System (ADS)

    Xie, Yangbo; Wang, Wenqi; Chen, Huanyang; Konneker, Adam; Popa, Bogdan-Ioan; Cummer, Steven A.

    2014-11-01

    Metasurfaces are a family of novel wavefront-shaping devices with planar profile and subwavelength thickness. Acoustic metasurfaces with ultralow profile yet extraordinary wave manipulating properties would be highly desirable for improving the performance of many acoustic wave-based applications. However, designing acoustic metasurfaces with similar functionality to their electromagnetic counterparts remains challenging with traditional metamaterial design approaches. Here we present a design and realization of an acoustic metasurface based on tapered labyrinthine metamaterials. The demonstrated metasurface can not only steer an acoustic beam as expected from the generalized Snell’s law, but also exhibits various unique properties such as conversion from propagating wave to surface mode, extraordinary beam-steering and apparent negative refraction through higher-order diffraction. Such designer acoustic metasurfaces provide a new design methodology for acoustic signal modulation devices and may be useful for applications such as acoustic imaging, beam steering, ultrasound lens design and acoustic surface wave-based applications.

  7. Wavefront modulation and subwavelength diffractive acoustics with an acoustic metasurface.

    PubMed

    Xie, Yangbo; Wang, Wenqi; Chen, Huanyang; Konneker, Adam; Popa, Bogdan-Ioan; Cummer, Steven A

    2014-11-24

    Metasurfaces are a family of novel wavefront-shaping devices with planar profile and subwavelength thickness. Acoustic metasurfaces with ultralow profile yet extraordinary wave manipulating properties would be highly desirable for improving the performance of many acoustic wave-based applications. However, designing acoustic metasurfaces with similar functionality to their electromagnetic counterparts remains challenging with traditional metamaterial design approaches. Here we present a design and realization of an acoustic metasurface based on tapered labyrinthine metamaterials. The demonstrated metasurface can not only steer an acoustic beam as expected from the generalized Snell's law, but also exhibits various unique properties such as conversion from propagating wave to surface mode, extraordinary beam-steering and apparent negative refraction through higher-order diffraction. Such designer acoustic metasurfaces provide a new design methodology for acoustic signal modulation devices and may be useful for applications such as acoustic imaging, beam steering, ultrasound lens design and acoustic surface wave-based applications.

  8. Potential pitfalls of CRISPR/Cas9-mediated genome editing.

    PubMed

    Peng, Rongxue; Lin, Guigao; Li, Jinming

    2016-04-01

    Recently, a novel technique named the clustered regularly interspaced short palindromic repeat (CRISPR)/CRISPR-associated protein (Cas)9 system has been rapidly developed. This genome editing tool has improved our ability tremendously with respect to exploring the pathogenesis of diseases and correcting disease mutations, as well as phenotypes. With a short guide RNA, Cas9 can be precisely directed to target sites, and functions as an endonuclease to efficiently produce breaks in DNA double strands. Over the past 30 years, CRISPR has evolved from the 'curious sequences of unknown biological function' into a promising genome editing tool. As a result of the incessant development in the CRISPR/Cas9 system, Cas9 co-expressed with custom guide RNAs has been successfully used in a variety of cells and organisms. This genome editing technology can also be applied to synthetic biology, functional genomic screening, transcriptional modulation and gene therapy. However, although CRISPR/Cas9 has a broad range of action in science, there are several aspects that affect its efficiency and specificity, including Cas9 activity, target site selection and short guide RNA design, delivery methods, off-target effects and the incidence of homology-directed repair. In the present review, we highlight the factors that affect the utilization of CRISPR/Cas9, as well as possible strategies for handling any problems. Addressing these issues will allow us to take better advantage of this technique. In addition, we also review the history and rapid development of the CRISPR/Cas system from the time of its initial discovery in 2012.

  9. Calibrated Ancillary System (CAS) user's guide, volume 7

    NASA Technical Reports Server (NTRS)

    1986-01-01

    The Calibrated Ancillary System (CAS) provides real-time calibrated parameters from the orbiter downlink (ancillary data) to the Goddard Space Flight Center (GSFC). This user's guide contains the introduction to the equipment, operation, general procedures, and specific procedures of CAS. Volume 7 describes the data flow engineer (DFE) user mission planning procedures which include instructions for processing the SDT/TDT (shuttle data tape/telemetry descriptor tape).

  10. Calibrated Ancillary System (CAS) user's guide, volume 5

    NASA Technical Reports Server (NTRS)

    1986-01-01

    The Calibrated Ancillary System (CAS) provides real-time parameters from the orbiter downlink (ancillary data) to the Goddard Space Flight Center (GSFC). This user's guide contains the introduction to the equipment, operation, general procedures, and specific procedures of CAS. Volume 5 describes the testing user mission planning procedures including the bulletin board system and ancillary products procedures. Instructions for viewing the SDT/TDT (shuttle data tape/telemetry descriptor tape) data base and the file management menu are also given.

  11. Calibrated Ancillary System (CAS) user's guide, volume 6

    NASA Technical Reports Server (NTRS)

    1986-01-01

    The Calibrated Ancillary System (CAS) provides real-time calibrated parameters from the orbiter downlink (ancillary data) to the Goddard Space Flight Center (GSFC). This user's guide contains the introduction to the equipment, operation, general procedures, and specific procedures of CAS. Volume 6 describes ancillary products procedures, enhancement menu and processing task procedures for SDT/TDT (shuttle data tape/telemetry descriptor tape), database errors and network data driver (NDD) product menu procedures, and utility menu procedures.

  12. Calibrated Ancillary System (CAS) user's guide, volume 4

    NASA Technical Reports Server (NTRS)

    1986-01-01

    The Calibrated Ancillary System (CAS) provides real-time calibrated parameters from the orbiter downlink (ancillary data) to the Goddard Space Flight Center (GSFC). This user's guide contains the introduction to the equipment, operation, general procedures, and specific procedures of the CAS. Volume 4 presents the GSFC user mission planning procedures covering the mission planning main menu, bulletin board system, ancillary products menu, utility menu procedures, and ancillary support files procedures.

  13. Ocean Acoustic Observatory Federation

    DTIC Science & Technology

    2001-09-30

    J., C. G. Fox, and F. K. Duennebier, Hydroacoustic detection of submarine landslides on Kilauea volcano , Geophys. Res. Lett., vol. 28, 1811-1814...acoustic tomography experiments in the vicinity of coastal North America, • Monitor, in real time, marine mammals, earthquakes and volcanoes in the...distances, coastal tomography and thermometry, and earthquakes and volcanoes in the northern Pacific. APPROACH The members of the Ocean Acoustic

  14. Numerical Techniques in Acoustics

    NASA Technical Reports Server (NTRS)

    Baumeister, K. J. (Compiler)

    1985-01-01

    This is the compilation of abstracts of the Numerical Techniques in Acoustics Forum held at the ASME's Winter Annual Meeting. This forum was for informal presentation and information exchange of ongoing acoustic work in finite elements, finite difference, boundary elements and other numerical approaches. As part of this forum, it was intended to allow the participants time to raise questions on unresolved problems and to generate discussions on possible approaches and methods of solution.

  15. The neonatal acoustic reflex.

    PubMed

    Weatherby, L A; Bennett, M J

    1980-01-01

    Probe tones from 220 Hz to 2 000 Hz were used to measure the static and dynamic acoustic impedance of 44 neonates. Acoustic reflex thresholds to broad band noise were obtained from every neonate tested when employing the higher frequency probe tones. The reflex threshold levels measured are similar to those of adults. The static impedance values are discussed to give a possible explanation of why reflex thresholds cannot be detected using conventional 220 Hz impedance bridges.

  16. Directional Acoustic Density Sensor

    DTIC Science & Technology

    2010-09-13

    fluctuations of fluid density at a point . (2) DESCRIPTION OF THE PRIOR ART [0004] Conventional vector sensors measure particle velocity, v (vx,Vytvz...dipole-type or first order sensor that is realized by measuring particle velocity at a point , (which is the vector sensor sensing approach for...underwater sensors), or by measuring the gradient of the acoustic pressure at two closely spaced (less than the wavelength of an acoustic wave) points as it

  17. Rational design of a split-Cas9 enzyme complex

    SciTech Connect

    Wright, Addison V.; Sternberg, Samuel H.; Taylor, David W.; Staahl, Brett T.; Bardales, Jorge A.; Kornfeld, Jack E.; Doudna, Jennifer A.

    2015-02-23

    Cas9, an RNA-guided DNA endonuclease found in clustered regularly interspaced short palindromic repeats (CRISPR) bacterial immune systems, is a versatile tool for genome editing, transcriptional regulation, and cellular imaging applications. Structures of Streptococcus pyogenes Cas9 alone or bound to single-guide RNA (sgRNA) and target DNA revealed a bilobed protein architecture that undergoes major conformational changes upon guide RNA and DNA binding. To investigate the molecular determinants and relevance of the interlobe rearrangement for target recognition and cleavage, we designed a split-Cas9 enzyme in which the nuclease lobe and α-helical lobe are expressed as separate polypeptides. The lobes do not interact on their own, the sgRNA recruits them into a ternary complex that recapitulates the activity of full-length Cas9 and catalyzes site-specific DNA cleavage. The use of a modified sgRNA abrogates split-Cas9 activity by preventing dimerization, allowing for the development of an inducible dimerization system. We propose that split-Cas9 can act as a highly regulatable platform for genome-engineering applications.

  18. Rational design of a split-Cas9 enzyme complex

    DOE PAGES

    Wright, Addison V.; Sternberg, Samuel H.; Taylor, David W.; ...

    2015-02-23

    Cas9, an RNA-guided DNA endonuclease found in clustered regularly interspaced short palindromic repeats (CRISPR) bacterial immune systems, is a versatile tool for genome editing, transcriptional regulation, and cellular imaging applications. Structures of Streptococcus pyogenes Cas9 alone or bound to single-guide RNA (sgRNA) and target DNA revealed a bilobed protein architecture that undergoes major conformational changes upon guide RNA and DNA binding. To investigate the molecular determinants and relevance of the interlobe rearrangement for target recognition and cleavage, we designed a split-Cas9 enzyme in which the nuclease lobe and α-helical lobe are expressed as separate polypeptides. The lobes do not interactmore » on their own, the sgRNA recruits them into a ternary complex that recapitulates the activity of full-length Cas9 and catalyzes site-specific DNA cleavage. The use of a modified sgRNA abrogates split-Cas9 activity by preventing dimerization, allowing for the development of an inducible dimerization system. We propose that split-Cas9 can act as a highly regulatable platform for genome-engineering applications.« less

  19. Rational design of a split-Cas9 enzyme complex.

    PubMed

    Wright, Addison V; Sternberg, Samuel H; Taylor, David W; Staahl, Brett T; Bardales, Jorge A; Kornfeld, Jack E; Doudna, Jennifer A

    2015-03-10

    Cas9, an RNA-guided DNA endonuclease found in clustered regularly interspaced short palindromic repeats (CRISPR) bacterial immune systems, is a versatile tool for genome editing, transcriptional regulation, and cellular imaging applications. Structures of Streptococcus pyogenes Cas9 alone or bound to single-guide RNA (sgRNA) and target DNA revealed a bilobed protein architecture that undergoes major conformational changes upon guide RNA and DNA binding. To investigate the molecular determinants and relevance of the interlobe rearrangement for target recognition and cleavage, we designed a split-Cas9 enzyme in which the nuclease lobe and α-helical lobe are expressed as separate polypeptides. Although the lobes do not interact on their own, the sgRNA recruits them into a ternary complex that recapitulates the activity of full-length Cas9 and catalyzes site-specific DNA cleavage. The use of a modified sgRNA abrogates split-Cas9 activity by preventing dimerization, allowing for the development of an inducible dimerization system. We propose that split-Cas9 can act as a highly regulatable platform for genome-engineering applications.

  20. Ocean acoustic reverberation tomography.

    PubMed

    Dunn, Robert A

    2015-12-01

    Seismic wide-angle imaging using ship-towed acoustic sources and networks of ocean bottom seismographs is a common technique for exploring earth structure beneath the oceans. In these studies, the recorded data are dominated by acoustic waves propagating as reverberations in the water column. For surveys with a small receiver spacing (e.g., <10 km), the acoustic wave field densely samples properties of the water column over the width of the receiver array. A method, referred to as ocean acoustic reverberation tomography, is developed that uses the travel times of direct and reflected waves to image ocean acoustic structure. Reverberation tomography offers an alternative approach for determining the structure of the oceans and advancing the understanding of ocean heat content and mixing processes. The technique has the potential for revealing small-scale ocean thermal structure over the entire vertical height of the water column and along long survey profiles or across three-dimensional volumes of the ocean. For realistic experimental geometries and data noise levels, the method can produce images of ocean sound speed on a smaller scale than traditional acoustic tomography.

  1. Measuring acoustic habitats.

    PubMed

    Merchant, Nathan D; Fristrup, Kurt M; Johnson, Mark P; Tyack, Peter L; Witt, Matthew J; Blondel, Philippe; Parks, Susan E

    2015-03-01

    1. Many organisms depend on sound for communication, predator/prey detection and navigation. The acoustic environment can therefore play an important role in ecosystem dynamics and evolution. A growing number of studies are documenting acoustic habitats and their influences on animal development, behaviour, physiology and spatial ecology, which has led to increasing demand for passive acoustic monitoring (PAM) expertise in the life sciences. However, as yet, there has been no synthesis of data processing methods for acoustic habitat monitoring, which presents an unnecessary obstacle to would-be PAM analysts. 2. Here, we review the signal processing techniques needed to produce calibrated measurements of terrestrial and aquatic acoustic habitats. We include a supplemental tutorial and template computer codes in matlab and r, which give detailed guidance on how to produce calibrated spectrograms and statistical analyses of sound levels. Key metrics and terminology for the characterisation of biotic, abiotic and anthropogenic sound are covered, and their application to relevant monitoring scenarios is illustrated through example data sets. To inform study design and hardware selection, we also include an up-to-date overview of terrestrial and aquatic PAM instruments. 3. Monitoring of acoustic habitats at large spatiotemporal scales is becoming possible through recent advances in PAM technology. This will enhance our understanding of the role of sound in the spatial ecology of acoustically sensitive species and inform spatial planning to mitigate the rising influence of anthropogenic noise in these ecosystems. As we demonstrate in this work, progress in these areas will depend upon the application of consistent and appropriate PAM methodologies.

  2. Measuring acoustic habitats

    PubMed Central

    Merchant, Nathan D; Fristrup, Kurt M; Johnson, Mark P; Tyack, Peter L; Witt, Matthew J; Blondel, Philippe; Parks, Susan E

    2015-01-01

    1. Many organisms depend on sound for communication, predator/prey detection and navigation. The acoustic environment can therefore play an important role in ecosystem dynamics and evolution. A growing number of studies are documenting acoustic habitats and their influences on animal development, behaviour, physiology and spatial ecology, which has led to increasing demand for passive acoustic monitoring (PAM) expertise in the life sciences. However, as yet, there has been no synthesis of data processing methods for acoustic habitat monitoring, which presents an unnecessary obstacle to would-be PAM analysts. 2. Here, we review the signal processing techniques needed to produce calibrated measurements of terrestrial and aquatic acoustic habitats. We include a supplemental tutorial and template computer codes in matlab and r, which give detailed guidance on how to produce calibrated spectrograms and statistical analyses of sound levels. Key metrics and terminology for the characterisation of biotic, abiotic and anthropogenic sound are covered, and their application to relevant monitoring scenarios is illustrated through example data sets. To inform study design and hardware selection, we also include an up-to-date overview of terrestrial and aquatic PAM instruments. 3. Monitoring of acoustic habitats at large spatiotemporal scales is becoming possible through recent advances in PAM technology. This will enhance our understanding of the role of sound in the spatial ecology of acoustically sensitive species and inform spatial planning to mitigate the rising influence of anthropogenic noise in these ecosystems. As we demonstrate in this work, progress in these areas will depend upon the application of consistent and appropriate PAM methodologies. PMID:25954500

  3. Cas9 in Genetically Modified Food Is Unlikely to Cause Food Allergy.

    PubMed

    Nakajima, Osamu; Nishimaki-Mogami, Tomoko; Kondo, Kazunari

    2016-01-01

    Genome editing has undergone rapid development during the last three years. It is anticipated that genetically modified organisms (GMOs) for food purposes will be widely produced using the clustered regularly interspaced short palindromic repeat/Cas9 (CRISPR)/Cas9 system in the near future. However, the Cas9 gene may then enter the genomes of GMOs for food if the breeding process is not strictly managed, which could lead to the Cas9 protein or associated peptides being produced within these organisms. A variety of peptides could theoretically be produced from the Cas9 gene by using open reading frames different from that of Cas9 in the GMOs. In this study, Cas9 and the peptides potentially encoded by Cas9 genes were studied regarding their immunogenicity, in terms of the digestibility of Cas9 and the homology of the peptides to food allergens. First, the digestibility and thermal stability of Cas9 were studied. Digestibility was tested with natural or heat-denatured Cas9 in simulated gastric fluid in vitro. The two types of Cas9 were digested rapidly. Cas9 was also gradually degraded during heat treatment. Second, the peptides potentially encoded by Cas9 genes were examined for their homology to food allergens. Specifically, an 8-mer exact match search and a sliding 80-mer window search were performed using allergen databases. One of the peptides was found to have homology with a food allergen.

  4. Tyrosine phosphorylation within the SH3 domain regulates CAS subcellular localization, cell migration, and invasiveness.

    PubMed

    Janoštiak, Radoslav; Tolde, Ondřej; Brůhová, Zuzana; Novotný, Marian; Hanks, Steven K; Rösel, Daniel; Brábek, Jan

    2011-11-01

    Crk-associated substrate (CAS) is a major tyrosine-phosphorylated protein in cells transformed by v-crk and v-src oncogenes and plays an important role in invasiveness of Src-transformed cells. A novel phosphorylation site on CAS, Tyr-12 (Y12) within the ligand-binding hydrophobic pocket of the CAS SH3 domain, was identified and found to be enriched in Src-transformed cells and invasive human carcinoma cells. To study the biological significance of CAS Y12 phosphorylation, phosphomimicking Y12E and nonphosphorylatable Y12F mutants of CAS were studied. The phosphomimicking mutation decreased interaction of the CAS SH3 domain with focal adhesion kinase (FAK) and PTP-PEST and reduced tyrosine phosphorylation of FAK. Live-cell imaging showed that green fluorescent protein-tagged CAS Y12E mutant is, in contrast to wild-type or Y12F CAS, excluded from focal adhesions but retains its localization to podosome-type adhesions. Expression of CAS-Y12F in cas-/- mouse embryonic fibroblasts resulted in hyperphosphorylation of the CAS substrate domain, and this was associated with slower turnover of focal adhesions and decreased cell migration. Moreover, expression of CAS Y12F in Src-transformed cells greatly decreased invasiveness when compared to wild-type CAS expression. These findings reveal an important role of CAS Y12 phosphorylation in the regulation of focal adhesion assembly, cell migration, and invasiveness of Src-transformed cells.

  5. A non-inheritable maternal Cas9-based multiple-gene editing system in mice.

    PubMed

    Sakurai, Takayuki; Kamiyoshi, Akiko; Kawate, Hisaka; Mori, Chie; Watanabe, Satoshi; Tanaka, Megumu; Uetake, Ryuichi; Sato, Masahiro; Shindo, Takayuki

    2016-01-28

    The CRISPR/Cas9 system is capable of editing multiple genes through one-step zygote injection. The preexisting method is largely based on the co-injection of Cas9 DNA (or mRNA) and guide RNAs (gRNAs); however, it is unclear how many genes can be simultaneously edited by this method, and a reliable means to generate transgenic (Tg) animals with multiple gene editing has yet to be developed. Here, we employed non-inheritable maternal Cas9 (maCas9) protein derived from Tg mice with systemic Cas9 overexpression (Cas9 mice). The maCas9 protein in zygotes derived from mating or in vitro fertilization of Tg/+ oocytes and +/+ sperm could successfully edit the target genome. The efficiency of such maCas9-based genome editing was comparable to that of zygote microinjection-based genome editing widely used at present. Furthermore, we demonstrated a novel approach to create "Cas9 transgene-free" gene-modified mice using non-Tg (+/+) zygotes carrying maCas9. The maCas9 protein in mouse zygotes edited nine target loci simultaneously after injection with nine different gRNAs alone. Cas9 mouse-derived zygotes have the potential to facilitate the creation of genetically modified animals carrying the Cas9 transgene, enabling repeatable genome engineering and the production of Cas9 transgene-free mice.

  6. Comparative analysis of CRISPR-Cas systems in Klebsiella genomes.

    PubMed

    Shen, Juntao; Lv, Li; Wang, Xudong; Xiu, Zhilong; Chen, Guoqiang

    2017-02-03

    Prokaryotic CRISPR-Cas system provides adaptive immunity against invasive genetic elements. Bacteria of the genus Klebsiella are important nosocomial opportunistic pathogens. However, information of CRISPR-Cas system in Klebsiella remains largely unknown. Here, we analyzed the CRISPR-Cas systems of 68 complete genomes of Klebsiella representing four species. All the elements for CRISPR-Cas system (cas genes, repeats, leader sequences, and PAMs) were characterized. Besides the typical Type I-E and I-F CRISPR-Cas systems, a new Subtype I system located in the ABC transport system-glyoxalase region was found. The conservation of the new subtype CRISPR system between different species showed new evidence for CRISPR horizontal transfer. CRISPR polymorphism was strongly correlated both with species and multilocus sequence types. Some results indicated the function of adaptive immunity: most spacers (112 of 124) matched to prophages and plasmids and no matching housekeeping genes; new spacer acquisition was observed within the same sequence type (ST) and same clonal complex; the identical spacers were observed only in the ancient position (far from the leader) between different STs and clonal complexes. Interestingly, a high ratio of self-targeting spacers (7.5%, 31 of 416) was found in CRISPR-bearing Klebsiella pneumoniae (61%, 11 of 18). In some strains, there even were multiple full matching self-targeting spacers. Some self-targeting spacers were conserved even between different STs. These results indicated that some unknown mechanisms existed to compromise the function of self-targets of CRISPR-Cas systems in K. pneumoniae.

  7. Acoustic emission monitoring system

    DOEpatents

    Romrell, Delwin M.

    1977-07-05

    Methods and apparatus for identifying the source location of acoustic emissions generated within an acoustically conductive medium. A plurality of acoustic receivers are communicably coupled to the surface of the medium at a corresponding number of spaced locations. The differences in the reception time of the respective sensors in response to a given acoustic event are measured among various sensor combinations prescribed by the monitoring mode employed. Acoustic reception response encountered subsequent to the reception by a predetermined number of the prescribed sensor combinations are inhibited from being communicated to the processing circuitry, while the time measurements obtained from the prescribed sensor combinations are translated into a position measurement representative of the location on the surface most proximate the source of the emission. The apparatus is programmable to function in six separate and five distinct operating modes employing either two, three or four sensory locations. In its preferred arrangement the apparatus of this invention will re-initiate a monitoring interval if the predetermined number of sensors do not respond to a particular emission within a given time period.

  8. ACOUSTICS IN ARCHITECTURAL DESIGN, AN ANNOTATED BIBLIOGRAPHY ON ARCHITECTURAL ACOUSTICS.

    ERIC Educational Resources Information Center

    DOELLE, LESLIE L.

    THE PURPOSE OF THIS ANNOTATED BIBLIOGRAPHY ON ARCHITECTURAL ACOUSTICS WAS--(1) TO COMPILE A CLASSIFIED BIBLIOGRAPHY, INCLUDING MOST OF THOSE PUBLICATIONS ON ARCHITECTURAL ACOUSTICS, PUBLISHED IN ENGLISH, FRENCH, AND GERMAN WHICH CAN SUPPLY A USEFUL AND UP-TO-DATE SOURCE OF INFORMATION FOR THOSE ENCOUNTERING ANY ARCHITECTURAL-ACOUSTIC DESIGN…

  9. Chemosensory stimulation during sleep - Arousal responses to gustatory stimulation.

    PubMed

    Stuck, B A; Moutsis, T T; Bingel, U; Sommer, J U

    2016-05-13

    The processing of nociceptive, visual, vibrotactile, thermal and acoustic stimuli during sleep has been extensively investigated in the past. Recently, interest has focused on the impact of olfactory stimulation on sleep. In contrast to all other sensory systems, olfactory stimulation does not lead to an increased arousal frequency, regardless of hedonicity and concentration. The impact of the second chemosensory system, gustation, on sleep however has not been investigated to date. Twenty-one normosmic and normogeusic volunteers of both genders, aged 19-33 years, participated in the trial. Stimulation was performed with a gustometer using the following aqueous solutions: saccharose 20% (sweet), sodium chloride (NaCl) 7.5% (salty), citrate 5% (sour), and quinine 0.02% (bitter). A tasteless solution was used as negative control. Capsaicin, a strong trigeminal stimulus, served as positive control. Primary outcome was arousal frequency per stimulus in each sleep stage, as assessed with polysomnography. The frequency of arousals decreased in deeper sleep stages (N1: 211 arousals of 333 stimuli=63%, N2: 676/2728=25%, N3: 43/1378=3%, REM: 57/1010=6%). Statistically significant differences in terms of arousal frequency were found in N2 between the negative control and NaCl 100 μl (p<0.001), saccharose 100 μl, citrate 50 μl & 100 μl, and quinine 100 μl (p<0.05). Capsaicin led to complete awakenings in 94% of stimuli (30/32). These results demonstrate that gustatory stimulation during sleep induces arousals depending on stimulus intensity and sleep stage, which is different to olfactory stimulation and may be related to differences in central processing of the two chemosensory systems.

  10. Spectroscopic studies of three Cepheids with high positive pulsation period increments: SZ Cas, BY Cas, and RU Sct

    NASA Astrophysics Data System (ADS)

    Usenko, I. A.; Klochkova, V. G.

    2015-07-01

    Three high-resolution spectra have been taken at different times with the 6-m SAO RAS telescope (LYNX and PFES spectrographs) for three Cepheids exhibiting high positive period increments: the small-amplitude (DCEPS) SZ Cas and BY Cas and the classical (DCEP) RU Sct. SZ Cas and RU Sct are members of the Galactic open clusters χ and h Per and Trump 35, respectively. Analysis of the spectra has shown that the interstellar Na I D1 and D2 lines in all objects are considerably stronger than the atmospheric ones and are redshifted in SZ Cas and BY Cas and blushifted in RU Sct. The core of the H α absorption line in BY Cas has an asymmetric knifelike shape, while RU Sct exhibits an intense emission in the blue wing of this line. Such phenomena are observed in long-period Cepheids and bright hypergiants with an extended envelope. In this case, the strong Mg Ib 5183.62 Å and Ba II 5853.67, 6141.713, and 6496.90 Å lines with low χlow in SZ Cas and RU Sct also show characteristic knifelike profiles with an asymmetry in the red region, while the Ba II 4934.095 Å line shows similar profiles in the blue one. The absorption lines of neutral atoms and singly ionized metals with different lowerlevel excitation potentials exhibit different degrees of asymmetry: from a pronounced one with secondary components in BY Cas (similar to those in the small-amplitude Cepheid BG Cru pulsating in the first overtone and having an envelope) to its insignificance or virtual absence in SZ Cas and RU Sct. Analysis of the secular changes in mean T eff determined from photometric color indices and spectra over the last 55 years for these stars has revealed periodic fluctuations of 200 K for SZ Cas and BY Cas and 500 K for RU Sct. For SZ Cas and RU Sct, T eff determined in some years from some color indices show much lower values, which together with the temperature fluctuations can be associated with mass loss and dust formation. Based on these facts, we hypothesize the existence of

  11. A New Wave of Acoustics.

    ERIC Educational Resources Information Center

    Beyer, Robert

    1981-01-01

    Surveys 50 years of acoustical studies by discussing selected topics including the ear, nonlinear representations, underwater sound, acoustical diagnostics, absorption, electrolytes, phonons, magnetic interaction, and superfluidity and the five sounds. (JN)

  12. Pyo-pneumothorax tuberculeux: à propos de 18 cas

    PubMed Central

    Hicham, Souhi; Hanane, El Ouazzani; Hicham, Janah; Ismaïl, Rhorfi; Ahmed, Abid

    2016-01-01

    Le pyo-pneumothorax tuberculeux est une complication rare mais grave de la tuberculose pulmonaire évolutive. Nous rapportons une série de 18 cas de pyo-pneumothorax tuberculeux colligés au service de Pneumo-Phtisiologie de l'Hôpital Militaire d'Instruction Mohammed V de Rabat entre janvier 2005 et décembre 2009. Il s'agit de 15 hommes et 3 femmes d’âge moyen de 35 ans ±7 ans. 4 patients étaient diabétiques. Le tabagisme était retrouvé chez 9 cas. Le pyo-pneumothorax était du coté droit dans 13 cas. La radiographie thoracique avait montré des lésions cavitaires chez 15 patients et des lésions étendues et bilatérales chez 8 cas. La recherche de BK dans le liquide de tubage gastrique était positive chez 16 cas. Un drainage thoracique associé à un traitement antituberculeux selon le régime 2SRHZ/7RH et une kinésithérapie respiratoire ont été instaurés chez tous les cas. La durée moyenne de drainage pleural était de 4 semaines. Chez 3 cas on avait noté la persistance de la suppuration pleurale ayant nécessité une toilette pleurale sous thoracoscopie avec pleurectomie et exérèse pulmonaire limitée emportant la lésion parenchymateuse tuberculeuse et la persistance d'une volumineuse poche pleurale avec trouble ventilatoire restrictif ayant nécessité une décortication pleurale chirurgicale chez deux cas. L’évolution était favorable avec pachypleurite séquellaire minime chez le reste des cas. Le pyo-pneumothorax tuberculeux est une forme grave, qui est souvent en rapport avec une tuberculose cavitaire active. L’évolution est généralement trainante malgré le traitement antituberculeux et le drainage thoracique, d'où la nécessité d'un diagnostic et un traitement précoce de toute forme de tuberculose. PMID:27583090

  13. Passive broadband acoustic thermometry

    NASA Astrophysics Data System (ADS)

    Anosov, A. A.; Belyaev, R. V.; Klin'shov, V. V.; Mansfel'd, A. D.; Subochev, P. V.

    2016-04-01

    The 1D internal (core) temperature profiles for the model object (plasticine) and the human hand are reconstructed using the passive acoustothermometric broadband probing data. Thermal acoustic radiation is detected by a broadband (0.8-3.5 MHz) acoustic radiometer. The temperature distribution is reconstructed using a priori information corresponding to the experimental conditions. The temperature distribution for the heated model object is assumed to be monotonic. For the hand, we assume that the temperature distribution satisfies the heat-conduction equation taking into account the blood flow. The average error of reconstruction determined for plasticine from the results of independent temperature measurements is 0.6 K for a measuring time of 25 s. The reconstructed value of the core temperature of the hand (36°C) generally corresponds to physiological data. The obtained results make it possible to use passive broadband acoustic probing for measuring the core temperatures in medical procedures associated with heating of human organism tissues.

  14. Architectural-acoustics consulting

    NASA Astrophysics Data System (ADS)

    Hoover, Anthony K.

    2004-05-01

    Consulting involves both the science of acoustics and the art of communication, requiring an array of inherent and created skills. Perhaps because consulting on architectural acoustics is a relatively new field, there is a remarkable variety of career paths, all influenced by education, interest, and experience. Many consultants juggle dozens of chargeable projects at a time, not to mention proposals, seminars, teaching, articles, business concerns, and professional-society activities. This paper will discuss various aspects of career paths, projects, and clients as they relate to architectural-acoustics consulting. The intended emphasis will be considerations for those who may be interested in such a career, noting that consultants generally seem to thrive on the numerous challenges.

  15. High temperature acoustic levitator

    NASA Technical Reports Server (NTRS)

    Barmatz, M. B. (Inventor)

    1984-01-01

    A system is described for acoustically levitating an object within a portion of a chamber that is heated to a high temperature, while a driver at the opposite end of the chamber is maintained at a relatively low temperature. The cold end of the chamber is constructed so it can be telescoped to vary the length (L sub 1) of the cold end portion and therefore of the entire chamber, so that the chamber remains resonant to a normal mode frequency, and so that the pressure at the hot end of the chamber is maximized. The precise length of the chamber at any given time, is maintained at an optimum resonant length by a feedback loop. The feedback loop includes an acoustic pressure sensor at the hot end of the chamber, which delivers its output to a control circuit which controls a motor that varies the length (L) of the chamber to a level where the sensed acoustic pressure is a maximum.

  16. Basic Linear Acoustics

    NASA Astrophysics Data System (ADS)

    Pierce, Alan

    This chapter deals with the physical and mathematical aspects of sound when the disturbances are, in some sense, small. Acoustics is usually concerned with small-amplitude phenomena, and consequently a linear description is usually applicable. Disturbances are governed by the properties of the medium in which they occur, and the governing equations are the equations of continuum mechanics, which apply equally to gases, liquids, and solids. These include the mass, momentum, and energy equations, as well as thermodynamic principles. The viscosity and thermal conduction enter into the versions of these equations that apply to fluids. Fluids of typical great interest are air and sea water, and consequently this chapter includes a summary of their relevant acoustic properties. The foundation is also laid for the consideration of acoustic waves in elastic solids, suspensions, bubbly liquids, and porous media.

  17. Cornerstones of CRISPR-Cas in drug discovery and therapy.

    PubMed

    Fellmann, Christof; Gowen, Benjamin G; Lin, Pei-Chun; Doudna, Jennifer A; Corn, Jacob E

    2017-02-01

    The recent development of CRISPR-Cas systems as easily accessible and programmable tools for genome editing and regulation is spurring a revolution in biology. Paired with the rapid expansion of reference and personalized genomic sequence information, technologies based on CRISPR-Cas are enabling nearly unlimited genetic manipulation, even in previously difficult contexts, including human cells. Although much attention has focused on the potential of CRISPR-Cas to cure Mendelian diseases, the technology also holds promise to transform the development of therapies to treat complex heritable and somatic disorders. In this Review, we discuss how CRISPR-Cas can affect the next generation of drugs by accelerating the identification and validation of high-value targets, uncovering high-confidence biomarkers and developing differentiated breakthrough therapies. We focus on the promises, pitfalls and hurdles of this revolutionary gene-editing technology, discuss key aspects of different CRISPR-Cas screening platforms and offer our perspectives on the best practices in genome engineering.

  18. SD-CAS: Spin Dynamics by Computer Algebra System.

    PubMed

    Filip, Xenia; Filip, Claudiu

    2010-11-01

    A computer algebra tool for describing the Liouville-space quantum evolution of nuclear 1/2-spins is introduced and implemented within a computational framework named Spin Dynamics by Computer Algebra System (SD-CAS). A distinctive feature compared with numerical and previous computer algebra approaches to solving spin dynamics problems results from the fact that no matrix representation for spin operators is used in SD-CAS, which determines a full symbolic character to the performed computations. Spin correlations are stored in SD-CAS as four-entry nested lists of which size increases linearly with the number of spins into the system and are easily mapped into analytical expressions in terms of spin operator products. For the so defined SD-CAS spin correlations a set of specialized functions and procedures is introduced that are essential for implementing basic spin algebra operations, such as the spin operator products, commutators, and scalar products. They provide results in an abstract algebraic form: specific procedures to quantitatively evaluate such symbolic expressions with respect to the involved spin interaction parameters and experimental conditions are also discussed. Although the main focus in the present work is on laying the foundation for spin dynamics symbolic computation in NMR based on a non-matrix formalism, practical aspects are also considered throughout the theoretical development process. In particular, specific SD-CAS routines have been implemented using the YACAS computer algebra package (http://yacas.sourceforge.net), and their functionality was demonstrated on a few illustrative examples.

  19. Acoustic Liners for Turbine Engines

    NASA Technical Reports Server (NTRS)

    Jones, Michael G (Inventor); Grady, Joseph E (Inventor); Kiser, James D. (Inventor); Miller, Christopher (Inventor); Heidmann, James D. (Inventor)

    2016-01-01

    An improved acoustic liner for turbine engines is disclosed. The acoustic liner may include a straight cell section including a plurality of cells with straight chambers. The acoustic liner may also include a bent cell section including one or more cells that are bent to extend chamber length without increasing the overall height of the acoustic liner by the entire chamber length. In some cases, holes are placed between cell chambers in addition to bending the cells, or instead of bending the cells.

  20. Spacecraft Internal Acoustic Environment Modeling

    NASA Technical Reports Server (NTRS)

    Allen, Christopher; Chu, S. Reynold

    2008-01-01

    The objective of the project is to develop an acoustic modeling capability, based on commercial off-the-shelf software, to be used as a tool for oversight of the future manned Constellation vehicles to ensure compliance with acoustic requirements and thus provide a safe and habitable acoustic environment for the crews, and to validate developed models via building physical mockups and conducting acoustic measurements.

  1. Acoustically Induced Vibration of Structures: Reverberant Vs. Direct Acoustic Testing

    NASA Technical Reports Server (NTRS)

    Kolaini, Ali R.; O'Connell, Michael R.; Tsoi, Wan B.

    2009-01-01

    Large reverberant chambers have been used for several decades in the aerospace industry to test larger structures such as solar arrays and reflectors to qualify and to detect faults in the design and fabrication of spacecraft and satellites. In the past decade some companies have begun using direct near field acoustic testing, employing speakers, for qualifying larger structures. A limited test data set obtained from recent acoustic tests of the same hardware exposed to both direct and reverberant acoustic field testing has indicated some differences in the resulting structural responses. In reverberant acoustic testing, higher vibration responses were observed at lower frequencies when compared with the direct acoustic testing. In the case of direct near field acoustic testing higher vibration responses appeared to occur at higher frequencies as well. In reverberant chamber testing and direct acoustic testing, standing acoustic modes of the reverberant chamber or the speakers and spacecraft parallel surfaces can strongly couple with the fundamental structural modes of the test hardware. In this paper data from recent acoustic testing of flight hardware, that yielded evidence of acoustic standing wave coupling with structural responses, are discussed in some detail. Convincing evidence of the acoustic standing wave/structural coupling phenomenon will be discussed, citing observations from acoustic testing of a simple aluminum plate. The implications of such acoustic coupling to testing of sensitive flight hardware will be discussed. The results discussed in this paper reveal issues with over or under testing of flight hardware that could pose unanticipated structural and flight qualification issues. Therefore, it is of paramount importance to understand the structural modal coupling with standing acoustic waves that has been observed in both methods of acoustic testing. This study will assist the community to choose an appropriate testing method and test setup in

  2. Acoustic bubble removal method

    NASA Technical Reports Server (NTRS)

    Trinh, E. H.; Elleman, D. D.; Wang, T. G. (Inventor)

    1983-01-01

    A method is described for removing bubbles from a liquid bath such as a bath of molten glass to be used for optical elements. Larger bubbles are first removed by applying acoustic energy resonant to a bath dimension to drive the larger bubbles toward a pressure well where the bubbles can coalesce and then be more easily removed. Thereafter, submillimeter bubbles are removed by applying acoustic energy of frequencies resonant to the small bubbles to oscillate them and thereby stir liquid immediately about the bubbles to facilitate their breakup and absorption into the liquid.

  3. Broadband Acoustic Hyperbolic Metamaterial.

    PubMed

    Shen, Chen; Xie, Yangbo; Sui, Ni; Wang, Wenqi; Cummer, Steven A; Jing, Yun

    2015-12-18

    In this Letter, we report on the design and experimental characterization of a broadband acoustic hyperbolic metamaterial. The proposed metamaterial consists of multiple arrays of clamped thin plates facing the y direction and is shown to yield opposite signs of effective density in the x and y directions below a certain cutoff frequency, therefore, yielding a hyperbolic dispersion. Partial focusing and subwavelength imaging are experimentally demonstrated at frequencies between 1.0 and 2.5 kHz. The proposed metamaterial could open up new possibilities for acoustic wave manipulation and may find usage in medical imaging and nondestructive testing.

  4. Acoustic emission intrusion detector

    DOEpatents

    Carver, Donald W.; Whittaker, Jerry W.

    1980-01-01

    An intrusion detector is provided for detecting a forcible entry into a secured structure while minimizing false alarms. The detector uses a piezoelectric crystal transducer to sense acoustic emissions. The transducer output is amplified by a selectable gain amplifier to control the sensitivity. The rectified output of the amplifier is applied to a Schmitt trigger circuit having a preselected threshold level to provide amplitude discrimination. Timing circuitry is provided which is activated by successive pulses from the Schmitt trigger which lie within a selected time frame for frequency discrimination. Detected signals having proper amplitude and frequency trigger an alarm within the first complete cycle time of a detected acoustical disturbance signal.

  5. Electromechanical acoustic liner

    NASA Technical Reports Server (NTRS)

    Sheplak, Mark (Inventor); Cattafesta, III, Louis N. (Inventor); Nishida, Toshikazu (Inventor); Horowitz, Stephen Brian (Inventor)

    2007-01-01

    A multi-resonator-based system responsive to acoustic waves includes at least two resonators, each including a bottom plate, side walls secured to the bottom plate, and a top plate disposed on top of the side walls. The top plate includes an orifice so that a portion of an incident acoustical wave compresses gas in the resonators. The bottom plate or the side walls include at least one compliant portion. A reciprocal electromechanical transducer coupled to the compliant portion of each of the resonators forms a first and second transducer/compliant composite. An electrical network is disposed between the reciprocal electromechanical transducer of the first and second resonator.

  6. Broadband Acoustic Clutter

    DTIC Science & Technology

    2010-09-30

    fluidized mud, which has sound speeds at (or sometimes below) the sound speed of the water column, here 1512 m/s. Interestingly, there is a sound speed...data. 3 specular 25m Figure 1. The map shows the AUV track (red line) overlaid on multibeam bathymetry. Mean water depth is about 165m...Preston, and D.A. Abraham, Long-range acoustic scattering from a shallow- water mud volcano cluster J. Acoust. Soc. Am., 122, 1946-1958, 2007. [3

  7. Acoustic tooth cleaner

    NASA Technical Reports Server (NTRS)

    Heyman, J. S. (Inventor)

    1982-01-01

    An acoustic oral hygiene unit is described that uses acoustic energy to oscillate mild abrasive particles in a water suspension which is then directed in a low pressure stream onto the teeth. The oscillating abrasives scrub the teeth clean removing food particles, plaque, calculous, and other foreign material from tooth surfaces, interproximal areas, and tooth-gingiva interface more effectively than any previous technique. The relatively low power output and the basic design makes the invention safe and convenient for everyday use in the home without special training. This invention replaces all former means of home dental prophylaxis, and requires no augmentation to fulfill all requirements for daily oral hygienic care.

  8. Post Treatment of Acoustic Neuroma

    MedlinePlus

    Home What is an AN What is an Acoustic Neuroma? Identifying an AN Symptoms Acoustic Neuroma Keywords Educational Video Pre-Treatment Treatment Options Summary Treatment Options Watch and Wait Radiation Microsurgery Acoustic Neuroma Decision Tree Questions for Your Physician Questions ...

  9. Fundamentals of Acoustics. Psychoacoustics and Hearing. Acoustical Measurements

    NASA Technical Reports Server (NTRS)

    Begault, Durand R.; Ahumada, Al (Technical Monitor)

    1997-01-01

    These are 3 chapters that will appear in a book titled "Building Acoustical Design", edited by Charles Salter. They are designed to introduce the reader to fundamental concepts of acoustics, particularly as they relate to the built environment. "Fundamentals of Acoustics" reviews basic concepts of sound waveform frequency, pressure, and phase. "Psychoacoustics and Hearing" discusses the human interpretation sound pressure as loudness, particularly as a function of frequency. "Acoustic Measurements" gives a simple overview of the time and frequency weightings for sound pressure measurements that are used in acoustical work.

  10. Is dust acoustic wave a new plasma acoustic mode?

    NASA Astrophysics Data System (ADS)

    Dwivedi, C. B.

    1997-09-01

    In this Brief Communication, the claim of the novelty of the dust acoustic wave in a dusty plasma within the constant dust charge model is questioned. Conceptual lacunas behind the claim have been highlighted and appropriate physical arguments have been forwarded against the claim. It is demonstrated that the so-called dust acoustic wave could better be termed as a general acoustic fluctuation response with a dominant characteristic feature of the acoustic-like mode (ALM) fluctuation response reported by Dwivedi et al. [J. Plasma Phys. 41, 219 (1989)]. It is suggested that both correct and more usable nomenclature of the ALM should be the so-called acoustic mode.

  11. Acoustic subwavelength imaging of subsurface objects with acoustic resonant metalens

    SciTech Connect

    Cheng, Ying; Liu, XiaoJun; Zhou, Chen; Wei, Qi; Wu, DaJian

    2013-11-25

    Early research into acoustic metamaterials has shown the possibility of achieving subwavelength near-field acoustic imaging. However, a major restriction of acoustic metamaterials is that the imaging objects must be placed in close vicinity of the devices. Here, we present an approach for acoustic imaging of subsurface objects far below the diffraction limit. An acoustic metalens made of holey-structured metamaterials is used to magnify evanescent waves, which can rebuild an image at the central plane. Without changing the physical structure of the metalens, our proposed approach can image objects located at certain distances from the input surface, which provides subsurface signatures of the objects with subwavelength spatial resolution.

  12. Influences of noise-interruption and information-bearing acoustic changes on understanding simulated electric-acoustic speech.

    PubMed

    Stilp, Christian; Donaldson, Gail; Oh, Soohee; Kong, Ying-Yee

    2016-11-01

    In simulations of electrical-acoustic stimulation (EAS), vocoded speech intelligibility is aided by preservation of low-frequency acoustic cues. However, the speech signal is often interrupted in everyday listening conditions, and effects of interruption on hybrid speech intelligibility are poorly understood. Additionally, listeners rely on information-bearing acoustic changes to understand full-spectrum speech (as measured by cochlea-scaled entropy [CSE]) and vocoded speech (CSECI), but how listeners utilize these informational changes to understand EAS speech is unclear. Here, normal-hearing participants heard noise-vocoded sentences with three to six spectral channels in two conditions: vocoder-only (80-8000 Hz) and simulated hybrid EAS (vocoded above 500 Hz; original acoustic signal below 500 Hz). In each sentence, four 80-ms intervals containing high-CSECI or low-CSECI acoustic changes were replaced with speech-shaped noise. As expected, performance improved with the preservation of low-frequency fine-structure cues (EAS). This improvement decreased for continuous EAS sentences as more spectral channels were added, but increased as more channels were added to noise-interrupted EAS sentences. Performance was impaired more when high-CSECI intervals were replaced by noise than when low-CSECI intervals were replaced, but this pattern did not differ across listening modes. Utilizing information-bearing acoustic changes to understand speech is predicted to generalize to cochlear implant users who receive EAS inputs.

  13. Stimulated Optomechanical Excitation of Surface Acoustic Waves in a Microdevice

    DTIC Science & Technology

    2011-07-26

    limit, and are consequently very useful in oscillator applications as well. Methods Numerical modelling of optical and mechanical modes. The mechanical...pairs of optical modes that satisfy phase match to excite these mechanical modes was confirmed using the numerical method described in ref. 22. Gross...and light, known to be the strongest optical nonlinearity common to all amorphous and crystalline dielectrics , has been widely studied in fibres and

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

    PubMed

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

    2017-03-16

    The recent adaptation of the CRISPR/Cas9 system for targeted genome engineering has led to its widespread applications in many fields worldwide. In order to better understand the design rules of CRISPR/Cas9 systems, several groups have carried out large library-based screens leading to some insight into sequence preferences among highly active target sites. To facilitate CRISPR/Cas9 design these studies have spawned a plethora of gRNA design tools with algorithms based solely on direct or indirect sequence features. Here we demonstrate that the predictive power of these tools is poor, suggesting that sequence features alone cannot accurately inform the cutting efficiency of a particular CRISPR/Cas9 gRNA design. Furthermore we demonstrate that DNA target site accessibility influences the activity of CRISPR/Cas9. With further optimisation we hypothesise that it will be possible to increase the predictive power of gRNA design tools by including both sequence and target site accessibility metrics. This article is protected by copyright. All rights reserved.

  15. Genome Editing in Human Cells Using CRISPR/Cas Nucleases.

    PubMed

    Wyvekens, Nicolas; Tsai, Shengdar Q; Joung, J Keith

    2015-10-01

    The clustered regularly interspaced short palindromic repeat (CRISPR)/CRISPR-associated (Cas) system has been broadly adopted for highly efficient genome editing in a variety of model organisms and human cell types. Unlike previous genome editing technologies such as zinc finger nucleases (ZFNs) and transcription activator-like effector nucleases (TALENs), CRISPR/Cas technology does not require complex protein engineering and can be utilized by any researcher proficient in basic molecular biology and cell culture techniques. This unit describes protocols for design and cloning of vectors expressing single or multiplex gRNAs, for transient transfection of human cell lines, and for quantitation of mutation frequencies by T7 endonuclease I assay. These protocols also include guidance for using two improvements that increase the specificity of CRISPR/Cas nucleases: truncated gRNAs and dimeric RNA-guided FokI nucleases.

  16. Harnessing CRISPR-Cas systems for bacterial genome editing.

    PubMed

    Selle, Kurt; Barrangou, Rodolphe

    2015-04-01

    Manipulation of genomic sequences facilitates the identification and characterization of key genetic determinants in the investigation of biological processes. Genome editing via clustered regularly interspaced short palindromic repeats (CRISPR)-CRISPR-associated (Cas) constitutes a next-generation method for programmable and high-throughput functional genomics. CRISPR-Cas systems are readily reprogrammed to induce sequence-specific DNA breaks at target loci, resulting in fixed mutations via host-dependent DNA repair mechanisms. Although bacterial genome editing is a relatively unexplored and underrepresented application of CRISPR-Cas systems, recent studies provide valuable insights for the widespread future implementation of this technology. This review summarizes recent progress in bacterial genome editing and identifies fundamental genetic and phenotypic outcomes of CRISPR targeting in bacteria, in the context of tool development, genome homeostasis, and DNA repair.

  17. CRISPR-Cas adaptation: insights into the mechanism of action.

    PubMed

    Amitai, Gil; Sorek, Rotem

    2016-02-01

    Since the first demonstration that CRISPR-Cas systems provide bacteria and archaea with adaptive immunity against phages and plasmids, numerous studies have yielded key insights into the molecular mechanisms governing how these systems attack and degrade foreign DNA. However, the molecular mechanisms underlying the adaptation stage, in which new immunological memory is formed, have until recently represented a major unresolved question. In this Progress article, we discuss recent discoveries that have shown both how foreign DNA is identified by the CRISPR-Cas adaptation machinery and the molecular basis for its integration into the chromosome to form an immunological memory. Furthermore, we describe the roles of each of the specific CRISPR-Cas components that are involved in memory formation, and consider current models for their evolutionary origin.

  18. Exploiting CRISPR/Cas: interference mechanisms and applications.

    PubMed

    Richter, Hagen; Randau, Lennart; Plagens, André

    2013-07-12

    The discovery of biological concepts can often provide a framework for the development of novel molecular tools, which can help us to further understand and manipulate life. One recent example is the elucidation of the prokaryotic adaptive immune system, clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated (Cas) that protects bacteria and archaea against viruses or conjugative plasmids. The immunity is based on small RNA molecules that are incorporated into versatile multi-domain proteins or protein complexes and specifically target viral nucleic acids via base complementarity. CRISPR/Cas interference machines are utilized to develop novel genome editing tools for different organisms. Here, we will review the latest progress in the elucidation and application of prokaryotic CRISPR/Cas systems and discuss possible future approaches to exploit the potential of these interference machineries.

  19. DNA fragment editing of genomes by CRISPR/Cas9.

    PubMed

    Jinhuan, Li; Jia, Shou; Qiang, Wu

    2015-10-01

    The clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated nuclease 9 (Cas9) system from bacteria and archaea emerged recently as a new powerful technology of genome editing in virtually any organism. Due to its simplicity and cost effectiveness, a revolutionary change of genetics has occurred. Here, we summarize the recent development of DNA fragment editing methods by CRISPR/Cas9 and describe targeted DNA fragment deletions, inversions, duplications, insertions, and translocations. The efficient method of DNA fragment editing provides a powerful tool for studying gene function, regulatory elements, tissue development, and disease progression. Finally, we discuss the prospects of CRISPR/Cas9 system and the potential applications of other types of CRISPR system.

  20. Genome engineering using CRISPR-Cas9 system.

    PubMed

    Cong, Le; Zhang, Feng

    2015-01-01

    The Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)-Cas9 system is an adaptive immune system that exists in a variety of microbes. It could be engineered to function in eukaryotic cells as a fast, low-cost, efficient, and scalable tool for manipulating genomic sequences. In this chapter, detailed protocols are described for harnessing the CRISPR-Cas9 system from Streptococcus pyogenes to enable RNA-guided genome engineering applications in mammalian cells. We present all relevant methods including the initial site selection, molecular cloning, delivery of guide RNAs (gRNAs) and Cas9 into mammalian cells, verification of target cleavage, and assays for detecting genomic modification including indels and homologous recombination. These tools provide researchers with new instruments that accelerate both forward and reverse genetics efforts.

  1. Optogenetic Stimulation of the Auditory Nerve

    PubMed Central

    Hernandez, Victor H.; Gehrt, Anna; Jing, Zhizi; Hoch, Gerhard; Jeschke, Marcus; Strenzke, Nicola; Moser, Tobias

    2014-01-01

    Direct electrical stimulation of spiral ganglion neurons (SGNs) by cochlear implants (CIs) enables open speech comprehension in the majority of implanted deaf subjects1-6. Nonetheless, sound coding with current CIs has poor frequency and intensity resolution due to broad current spread from each electrode contact activating a large number of SGNs along the tonotopic axis of the cochlea7-9. Optical stimulation is proposed as an alternative to electrical stimulation that promises spatially more confined activation of SGNs and, hence, higher frequency resolution of coding. In recent years, direct infrared illumination of the cochlea has been used to evoke responses in the auditory nerve10. Nevertheless it requires higher energies than electrical stimulation10,11 and uncertainty remains as to the underlying mechanism12. Here we describe a method based on optogenetics to stimulate SGNs with low intensity blue light, using transgenic mice with neuronal expression of channelrhodopsin 2 (ChR2)13 or virus-mediated expression of the ChR2-variant CatCh14. We used micro-light emitting diodes (µLEDs) and fiber-coupled lasers to stimulate ChR2-expressing SGNs through a small artificial opening (cochleostomy) or the round window. We assayed the responses by scalp recordings of light-evoked potentials (optogenetic auditory brainstem response: oABR) or by microelectrode recordings from the auditory pathway and compared them with acoustic and electrical stimulation. PMID:25350571

  2. Acoustic analog of a free-electron laser

    SciTech Connect

    Zavtrak, S.T.

    1995-12-31

    As well known, at the present time there are many types of laser the operation of which is based on the stimulated emission of light by an active medium. Lasers are generators of coherent electromagnetic waves in the range from ultraviolet to submillimeters. But acoustic analogs of such devices have not been created up to now in spite of the progress in laser technology. Meanwhile, an acoustic laser could have a lot of interesting applications. Recently a theoretical scheme for an acoustic laser was proposed by the present author. A liquid dielectric with dispersed particles was considered as an active medium. The pumping was created by an oscillating electric field deforming dispersed particle volumes. Different types of oils or distilled water can serve as a liquid dielectric with gas bubbles as dispersed particles. Gas bubbles in water can be created by an electrolysis. The phase bunching of the initially incoherent emitters (gas bubbles) was realized by acoustic radiation forces. This scheme is an analog of the free-electron laser (FEL). It was shown that two types of losses must be overcome for the beginning of a generation. The first type results from the energy dissipation in the active medium and the second one is caused by radiation losses at the boundaries of the resonator. The purposes of this report are: (1) to discuss the analogies between the acoustic laser and FEL; (2) to propose an effective scheme of an acoustic laser with a mechanical pumping (by a piezoelectric emitter of the piston type); (3) to consider the schemes of acoustic lasers with the different types of the resonators (rectangular and cylindrical); (4) to discuss the possibility of the creation of an impact acoustic laser (5) to discuss the experimental works which are planned to be carried out in cooperation with prof. L.A. Crum.

  3. The effects of acoustic vibration on fibroblast cell migration.

    PubMed

    Mohammed, Taybia; Murphy, Mark F; Lilley, Francis; Burton, David R; Bezombes, Frederic

    2016-12-01

    Cells are known to interact and respond to external mechanical cues and recent work has shown that application of mechanical stimulation, delivered via acoustic vibration, can be used to control complex cell behaviours. Fibroblast cells are known to respond to physical cues generated in the extracellular matrix and it is thought that such cues are important regulators of the wound healing process. Many conditions are associated with poor wound healing, so there is need for treatments/interventions, which can help accelerate the wound healing process. The primary aim of this research was to investigate the effects of mechanical stimulation upon the migratory and morphological properties of two different fibroblast cells namely; human lung fibroblast cells (LL24) and subcutaneous areolar/adipose mouse fibroblast cells (L929). Using a speaker-based system, the effects of mechanical stimulation (0-1600Hz for 5min) on the mean cell migration distance (μm) and actin organisation was investigated. The results show that 100Hz acoustic vibration enhanced cell migration for both cell lines whereas acoustic vibration above 100Hz was found to decrease cell migration in a frequency dependent manner. Mechanical stimulation was also found to promote changes to the morphology of both cell lines, particularly the formation of lamellipodia and filopodia. Overall lamellipodia was the most prominent actin structure displayed by the lung cell (LL24), whereas filopodia was the most prominent actin feature displayed by the fibroblast derived from subcutaneous areolar/adipose tissue. Mechanical stimulation at all the frequencies used here was found not to affect cell viability. These results suggest that low-frequency acoustic vibration may be used as a tool to manipulate the mechanosensitivity of cells to promote cell migration.

  4. Targeted heritable mutation and gene conversion by Cas9-CRISPR in Caenorhabditis elegans.

    PubMed

    Katic, Iskra; Großhans, Helge

    2013-11-01

    We have achieved targeted heritable genome modification in Caenorhabditis elegans by injecting mRNA of the nuclease Cas9 and Cas9 guide RNAs. This system rapidly creates precise genomic changes, including knockouts and transgene-instructed gene conversion.

  5. Rapid and tunable method to temporally control gene editing based on conditional Cas9 stabilization.

    PubMed

    Senturk, Serif; Shirole, Nitin H; Nowak, Dawid G; Corbo, Vincenzo; Pal, Debjani; Vaughan, Alexander; Tuveson, David A; Trotman, Lloyd C; Kinney, Justin B; Sordella, Raffaella

    2017-02-22

    The CRISPR/Cas9 system is a powerful tool for studying gene function. Here, we describe a method that allows temporal control of CRISPR/Cas9 activity based on conditional Cas9 destabilization. We demonstrate that fusing an FKBP12-derived destabilizing domain to Cas9 (DD-Cas9) enables conditional Cas9 expression and temporal control of gene editing in the presence of an FKBP12 synthetic ligand. This system can be easily adapted to co-express, from the same promoter, DD-Cas9 with any other gene of interest without co-modulation of the latter. In particular, when co-expressed with inducible Cre-ER(T2), our system enables parallel, independent manipulation of alleles targeted by Cas9 and traditional recombinase with single-cell specificity. We anticipate this platform will be used for the systematic characterization and identification of essential genes, as well as the investigation of the interactions between functional genes.

  6. Acoustics- Version 1.0

    SciTech Connect

    2012-09-13

    This package contains modules that model acoustic sensors and acoustic sources (hearable) in Umbra. It is typically used to represent hearing in characters within Umbra. Typically, the acoustic sensors detect acoustic sources at a given point; however, it also contains the capability to detect bullet cracks by detecting the sound along the bullet path that is closest to the sensor. A memory module, acoustic memory, represents remembered sounds within a given character. Over time, the sounds are removed, as a character forgets what it has heard.

  7. Acoustic visualizations using surface mapping.

    PubMed

    Siltanen, Samuel; Robinson, Philip W; Saarelma, Jukka; Pätynen, Jukka; Tervo, Sakari; Savioja, Lauri; Lokki, Tapio

    2014-06-01

    Sound visualizations have been an integral part of room acoustics studies for more than a century. As acoustic measurement techniques and knowledge of hearing evolve, acousticians need more intuitive ways to represent increasingly complex data. Microphone array processing now allows accurate measurement of spatio-temporal acoustic properties. However, the multidimensional data can be a challenge to display coherently. This letter details a method of mapping visual representations of acoustic reflections from a receiver position to the surfaces from which the reflections originated. The resulting animations are presented as a spatial acoustic analysis tool.

  8. Intelligent Engine Systems: Acoustics

    NASA Technical Reports Server (NTRS)

    Wojno, John; Martens, Steve; Simpson, Benjamin

    2008-01-01

    An extensive study of new fan exhaust nozzle technologies was performed. Three new uniform chevron nozzles were designed, based on extensive CFD analysis. Two new azimuthally varying variants were defined. All five were tested, along with two existing nozzles, on a representative model-scale, medium BPR exhaust nozzle. Substantial acoustic benefits were obtained from the uniform chevron nozzle designs, the best benefit being provided by an existing design. However, one of the azimuthally varying nozzle designs exhibited even better performance than any of the uniform chevron nozzles. In addition to the fan chevron nozzles, a new technology was demonstrated, using devices that enhance mixing when applied to an exhaust nozzle. The acoustic benefits from these devices applied to medium BPR nozzles were similar, and in some cases superior to, those obtained from conventional uniform chevron nozzles. However, none of the low noise technologies provided equivalent acoustic benefits on a model-scale high BPR exhaust nozzle, similar to current large commercial applications. New technologies must be identified to improve the acoustics of state-of-the-art high BPR jet engines.

  9. Concert hall acoustics

    NASA Astrophysics Data System (ADS)

    Schroeder, Manfred

    2004-05-01

    I will review some work at Bell Laboratories on artificial reverberation and concert hall acoustics including Philharmonic Hall (Lincoln Center for the Performing Arts, New York). I will also touch on sound diffusion by number-theoretic surfaces and the measurement of reverberation time using the music as played in the hall as a ``test'' signal.

  10. Acoustics in Schools.

    ERIC Educational Resources Information Center

    Singer, Miriam J.

    This paper explores the issues associated with poor acoustics within schools. Additionally, it suggests remedies for existing buildings and those under renovation, as well as concerns for new construction. The paper discusses the effects of unwanted noise on students in terms of physiological, motivational, and cognitive influences. Issues are…

  11. Micro acoustic spectrum analyzer

    DOEpatents

    Schubert, W. Kent; Butler, Michael A.; Adkins, Douglas R.; Anderson, Larry F.

    2004-11-23

    A micro acoustic spectrum analyzer for determining the frequency components of a fluctuating sound signal comprises a microphone to pick up the fluctuating sound signal and produce an alternating current electrical signal; at least one microfabricated resonator, each resonator having a different resonant frequency, that vibrate in response to the alternating current electrical signal; and at least one detector to detect the vibration of the microfabricated resonators. The micro acoustic spectrum analyzer can further comprise a mixer to mix a reference signal with the alternating current electrical signal from the microphone to shift the frequency spectrum to a frequency range that is a better matched to the resonant frequencies of the microfabricated resonators. The micro acoustic spectrum analyzer can be designed specifically for portability, size, cost, accuracy, speed, power requirements, and use in a harsh environment. The micro acoustic spectrum analyzer is particularly suited for applications where size, accessibility, and power requirements are limited, such as the monitoring of industrial equipment and processes, detection of security intrusions, or evaluation of military threats.

  12. Detecting Contaminant Particles Acoustically

    NASA Technical Reports Server (NTRS)

    Wyett, L. M.

    1986-01-01

    Apparatus "listens" for particles in interior of complex turbomachinery. Contact microphones are attached at several points on pump housing. Acoustic transducer also attached to housing to excite entire pump with sound. Frequency of sound is slowly raised until pump resonates. Microphones detect noise of loose particles scraping against pump parts. Such as machining chips in turbopumps or other machinery without disassembly.

  13. Indigenous Acoustic Detection.

    DTIC Science & Technology

    1982-01-26

    considerable distances, and they act as good sensors of human presence. Though singing insects are ubiquitous in warm areas, even in the desert ( Nevo and...methodology. DTIC. CD-58-PL. Lloyd, J. E. 1981. Personnel communication. Nevo , E. and S. A. Blondheim. 1972. Acoustic isolation in the speciation of

  14. Mouse Genome Editing Using the CRISPR/Cas System.

    PubMed

    Harms, Donald W; Quadros, Rolen M; Seruggia, Davide; Ohtsuka, Masato; Takahashi, Gou; Montoliu, Lluis; Gurumurthy, Channabasavaiah B

    2014-10-01

    The availability of techniques to create desired genetic mutations has enabled the laboratory mouse as an extensively used model organism in biomedical research including human genetics. A new addition to this existing technical repertoire is the CRISPR/Cas system. Specifically, this system allows editing of the mouse genome much more quickly than the previously used techniques, and, more importantly, multiple mutations can be created in a single experiment. Here we provide protocols for preparation of CRISPR/Cas reagents and microinjection into one-cell mouse embryos to create knockout or knock-in mouse models.

  15. [CRISPR-Cas system as molecular scissors for gene therapy].

    PubMed

    Heinz, G A; Mashreghi, M-F

    2017-02-01

    Since the discovery of the CRISPR-Cas system as the adaptive immune system of prokaryotes, the underlying mechanism has proven to be a precise molecular tool for the targeted editing of genetic information in various cell types. By using the CRISPR-Cas9 system DNA sequences can be cut out at any site in the genome and changed in a sequence-specific manner. In the long term this provides the opportunity to cure diseases caused by gene mutations.

  16. Mouse Genome Editing using CRISPR/Cas System

    PubMed Central

    Harms, Donald W; Quadros, Rolen M; Seruggia, Davide; Ohtsuka, Masato; Takahashi, Gou

    2015-01-01

    The availability of techniques to create desired genetic mutations has enabled the laboratory mouse as an extensively used model organism in biomedical research including human genetics. A new addition to this existing technical repertoire is the CRISPR/Cas system. Specifically, this system allows editing of the mouse genome much faster than the previously used techniques and more importantly multiple mutations can be created in a single experiment. Here we provide protocols for preparation of CRISPR/Cas reagents and microinjection into one cell mouse embryos to create knockout or knock-in mouse models. PMID:25271839

  17. Les sarcomes des tissus mous: à propos de 33 cas

    PubMed Central

    Abdou, Jiddou; Elkabous, Mustapha; M'rabti, Hind; Errihani, Hassan

    2015-01-01

    L'objectif de cette étude est de rapporter les particularités épidémiologiques, cliniques, histologiques, thérapeutiques et évolutives des sarcomes des tissus mous à l'Institut National d'Oncologie et de définir les facteurs influençant la survie des patients. C'est une étude rétrospective de 33 cas de sarcome des tissus mous, colligés entre janvier 2008 et décembre 2010. Les critères d’éligibilité étaient un âge supérieur à 16 ans, une épreuve histologique d'un sarcome des tissus mous à l'exclusion des tumeurs stromales gastro-intestinales (GIST). Les items recueillis étaient: épidémiologiques, cliniques, histologiques, Radiologiques, et thérapeutiques. Des analyses univariées puis multivariées ont été réalisées à la recherche de facteurs influençant la survie à 2 ans. Il s'agit de 33 cas, 17 Hommes et 16 Femmes, l’âge moyen était de 43,21 ans (Extrêmes= 18-76 ans). La tumeur était localisée aux extrémités dans 24 cas (72,72%). Le type histologique prédominant était le Liposarcome dans 9 cas (27,27%). Le stade tumoral était localisé dans 25 cas (75,8%), métastatique dans 8 cas (24,2%). Vingt-cinq tumeurs ont été traitées chirurgicalement dont 21 cas (84%) de chirurgie conservatrice et 4 cas (16%) de chirurgie radicale. La radiothérapie a été réalisée chez 10 patients (30,3%). La chimiothérapie a été faite chez 20 patients. En analyse univariée les facteurs pronostiques étaient l’âge (p=0,03) et le stade tumoral (p=0,09). L’âge et le stade tumoral sont des facteurs pronostiques influençant la survie des sarcomes des tissus mous. PMID:27022434

  18. Applications of CRISPR-Cas systems in neuroscience

    PubMed Central

    Heidenreich, Matthias; Zhang, Feng

    2016-01-01

    Genome editing tools, and in particular those based on CRISPR-Cas systems, are accelerating the pace of biological research and enabling targeted genetic interrogation in virtually any organism and cell type. These tools have opened the door to the development of new model systems for studying the complexity of the nervous system, including animal and stem cell-derived in vitro models. Precise and efficient gene editing using CRISPR-Cas systems has the potential to advance both basic and translational neuroscience research. PMID:26656253

  19. Expanding the Biologist's Toolkit with CRISPR-Cas9.

    PubMed

    Sternberg, Samuel H; Doudna, Jennifer A

    2015-05-21

    Few discoveries transform a discipline overnight, but biologists today can manipulate cells in ways never possible before, thanks to a peculiar form of prokaryotic adaptive immunity mediated by clustered regularly interspaced short palindromic repeats (CRISPR). From elegant studies that deciphered how these immune systems function in bacteria, researchers quickly uncovered the technological potential of Cas9, an RNA-guided DNA cleaving enzyme, for genome engineering. Here we highlight the recent explosion in visionary applications of CRISPR-Cas9 that promises to usher in a new era of biological understanding and control.

  20. Fusion of SpCas9 to E. coli Rec A protein enhances CRISPR-Cas9 mediated gene knockout in mammalian cells.

    PubMed

    Lin, Lin; Petersen, Trine Skov; Jensen, Kristopher Torp; Bolund, Lars; Kühn, Ralf; Luo, Yonglun

    2017-03-01

    Mammalian cells repair double-strand DNA breaks (DSB) by a range of different pathways following DSB induction by the engineered clustered regularly interspaced short palindromic repeats (CRISPR)-associated protein Cas9. While CRISPR-Cas9 thus enables predesigned modifications of the genome, applications of CRISPR-Cas9-mediated genome-editing are frequently hampered by the unpredictable and varying pathways for DSB repair in mammalian cells. Here we present a strategy of fusing Cas9 to recombinant proteins for fine-tuning of the DSB repair preferences in mammalian cells. By fusing Streptococcus Pyogenes Cas9 (SpCas9) to the recombinant protein A (Rec A, NP_417179.1) from Escherichia coli, we create a recombinant Cas9 protein (rSpCas9) which enhances the generation of indel mutations at DSB sites in mammalian cells, increases the frequency of DSB repair by homology-directed single-strand annealing (SSA), and represses homology-directed gene conversion by approximately 33%. Our study thus proves for the first time that fusing SpCas9 to recombinant proteins can influence the balance between DSB repair pathways in mammalian cells. This approach may form the basis for further investigations of the applications of recombinant Cas9 proteins to fine-tuning DSB repair pathways in eukaryotic cells.

  1. Cas9 gRNA engineering for genome editing, activation and repression

    PubMed Central

    Kiani, Samira; Chavez, Alejandro; Tuttle, Marcelle; Hall, Richard N; Chari, Raj; Ter-Ovanesyan, Dmitry; Qian, Jason; Pruitt, Benjamin W; Beal, Jacob; Vora, Suhani; Buchthal, Joanna; Kowal, Emma J K; Ebrahimkhani, Mohammad R; Collins, James J; Weiss, Ron; Church, George

    2015-01-01

    We demonstrate that by altering the length of Cas9-associated guide RNA(gRNA) we were able to control Cas9 nuclease activity and simultaneously perform genome editing and transcriptional regulation with a single Cas9 protein. We exploited these principles to engineer mammalian synthetic circuits with combined transcriptional regulation and kill functions governed by a single multifunctional Cas9 protein. PMID:26344044

  2. Application of CRISPR-Cas system in gene therapy: Pre-clinical progress in animal model.

    PubMed

    Guan, Lihong; Han, Yawei; Zhu, Shaoyi; Lin, Juntang

    2016-10-01

    The clustered regularly interspaced short palindromic repeats (CRISPRs) and their associated proteins (Cas) belong to the crucial adaptive immune system, which exist in archaea and bacteria. Currently, CRISPR-Cas9 system has been modified and widely used to edit genome. In this review, we summarized the discovery, classification and mechanism of CRISPR-Cas system and further discussed the application of CRISPR-Cas9 in gene therapy, mainly in disease models.

  3. Holograms for acoustics

    NASA Astrophysics Data System (ADS)

    Melde, Kai; Mark, Andrew G.; Qiu, Tian; Fischer, Peer

    2016-09-01

    Holographic techniques are fundamental to applications such as volumetric displays, high-density data storage and optical tweezers that require spatial control of intricate optical or acoustic fields within a three-dimensional volume. The basis of holography is spatial storage of the phase and/or amplitude profile of the desired wavefront in a manner that allows that wavefront to be reconstructed by interference when the hologram is illuminated with a suitable coherent source. Modern computer-generated holography skips the process of recording a hologram from a physical scene, and instead calculates the required phase profile before rendering it for reconstruction. In ultrasound applications, the phase profile is typically generated by discrete and independently driven ultrasound sources; however, these can only be used in small numbers, which limits the complexity or degrees of freedom that can be attained in the wavefront. Here we introduce monolithic acoustic holograms, which can reconstruct diffraction-limited acoustic pressure fields and thus arbitrary ultrasound beams. We use rapid fabrication to craft the holograms and achieve reconstruction degrees of freedom two orders of magnitude higher than commercial phased array sources. The technique is inexpensive, appropriate for both transmission and reflection elements, and scales well to higher information content, larger aperture size and higher power. The complex three-dimensional pressure and phase distributions produced by these acoustic holograms allow us to demonstrate new approaches to controlled ultrasonic manipulation of solids in water, and of liquids and solids in air. We expect that acoustic holograms will enable new capabilities in beam-steering and the contactless transfer of power, improve medical imaging, and drive new applications of ultrasound.

  4. CRISPR-Cas immunity and mobile DNA: a new superfamily of DNA transposons encoding a Cas1 endonuclease.

    PubMed

    Hickman, Alison B; Dyda, Fred

    2014-01-01

    Mobile genetic elements such as DNA transposons are a feature of most genomes. The existence of novel DNA transposons can be inferred when whole genome sequencing reveals the presence of hallmarks of mobile elements such as terminal inverted repeats (TIRs) flanked by target site duplications (TSDs). A recent report describes a new superfamily of DNA transposons in the genomes of a few bacteria and archaea that possess TIRs and TSDs, and encode several conserved genes including a cas1 endonuclease gene, previously associated only with CRISPR-Cas adaptive immune systems. The data strongly suggests that these elements, designated 'casposons', are likely to be bona fide DNA transposons and that their Cas1 nucleases act as transposases and are possibly still active.

  5. Acoustic field modulation in regenerators

    NASA Astrophysics Data System (ADS)

    Hu, J. Y.; Wang, W.; Luo, E. C.; Chen, Y. Y.

    2016-12-01

    The regenerator is a key component that transfers energy between heat and work. The conversion efficiency is significantly influenced by the acoustic field in the regenerator. Much effort has been spent to quantitatively determine this influence, but few comprehensive experimental verifications have been performed because of difficulties in modulating and measuring the acoustic field. In this paper, a method requiring two compressors is introduced and theoretically investigated that achieves acoustic field modulation in the regenerator. One compressor outputs the acoustic power for the regenerator; the other acts as a phase shifter. A RC load dissipates the acoustic power out of both the regenerator and the latter compressor. The acoustic field can be modulated by adjusting the current in the two compressors and opening the RC load. The acoustic field is measured with pressure sensors instead of flow-field imaging equipment, thereby greatly simplifying the experiment.

  6. Acoustic Suppression Systems and Related Methods

    NASA Technical Reports Server (NTRS)

    Kolaini, Ali R. (Inventor); Kern, Dennis L. (Inventor)

    2013-01-01

    An acoustic suppression system for absorbing and/or scattering acoustic energy comprising a plurality of acoustic targets in a containment is described, the acoustic targets configured to have resonance frequencies allowing the targets to be excited by incoming acoustic waves, the resonance frequencies being adjustable to suppress acoustic energy in a set frequency range. Methods for fabricating and implementing the acoustic suppression system are also provided.

  7. Creating Genome Modifications in C. elegans Using the CRISPR/Cas9 System.

    PubMed

    Calarco, John A; Friedland, Ari E

    2015-01-01

    The clustered, regularly interspaced, short, palindromic repeat (CRISPR)-associated (CAS) nuclease Cas9 has been used in many organisms to generate specific mutations and transgene insertions. Here we describe a method using the S. pyogenes Cas9 in C. elegans that provides a convenient and effective approach for making heritable changes to the worm genome.

  8. CAS or Pen-and-Paper: Factors That Influence Students' Choices

    ERIC Educational Resources Information Center

    Cameron, Scott; Ball, Lynda

    2015-01-01

    This paper reports on a study of choices about the use of a computer algebra system (CAS) or pen-and-paper (p&p) by a class of seven Year 11 Mathematical Methods (CAS) students as they completed a calculus worksheet. Factors that influenced students' choices are highlighted by comparing and contrasting the use of CAS and p&p between…

  9. After 16 Years of Publishing Standards, Do CAS Standards Make a Difference?

    ERIC Educational Resources Information Center

    Arminio, Jan; Gochenauer, Patty

    2004-01-01

    Using members of professional associations who are a part of the Council for the Advancement of Standards in Higher Education (CAS) consortia as a sample, this study investigated who uses CAS Standards, how and why they are used, and whether CAS Standards are associated with enhanced student learning. Using a quantitative analysis, this study…

  10. Mismatch Negativity Responses in Children with a Diagnosis of Childhood Apraxia of Speech (CAS)

    ERIC Educational Resources Information Center

    Froud, Karen; Khamis-Dakwar, Reem

    2012-01-01

    Purpose: To evaluate whether a hypothesis suggesting that apraxia of speech results from phonological overspecification could be relevant for childhood apraxia of speech (CAS). Method: High-density EEG was recorded from 5 children with CAS and 5 matched controls, ages 5-8 years, with and without CAS, as they listened to randomized sequences of CV…

  11. A Hardware-and-Software System for Experimental Studies of the Acoustic Startle Response in Laboratory Rodents.

    PubMed

    Pevtsov, E F; Storozheva, Z I; Proshin, A T; Pevtsova, E I

    2016-02-01

    We developed and tested a novel hardware-and-software system for recording the amplitude of the acoustic startle response in rodents. In our experiments, the baseline indexes of acoustic startle response in laboratory rats and pre-stimulation inhibition under the standard delivery of acoustic stimulation were similar to those evaluated by other investigators on foreign devices. The proposed system is relatively cheap and provides the possibility of performing experiments on freely moving specimens. It should be emphasized that the results of studies can be processed with free-access software.

  12. Vagus Nerve Stimulation

    MedlinePlus

    Vagus nerve stimulation Overview By Mayo Clinic Staff Vagus nerve stimulation is a procedure that involves implantation of a device that stimulates the vagus nerve with electrical impulses. There's one vagus nerve on ...

  13. Preparing Students to Take SOA/CAS Exam FM/2

    ERIC Educational Resources Information Center

    Marchand, Richard J.

    2014-01-01

    This paper provides suggestions for preparing students to take the actuarial examination on financial mathematics, SOA/CAS Exam FM/2. It is based on current practices employed at Slippery Rock University, a small public liberal arts university. Detailed descriptions of our Theory of Interest course and subsequent Exam FM/2 prep course are provided…

  14. CRISPR/Cas9 advances engineering of microbial cell factories.

    PubMed

    Jakočiūnas, Tadas; Jensen, Michael K; Keasling, Jay D

    2016-03-01

    One of the key drivers for successful metabolic engineering in microbes is the efficacy by which genomes can be edited. As such there are many methods to choose from when aiming to modify genomes, especially those of model organisms like yeast and bacteria. In recent years, clustered regularly interspaced palindromic repeats (CRISPR) and its associated proteins (Cas) have become the method of choice for precision genome engineering in many organisms due to their orthogonality, versatility and efficacy. Here we review the strategies adopted for implementation of RNA-guided CRISPR/Cas9 genome editing with special emphasis on their application for metabolic engineering of yeast and bacteria. Also, examples of how nuclease-deficient Cas9 has been applied for RNA-guided transcriptional regulation of target genes will be reviewed, as well as tools available for computer-aided design of guide-RNAs will be highlighted. Finally, this review will provide a perspective on the immediate challenges and opportunities foreseen by the use of CRISPR/Cas9 genome engineering and regulation in the context of metabolic engineering.

  15. Light Echoes and Cold Dust in Cas A

    NASA Astrophysics Data System (ADS)

    Krause, O.; Rieke, G. H.; Birkmann, S.

    2006-06-01

    We report on infrared observations of the prototypical supernova remnant Cassiopeia A obtained with the Spitzer Space Telescope. Two images of Cas A taken at 24 micrometers with the MIPS instrument over a 1-year time interval revealed moving structures outside the shell of the supernova remnant to a distance of more than 20 arc minutes. The observed tangential velocities are at roughly the speed of light. The moving structures are infrared echoes, in which interstellar dust is heated by the explosion and by flares from the compact object near the center of the remnant. Far-infrared maps of the remnant at 160 micrometers in combination with molecular line observations demonstrate that most of recently detected submillimetre emission towards Cas A originates from interstellar dust in a molecular cloud complex located in the line of sight between the Earth and the remnant, rather than from a large amount (about three solar masses) of cold (18K) dust within Cas A. The argument that type II supernovae produce copious amounts of dust is therefore not supported by the case of Cas A, which previously appeared to provide the best evidence for this possibility.

  16. What rheumatologists need to know about CRISPR/Cas9.

    PubMed

    Gibson, Gary J; Yang, Maozhou

    2017-02-09

    CRISPR/Cas9 genome editing technology has taken the research world by storm since its use in eukaryotes was first proposed in 2012. Publications describing advances in technology and new applications have continued at an unrelenting pace since that time. In this Review, we discuss the application of CRISPR/Cas9 for creating gene mutations - the application that initiated the current avalanche of interest - and new developments that have largely answered initial concerns about its specificity and ability to introduce new gene sequences. We discuss the new, diverse and rapidly growing adaptations of the CRISPR/Cas9 technique that enable activation, repression, multiplexing and gene screening. These developments have enabled researchers to create sophisticated tools for dissecting the function and inter-relatedness of genes, as well as noncoding regions of the genome, and to identify gene networks and noncoding regions that promote disease or confer disease susceptibility. These approaches are beginning to be used to interrogate complex and multilayered biological systems and to produce complex animal models of disease. CRISPR/Cas9 technology has enabled the application of new therapeutic approaches to treating disease in animal models, some of which are beginning to be seen in the first human clinical trials. We discuss the direct application of these techniques to rheumatic diseases, which are currently limited but are sure to increase rapidly in the near future.

  17. Technological Discourse on CAS-Based Operative Knowledge

    ERIC Educational Resources Information Center

    Mann, Giora; Dana-Picard, Thierry; Zehavi, Nurit

    2007-01-01

    This article begins with a comparison of two groups of teachers, working on the same tasks in Analytic Geometry. One group has only basic experience in CAS-assisted problem solving, and the other group has extensive experience. The comparison is discussed in terms of the interplay between reflection, operative knowledge and execution. The findings…

  18. Targeted mutagenesis in chicken using CRISPR/Cas9 system

    PubMed Central

    Oishi, Isao; Yoshii, Kyoko; Miyahara, Daichi; Kagami, Hiroshi; Tagami, Takahiro

    2016-01-01

    The CRISPR/Cas9 system is a simple and powerful tool for genome editing in various organisms including livestock animals. However, the system has not been applied to poultry because of the difficulty in accessing their zygotes. Here we report the implementation of CRISPR/Cas9-mediated gene targeting in chickens. Two egg white genes, ovalbumin and ovomucoid, were efficiently (>90%) mutagenized in cultured chicken primordial germ cells (PGCs) by transfection of circular plasmids encoding Cas9, a single guide RNA, and a gene encoding drug resistance, followed by transient antibiotic selection. We transplanted CRISPR-induced mutant-ovomucoid PGCs into recipient chicken embryos and established three germline chimeric roosters (G0). All of the roosters had donor-derived mutant-ovomucoid spermatozoa, and the two with a high transmission rate of donor-derived gametes produced heterozygous mutant ovomucoid chickens as about half of their donor-derived offspring in the next generation (G1). Furthermore, we generated ovomucoid homozygous mutant offspring (G2) by crossing the G1 mutant chickens. Taken together, these results demonstrate that the CRISPR/Cas9 system is a simple and effective gene-targeting method in chickens. PMID:27050479

  19. Problem Solving in Calculus with Symbolic Geometry and CAS

    ERIC Educational Resources Information Center

    Todd, Philip; Wiechmann, James

    2008-01-01

    Computer algebra systems (CAS) have been around for a number of years, as has dynamic geometry. Symbolic geometry software is new. It bears a superficial similarity to dynamic geometry software, but differs in that problems may be set up involving symbolic variables and constants, and measurements are given as symbolic expressions. Mathematical…

  20. Prospective Mathematics Teachers' Interactions with CAS-Based Textbook Elements

    ERIC Educational Resources Information Center

    Davis, Jon D.

    2015-01-01

    This study investigated how a group of 10 prospective secondary mathematics teachers (PST) read, evaluated, and adapted a textbook lesson involving the symbolic manipulation capabilities of computer algebra systems (CASS). PST read the entire lesson and tended to focus on the organizing question at the beginning of the student lesson and the CAS-S…

  1. CRISPR-Cas9 technology: applications and human disease modelling.

    PubMed

    Torres-Ruiz, Raul; Rodriguez-Perales, Sandra

    2017-01-01

    Genome engineering is a powerful tool for a wide range of applications in biomedical research and medicine. The development of the clustered regularly interspaced short palindromic repeats (CRISPR)-Cas9 system has revolutionized the field of gene editing, thus facilitating efficient genome editing through the creation of targeted double-strand breaks of almost any organism and cell type. In addition, CRISPR-Cas9 technology has been used successfully for many other purposes, including regulation of endogenous gene expression, epigenome editing, live-cell labelling of chromosomal loci, edition of single-stranded RNA and high-throughput gene screening. The implementation of the CRISPR-Cas9 system has increased the number of available technological alternatives for studying gene function, thus enabling generation of CRISPR-based disease models. Although many mechanistic questions remain to be answered and several challenges have yet to be addressed, the use of CRISPR-Cas9-based genome engineering technologies will increase our knowledge of disease processes and their treatment in the near future.

  2. Building the Class 2 CRISPR-Cas Arsenal.

    PubMed

    Lewis, Kevin M; Ke, Ailong

    2017-02-02

    Adaptation of CRISPR-Cas9 for genome-editing applications has revolutionized biomedical research. New single-component effector CRISPR systems are emerging from the bioinformatics pipeline. How can we best harness their power? Three new studies will no doubt facilitate this transition by generating the C2c1 and C2c2 structure snapshots in different functional states.

  3. CRISPR-Cas9 genome editing in Drosophila

    PubMed Central

    Gratz, Scott J.; Rubinstein, C. Dustin; Harrison, Melissa M.; Wildonger, Jill; O’Connor-Giles, Kate M.

    2015-01-01

    The CRISPR-Cas9 system has transformed genome engineering of model organisms from possible to practical. CRISPR-Cas9 can be readily programmed to generate sequence-specific double-strand breaks that disrupt targeted loci when repaired by error-prone non-homologous end joining or to catalyze precise genome modification through homology-directed repair (HDR). Here we describe a streamlined approach for rapid and highly efficient engineering of the Drosophila genome via CRISPR-Cas9-mediated HDR. In this approach, transgenic flies expressing Cas9 are injected with plasmids to express guide RNAs (gRNAs) and positively marked donor templates. We detail target site selection; gRNA plasmid generation; donor template design and construction; and the generation, identification and molecular confirmation of engineered lines. We also present alternative approaches and highlight key considerations for experimental design. The approach outlined here can be used to rapidly and reliably generate a variety of engineered modifications, including genomic deletions and replacements, precise sequence edits, and incorporation of protein tags. PMID:26131852

  4. 48 CFR 9903.201-2 - Types of CAS coverage.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 48 Federal Acquisition Regulations System 7 2013-10-01 2012-10-01 true Types of CAS coverage. 9903.201-2 Section 9903.201-2 Federal Acquisition Regulations System COST ACCOUNTING STANDARDS BOARD... college or university, as defined in section 1201(a) of Public Law 89-329, November 8, 1965,...

  5. New Insight in Mathematics by Live CAS Documents.

    ERIC Educational Resources Information Center

    Cnop, Ivan

    Traditional education in mathematics is mostly a matter of hindsight, and many mathematics texts offer little opportunity for students and learners to gain insight. This paper shows how experiments in CAS (computer algebra systems) can lead to new ways of handling problems, new conjectures, new visualizations, new proofs, new correspondences…

  6. Equivalent Expressions Using CAS and Paper-and-Pencil Techniques

    ERIC Educational Resources Information Center

    Fonger, Nicole L.

    2014-01-01

    How can the key concept of equivalent expressions be addressed so that students strengthen their representational fluency with symbols, graphs, and numbers? How can research inform the synergistic use of both paper-and-pencil analysis and computer algebra systems (CAS) in a classroom learning environment? These and other related questions have…

  7. CRISPR-Cas9: from Genome Editing to Cancer Research

    PubMed Central

    Chen, Si; Sun, Heng; Miao, Kai; Deng, Chu-Xia

    2016-01-01

    Cancer development is a multistep process triggered by innate and acquired mutations, which cause the functional abnormality and determine the initiation and progression of tumorigenesis. Gene editing is a widely used engineering tool for generating mutations that enhance tumorigenesis. The recent developed clustered regularly interspaced short palindromic repeats-CRISPR-associated 9 (CRISPR-Cas9) system renews the genome editing approach into a more convenient and efficient way. By rapidly introducing genetic modifications in cell lines, organs and animals, CRISPR-Cas9 system extends the gene editing into whole genome screening, both in loss-of-function and gain-of-function manners. Meanwhile, the system accelerates the establishment of animal cancer models, promoting in vivo studies for cancer research. Furthermore, CRISPR-Cas9 system is modified into diverse innovative tools for observing the dynamic bioprocesses in cancer studies, such as image tracing for targeted DNA, regulation of transcription activation or repression. Here, we view recent technical advances in the application of CRISPR-Cas9 system in cancer genetics, large-scale cancer driver gene hunting, animal cancer modeling and functional studies. PMID:27994508

  8. A New Outburst of the Yellow Hypergiant Star ρ Cas

    NASA Astrophysics Data System (ADS)

    Aret, A.; Kraus, M.; Kolka, I.; Maravelias, G.

    2017-02-01

    Spectroscopic monitoring of the yellow hypergiant ρ Cas revealed a new outburst in 2013, which is obvious from the development of TiO bands in the spectra. Also many atmospheric lines characteristic of a later spectral type appear. This spectroscopic outburst is in agreement with the photometric light curve, which displays a drop by about 0.6 mag during the same period.

  9. Medical marijuana: CAS releases report, government cuts research funding.

    PubMed

    Betteridge, Glenn

    2006-12-01

    In June 2006, the Canadian AIDS Society (CAS) released a comprehensive report with recommendations to overcome barriers to the use of cannabis for medical purposes faced by people living with HIV/AIDS in Canada. On 25 September 2006, as part of package of spending cuts, the federal government announced plans to eliminate its marijuana medical research program.

  10. CRISPR-Cas9: from Genome Editing to Cancer Research.

    PubMed

    Chen, Si; Sun, Heng; Miao, Kai; Deng, Chu-Xia

    2016-01-01

    Cancer development is a multistep process triggered by innate and acquired mutations, which cause the functional abnormality and determine the initiation and progression of tumorigenesis. Gene editing is a widely used engineering tool for generating mutations that enhance tumorigenesis. The recent developed clustered regularly interspaced short palindromic repeats-CRISPR-associated 9 (CRISPR-Cas9) system renews the genome editing approach into a more convenient and efficient way. By rapidly introducing genetic modifications in cell lines, organs and animals, CRISPR-Cas9 system extends the gene editing into whole genome screening, both in loss-of-function and gain-of-function manners. Meanwhile, the system accelerates the establishment of animal cancer models, promoting in vivo studies for cancer research. Furthermore, CRISPR-Cas9 system is modified into diverse innovative tools for observing the dynamic bioprocesses in cancer studies, such as image tracing for targeted DNA, regulation of transcription activation or repression. Here, we view recent technical advances in the application of CRISPR-Cas9 system in cancer genetics, large-scale cancer driver gene hunting, animal cancer modeling and functional studies.

  11. Education in acoustics in Argentina

    NASA Astrophysics Data System (ADS)

    Miyara, Federico

    2002-11-01

    Over the last decades, education in acoustics (EA) in Argentina has experienced ups and downs due to economic and political issues interfering with long term projects. Unlike other countries, like Chile, where EA has reached maturity in spite of the acoustical industry having shown little development, Argentina has several well-established manufacturers of acoustic materials and equipment but no specific career with a major in acoustics. At the university level, acoustics is taught as a complementary--often elective--course for careers such as architecture, communication engineering, or music. In spite of this there are several research centers with programs covering environmental and community noise, effects of noise on man, acoustic signal processing, musical acoustics and acoustic emission, and several national and international meetings are held each year in which results are communicated and discussed. Several books on a variety of topics such as sound system, architectural acoustics, and noise control have been published as well. Another chapter in EA is technical and vocational education, ranging between secondary and postsecondary levels, with technical training on sound system operation or design. Over the last years there have been several attempts to implement master degrees in acoustics or audio engineering, with little or no success.

  12. Acoustic energy harvesting based on a planar acoustic metamaterial

    NASA Astrophysics Data System (ADS)

    Qi, Shuibao; Oudich, Mourad; Li, Yong; Assouar, Badreddine

    2016-06-01

    We theoretically report on an innovative and practical acoustic energy harvester based on a defected acoustic metamaterial (AMM) with piezoelectric material. The idea is to create suitable resonant defects in an AMM to confine the strain energy originating from an acoustic incidence. This scavenged energy is converted into electrical energy by attaching a structured piezoelectric material into the defect area of the AMM. We show an acoustic energy harvester based on a meta-structure capable of producing electrical power from an acoustic pressure. Numerical simulations are provided to analyze and elucidate the principles and the performances of the proposed system. A maximum output voltage of 1.3 V and a power density of 0.54 μW/cm3 are obtained at a frequency of 2257.5 Hz. The proposed concept should have broad applications on energy harvesting as well as on low-frequency sound isolation, since this system acts as both acoustic insulator and energy harvester.

  13. Manipulate acoustic waves by impedance matched acoustic metasurfaces

    NASA Astrophysics Data System (ADS)

    Wu, Ying; Mei, Jun; Aljahdali, Rasha

    We design a type of acoustic metasurface, which is composed of carefully designed slits in a rigid thin plate. The effective refractive indices of different slits are different but the impedances are kept the same as that of the host medium. Numerical simulations show that such a metasurface can redirect or reflect a normally incident wave at different frequencies, even though it is impedance matched to the host medium. We show that the underlying mechanisms can be understood by using the generalized Snell's law, and a unified analytic model based on mode-coupling theory. We demonstrate some simple realization of such acoustic metasurface with real materials. The principle is also extended to the design of planar acoustic lens which can focus acoustic waves. Manipulate acoustic waves by impedance matched acoustic metasurfaces.

  14. Acoustic Environment Simulation Study; Acoustic Intrusion Sensor Performance.

    DTIC Science & Technology

    1983-01-01

    RD-R149 245 ACOUSTIC ENVIRONMENT SIMULATION STUDY; ACOUSTIC is INTRUSION SENSOR PERFORMANCE(U) TIME SERIES ASSOCIATES PALO ALTO CA L ENOCHSON ET AL...ACOUSTIC ENVIRONMENT SIMULATION STUDY PREPARED BY: LOREN ENOCHSON TIME SERIES ASSOCIATES 920 WEST 33RD AVENUE SPOKANE, WA 99203 PREPARED FOR: NAVAL... TIME COVERED 5A0pA OF 1 jeamonth, Day) S, 54 ( 4UNT ,inal; .. na, F ROM TO o . !L,,Nv; REJa- ,GE U -. ,16. SUPPLEMENTARY NOTATION COSATI CODES 18

  15. Structural Acoustics and Vibrations

    NASA Astrophysics Data System (ADS)

    Chaigne, Antoine

    This structural chapter is devoted to vibrations of structures and to their coupling with the acoustic field. Depending on the context, the radiated sound can be judged as desirable, as is mostly the case for musical instruments, or undesirable, like noise generated by machinery. In architectural acoustics, one main goal is to limit the transmission of sound through walls. In the automobile industry, the engineers have to control the noise generated inside and outside the passenger compartment. This can be achieved by means of passive or active damping. In general, there is a strong need for quieter products and better sound quality generated by the structures in our daily environment.

  16. A Martian acoustic anemometer.

    PubMed

    Banfield, Don; Schindel, David W; Tarr, Steve; Dissly, Richard W

    2016-08-01

    An acoustic anemometer for use on Mars has been developed. To understand the processes that control the interaction between surface and atmosphere on Mars, not only the mean winds, but also the turbulent boundary layer, the fluxes of momentum, heat and molecular constituents between surface and atmosphere must be measured. Terrestrially this is done with acoustic anemometers, but the low density atmosphere on Mars makes it challenging to adapt such an instrument for use on Mars. This has been achieved using capacitive transducers and pulse compression, and was successfully demonstrated on a stratospheric balloon (simulating the Martian environment) and in a dedicated Mars Wind Tunnel facility. This instrument achieves a measurement accuracy of ∼5 cm/s with an update rate of >20 Hz under Martian conditions.

  17. Acoustic methodology review

    NASA Technical Reports Server (NTRS)

    Schlegel, R. G.

    1982-01-01

    It is important for industry and NASA to assess the status of acoustic design technology for predicting and controlling helicopter external noise in order for a meaningful research program to be formulated which will address this problem. The prediction methodologies available to the designer and the acoustic engineer are three-fold. First is what has been described as a first principle analysis. This analysis approach attempts to remove any empiricism from the analysis process and deals with a theoretical mechanism approach to predicting the noise. The second approach attempts to combine first principle methodology (when available) with empirical data to formulate source predictors which can be combined to predict vehicle levels. The third is an empirical analysis, which attempts to generalize measured trends into a vehicle noise prediction method. This paper will briefly address each.

  18. Radiosurgery of acoustic neurinomas

    SciTech Connect

    Flickinger, J.C.; Lunsford, L.D.; Coffey, R.J.; Linskey, M.E.; Bissonette, D.J.; Maitz, A.H.; Kondziolka, D. )

    1991-01-15

    Eighty-five patients with acoustic neurinomas underwent stereotactic radiosurgery with the gamma unit at the University of Pittsburgh (Pittsburgh, PA) during its first 30 months of operation. Neuroimaging studies performed in 40 patients with more than 1 year follow-up showed that tumors were smaller in 22 (55%), unchanged in 17 (43%), and larger in one (2%). The 2-year actuarial rates for preservation of useful hearing and any hearing were 46% and 62%, respectively. Previously undetected neuropathies of the trigeminal (n = 12) and facial nerves (n = 14) occurred 1 week to 1 year after radiosurgery (median, 7 and 6 months, respectively), and improved at median intervals of 13 and 8 months, respectively, after onset. Hearing loss was significantly associated with increasing average tumor diameter (P = 0.04). No deterioration of any cranial nerve function has yet developed in seven patients with average tumor diameters less than 10 mm. Radiosurgery is an important treatment alternative for selected acoustic neurinoma patients.

  19. Acoustics Discipline Overview

    NASA Technical Reports Server (NTRS)

    Envia, Edmane; Thomas, Russell

    2007-01-01

    As part of the Fundamental Aeronautics Program Annual Review, a summary of the progress made in 2007 in acoustics research under the Subsonic Fixed Wing project is given. The presentation describes highlights from in-house and external activities including partnerships and NRA-funded research with industry and academia. Brief progress reports from all acoustics Phase 1 NRAs are also included as are outlines of the planned activities for 2008 and all Phase 2 NRAs. N+1 and N+2 technology paths outlined for Subsonic Fixed Wing noise targets. NRA Round 1 progressing with focus on prediction method advancement. NRA Round 2 initiating work focused on N+2 technology, prediction methods, and validation. Excellent partnerships in progress supporting N+1 technology targets and providing key data sets.

  20. Acoustic absorption by sunspots

    NASA Technical Reports Server (NTRS)

    Braun, D. C.; Labonte, B. J.; Duvall, T. L., Jr.

    1987-01-01

    The paper presents the initial results of a series of observations designed to probe the nature of sunspots by detecting their influence on high-degree p-mode oscillations in the surrounding photosphere. The analysis decomposes the observed oscillations into radially propagating waves described by Hankel functions in a cylindrical coordinate system centered on the sunspot. From measurements of the differences in power between waves traveling outward and inward, it is demonstrated that sunspots appear to absorb as much as 50 percent of the incoming acoustic waves. It is found that for all three sunspots observed, the amount of absorption increases linearly with horizontal wavenumber. The effect is present in p-mode oscillations with wavelengths both significantly larger and smaller than the diameter of the sunspot umbrae. Actual absorption of acoustic energy of the magnitude observed may produce measurable decreases in the power and lifetimes of high-degree p-mode oscillations during periods of high solar activity.

  1. Electromagnetic acoustic imaging.

    PubMed

    Emerson, Jane F; Chang, David B; McNaughton, Stuart; Jeong, Jong Seob; Shung, K K; Cerwin, Stephen A

    2013-02-01

    Electromagnetic acoustic imaging (EMAI) is a new imaging technique that uses long-wavelength RF electromagnetic (EM) waves to induce ultrasound emission. Signal intensity and image contrast have been found to depend on spatially varying electrical conductivity of the medium in addition to conventional acoustic properties. The resultant conductivity- weighted ultrasound data may enhance the diagnostic performance of medical ultrasound in cancer and cardiovascular applications because of the known changes in conductivity of malignancy and blood-filled spaces. EMAI has a potential advantage over other related imaging techniques because it combines the high resolution associated with ultrasound detection with the generation of the ultrasound signals directly related to physiologically important electrical properties of the tissues. Here, we report the theoretical development of EMAI, implementation of a dual-mode EMAI/ultrasound apparatus, and successful demonstrations of EMAI in various phantoms designed to establish feasibility of the approach for eventual medical applications.

  2. Suppression through acoustics

    NASA Astrophysics Data System (ADS)

    Beck, Kevin D.; Short, Kenneth R.; VanMeenen, Kirsten M.; Servatius, Richard J.

    2006-05-01

    This paper reviews research conducted by our laboratory exploring the possible use of acoustical stimuli as a tool for influencing behavior. Over the course of several programs, different types of acoustic stimuli have been evaluated for their effectiveness in disrupting targeting, balance, and high-order cognitive processes in both humans and animals. Escape responses are of particular use in this regard. An escape response serves not only as an objective measure of aversion, but as a potential substitute for ongoing behavior. We have also assessed whether the level of performance changes if the individual does not perform an escape response. In general these studies have both suggested certain types of sounds are more aversive or distracting than others. Although the laboratory development of additional stimuli needs to continue, we are taking the next step by testing some of the more effective stimuli in more applied experimental scenarios including those involving group dynamics.

  3. Direct Cytosolic Delivery of CRISPR/Cas9-Ribonucleoprotein for Efficient Gene Editing.

    PubMed

    Mout, Rubul; Ray, Moumita; Yesilbag Tonga, Gulen; Lee, Yi-Wei; Tay, Tristan; Sasaki, Kanae; Rotello, Vincent M

    2017-03-28

    Genome editing through the delivery of CRISPR/Cas9-ribonucleoprotein (Cas9-RNP) reduces unwanted gene targeting and avoids integrational mutagenesis that can occur through gene delivery strategies. Direct and efficient delivery of Cas9-RNP into the cytosol followed by translocation to the nucleus remains a challenge. Here, we report a remarkably highly efficient (∼90%) direct cytoplasmic/nuclear delivery of Cas9 protein complexed with a guide RNA (sgRNA) through the coengineering of Cas9 protein and carrier nanoparticles. This construct provides effective (∼30%) gene editing efficiency and opens up opportunities in studying genome dynamics.

  4. CRISPR/Cas9-mediated targeted mutagenesis in Nicotiana tabacum.

    PubMed

    Gao, Junping; Wang, Genhong; Ma, Sanyuan; Xie, Xiaodong; Wu, Xiangwei; Zhang, Xingtan; Wu, Yuqian; Zhao, Ping; Xia, Qingyou

    2015-01-01

    Genome editing is one of the most powerful tools for revealing gene function and improving crop plants. Recently, RNA-guided genome editing using the type II clustered regularly interspaced short palindromic repeats (CRISPR)-associated protein (Cas) system has been used as a powerful and efficient tool for genome editing in various organisms. Here, we report genome editing in tobacco (Nicotiana tabacum) mediated by the CRISPR/Cas9 system. Two genes, NtPDS and NtPDR6, were used for targeted mutagenesis. First, we examined the transient genome editing activity of this system in tobacco protoplasts, insertion and deletion (indel) mutations were observed with frequencies of 16.2-20.3% after transfecting guide RNA (gRNA) and the nuclease Cas9 in tobacco protoplasts. The two genes were also mutated using multiplexing gRNA at a time. Additionally, targeted deletions and inversions of a 1.8-kb fragment between two target sites in the NtPDS locus were demonstrated, while indel mutations were also detected at both the sites. Second, we obtained transgenic tobacco plants with NtPDS and NtPDR6 mutations induced by Cas9/gRNA. The mutation percentage was 81.8% for NtPDS gRNA4 and 87.5% for NtPDR6 gRNA2. Obvious phenotypes were observed, etiolated leaves for the psd mutant and more branches for the pdr6 mutant, indicating that highly efficient biallelic mutations occurred in both transgenic lines. No significant off-target mutations were obtained. Our results show that the CRISPR/Cas9 system is a useful tool for targeted mutagenesis of the tobacco genome.

  5. FY 89 Acoustics Research

    DTIC Science & Technology

    1990-09-11

    small. (=0.3%) a result which exhibits qualitative agreemnent with the results of Korobko and Chernobaiŕ . We saw no detectable change in...Senlis, France, (1990). 5. A Practical Sensor for Acoustic Detection of Larvae and Insects in Harvested Commodities, R. Hickling, S.T. Chang , J.C. Webb...to detect or gene;rate ;Couste ,,vc’-. "hcsc mater;als are unitiue in that thcv can he formed into largecxihlc sheet. lhmrelut, it is possible to

  6. Structures and Acoustics Division

    NASA Technical Reports Server (NTRS)

    Acquaviva, Cynthia S.

    1999-01-01

    The Structures and Acoustics Division of NASA Glenn Research Center is an international leader in rotating structures, mechanical components, fatigue and fracture, and structural aeroacoustics. Included are disciplines related to life prediction and reliability, nondestructive evaluation, and mechanical drive systems. Reported are a synopsis of the work and accomplishments reported by the Division during the 1996 calendar year. A bibliography containing 42 citations is provided.

  7. Ocean acoustic tomography

    NASA Astrophysics Data System (ADS)

    Cornuelle, Bruce D.; Worcester, Peter F.; Dzieciuch, Matthew A.

    2008-10-01

    Ocean acoustic tomography (OAT) was proposed in 1979 by Walter Munk and Carl Wunsch as an analogue to x-ray computed axial tomography for the oceans. The oceans are opaque to most electromagnetic radiation, but there is a strong acoustic waveguide, and sound can propagate for 10 Mm and more with distinct multiply-refracted ray paths. Transmitting broadband pulses in the ocean leads to a set of impulsive arrivals at the receiver which characterize the impulse response of the sound channel. The peaks observed at the receiver are assumed to represent the arrival of energy traveling along geometric ray paths. These paths can be distinguished by arrival time, and by arrival angle when a vertical array of receivers is available. Changes in ray arrival time can be used to infer changes in ocean structure. Ray travel time measurements have been a mainstay of long-range acoustic measurements, but the strong sensitivity of ray paths to range-dependent sound speed perturbations makes the ray sampling functions uncertain in real cases. In the ray approximation travel times are sensitive to medium changes only along the corresponding eigenrays. Ray theory is an infinite-frequency approximation, and its eikonal equation has nonlinearities not found in the acoustic wave equation. We build on recent seismology results (kernels for body wave arrivals in the earth) to characterize the kernel for converting sound speed change in the ocean to travel time changes using more complete propagation physics. Wave-theoretic finite frequency kernels may show less sensitivity to small-scale sound speed structure.

  8. Broadband Acoustic Clutter

    DTIC Science & Technology

    2008-09-30

    shallow water 1 Report Documentation Page Form ApprovedOMB No. 0704-0188 Public reporting burden for the collection of information is estimated to...claims to the contrary in the ocean acoustics community, sub-bottom clutter can and does occur in shallow water environments. A step-by-step detailed...that of the overlying water column and hence there is no critical angle. Thus, the reflection, scattering, propagation and reverberation are

  9. Advanced Broadband Acoustic Clutter

    DTIC Science & Technology

    2010-10-31

    7, 18]). Key result: despite some claims to the contrary in the ocean acoustics community, sub-bottom clutter can and does occur in shallow water ...propagation, and clutter in both theory and measurements. This is important because in some shallow water areas (especially those with significant riverine...Abraham, data from Clutter󈧋 Experiment) to examine dependence of clutter statistics on multipath (Ref [8]). Key result: in the shallow water

  10. Acoustics Local Area Network

    DTIC Science & Technology

    2013-01-31

    contract was to provide a shared computing i : resource - the acou tics local area network (ALAN) - to support ocean acoustic and related oceanographic...SECURITY CLASSIFICATION 20. UMITATION OF ABSTRACT OF REPORT: THIS PAGE OF ABSTRACT Unclassified I I ONRCtI COMPUTER V 10 11/94 STANDARD FORM 233 (REV 241) oo 0 90 " VLNV1LV HNO Og6OuLtOI, CT:tT 96/OT/0

  11. Acoustic Communications for UUVs

    DTIC Science & Technology

    2016-06-07

    Acoustic Communications for UUVs Josko Catipovic Lee Freitag Naval Undersea Warfare Center Woods Hole Oceanographic Institution Newport, RI 02841... Woods Hole, MA 02543 (401) 832-3259 (508) 289-3285 catipovicj@npt.nuwc.navy.mil lfreitag@whoi.edu Dan Nagle Sam Smith Naval Undersea Warfare Center...positioned within a streamlined flow shield which reduces drag and protects them from damage. While the HF transducers are placed on the structure and the

  12. Acoustic Characterization of Soil

    DTIC Science & Technology

    2007-11-02

    modified SAR imaging algorithm. Page 26 Final Report In the acoustic subsurface imaging scenario, the "object" to be imaged (i.e., cultural artifacts... subsurface imaging scenario. To combat this potential difficulty we can utilize a new SAR imaging algorithm (Lee et al., 1996) derived from a geophysics...essentially a transmit plane wave. This is a cost-effective means to evaluate the feasibility of subsurface imaging . A more complete (and costly

  13. Acoustic velocity meter systems

    USGS Publications Warehouse

    Laenen, Antonius

    1985-01-01

    Acoustic velocity meter (AVM) systems operate on the principles that the point-to-point upstream traveltime of an acoustic pulse is longer than the downstream traveltime and that this difference in traveltime can be accurately measured by electronic devices. An AVM system is capable of recording water velocity (and discharge) under a wide range of conditions, but some constraints apply: 1. Accuracy is reduced and performance is degraded if the acoustic path is not a continuous straight line. The path can be bent by reflection if it is too close to a stream boundary or by refraction if it passes through density gradients resulting from variations in either water temperature or salinity. For paths of less than 100 m, a temperature gradient of 0.1' per meter causes signal bending less than 0.6 meter at midchannel, and satisfactory velocity results can be obtained. Reflection from stream boundaries can cause signal cancellation if boundaries are too close to signal path. 2. Signal strength is attenuated by particles or bubbles that absorb, spread, or scatter sound. The concentration of particles or bubbles that can be tolerated is a function of the path length and frequency of the acoustic signal. 3. Changes in streamline orientation can affect system accuracy if the variability is random. 4. Errors relating to signal resolution are much larger for a single threshold detection scheme than for multiple threshold schemes. This report provides methods for computing the effect of various conditions on the accuracy of a record obtained from an AVM. The equipment must be adapted to the site. Field reconnaissance and preinstallation analysis to detect possible problems are critical for proper installation and operation of an AVM system.

  14. Structures and Acoustics Division

    NASA Technical Reports Server (NTRS)

    Acquaviva, Cynthia S.

    2001-01-01

    The Structures and Acoustics Division of the NASA Glenn Research Center is an international leader in rotating structures, mechanical components, fatigue and fracture, and structural aeroacoustics. Included in this report are disciplines related to life prediction and reliability, nondestructive evaluation, and mechanical drive systems. Reported is a synopsis of the work and accomplishments completed by the Division during the 1997, 1998, and 1999 calendar years. A bibliography containing 93 citations is provided.

  15. Speech Recognition and Acoustic Features in Combined Electric and Acoustic Stimulation

    PubMed Central

    Yoon, Yang-soo; Li, Yongxin; Fu, Qian-Jie

    2011-01-01

    Purpose This study aimed to identify speech information processed by a hearing aid (HA) that is additive to information processed by a cochlear implant (CI) as a function of signal-to-noise ratio (SNR). Method Speech recognition was measured with CI alone, HA alone, and CI+HA. Ten participants were separated into two groups; good (aided pure-tone average (PTA) < 55 dB) and poor (aided PTA ≥ 55 dB) at audiometric frequencies ≤ 1 kHz in HA. Results Results showed that the good aided PTA group derived a clear bimodal benefit (performance difference between CI+HA and CI alone) for vowel and sentence recognition in noise while the poor aided PTA group received little benefit across speech tests and SNRs. Results also showed that a better aided PTA helped in processing cues embedded in both low and high frequencies; none of these cues were significantly perceived by the poor aided PTA group. Conclusions The aided PTA is an important indicator for bimodal advantage in speech perception. The lack of bimodal benefits in the poor group may be attributed to the non-optimal HA fitting. Bimodal listening provides a synergistic effect for cues in both low and high frequency components in speech. PMID:22199183

  16. Speech Recognition and Acoustic Features in Combined Electric and Acoustic Stimulation

    ERIC Educational Resources Information Center

    Yoon, Yang-soo; Li, Yongxin; Fu, Qian-Jie

    2012-01-01

    Purpose: In this study, the authors aimed to identify speech information processed by a hearing aid (HA) that is additive to information processed by a cochlear implant (CI) as a function of signal-to-noise ratio (SNR). Method: Speech recognition was measured with CI alone, HA alone, and CI + HA. Ten participants were separated into 2 groups; good…

  17. Adenovirus-Mediated Somatic Genome Editing of Pten by CRISPR/Cas9 in Mouse Liver in Spite of Cas9-Specific Immune Responses.

    PubMed

    Wang, Dan; Mou, Haiwei; Li, Shaoyong; Li, Yingxiang; Hough, Soren; Tran, Karen; Li, Jia; Yin, Hao; Anderson, Daniel G; Sontheimer, Erik J; Weng, Zhiping; Gao, Guangping; Xue, Wen

    2015-07-01

    CRISPR/Cas9 derived from the bacterial adaptive immunity pathway is a powerful tool for genome editing, but the safety profiles of in vivo delivered Cas9 (including host immune responses to the bacterial Cas9 protein) have not been comprehensively investigated in model organisms. Nonalcoholic steatohepatitis (NASH) is a prevalent human liver disease characterized by excessive fat accumulation in the liver. In this study, we used adenovirus (Ad) vector to deliver a Streptococcus pyogenes-derived Cas9 system (SpCas9) targeting Pten, a gene involved in NASH and a negative regulator of the PI3K-AKT pathway, in mouse liver. We found that the Ad vector mediated efficient Pten gene editing even in the presence of typical Ad vector-associated immunotoxicity in the liver. Four months after vector infusion, mice receiving the Pten gene-editing Ad vector showed massive hepatomegaly and features of NASH, consistent with the phenotypes following Cre-loxP-induced Pten deficiency in mouse liver. We also detected induction of humoral immunity against SpCas9 and the potential presence of an SpCas9-specific cellular immune response. Our findings provide a strategy to model human liver diseases in mice and highlight the importance considering Cas9-specific immune responses in future translational studies involving in vivo delivery of CRISPR/Cas9.

  18. Acoustic Force Density Acting on Inhomogeneous Fluids in Acoustic Fields

    NASA Astrophysics Data System (ADS)

    Karlsen, Jonas T.; Augustsson, Per; Bruus, Henrik

    2016-09-01

    We present a theory for the acoustic force density acting on inhomogeneous fluids in acoustic fields on time scales that are slow compared to the acoustic oscillation period. The acoustic force density depends on gradients in the density and compressibility of the fluid. For microfluidic systems, the theory predicts a relocation of the inhomogeneities into stable field-dependent configurations, which are qualitatively different from the horizontally layered configurations due to gravity. Experimental validation is obtained by confocal imaging of aqueous solutions in a glass-silicon microchip.

  19. Acoustically enhanced heat transport

    NASA Astrophysics Data System (ADS)

    Ang, Kar M.; Yeo, Leslie Y.; Friend, James R.; Hung, Yew Mun; Tan, Ming K.

    2016-01-01

    We investigate the enhancement of heat transfer in the nucleate boiling regime by inducing high frequency acoustic waves (f ˜ 106 Hz) on the heated surface. In the experiments, liquid droplets (deionized water) are dispensed directly onto a heated, vibrating substrate. At lower vibration amplitudes (ξs ˜ 10-9 m), the improved heat transfer is mainly due to the detachment of vapor bubbles from the heated surface and the induced thermal mixing. Upon increasing the vibration amplitude (ξs ˜ 10-8 m), the heat transfer becomes more substantial due to the rapid bursting of vapor bubbles happening at the liquid-air interface as a consequence of capillary waves travelling in the thin liquid film between the vapor bubble and the air. Further increases then lead to rapid atomization that continues to enhance the heat transfer. An acoustic wave displacement amplitude on the order of 10-8 m with 106 Hz order frequencies is observed to produce an improvement of up to 50% reduction in the surface temperature over the case without acoustic excitation.

  20. Virtual acoustic prototyping

    NASA Astrophysics Data System (ADS)

    Johnson, Marty

    2003-10-01

    In this paper the re-creation of 3-D sound fields so the full psycho-acoustic impact of sound sources can be assessed before the manufacture of a product or environment is examined. Using head related transfer functions (HRTFs) coupled with a head tracked set of headphones the sound field at the left and right ears of a listener can be re-created for a set of sound sources. However, the HRTFs require that sources have a defined location and this is not the typical output from numerical codes which describe the sound field as a set of distributed modes. In this paper a method of creating a set of equivalent sources is described such that the standard set of HRTFs can be applied in real time. A structural-acoustic model of a cylinder driving an enclosed acoustic field will be used as an example. It will be shown that equivalent sources can be used to recreate all of the reverberation of the enclosed space. An efficient singular value decomposition technique allows the large number of sources required to be simulated in real time. An introduction to the requirements necessary for 3-D virtual prototyping using high frequency Statistical Energy Analysis models will be presented. [Work supported by AuSim and NASA.

  1. Acoustically enhanced heat transport

    SciTech Connect

    Ang, Kar M.; Hung, Yew Mun; Tan, Ming K.; Yeo, Leslie Y.

    2016-01-15

    We investigate the enhancement of heat transfer in the nucleate boiling regime by inducing high frequency acoustic waves (f ∼ 10{sup 6} Hz) on the heated surface. In the experiments, liquid droplets (deionized water) are dispensed directly onto a heated, vibrating substrate. At lower vibration amplitudes (ξ{sub s} ∼ 10{sup −9} m), the improved heat transfer is mainly due to the detachment of vapor bubbles from the heated surface and the induced thermal mixing. Upon increasing the vibration amplitude (ξ{sub s} ∼ 10{sup −8} m), the heat transfer becomes more substantial due to the rapid bursting of vapor bubbles happening at the liquid-air interface as a consequence of capillary waves travelling in the thin liquid film between the vapor bubble and the air. Further increases then lead to rapid atomization that continues to enhance the heat transfer. An acoustic wave displacement amplitude on the order of 10{sup −8} m with 10{sup 6} Hz order frequencies is observed to produce an improvement of up to 50% reduction in the surface temperature over the case without acoustic excitation.

  2. Acoustically enhanced heat transport.

    PubMed

    Ang, Kar M; Yeo, Leslie Y; Friend, James R; Hung, Yew Mun; Tan, Ming K

    2016-01-01

    We investigate the enhancement of heat transfer in the nucleate boiling regime by inducing high frequency acoustic waves (f ∼ 10(6) Hz) on the heated surface. In the experiments, liquid droplets (deionized water) are dispensed directly onto a heated, vibrating substrate. At lower vibration amplitudes (ξs ∼ 10(-9) m), the improved heat transfer is mainly due to the detachment of vapor bubbles from the heated surface and the induced thermal mixing. Upon increasing the vibration amplitude (ξs ∼ 10(-8) m), the heat transfer becomes more substantial due to the rapid bursting of vapor bubbles happening at the liquid-air interface as a consequence of capillary waves travelling in the thin liquid film between the vapor bubble and the air. Further increases then lead to rapid atomization that continues to enhance the heat transfer. An acoustic wave displacement amplitude on the order of 10(-8) m with 10(6) Hz order frequencies is observed to produce an improvement of up to 50% reduction in the surface temperature over the case without acoustic excitation.

  3. Acoustic paramagnetic logging tool

    DOEpatents

    Vail, III, William B.

    1988-01-01

    New methods and apparatus are disclosed which allow measurement of the presence of oil and water in geological formations using a new physical effect called the Acoustic Paramagnetic Logging Effect (APLE). The presence of petroleum in formation causes a slight increase in the earth's magnetic field in the vicinity of the reservoir. This is the phenomena of paramagnetism. Application of an acoustic source to a geological formation at the Larmor frequency of the nucleons present causes the paramagnetism of the formation to disappear. This results in a decrease in the earth3 s magnetic field in the vicinity of the oil bearing formation. Repetitively frequency sweeping the acoustic source through the Larmor frequency of the nucleons present (approx. 2 kHz) causes an amplitude modulation of the earth's magnetic field which is a consequence of the APLE. The amplitude modulation of the earth's magnetic field is measured with an induction coil gradiometer and provides a direct measure of the amount of oil and water in the excitation zone of the formation . The phase of the signal is used to infer the longitudinal relaxation times of the fluids present, which results in the ability in general to separate oil and water and to measure the viscosity of the oil present. Such measurements may be preformed in open boreholes and in cased well bores.

  4. The Aspergillus fumigatus metacaspases CasA and CasB facilitate growth under conditions of endoplasmic reticulum stress.

    PubMed

    Richie, Daryl L; Miley, Michael D; Bhabhra, Ruchi; Robson, Geoffrey D; Rhodes, Judith C; Askew, David S

    2007-01-01

    We have examined the contribution of metacaspases to the growth and stress response of the opportunistic human mould pathogen, Aspergillus fumigatus, based on increasing evidence implicating the yeast metacaspase Yca1p in apoptotic-like programmed cell death. Single metacaspase-deficient mutants were constructed by targeted disruption of each of the two metacaspase genes in A. fumigatus, casA and casB, and a metacaspase-deficient mutant, DeltacasA/DeltacasB, was constructed by disrupting both genes. Stationary phase cultures of wild-type A. fumigatus were associated with the appearance of typical markers of apoptosis, including elevated proteolytic activity against caspase substrates, phosphatidylserine exposure on the outer leaflet of the membrane, and loss of viability. By contrast, phosphatidylserine exposure was not observed in stationary phase cultures of the DeltacasA/DeltacasB mutant, although caspase activity and viability was indistinguishable from wild type. The mutant retained wild-type virulence and showed no difference in sensitivity to a range of pro-apoptotic stimuli that have been reported to initiate yeast apoptosis. However, the DeltacasA/DeltacasB mutant showed a growth detriment in the presence of agents that disrupt endoplasmic reticulum homeostasis. These findings demonstrate that metacaspase activity in A. fumigatus contributes to the apoptotic-like loss of membrane phospholipid asymmetry at stationary phase, and suggest that CasA and CasB have functions that support growth under conditions of endoplasmic reticulum stress.

  5. Efficient mutagenesis by CRISPR/Cas system during meiotic maturation of porcine oocytes

    PubMed Central

    ONUMA, Asuka; FUJII, Wataru; SUGIURA, Koji; NAITO, Kunihiko

    2016-01-01

    Genome editing using the CRISPR/Cas system can induce mutations with high efficiency, and allows easier production of genome-modified animals than that offered by the conventional method where embryonic stem cells are used. However, studies using CRISPR/Cas systems have been mostly limited to proliferating somatic cells and pronuclear-stage fertilized eggs. In contrast, the efficiency of a CRISPR/Cas system in immature and maturing oocytes progressing through meiosis has not yet been assessed. In the present study, we evaluated the genome-modification efficiency of the CRISPR/Cas system during meiotic maturation of porcine oocytes. Additionally, the localization of the Cas9 protein in immature oocytes was analyzed in relation to nuclear transport and mutation induction. The results showed that CRISPR/Cas induced mutation with high efficiency even in maturing oocytes with condensed chromosomes, whereas mutations were not induced in GV-stage oocytes. The localization analysis of enhanced green fluorescent protein (EGFP)-tagged Cas9 (Cas9-EGFP) revealed that the nuclei contained lesser Cas9 than the cytoplasm in immature oocytes. Treatment with leptomycin B, a nuclear export inhibitor, increased the amount of nuclear Cas9 and enabled mutation induction in GV oocytes. Our results suggest that CRISPR/Cas systems can be applied to oocytes during meiotic maturation and be implemented in novel applications targeting female genomes. PMID:27773884

  6. Efficient mutagenesis by CRISPR/Cas system during meiotic maturation of porcine oocytes.

    PubMed

    Onuma, Asuka; Fujii, Wataru; Sugiura, Koji; Naito, Kunihiko

    2017-02-16

    Genome editing using the CRISPR/Cas system can induce mutations with high efficiency, and allows easier production of genome-modified animals than that offered by the conventional method where embryonic stem cells are used. However, studies using CRISPR/Cas systems have been mostly limited to proliferating somatic cells and pronuclear-stage fertilized eggs. In contrast, the efficiency of a CRISPR/Cas system in immature and maturing oocytes progressing through meiosis has not yet been assessed. In the present study, we evaluated the genome-modification efficiency of the CRISPR/Cas system during meiotic maturation of porcine oocytes. Additionally, the localization of the Cas9 protein in immature oocytes was analyzed in relation to nuclear transport and mutation induction. The results showed that CRISPR/Cas induced mutation with high efficiency even in maturing oocytes with condensed chromosomes, whereas mutations were not induced in GV-stage oocytes. The localization analysis of enhanced green fluorescent protein (EGFP)-tagged Cas9 (Cas9-EGFP) revealed that the nuclei contained lesser Cas9 than the cytoplasm in immature oocytes. Treatment with leptomycin B, a nuclear export inhibitor, increased the amount of nuclear Cas9 and enabled mutation induction in GV oocytes. Our results suggest that CRISPR/Cas systems can be applied to oocytes during meiotic maturation and be implemented in novel applications targeting female genomes.

  7. HMMCAS: a web tool for the identification and domain annotations of Cas proteins.

    PubMed

    Chai, Guoshi; Yu, Min; Jiang, Lixu; Duan, Yaocong; Huang, Jian

    2017-02-07

    The CRISPR-Cas (clustered regularly interspaced short palindromic repeats-CRISPR-associated proteins) adaptive immune systems are discovered in many bacteria and most archaea. These systems are encoded by cas (CRISPR-associated) operons that have an extremely diverse architecture. The most crucial step in the depiction of cas operons composition is the identification of cas genes or Cas proteins. With the continuous increase of the newly sequenced archaeal and bacterial genomes, the recognition of new Cas proteins is becoming possible, which not only provides candidates for novel genome editing tools but also helps to understand the prokaryotic immune system better. Here we describe HMMCAS, a web service for the detection of CRISPR-associated structural and functional domains in protein sequences. HMMCAS uses hmmscan similarity search algorithm in HMMER3.1 to provide a fast, interactive service based on a comprehensive collection of hidden Markov models of Cas protein family. It can accurately identify the Cas proteins including those fusion proteins, for example the Cas1-Cas4 fusion protein in Candidatus Chloracidobacterium thermophilum B (Cab. thermophilum B). HMMCAS can also find putative cas operon and determine which type it belongs to. HMMCAS is freely available at http://i.uestc.edu.cn/hmmcas.

  8. Chemical and Biophysical Modulation of Cas9 for Tunable Genome Engineering.

    PubMed

    Nuñez, James K; Harrington, Lucas B; Doudna, Jennifer A

    2016-03-18

    The application of the CRISPR-Cas9 system for genome engineering has revolutionized the ability to interrogate genomes of mammalian cells. Programming the Cas9 endonuclease to induce DNA breaks at specified sites is achieved by simply modifying the sequence of its cognate guide RNA. Although Cas9-mediated genome editing has been shown to be highly specific, cleavage events at off-target sites have also been reported. Minimizing, and eventually abolishing, unwanted off-target cleavage remains a major goal of the CRISPR-Cas9 technology before its implementation for therapeutic use. Recent efforts have turned to chemical biology and biophysical approaches to engineer inducible genome editing systems for controlling Cas9 activity at the transcriptional and protein levels. Here, we review recent advancements to modulate Cas9-mediated genome editing by engineering split-Cas9 constructs, inteins, small molecules, protein-based dimerizing domains, and light-inducible systems.

  9. A simplified and efficient germline-specific CRISPR/Cas9 system for Drosophila genomic engineering.

    PubMed

    Sebo, Zachary L; Lee, Han B; Peng, Ying; Guo, Yi

    2014-01-01

    The type II CRISPR/Cas9 system (clustered regularly interspaced short palindromic repeats/CRISPR-associated) has recently emerged as an efficient and simple tool for site-specific engineering of eukaryotic genomes. To improve its applications in Drosophila genome engineering, we simplified the standard two-component CRISPR/Cas9 system by generating a stable transgenic fly line expressing the Cas9 endonuclease in the germline (Vasa-Cas9 line). By injecting vectors expressing engineered target-specific guide RNAs into Vasa-Cas9 fly embryos, mutations were generated from site-specific DNA cleavages and efficiently transmitted into progenies. Because Cas9 endonuclease is the universal component of the type II CRISPR/Cas9 system, site-specific genomic engineering based on this improved platform can be achieved with lower complexity and toxicity, greater consistency, and excellent versatility.

  10. Primary processing of CRISPR RNA by the endonuclease Cas6 in Staphylococcus epidermidis.

    PubMed

    Wakefield, Noelle; Rajan, Rakhi; Sontheimer, Erik J

    2015-10-07

    In many bacteria and archaea, an adaptive immune system (CRISPR-Cas) provides immunity against foreign genetic elements. This system uses CRISPR RNAs (crRNAs) derived from the CRISPR array, along with CRISPR-associated (Cas) proteins, to target foreign nucleic acids. In most CRISPR systems, endonucleolytic processing of crRNA precursors (pre-crRNAs) is essential for the pathway. Here we study the Cas6 endonuclease responsible for crRNA processing in the Type III-A CRISPR-Cas system from Staphylococcus epidermidis RP62a, a model for Type III-A CRISPR-Cas systems, and define substrate requirements for SeCas6 activity. We find that SeCas6 is necessary and sufficient for full-length crRNA biogenesis in vitro, and that it relies on both sequence and stem-loop structure in the 3' half of the CRISPR repeat for recognition and processing.

  11. Structures of Cas9 endonucleases reveal RNA-mediated conformational activation.

    PubMed

    Jinek, Martin; Jiang, Fuguo; Taylor, David W; Sternberg, Samuel H; Kaya, Emine; Ma, Enbo; Anders, Carolin; Hauer, Michael; Zhou, Kaihong; Lin, Steven; Kaplan, Matias; Iavarone, Anthony T; Charpentier, Emmanuelle; Nogales, Eva; Doudna, Jennifer A

    2014-03-14

    Type II CRISPR (clustered regularly interspaced short palindromic repeats)-Cas (CRISPR-associated) systems use an RNA-guided DNA endonuclease, Cas9, to generate double-strand breaks in invasive DNA during an adaptive bacterial immune response. Cas9 has been harnessed as a powerful tool for genome editing and gene regulation in many eukaryotic organisms. We report 2.6 and 2.2 angstrom resolution crystal structures of two major Cas9 enzyme subtypes, revealing the structural core shared by all Cas9 family members. The architectures of Cas9 enzymes define nucleic acid binding clefts, and single-particle electron microscopy reconstructions show that the two structural lobes harboring these clefts undergo guide RNA-induced reorientation to form a central channel where DNA substrates are bound. The observation that extensive structural rearrangements occur before target DNA duplex binding implicates guide RNA loading as a key step in Cas9 activation.

  12. Magnetomechanical Acoustic Emission - A Review

    DTIC Science & Technology

    1986-09-01

    Nickel Alloys Ferromagnetic Materials LA Acoustic Emission Barkhausen noise O-A Residual Stress ’~20 ABSTWA 7- ontinue reverse ad. Ii nedceeory and...also called magneto-acoustic emission [13], or acoustic Barkhausen effect [1]. When a ferromagnetic sample is placed in an alternating magnetic field...transducer, which should be insensitive to a magnetic field, was attached to a sample. A flux sensing coil and a Barkhausen noise (BN) probe are also

  13. Acoustic Imaging of Combustion Noise

    NASA Technical Reports Server (NTRS)

    Ramohalli, K. N.; Seshan, P. K.

    1984-01-01

    Elliposidal acoustic mirror used to measure sound emitted at discrete points in burning turbulent jets. Mirror deemphasizes sources close to target source and excludes sources far from target. At acoustic frequency of 20 kHz, mirror resolves sound from region 1.25 cm wide. Currently used by NASA for research on jet flames. Produces clearly identifiable and measurable variation of acoustic spectral intensities along length of flame. Utilized in variety of monitoring or control systems involving flames or other reacting flows.

  14. Wavelet Preprocessing of Acoustic Signals

    DTIC Science & Technology

    1991-12-01

    wavelet transform to preprocess acoustic broadband signals in a system that discriminates between different classes of acoustic bursts. This is motivated by the similarity between the proportional bandwidth filters provided by the wavelet transform and those found in biological hearing systems. The experiment involves comparing statistical pattern classifier effects of wavelet and FFT preprocessed acoustic signals. The data used was from the DARPA Phase I database, which consists of artificially generated signals with real ocean background. The

  15. Acoustic actuation of bioinspired microswimmers.

    PubMed

    Kaynak, Murat; Ozcelik, Adem; Nourhani, Amir; Lammert, Paul E; Crespi, Vincent H; Huang, Tony Jun

    2017-01-31

    Acoustic actuation of bioinspired microswimmers is experimentally demonstrated. Microswimmers are fabricated in situ in a microchannel. Upon acoustic excitation, the flagellum of the microswimmer oscillates, which in turn generates linear or rotary movement depending on the swimmer design. The speed of these bioinspired microswimmers is tuned by adjusting the voltage amplitude applied to the acoustic transducer. Simple microfabrication and remote actuation are promising for biomedical applications.

  16. A Brief History of Acoustics

    NASA Astrophysics Data System (ADS)

    Rossing, Thomas

    Although there are certainly some good historical treatments of acoustics in the literature, it still seems appropriate to begin a handbook of acoustics with a brief history of the subject. We begin by mentioning some important experiments that took place before the 19th century. Acoustics in the 19th century is characterized by describing the work of seven outstanding acousticians: Tyndall, von Helmholtz, Rayleigh, Stokes, Bell, Edison, and Koenig. Of course this sampling omits the mention of many other outstanding investigators.

  17. APL - North Pacific Acoustic Laboratory

    DTIC Science & Technology

    2015-03-04

    Acoustic Lab” Encl: (1) Final Technical Report for Subject Grant (2) SF298 for Enclosure Enclosure (1) is the Final Technical Report for the subject...Laboratory (hard copy with SF 298) Defense Technical Information Center (electronic files with SF298) APL - North Pacific Acoustic ...speed perturbations and the characteristics of the ambient acoustic noise field. Scattering and diffraction resulting from internal waves and other

  18. Spacecraft Internal Acoustic Environment Modeling

    NASA Technical Reports Server (NTRS)

    Chu, S. Reynold; Allen, Chris

    2009-01-01

    The objective of the project is to develop an acoustic modeling capability, based on commercial off-the-shelf software, to be used as a tool for oversight of the future manned Constellation vehicles. The use of such a model will help ensure compliance with acoustic requirements. Also, this project includes modeling validation and development feedback via building physical mockups and conducting acoustic measurements to compare with the predictions.

  19. Wireless Acoustic Measurement System

    NASA Technical Reports Server (NTRS)

    Anderson, Paul D.; Dorland, Wade D.

    2005-01-01

    A prototype wireless acoustic measurement system (WAMS) is one of two main subsystems of the Acoustic Prediction/Measurement Tool, which comprises software, acoustic instrumentation, and electronic hardware combined to afford integrated capabilities for predicting and measuring noise emitted by rocket and jet engines. The other main subsystem is described in "Predicting Rocket or Jet Noise in Real Time" (SSC-00215-1), which appears elsewhere in this issue of NASA Tech Briefs. The WAMS includes analog acoustic measurement instrumentation and analog and digital electronic circuitry combined with computer wireless local-area networking to enable (1) measurement of sound-pressure levels at multiple locations in the sound field of an engine under test and (2) recording and processing of the measurement data. At each field location, the measurements are taken by a portable unit, denoted a field station. There are ten field stations, each of which can take two channels of measurements. Each field station is equipped with two instrumentation microphones, a micro-ATX computer, a wireless network adapter, an environmental enclosure, a directional radio antenna, and a battery power supply. The environmental enclosure shields the computer from weather and from extreme acoustically induced vibrations. The power supply is based on a marine-service lead-acid storage battery that has enough capacity to support operation for as long as 10 hours. A desktop computer serves as a control server for the WAMS. The server is connected to a wireless router for communication with the field stations via a wireless local-area network that complies with wireless-network standard 802.11b of the Institute of Electrical and Electronics Engineers. The router and the wireless network adapters are controlled by use of Linux-compatible driver software. The server runs custom Linux software for synchronizing the recording of measurement data in the field stations. The software includes a module that

  20. Wireless Acoustic Measurement System

    NASA Technical Reports Server (NTRS)

    Anderson, Paul D.; Dorland, Wade D.; Jolly, Ronald L.

    2007-01-01

    A prototype wireless acoustic measurement system (WAMS) is one of two main subsystems of the Acoustic Prediction/ Measurement Tool, which comprises software, acoustic instrumentation, and electronic hardware combined to afford integrated capabilities for predicting and measuring noise emitted by rocket and jet engines. The other main subsystem is described in the article on page 8. The WAMS includes analog acoustic measurement instrumentation and analog and digital electronic circuitry combined with computer wireless local-area networking to enable (1) measurement of sound-pressure levels at multiple locations in the sound field of an engine under test and (2) recording and processing of the measurement data. At each field location, the measurements are taken by a portable unit, denoted a field station. There are ten field stations, each of which can take two channels of measurements. Each field station is equipped with two instrumentation microphones, a micro- ATX computer, a wireless network adapter, an environmental enclosure, a directional radio antenna, and a battery power supply. The environmental enclosure shields the computer from weather and from extreme acoustically induced vibrations. The power supply is based on a marine-service lead-acid storage battery that has enough capacity to support operation for as long as 10 hours. A desktop computer serves as a control server for the WAMS. The server is connected to a wireless router for communication with the field stations via a wireless local-area network that complies with wireless-network standard 802.11b of the Institute of Electrical and Electronics Engineers. The router and the wireless network adapters are controlled by use of Linux-compatible driver software. The server runs custom Linux software for synchronizing the recording of measurement data in the field stations. The software includes a module that provides an intuitive graphical user interface through which an operator at the control server

  1. Nuclease activity of Legionella pneumophila Cas2 promotes intracellular infection of amoebal host cells.

    PubMed

    Gunderson, Felizza F; Mallama, Celeste A; Fairbairn, Stephanie G; Cianciotto, Nicholas P

    2015-03-01

    Legionella pneumophila, the primary agent of Legionnaires' disease, flourishes in both natural and man-made environments by growing in a wide variety of aquatic amoebae. Recently, we determined that the Cas2 protein of L. pneumophila promotes intracellular infection of Acanthamoeba castellanii and Hartmannella vermiformis, the two amoebae most commonly linked to cases of disease. The Cas2 family of proteins is best known for its role in the bacterial and archeal clustered regularly interspaced short palindromic repeat (CRISPR)-CRISPR-associated protein (Cas) system that constitutes a form of adaptive immunity against phage and plasmid. However, the infection event mediated by L. pneumophila Cas2 appeared to be distinct from this function, because cas2 mutants exhibited infectivity defects in the absence of added phage or plasmid and since mutants lacking the CRISPR array or any one of the other cas genes were not impaired in infection ability. We now report that the Cas2 protein of L. pneumophila has both RNase and DNase activities, with the RNase activity being more pronounced. By characterizing a catalytically deficient version of Cas2, we determined that nuclease activity is critical for promoting infection of amoebae. Also, introduction of Cas2, but not its catalytic mutant form, into a strain of L. pneumophila that naturally lacks a CRISPR-Cas locus caused that strain to be 40- to 80-fold more infective for amoebae, unequivocally demonstrating that Cas2 facilitates the infection process independently of any other component encoded within the CRISPR-Cas locus. Finally, a cas2 mutant was impaired for infection of Willaertia magna but not Naegleria lovaniensis, suggesting that Cas2 promotes infection of most but not all amoebal hosts.

  2. Nuclease Activity of Legionella pneumophila Cas2 Promotes Intracellular Infection of Amoebal Host Cells

    PubMed Central

    Gunderson, Felizza F.; Mallama, Celeste A.; Fairbairn, Stephanie G.

    2014-01-01

    Legionella pneumophila, the primary agent of Legionnaires' disease, flourishes in both natural and man-made environments by growing in a wide variety of aquatic amoebae. Recently, we determined that the Cas2 protein of L. pneumophila promotes intracellular infection of Acanthamoeba castellanii and Hartmannella vermiformis, the two amoebae most commonly linked to cases of disease. The Cas2 family of proteins is best known for its role in the bacterial and archeal clustered regularly interspaced short palindromic repeat (CRISPR)–CRISPR-associated protein (Cas) system that constitutes a form of adaptive immunity against phage and plasmid. However, the infection event mediated by L. pneumophila Cas2 appeared to be distinct from this function, because cas2 mutants exhibited infectivity defects in the absence of added phage or plasmid and since mutants lacking the CRISPR array or any one of the other cas genes were not impaired in infection ability. We now report that the Cas2 protein of L. pneumophila has both RNase and DNase activities, with the RNase activity being more pronounced. By characterizing a catalytically deficient version of Cas2, we determined that nuclease activity is critical for promoting infection of amoebae. Also, introduction of Cas2, but not its catalytic mutant form, into a strain of L. pneumophila that naturally lacks a CRISPR-Cas locus caused that strain to be 40- to 80-fold more infective for amoebae, unequivocally demonstrating that Cas2 facilitates the infection process independently of any other component encoded within the CRISPR-Cas locus. Finally, a cas2 mutant was impaired for infection of Willaertia magna but not Naegleria lovaniensis, suggesting that Cas2 promotes infection of most but not all amoebal hosts. PMID:25547789

  3. Acoustic confinement in superlattice cavities

    NASA Astrophysics Data System (ADS)

    Garcia-Sanchez, Daniel; Déleglise, Samuel; Thomas, Jean-Louis; Atkinson, Paola; Lagoin, Camille; Perrin, Bernard

    2016-09-01

    The large coupling rate between the acoustic and optical fields confined in GaAs/AlAs superlattice cavities makes them appealing systems for cavity optomechanics. We have developed a mathematical model based on the scattering matrix that allows the acoustic guided modes to be predicted in nano and micropillar superlattice cavities. We demonstrate here that the reflection at the surface boundary considerably modifies the acoustic quality factor and leads to significant confinement at the micropillar center. Our mathematical model also predicts unprecedented acoustic Fano resonances on nanopillars featuring small mode volumes and very high mechanical quality factors, making them attractive systems for optomechanical applications.

  4. Double-negative acoustic metamaterial.

    PubMed

    Li, Jensen; Chan, C T

    2004-11-01

    We show here the existence of acoustic metamaterial, in which both the effective density and bulk modulus are simultaneously negative, in the true and strict sense of an effective medium. Our double-negative acoustic system is an acoustic analogue of Veselago's medium in electromagnetism, and shares many unique consequences, such as negative refractive index. The double negativity in acoustics is derived from low-frequency resonances, as in the case of electromagnetism, but the negative density and modulus are derived from a single resonance structure as distinct from electromagnetism in which the negative permeability and negative permittivity originates from different resonance mechanisms.

  5. Guided acoustic wave inspection system

    SciTech Connect

    Chinn, Diane J.

    2004-10-05

    A system for inspecting a conduit for undesirable characteristics. A transducer system induces guided acoustic waves onto said conduit. The transducer system detects the undesirable characteristics of the conduit by receiving guided acoustic waves that contain information about the undesirable characteristics. The conduit has at least two sides and the transducer system utilizes flexural modes of propagation to provide inspection using access from only the one side of the conduit. Cracking is detected with pulse-echo testing using one transducer to both send and receive the guided acoustic waves. Thinning is detected in through-transmission testing where one transducer sends and another transducer receives the guided acoustic waves.

  6. Truck acoustic data analyzer system

    SciTech Connect

    Haynes, Howard D.; Akerman, Alfred; Ayers, Curtis W.

    2006-07-04

    A passive vehicle acoustic data analyzer system having at least one microphone disposed in the acoustic field of a moving vehicle and a computer in electronic communication the microphone(s). The computer detects and measures the frequency shift in the acoustic signature emitted by the vehicle as it approaches and passes the microphone(s). The acoustic signature of a truck driving by a microphone can provide enough information to estimate the truck speed in miles-per-hour (mph), engine speed in rotations-per-minute (RPM), turbocharger speed in RPM, and vehicle weight.

  7. Transition section for acoustic waveguides

    DOEpatents

    Karplus, H.H.B.

    1975-10-28

    A means of facilitating the transmission of acoustic waves with minimal reflection between two regions having different specific acoustic impedances is described comprising a region exhibiting a constant product of cross-sectional area and specific acoustic impedance at each cross-sectional plane along the axis of the transition region. A variety of structures that exhibit this feature is disclosed, the preferred embodiment comprising a nested structure of doubly reentrant cones. This structure is useful for monitoring the operation of nuclear reactors in which random acoustic signals are generated in the course of operation.

  8. Powered-Lift Aerodynamics and Acoustics. [conferences

    NASA Technical Reports Server (NTRS)

    1976-01-01

    Powered lift technology is reviewed. Topics covered include: (1) high lift aerodynamics; (2) high speed and cruise aerodynamics; (3) acoustics; (4) propulsion aerodynamics and acoustics; (5) aerodynamic and acoustic loads; and (6) full-scale and flight research.

  9. Singing whales generate high levels of particle motion: implications for acoustic communication and hearing?

    PubMed

    Mooney, T Aran; Kaplan, Maxwell B; Lammers, Marc O

    2016-11-01

    Acoustic signals are fundamental to animal communication, and cetaceans are often considered bioacoustic specialists. Nearly all studies of their acoustic communication focus on sound pressure measurements, overlooking the particle motion components of their communication signals. Here we characterized the levels of acoustic particle velocity (and pressure) of song produced by humpback whales. We demonstrate that whales generate acoustic fields that include significant particle velocity components that are detectable over relatively long distances sufficient to play a role in acoustic communication. We show that these signals attenuate predictably in a manner similar to pressure and that direct particle velocity measurements can provide bearings to singing whales. Whales could potentially use such information to determine the distance of signalling animals. Additionally, the vibratory nature of particle velocity may stimulate bone conduction, a hearing modality found in other low-frequency specialized mammals, offering a parsimonious mechanism of acoustic energy transduction into the massive ossicles of whale ears. With substantial concerns regarding the effects of increasing anthropogenic ocean noise and major uncertainties surrounding mysticete hearing, these results highlight both an unexplored pathway that may be available for whale acoustic communication and the need to better understand the biological role of acoustic particle motion.

  10. Acoustic Enhancement of Sleep Slow Oscillations and Concomitant Memory Improvement in Older Adults.

    PubMed

    Papalambros, Nelly A; Santostasi, Giovanni; Malkani, Roneil G; Braun, Rosemary; Weintraub, Sandra; Paller, Ken A; Zee, Phyllis C

    2017-01-01

    Acoustic stimulation methods applied during sleep in young adults can increase slow wave activity (SWA) and improve sleep-dependent memory retention. It is unknown whether this approach enhances SWA and memory in older adults, who generally have reduced SWA compared to younger adults. Additionally, older adults are at risk for age-related cognitive impairment and therefore may benefit from non-invasive interventions. The aim of this study was to determine if acoustic stimulation can increase SWA and improve declarative memory in healthy older adults. Thirteen participants 60-84 years old completed one night of acoustic stimulation and one night of sham stimulation in random order. During sleep, a real-time algorithm using an adaptive phase-locked loop modeled the phase of endogenous slow waves in midline frontopolar electroencephalographic recordings. Pulses of pink noise were delivered when the upstate of the slow wave was predicted. Each interval of five pulses ("ON interval") was followed by a pause of approximately equal length ("OFF interval"). SWA during the entire sleep period was similar between stimulation and sham conditions, whereas SWA and spindle activity were increased during ON intervals compared to matched periods during the sham night. The increases in SWA and spindle activity were sustained across almost the entire five-pulse ON interval compared to matched sham periods. Verbal paired-associate memory was tested before and after sleep. Overnight improvement in word recall was significantly greater with acoustic stimulation compared to sham and was correlated with changes in SWA between ON and OFF intervals. Using the phase-locked-loop method to precisely target acoustic stimulation to the upstate of sleep slow oscillations, we were able to enhance SWA and improve sleep-dependent memory storage in older adults, which strengthens the theoretical link between sleep and age-related memory integrity.

  11. Acoustic Enhancement of Sleep Slow Oscillations and Concomitant Memory Improvement in Older Adults

    PubMed Central

    Papalambros, Nelly A.; Santostasi, Giovanni; Malkani, Roneil G.; Braun, Rosemary; Weintraub, Sandra; Paller, Ken A.; Zee, Phyllis C.

    2017-01-01

    Acoustic stimulation methods applied during sleep in young adults can increase slow wave activity (SWA) and improve sleep-dependent memory retention. It is unknown whether this approach enhances SWA and memory in older adults, who generally have reduced SWA compared to younger adults. Additionally, older adults are at risk for age-related cognitive impairment and therefore may benefit from non-invasive interventions. The aim of this study was to determine if acoustic stimulation can increase SWA and improve declarative memory in healthy older adults. Thirteen participants 60–84 years old completed one night of acoustic stimulation and one night of sham stimulation in random order. During sleep, a real-time algorithm using an adaptive phase-locked loop modeled the phase of endogenous slow waves in midline frontopolar electroencephalographic recordings. Pulses of pink noise were delivered when the upstate of the slow wave was predicted. Each interval of five pulses (“ON interval”) was followed by a pause of approximately equal length (“OFF interval”). SWA during the entire sleep period was similar between stimulation and sham conditions, whereas SWA and spindle activity were increased during ON intervals compared to matched periods during the sham night. The increases in SWA and spindle activity were sustained across almost the entire five-pulse ON interval compared to matched sham periods. Verbal paired-associate memory was tested before and after sleep. Overnight improvement in word recall was significantly greater with acoustic stimulation compared to sham and was correlated with changes in SWA between ON and OFF intervals. Using the phase-locked-loop method to precisely target acoustic stimulation to the upstate of sleep slow oscillations, we were able to enhance SWA and improve sleep-dependent memory storage in older adults, which strengthens the theoretical link between sleep and age-related memory integrity. PMID:28337134

  12. Is dust acoustic wave a new plasma acoustic mode?

    SciTech Connect

    Dwivedi, C.B.

    1997-09-01

    In this Brief Communication, the claim of the novelty of the dust acoustic wave in a dusty plasma within the constant dust charge model is questioned. Conceptual lacunas behind the claim have been highlighted and appropriate physical arguments have been forwarded against the claim. It is demonstrated that the so-called dust acoustic wave could better be termed as a general acoustic fluctuation response with a dominant characteristic feature of the acoustic-like mode (ALM) fluctuation response reported by Dwivedi {ital et al.} [J. Plasma Phys. {bold 41}, 219 (1989)]. It is suggested that both correct and more usable nomenclature of the ALM should be the so-called acoustic mode. {copyright} {ital 1997 American Institute of Physics.}

  13. Acoustic mechanical feedthroughs

    NASA Astrophysics Data System (ADS)

    Sherrit, Stewart; Walkemeyer, Phillip; Bao, Xiaoqi; Bar-Cohen, Yoseph; Badescu, Mircea

    2013-04-01

    Electromagnetic motors can have problems when operating in extreme environments. In addition, if one needs to do mechanical work outside a structure, electrical feedthroughs are required to transport the electric power to drive the motor. In this paper, we present designs for driving rotary and linear motors by pumping stress waves across a structure or barrier. We accomplish this by designing a piezoelectric actuator on one side of the structure and a resonance structure that is matched to the piezoelectric resonance of the actuator on the other side. Typically, piezoelectric motors can be designed with high torques and lower speeds without the need for gears. One can also use other actuation materials such as electrostrictive, or magnetostrictive materials in a benign environment and transmit the power in acoustic form as a stress wave and actuate mechanisms that are external to the benign environment. This technology removes the need to perforate a structure and allows work to be done directly on the other side of a structure without the use of electrical feedthroughs, which can weaken the structure, pipe, or vessel. Acoustic energy is pumped as a stress wave at a set frequency or range of frequencies to produce rotary or linear motion in a structure. This method of transferring useful mechanical work across solid barriers by pumping acoustic energy through a resonant structure features the ability to transfer work (rotary or linear motion) across pressure or thermal barriers, or in a sterile environment, without generating contaminants. Reflectors in the wall of barriers can be designed to enhance the efficiency of the energy/power transmission. The method features the ability to produce a bi-directional driving mechanism using higher-mode resonances. There are a variety of applications where the presence of a motor is complicated by thermal or chemical environments that would be hostile to the motor components and reduce life and, in some instances, not be

  14. Acoustic Mechanical Feedthroughs

    NASA Technical Reports Server (NTRS)

    Sherrit, Stewart; Walkemeyer, Phillip; Bao, Xiaoqi; Bar-Cohen, Yoseph; Badescu, Mircea

    2013-01-01

    Electromagnetic motors can have problems when operating in extreme environments. In addition, if one needs to do mechanical work outside a structure, electrical feedthroughs are required to transport the electric power to drive the motor. In this paper, we present designs for driving rotary and linear motors by pumping stress waves across a structure or barrier. We accomplish this by designing a piezoelectric actuator on one side of the structure and a resonance structure that is matched to the piezoelectric resonance of the actuator on the other side. Typically, piezoelectric motors can be designed with high torques and lower speeds without the need for gears. One can also use other actuation materials such as electrostrictive, or magnetostrictive materials in a benign environment and transmit the power in acoustic form as a stress wave and actuate mechanisms that are external to the benign environment. This technology removes the need to perforate a structure and allows work to be done directly on the other side of a structure without the use of electrical feedthroughs, which can weaken the structure, pipe, or vessel. Acoustic energy is pumped as a stress wave at a set frequency or range of frequencies to produce rotary or linear motion in a structure. This method of transferring useful mechanical work across solid barriers by pumping acoustic energy through a resonant structure features the ability to transfer work (rotary or linear motion) across pressure or thermal barriers, or in a sterile environment, without generating contaminants. Reflectors in the wall of barriers can be designed to enhance the efficiency of the energy/power transmission. The method features the ability to produce a bi-directional driving mechanism using higher-mode resonances. There are a variety of applications where the presence of a motor is complicated by thermal or chemical environments that would be hostile to the motor components and reduce life and, in some instances, not be

  15. Circulating leptin and inflammatory response in esophageal cancer, esophageal cancer-related cachexia-anorexia syndrome (CAS) and non-malignant CAS of the alimentary tract.

    PubMed

    Diakowska, Dorota; Krzystek-Korpacka, Malgorzata; Markocka-Maczka, Krystyna; Diakowski, Witold; Matusiewicz, Malgorzata; Grabowski, Krzysztof

    2010-08-01

    We investigated the association between esophageal cancer and cachexia-anorexia syndrome (CAS) of the alimentary tract and leptin, an adipocytokine crucial for body weight regulation, a modulator of inflammatory/immune response, implication of which in cancer and CAS development remains debatable. Circulating leptin was measured in 135 esophageal cancer patients (51 non-cachectic and 84 cachectic) and 83 controls (63 non-cachectic and 20 cachectic) and referred to cancer stage, CAS, and inflammatory and nutritional indices. Leptin was down-regulated in cancer patients and cachectic controls as compared to non-cachectic controls, with more pronounced hypoleptinemia in advanced cancers. Leptin correlated directly with BMI, TNF-alpha, albumin, and hemoglobin and indirectly with IL-6, IL-8, and hsCRP. The correlations, except for hsCRP, were more pronounced in females. BMI alone (females) and BMI and hsCRP (males) were independent predictors of leptin explaining over 60% of its variability. Following adjustment for BMI and gender, cancer-related CAS but not cancer itself negatively affected leptin. Leptin and BMI were independently associated with cancer-related and non-malignant CAS with diagnostic accuracy of 93% in identifying subjects with CAS. Pro-inflammatory, angiogenic and mitogenic properties of leptin do not seem to be important for esophageal cancer development but hypoleptinemia, independently from co-occurring reduction of adiposity, appears to be strongly associated with esophageal cancer-related CAS and non-malignant CAS of the alimentary tract.

  16. An Effective Strategy for Reliably Isolating Heritable and Cas9-Free Arabidopsis Mutants Generated by CRISPR/Cas9-Mediated Genome Editing.

    PubMed

    Gao, Xiuhua; Chen, Jilin; Dai, Xinhua; Zhang, Da; Zhao, Yunde

    2016-07-01

    Mutations generated by CRISPR/Cas9 in Arabidopsis (Arabidopsis thaliana) are often somatic and are rarely heritable. Isolation of mutations in Cas9-free Arabidopsis plants can ensure the stable transmission of the identified mutations to next generations, but the process is laborious and inefficient. Here, we present a simple visual screen for Cas9-free T2 seeds, allowing us to quickly obtain Cas9-free Arabidopsis mutants in the T2 generation. To demonstrate this in principle, we targeted two sites in the AUXIN-BINDING PROTEIN1 (ABP1) gene, whose function as a membrane-associated auxin receptor has been challenged recently. We obtained many T1 plants with detectable mutations near the target sites, but only a small fraction of T1 plants yielded Cas9-free abp1 mutations in the T2 generation. Moreover, the mutations did not segregate in Mendelian fashion in the T2 generation. However, mutations identified in the Cas9-free T2 plants were stably transmitted to the T3 generation following Mendelian genetics. To further simplify the screening procedure, we simultaneously targeted two sites in ABP1 to generate large deletions, which can be easily identified by PCR. We successfully generated two abp1 alleles that contained 1,141- and 711-bp deletions in the ABP1 gene. All of the Cas9-free abp1 alleles we generated were stable and heritable. The method described here allows for effectively isolating Cas9-free heritable CRISPR mutants in Arabidopsis.

  17. The acoustics of snoring.

    PubMed

    Pevernagie, Dirk; Aarts, Ronald M; De Meyer, Micheline

    2010-04-01

    Snoring is a prevalent disorder affecting 20-40% of the general population. The mechanism of snoring is vibration of anatomical structures in the pharyngeal airway. Flutter of the soft palate accounts for the harsh aspect of the snoring sound. Natural or drug-induced sleep is required for its appearance. Snoring is subject to many influences such as body position, sleep stage, route of breathing and the presence or absence of sleep-disordered breathing. Its presentation may be variable within or between nights. While snoring is generally perceived as a social nuisance, rating of its noisiness is subjective and, therefore, inconsistent. Objective assessment of snoring is important to evaluate the effect of treatment interventions. Moreover, snoring carries information relating to the site and degree of obstruction of the upper airway. If evidence for monolevel snoring at the site of the soft palate is provided, the patient may benefit from palatal surgery. These considerations have inspired researchers to scrutinize the acoustic characteristics of snoring events. Similarly to speech, snoring is produced in the vocal tract. Because of this analogy, existing techniques for speech analysis have been applied to evaluate snoring sounds. It appears that the pitch of the snoring sound is in the low-frequency range (<500 Hz) and corresponds to a fundamental frequency with associated harmonics. The pitch of snoring is determined by vibration of the soft palate, while nonpalatal snoring is more 'noise-like', and has scattered energy content in the higher spectral sub-bands (>500 Hz). To evaluate acoustic properties of snoring, sleep nasendoscopy is often performed. Recent evidence suggests that the acoustic quality of snoring is markedly different in drug-induced sleep as compared with natural sleep. Most often, palatal surgery alters sound characteristics of snoring, but is no cure for this disorder. It is uncertain whether the perceived improvement after palatal surgery, as

  18. Acoustic studies of solids

    SciTech Connect

    Granato, A.V.

    1987-01-01

    Acoustic technique have proven to be very useful in getting basic information on the configuration and dynamics of defects. Although the technique is indirect, the sensitivity is such that it often competes very favorably with more direct techniques such as neutron, x-ray, or phonon scattering. The symmetry information that comes directly from polarization control often also proves decisive in determining configurations. Many of the concepts that have been developed in explaining the various effects that have been seen in dislocation and point defect studies have proven also to be very useful when taken over almost directly into other areas of physics. 11 refs., 7 figs.

  19. Dynamic acoustic tractor beams

    SciTech Connect

    Mitri, F. G.

    2015-03-07

    Pulling a sphere and vibrating it around an equilibrium position by amplitude-modulation in the near-field of a single finite circular piston transducer is theoretically demonstrated. Conditions are found where a fluid hexane sphere (with arbitrary radius) chosen as an example, centered on the axis of progressive propagating waves and submerged in non-viscous water, experiences an attractive (steady) force pulling it towards the transducer, as well as an oscillatory force forcing it to vibrate back-and-forth. Numerical predictions for the dynamic force illustrate the theory and suggest an innovative method in designing dynamic acoustical tractor beams.

  20. Wind turbine acoustics

    NASA Technical Reports Server (NTRS)

    Hubbard, Harvey H.; Shepherd, Kevin P.

    1990-01-01

    Available information on the physical characteristics of the noise generated by wind turbines is summarized, with example sound pressure time histories, narrow- and broadband frequency spectra, and noise radiation patterns. Reviewed are noise measurement standards, analysis technology, and a method of characterizing wind turbine noise. Prediction methods are given for both low-frequency rotational harmonics and broadband noise components. Also included are atmospheric propagation data showing the effects of distance and refraction by wind shear. Human perception thresholds, based on laboratory and field tests, are given. Building vibration analysis methods are summarized. The bibliography of this report lists technical publications on all aspects of wind turbine acoustics.

  1. Quantum positron acoustic waves

    SciTech Connect

    Metref, Hassina; Tribeche, Mouloud

    2014-12-15

    Nonlinear quantum positron-acoustic (QPA) waves are investigated for the first time, within the theoretical framework of the quantum hydrodynamic model. In the small but finite amplitude limit, both deformed Korteweg-de Vries and generalized Korteweg-de Vries equations governing, respectively, the dynamics of QPA solitary waves and double-layers are derived. Moreover, a full finite amplitude analysis is undertaken, and a numerical integration of the obtained highly nonlinear equations is carried out. The results complement our previously published results on this problem.

  2. Broadband Acoustic Clutter

    DTIC Science & Technology

    2009-09-30

    height above the seabed of 18 m ( water depth was ~165m) in an area where there were few/no seabed features. Due to the proximity of the source and...understanding of the mechanisms associated with sonar clutter in shallow water . The statistical characterization of these features will lead to clutter...3285, 2007. 5 6 [5] Holland C.W., J.R. Preston, and D.A. Abraham, Long-range acoustic scattering from a shallow- water mud volcano cluster J

  3. Coffee roasting acoustics.

    PubMed

    Wilson, Preston S

    2014-06-01

    Cracking sounds emitted by coffee beans during the roasting process were recorded and analyzed to investigate the potential of using the sounds as the basis for an automated roast monitoring technique. Three parameters were found that could be exploited. Near the end of the roasting process, sounds known as "first crack" exhibit a higher acoustic amplitude than sounds emitted later, known as "second crack." First crack emits more low frequency energy than second crack. Finally, the rate of cracks appearing in the second crack chorus is higher than the rate in the first crack chorus.

  4. Chromosome engineering in zygotes with CRISPR/Cas9

    PubMed Central

    Boroviak, Katharina; Doe, Brendan; Banerjee, Ruby; Yang, Fengtang

    2016-01-01

    SUMMARY Deletions, duplications, and inversions of large genomic regions covering several genes are an important class of disease causing variants in humans. Modeling these structural variants in mice requires multistep processes in ES cells, which has limited their availability. Mutant mice containing small insertions, deletions, and single nucleotide polymorphisms can be reliably generated using CRISPR/Cas9 directly in mouse zygotes. Large structural variants can be generated using CRISPR/Cas9 in ES cells, but it has not been possible to generate these directly in zygotes. We now demonstrate the direct generation of deletions, duplications and inversions of up to one million base pairs by zygote injection. genesis 54:78–85, 2016. © 2016 The Authors. genesis Published by Wiley Periodicals, Inc. PMID:26742453

  5. Therapeutic genome engineering via CRISPR-Cas systems.

    PubMed

    Moreno, Ana M; Mali, Prashant

    2017-02-15

    Differences in genomes underlie most organismal diversity, and aberrations in genomes underlie many disease states. With the growing knowledge of the genetic and pathogenic basis of human disease, development of safe and efficient platforms for genome and epigenome engineering will transform our ability to therapeutically target human diseases and also potentially engineer disease resistance. In this regard, the recent advent of clustered regularly interspaced short palindromic repeats (CRISPR)-CRISPR-associated (Cas) RNA-guided nuclease systems have transformed our ability to target nucleic acids. Here we review therapeutic genome engineering applications with a specific focus on the CRISPR-Cas toolsets. We summarize past and current work, and also outline key challenges and future directions. For further resources related to this article, please visit the WIREs website.

  6. Analysis of estimation algorithms for CDTI and CAS applications

    NASA Technical Reports Server (NTRS)

    Goka, T.

    1985-01-01

    Estimation algorithms for Cockpit Display of Traffic Information (CDTI) and Collision Avoidance System (CAS) applications were analyzed and/or developed. The algorithms are based on actual or projected operational and performance characteristics of an Enhanced TCAS II traffic sensor developed by Bendix and the Federal Aviation Administration. Three algorithm areas are examined and discussed. These are horizontal x and y, range and altitude estimation algorithms. Raw estimation errors are quantified using Monte Carlo simulations developed for each application; the raw errors are then used to infer impacts on the CDTI and CAS applications. Applications of smoothing algorithms to CDTI problems are also discussed briefly. Technical conclusions are summarized based on the analysis of simulation results.

  7. Adapting CRISPR/Cas9 for functional genomics screens.

    PubMed

    Malina, Abba; Katigbak, Alexandra; Cencic, Regina; Maïga, Rayelle Itoua; Robert, Francis; Miura, Hisashi; Pelletier, Jerry

    2014-01-01

    The use of CRISPR/Cas9 (clustered regularly interspaced short palindromic repeats/CRISPR-associated protein) for targeted genome editing has been widely adopted and is considered a "game changing" technology. The ease and rapidity by which this approach can be used to modify endogenous loci in a wide spectrum of cell types and organisms makes it a powerful tool for customizable genetic modifications as well as for large-scale functional genomics. The development of retrovirus-based expression platforms to simultaneously deliver the Cas9 nuclease and single guide (sg) RNAs provides unique opportunities by which to ensure stable and reproducible expression of the editing tools and a broad cell targeting spectrum, while remaining compatible with in vivo genetic screens. Here, we describe methods and highlight considerations for designing and generating sgRNA libraries in all-in-one retroviral vectors for such applications.

  8. Energy biotechnology in the CRISPR-Cas9 era.

    PubMed

    Estrela, Raissa; Cate, Jamie Harrison Doudna

    2016-04-01

    The production of bioenergy from plant biomass previously relied on using microorganisms that rapidly and efficiently convert simple sugars into fuels and chemicals. However, to exploit the far more abundant carbon fixed in plant cell walls, future industrial production hosts will need to be engineered to leverage the most efficient biochemical pathways and most robust traits that can be found in nature. The CRISPR-Cas9 genome editing technology now enables writing the genome at will, which will allow biotechnology to become an 'information science.' This review covers recent advances in using CRISPR-Cas9 to engineer the genomes of a wide variety of organisms that could be use in the industrial production of biofuels and renewable chemicals.

  9. Photometry of stars in the Cas OB5 Associations

    NASA Astrophysics Data System (ADS)

    Tanriver, Mehmet; Keskin, Ahmet

    2016-07-01

    OB associations are a grouping of very young associations, contain 10-100 very hot massive stars, spectral types O and B. Also, the OB associations contain low and intermediate mass stars, too. Association members are believed to form within the same small volume inside a giant molecular cloud. Once the surrounding dust and gas is blown away, the remaining stars become not tied up and begin to drift separately. It is believed that the majority of all stars in the Milky Way were formed in OB associations. O type stars are short-lived, and will be at an end as supernovae after roundly a million years. OB associations are generally only a few million years in age or less. In this study, the photometry of UU Cas and field star which been Cas OB5 association member was carried out. Light curves and color diagrams are given in the study.

  10. CRISPR/Cas9-induced knockout and knock-in mutations in Chlamydomonas reinhardtii.

    PubMed

    Shin, Sung-Eun; Lim, Jong-Min; Koh, Hyun Gi; Kim, Eun Kyung; Kang, Nam Kyu; Jeon, Seungjib; Kwon, Sohee; Shin, Won-Sub; Lee, Bongsoo; Hwangbo, Kwon; Kim, Jungeun; Ye, Sung Hyeok; Yun, Jae-Young; Seo, Hogyun; Oh, Hee-Mock; Kim, Kyung-Jin; Kim, Jin-Soo; Jeong, Won-Joong; Chang, Yong Keun; Jeong, Byeong-Ryool

    2016-06-13

    Genome editing is crucial for genetic engineering of organisms for improved traits, particularly in microalgae due to the urgent necessity for the next generation biofuel production. The most advanced CRISPR/Cas9 system is simple, efficient and accurate in some organisms; however, it has proven extremely difficult in microalgae including the model alga Chlamydomonas. We solved this problem by delivering Cas9 ribonucleoproteins (RNPs) comprising the Cas9 protein and sgRNAs to avoid cytotoxicity and off-targeting associated with vector-driven expression of Cas9. We obtained CRISPR/Cas9-induced mutations at three loci including MAA7, CpSRP43 and ChlM, and targeted mutagenic efficiency was improved up to 100 fold compared to the first report of transgenic Cas9-induced mutagenesis. Interestingly, we found that unrelated vectors used for the selection purpose were predominantly integrated at the Cas9 cut site, indicative of NHEJ-mediated knock-in events. As expected with Cas9 RNPs, no off-targeting was found in one of the mutagenic screens. In conclusion, we improved the knockout efficiency by using Cas9 RNPs, which opens great opportunities not only for biological research but also industrial applications in Chlamydomonas and other microalgae. Findings of the NHEJ-mediated knock-in events will allow applications of the CRISPR/Cas9 system in microalgae, including "safe harboring" techniques shown in other organisms.

  11. CRISPR/Cas9-induced knockout and knock-in mutations in Chlamydomonas reinhardtii

    PubMed Central

    Shin, Sung-Eun; Lim, Jong-Min; Koh, Hyun Gi; Kim, Eun Kyung; Kang, Nam Kyu; Jeon, Seungjib; Kwon, Sohee; Shin, Won-Sub; Lee, Bongsoo; Hwangbo, Kwon; Kim, Jungeun; Ye, Sung Hyeok; Yun, Jae-Young; Seo, Hogyun; Oh, Hee-Mock; Kim, Kyung-Jin; Kim, Jin-Soo; Jeong, Won-Joong; Chang, Yong Keun; Jeong, Byeong-ryool

    2016-01-01

    Genome editing is crucial for genetic engineering of organisms for improved traits, particularly in microalgae due to the urgent necessity for the next generation biofuel production. The most advanced CRISPR/Cas9 system is simple, efficient and accurate in some organisms; however, it has proven extremely difficult in microalgae including the model alga Chlamydomonas. We solved this problem by delivering Cas9 ribonucleoproteins (RNPs) comprising the Cas9 protein and sgRNAs to avoid cytotoxicity and off-targeting associated with vector-driven expression of Cas9. We obtained CRISPR/Cas9-induced mutations at three loci including MAA7, CpSRP43 and ChlM, and targeted mutagenic efficiency was improved up to 100 fold compared to the first report of transgenic Cas9-induced mutagenesis. Interestingly, we found that unrelated vectors used for the selection purpose were predominantly integrated at the Cas9 cut site, indicative of NHEJ-mediated knock-in events. As expected with Cas9 RNPs, no off-targeting was found in one of the mutagenic screens. In conclusion, we improved the knockout efficiency by using Cas9 RNPs, which opens great opportunities not only for biological research but also industrial applications in Chlamydomonas and other microalgae. Findings of the NHEJ-mediated knock-in events will allow applications of the CRISPR/Cas9 system in microalgae, including “safe harboring” techniques shown in other organisms. PMID:27291619

  12. Structural roles of guide RNAs in the nuclease activity of Cas9 endonuclease

    PubMed Central

    Lim, Youngbin; Bak, So Young; Sung, Keewon; Jeong, Euihwan; Lee, Seung Hwan; Kim, Jin-Soo; Bae, Sangsu; Kim, Seong Keun

    2016-01-01

    The type II CRISPR-associated protein Cas9 recognizes and cleaves target DNA with the help of two guide RNAs (gRNAs; tracrRNA and crRNA). However, the detailed mechanisms and kinetics of these gRNAs in the Cas9 nuclease activity are unclear. Here, we investigate the structural roles of gRNAs in the CRISPR-Cas9 system by single-molecule spectroscopy and reveal a new conformation of inactive Cas9 that is thermodynamically more preferable than active apo-Cas9. We find that tracrRNA prevents Cas9 from changing into the inactive form and leads to the Cas9:gRNA complex. For the Cas9:gRNA complex, we identify sub-conformations of the RNA–DNA heteroduplex during R-loop expansion. Our single-molecule study indicates that the kinetics of the sub-conformations is controlled by the complementarity between crRNA and target DNA. We conclude that both tracrRNA and crRNA regulate the conformations and kinetics of the Cas9 complex, which are crucial in the DNA cleavage activity of the CRISPR-Cas9 system. PMID:27804953

  13. Structural roles of guide RNAs in the nuclease activity of Cas9 endonuclease.

    PubMed

    Lim, Youngbin; Bak, So Young; Sung, Keewon; Jeong, Euihwan; Lee, Seung Hwan; Kim, Jin-Soo; Bae, Sangsu; Kim, Seong Keun

    2016-11-02

    The type II CRISPR-associated protein Cas9 recognizes and cleaves target DNA with the help of two guide RNAs (gRNAs; tracrRNA and crRNA). However, the detailed mechanisms and kinetics of these gRNAs in the Cas9 nuclease activity are unclear. Here, we investigate the structural roles of gRNAs in the CRISPR-Cas9 system by single-molecule spectroscopy and reveal a new conformation of inactive Cas9 that is thermodynamically more preferable than active apo-Cas9. We find that tracrRNA prevents Cas9 from changing into the inactive form and leads to the Cas9:gRNA complex. For the Cas9:gRNA complex, we identify sub-conformations of the RNA-DNA heteroduplex during R-loop expansion. Our single-molecule study indicates that the kinetics of the sub-conformations is controlled by the complementarity between crRNA and target DNA. We conclude that both tracrRNA and crRNA regulate the conformations and kinetics of the Cas9 complex, which are crucial in the DNA cleavage activity of the CRISPR-Cas9 system.

  14. Nucleosomes impede Cas9 access to DNA in vivo and in vitro

    PubMed Central

    Horlbeck, Max A; Witkowsky, Lea B; Guglielmi, Benjamin; Replogle, Joseph M; Gilbert, Luke A; Villalta, Jacqueline E; Torigoe, Sharon E; Tjian, Robert; Weissman, Jonathan S

    2016-01-01

    The prokaryotic CRISPR (clustered regularly interspaced palindromic repeats)-associated protein, Cas9, has been widely adopted as a tool for editing, imaging, and regulating eukaryotic genomes. However, our understanding of how to select single-guide RNAs (sgRNAs) that mediate efficient Cas9 activity is incomplete, as we lack insight into how chromatin impacts Cas9 targeting. To address this gap, we analyzed large-scale genetic screens performed in human cell lines using either nuclease-active or nuclease-dead Cas9 (dCas9). We observed that highly active sgRNAs for Cas9 and dCas9 were found almost exclusively in regions of low nucleosome occupancy. In vitro experiments demonstrated that nucleosomes in fact directly impede Cas9 binding and cleavage, while chromatin remodeling can restore Cas9 access. Our results reveal a critical role of eukaryotic chromatin in dictating the targeting specificity of this transplanted bacterial enzyme, and provide rules for selecting Cas9 target sites distinct from and complementary to those based on sequence properties. DOI: http://dx.doi.org/10.7554/eLife.12677.001 PMID:26987018

  15. Stimulated Brillouin scatter and stimulated ion Bernstein scatter during electron gyroharmonic heating experiments

    NASA Astrophysics Data System (ADS)

    Fu, H.; Scales, W. A.; Bernhardt, P. A.; Samimi, A.; Mahmoudian, A.; Briczinski, S. J.; McCarrick, M. J.

    2013-09-01

    Results of secondary radiation, Stimulated Electromagnetic Emission (SEE), produced during ionospheric modification experiments using ground-based high-power radio waves are reported. These results obtained at the High Frequency Active Auroral Research Program (HAARP) facility specifically considered the generation of Magnetized Stimulated Brillouin Scatter (MSBS) and Stimulated Ion Bernstein Scatter (SIBS) lines in the SEE spectrum when the transmitter frequency is near harmonics of the electron gyrofrequency. The heater antenna beam angle effect was investigated on MSBS in detail and shows a new spectral line postulated to be generated near the upper hybrid resonance region due to ion acoustic wave interaction. Frequency sweeping experiments near the electron gyroharmonics show for the first time the transition from MSBS to SIBS lines as the heater pump frequency approaches the gyroharmonic. Significantly far from the gyroharmonic, MSBS lines dominate, while close to the gyroharmonic, SIBS lines strengthen while MSBS lines weaken. New possibilities for diagnostic information are discussed in light of these new observations.

  16. RNA and DNA Targeting by a Reconstituted Thermus thermophilus Type III-A CRISPR-Cas System

    PubMed Central

    Iavarone, Anthony T.; Doudna, Jennifer A.

    2017-01-01

    CRISPR-Cas (clustered regularly interspaced short palindromic repeats-CRISPR-associated) systems are RNA-guided adaptive immunity pathways used by bacteria and archaea to defend against phages and plasmids. Type III-A systems use a multisubunit interference complex called Csm, containing Cas proteins and a CRISPR RNA (crRNA) to target cognate nucleic acids. The Csm complex is intriguing in that it mediates RNA-guided targeting of both RNA and transcriptionally active DNA, but the mechanism is not well understood. Here, we overexpressed the five components of the Thermus thermophilus (T. thermophilus) Type III-A Csm complex (TthCsm) with a defined crRNA sequence, and purified intact TthCsm complexes from E. coli cells. The complexes were thermophilic, targeting complementary ssRNA more efficiently at 65°C than at 37°C. Sequence-independent, endonucleolytic cleavage of single-stranded DNA (ssDNA) by TthCsm was triggered by recognition of a complementary ssRNA, and required a lack of complementarity between the first 8 nucleotides (5′ tag) of the crRNA and the 3′ flanking region of the ssRNA. Mutation of the histidine-aspartate (HD) nuclease domain of the TthCsm subunit, Cas10/Csm1, abolished DNA cleavage. Activation of DNA cleavage was dependent on RNA binding but not cleavage. This leads to a model in which binding of an ssRNA target to the Csm complex would stimulate cleavage of exposed ssDNA in the cell, such as could occur when the RNA polymerase unwinds double-stranded DNA (dsDNA) during transcription. Our findings establish an amenable, thermostable system for more in-depth investigation of the targeting mechanism using structural biology methods, such as cryo-electron microscopy and x-ray crystallography. PMID:28114398

  17. RNA and DNA Targeting by a Reconstituted Thermus thermophilus Type III-A CRISPR-Cas System.

    PubMed

    Liu, Tina Y; Iavarone, Anthony T; Doudna, Jennifer A

    2017-01-01

    CRISPR-Cas (clustered regularly interspaced short palindromic repeats-CRISPR-associated) systems are RNA-guided adaptive immunity pathways used by bacteria and archaea to defend against phages and plasmids. Type III-A systems use a multisubunit interference complex called Csm, containing Cas proteins and a CRISPR RNA (crRNA) to target cognate nucleic acids. The Csm complex is intriguing in that it mediates RNA-guided targeting of both RNA and transcriptionally active DNA, but the mechanism is not well understood. Here, we overexpressed the five components of the Thermus thermophilus (T. thermophilus) Type III-A Csm complex (TthCsm) with a defined crRNA sequence, and purified intact TthCsm complexes from E. coli cells. The complexes were thermophilic, targeting complementary ssRNA more efficiently at 65°C than at 37°C. Sequence-independent, endonucleolytic cleavage of single-stranded DNA (ssDNA) by TthCsm was triggered by recognition of a complementary ssRNA, and required a lack of complementarity between the first 8 nucleotides (5' tag) of the crRNA and the 3' flanking region of the ssRNA. Mutation of the histidine-aspartate (HD) nuclease domain of the TthCsm subunit, Cas10/Csm1, abolished DNA cleavage. Activation of DNA cleavage was dependent on RNA binding but not cleavage. This leads to a model in which binding of an ssRNA target to the Csm complex would stimulate cleavage of exposed ssDNA in the cell, such as could occur when the RNA polymerase unwinds double-stranded DNA (dsDNA) during transcription. Our findings establish an amenable, thermostable system for more in-depth investigation of the targeting mechanism using structural biology methods, such as cryo-electron microscopy and x-ray crystallography.

  18. Electronic dummy for acoustical testing

    NASA Technical Reports Server (NTRS)

    Bauer, B. B.; Di Mattia, A. L.; Rosencheck, A. J.; Stern, M.; Torick, E. L.

    1967-01-01

    Electronic Dummy /ED/ used for acoustical testing represents the average male torso from the Xiphoid process upward and includes an acoustic replica of the human head. This head simulates natural flesh, and has an artificial voice and artificial ears that measure sound pressures at the eardrum or the entrance to the ear canal.

  19. Sound Advice on Classroom Acoustics.

    ERIC Educational Resources Information Center

    Sturgeon, Julie

    2003-01-01

    Discusses the importance of acoustic standards in classroom design, presenting an interview with the Acoustical Society of America's (ASA's) standards manager which focuses on reasons for the new ASA standards, the standards document (which was written for K-12 classroom but applies to college classrooms), the need to avoid echo and be able to…

  20. Automated Acoustic Identification of Bats

    DTIC Science & Technology

    2011-10-01

    discrimination for such acoustically similar and cryptic species. Quantitative methods depend upon automatically extracting call descriptive parameters...constructing a dichotomous key, we iterated the highest performing classification choices at each step in a hierarchical classification scheme to...prevents unambiguous discrimination (Figure 31). For such acoustically cryptic species, identification remains in the realm of calculating a statistical