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Sample records for acoustic stimulation cas

  1. Investigation of the nature of thermal stimulation of acoustic emission

    SciTech Connect

    Muravin, G.B.; Ship, V.V.; Lezvinskaya, L.M.

    1988-12-01

    The nature of thermal stimulation of acoustic emission was investigated. Data are given on the distribution of the density of the energy of deformation at a crack tip and the parameters of acoustic emission with different combinations of mechanical and thermal action. It was established that thermal stimulation of acoustic emission is related to advance and growth of a crack under the action of thermoelastic shear stresses. An increases in heating power causes an increase in the energy of deformation, shear stresses at the crack edges, and acoustic emission energy. The position of the minimum in the density of the energy of deformation and of the maximum in acoustic emission energy coincides with the direction of crack advance, which with the use of the method of thermally stimulated acoustic emission makes it possible to not only reveal crack-like defects but also to determine potentially dangerous directions of their development.

  2. 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. PMID:22739432

  3. Experimental study of displays in contralateral acoustic reflex auditory stimulation.

    PubMed

    Dragan, S P; Bogomolov, A V; Kotlyar-Shapirov, A D; Kondrat'eva, E A

    2016-05-01

    The results of an experimental study of manifestations of the acoustic reflex with contralateral auditory stimulation at a frequency of 1 kHz are presented, and the principal possibility and informativeness of its use for diagnosing the diseases of the organ of hearing are demonstrated. The principal difference of the developed approach is the use of polyharmonic signal for measuring acoustic reflex manifestations during contralateral stimulation, which allows accelerating the examination procedure. PMID:27417727

  4. Contralateral acoustic stimulation alters the magnitude and phase of distortion product otoacoustic emissions

    PubMed Central

    Deeter, Ryan; Abel, Rebekah; Calandruccio, Lauren; Dhar, Sumitrajit

    2009-01-01

    Activation of medial olivocochlear efferents through contralateral acoustic stimulation (CAS) has been shown to modulate distortion product otoacoustic emission (DPOAE) level in various ways (enhancement, reduction, or no change). The goal of this study was to investigate the effect of a range of CAS levels on DPOAE fine structure. The 2f1-f2 DPOAE was recorded (f2∕f1=1.22, L1=55 dB, and L2=40 dB) from eight normal-hearing subjects, using both a frequency-sweep paradigm and a fixed frequency paradigm. Contamination due to the middle ear muscle reflex was avoided by monitoring the magnitude and phase of a probe in the test ear and by monitoring DPOAE stimulus levels throughout testing. Results show modulations in both level and frequency of DPOAE fine structure patterns. Frequency shifts observed at DPOAE level minima could explain reports of enhancement in DPOAE level due to efferent activation. CAS affected the magnitude and phase of the DPOAE component from the characteristic frequency region to a greater extent than the component from the overlap region between the stimulus tones. This differential effect explains the occasional enhancement observed in DPOAE level as well as the frequency shift in fine structure patterns. PMID:19894823

  5. 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.

  6. 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

    2015-01-01

    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

  7. 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

  8. 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.

  9. 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. PMID:26338375

  10. Investigating the interaction between acoustically stimulated microbubbles and fibrin clots

    NASA Astrophysics Data System (ADS)

    Acconcia, Christopher; Leung, Ben; Hynynen, Kullervo; Goertz, David

    2012-11-01

    While it is well established that ultrasound stimulated microbubbles can potentiate thrombolysis, the mechanisms of action are poorly understood. The objective of this work was to gain a more fundamental understanding of how acoustically stimulated microbubbles interact with and potentially degrade fibrin clots. Owing to their optical transparency, the use of fibrin clots allowed to optically observe microbubbles interacting with the clot boundary and any resultant disruption of the fluorescently tagged fibrin network. It was found that microbubbles could readily penetrate into fibrin clots with velocities up to 0.2 m/s and to depths related to the number of pulses applied. At lower pressures (0.2-0.55 MPa), microbubbles as small as 3μm were observed to penetrate, whereas higher pressures (>0.9 MPa) caused the penetration of larger microbubbles (10-30μm), formed by coalescence prior to entry. In some cases, patent 'tunnels' remained along the path taken by penetrating microbubbles. Tunnel diameters ranged between 9-35μm depending largely on pressure and pulse duration. Two-photon microscopy indicated either patent tunnels or paths of disrupted fibers consistent with collapsed tunnel. Fluid flow within the clot was observed to accompany penetrating microbubbles, which may have implications for lytic enzyme penetration.

  11. 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.

  12. 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).

  13. 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

  14. Imatinib and Nilotinib increase glioblastoma cell invasion via Abl-independent stimulation of p130Cas and FAK signalling.

    PubMed

    Frolov, Antonina; Evans, Ian M; Li, Ningning; Sidlauskas, Kastytis; Paliashvili, Ketevan; Lockwood, Nicola; Barrett, Angela; Brandner, Sebastian; Zachary, Ian C; Frankel, Paul

    2016-01-01

    Imatinib was the first targeted tyrosine kinase inhibitor to be approved for clinical use, and remains first-line therapy for Philadelphia chromosome (Ph+)-positive chronic myelogenous leukaemia. We show that treatment of human glioblastoma multiforme (GBM) tumour cells with imatinib and the closely-related drug, nilotinib, strikingly increases tyrosine phosphorylation of p130Cas, focal adhesion kinase (FAK) and the downstream adaptor protein paxillin (PXN), resulting in enhanced cell migration and invasion. Imatinib and nilotinib-induced tyrosine phosphorylation was dependent on expression of p130Cas and FAK activity and was independent of known imatinib targets including Abl, platelet derived growth factor receptor beta (PDGFRβ) and the collagen receptor DDR1. Imatinib and nilotinib treatment increased two dimensional cell migration and three dimensional radial spheroid invasion in collagen. In addition, silencing of p130Cas and inhibition of FAK activity both strongly reduced imatinib and nilotinib stimulated invasion. Importantly, imatinib and nilotinib increased tyrosine phosphorylation of p130Cas, FAK, PXN and radial spheroid invasion in stem cell lines isolated from human glioma biopsies. These findings identify a novel mechanism of action in GBM cells for two well established front line therapies for cancer resulting in enhanced tumour cell motility. PMID:27293031

  15. Imatinib and Nilotinib increase glioblastoma cell invasion via Abl-independent stimulation of p130Cas and FAK signalling

    PubMed Central

    Frolov, Antonina; Evans, Ian M.; Li, Ningning; Sidlauskas, Kastytis; Paliashvili, Ketevan; Lockwood, Nicola; Barrett, Angela; Brandner, Sebastian; Zachary, Ian C.; Frankel, Paul

    2016-01-01

    Imatinib was the first targeted tyrosine kinase inhibitor to be approved for clinical use, and remains first-line therapy for Philadelphia chromosome (Ph+)-positive chronic myelogenous leukaemia. We show that treatment of human glioblastoma multiforme (GBM) tumour cells with imatinib and the closely-related drug, nilotinib, strikingly increases tyrosine phosphorylation of p130Cas, focal adhesion kinase (FAK) and the downstream adaptor protein paxillin (PXN), resulting in enhanced cell migration and invasion. Imatinib and nilotinib-induced tyrosine phosphorylation was dependent on expression of p130Cas and FAK activity and was independent of known imatinib targets including Abl, platelet derived growth factor receptor beta (PDGFRβ) and the collagen receptor DDR1. Imatinib and nilotinib treatment increased two dimensional cell migration and three dimensional radial spheroid invasion in collagen. In addition, silencing of p130Cas and inhibition of FAK activity both strongly reduced imatinib and nilotinib stimulated invasion. Importantly, imatinib and nilotinib increased tyrosine phosphorylation of p130Cas, FAK, PXN and radial spheroid invasion in stem cell lines isolated from human glioma biopsies. These findings identify a novel mechanism of action in GBM cells for two well established front line therapies for cancer resulting in enhanced tumour cell motility. PMID:27293031

  16. Observed Dependence of Stimulated Raman Scattering on Ion-Acoustic Damping in Hohlraum Plasmas

    SciTech Connect

    Fernandez, J.C.; Cobble, J.A.; Failor, B.H.; DuBois, D.F.; Montgomery, D.S.; Rose, H.A.; Vu, H.X.; Wilde, B.H.; Wilke, M.D.; Chrien, R.E. ||

    1996-09-01

    The reflectivity of a laser due to stimulated Raman scattering (SRS) from long scale-length hohlraum plasmas is shown to depend on the damping of ion-acoustic waves. This dependence is observed in plasmas with either low or high ionization states. Since the SRS process itself is unrelated to acoustic waves, these data are evidence of a nonlinear coupling of SRS to other parametric processes involving daughter acoustic waves. {copyright} {ital 1996 The American Physical Society.}

  17. 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

  18. Acoustic build-up in on-chip stimulated Brillouin scattering

    NASA Astrophysics Data System (ADS)

    Wolff, C.; Steel, M. J.; Eggleton, B. J.; Poulton, C. G.

    2015-09-01

    We investigate the role of the spatial evolution of the acoustic field in stimulated Brillouin scattering processes in short high-gain structures. When the gain is strong enough that the gain length becomes comparable to the acoustic wave decay length of order 100 microns, standard approximations treating the acoustic field as a local response no longer apply. Treating the acoustic evolution more accurately, we find that the backward SBS gain of sub-millimetre long waveguides is significantly reduced from the value obtained by the conventional treatment because the acoustic mode requires several decay lengths to build up to its nominal value. In addition, the corresponding resonance line is broadened with the development of side bands. In contrast, we argue that intra-mode forward SBS is not expected to show these effects. Our results have implications for several recent proposals and experiments on high-gain stimulated Brillouin scattering in short semiconductor waveguides.

  19. Acoustic build-up in on-chip stimulated Brillouin scattering

    PubMed Central

    Wolff, C.; Steel, M. J.; Eggleton, B. J.; Poulton, C. G.

    2015-01-01

    We investigate the role of the spatial evolution of the acoustic field in stimulated Brillouin scattering processes in short high-gain structures. When the gain is strong enough that the gain length becomes comparable to the acoustic wave decay length of order 100 microns, standard approximations treating the acoustic field as a local response no longer apply. Treating the acoustic evolution more accurately, we find that the backward SBS gain of sub-millimetre long waveguides is significantly reduced from the value obtained by the conventional treatment because the acoustic mode requires several decay lengths to build up to its nominal value. In addition, the corresponding resonance line is broadened with the development of side bands. In contrast, we argue that intra-mode forward SBS is not expected to show these effects. Our results have implications for several recent proposals and experiments on high-gain stimulated Brillouin scattering in short semiconductor waveguides. PMID:26338720

  20. 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.

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

    PubMed

    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. PMID:22326949

  2. 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.

  3. Optimisation of an acoustically antiguiding structure for raising the stimulated Brillouin scattering threshold in optical fibres

    NASA Astrophysics Data System (ADS)

    Khudyakov, M. M.; Likhachev, M. E.; Bubnov, M. M.; Lipatov, D. S.; Gur'yanov, A. N.; Temyanko, V.; Nagel, J.; Peyghambarian, N.

    2016-05-01

    Optical fibres having a radially nonuniform acoustically antiguiding structure produced by codoping their core with alumina and germania have been fabricated and investigated. The influence of the shape of the antiguiding acoustic refractive index profile and fibre core diameter on the stimulated Brillouin scattering (SBS) threshold and spectrum in the fibres has been assessed. An increase in SBS threshold by 4.4 dB with respect to a germanosilicate fibre having the same mode field diameter has been demonstrated.

  4. 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

  5. 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

  6. 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,…

  7. The Codacs™ Direct Acoustic Cochlear Implant Actuator: Exploring Alternative Stimulation Sites and Their Stimulation Efficiency

    PubMed Central

    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. PMID:25785860

  8. 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

  9. 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. PMID:27312123

  10. Effect of repetitive transcranial magnetic stimulation on auditory function following acoustic trauma.

    PubMed

    Yang, Haidi; Xiong, Hao; Ou, Yongkang; Xu, Yaodong; Pang, Jiaqi; Lai, Lan; Zheng, Yiqing

    2016-09-01

    Repetitive transcranial magnetic stimulation (rTMS) is one form of non-invasive brain stimulation and increasingly shows neuroprotection in multiple neurological disorders. However, the potential of rTMS for protective action on auditory function following acoustic trauma has not been investigated. Here, we examined effect of TMS on hearing conservation, neurons survival and brain-derived neurotrophin factor (BDNF) expression in the cochlea and auditory cortex following acoustic trauma in rats. Wistar rats were exposed to intense pure tone noise (10 kHz, 120 dB SPL for 2 h) followed by rTMS treatment or sham treatment (handling control) daily for 14 days. Auditory brainstem response revealed there was no significant difference in hearing threshold shifts between rTMS- and sham-treated rats, although rTMS-treated rats showed less neuron loss in the auditory cortex in comparison with sham rats. Additionally, acoustic trauma increased BDNF expression in the cochlea and auditory cortex, and this elevation could be attenuated by rTMS treatment. Our results suggest present regiment of rTMS does not protect hearing against acoustic trauma, but maybe have implications for tinnitus treatment. PMID:27230393

  11. Influence of Asymmetric Recurrent Laryngeal Nerve Stimulation on Vibration, Acoustics, and Aerodynamics

    PubMed Central

    Chhetri, Dinesh K.; Neubauer, Juergen; Sofer, Elazar

    2015-01-01

    Objectives/Hypothesis Evaluate the influence of asymmetric recurrent laryngeal nerve (RLN) stimulation on the vibratory phase, acoustics and aerodynamics of phonation. Study Design Basic science study using an in vivo canine model. Methods The RLNs were symmetrically and asymmetrically stimulated over eight graded levels to test a range of vocal fold activation conditions from subtle paresis to paralysis. Vibratory phase, fundamental frequency (F0), subglottal pressure, and airflow were noted at phonation onset. The evaluations were repeated for three levels of symmetric superior laryngeal nerve (SLN) stimulation. Results Asymmetric laryngeal adductor activation from asymmetric left-right RLN stimulation led to a consistent pattern of vibratory phase asymmetry, with the more activated vocal fold leading in the opening phase of the glottal cycle and in mucosal wave amplitude. Vibratory amplitude asymmetry was also observed, with more lateral excursion of the glottis of the less activated side. Onset fundamental frequency was higher with asymmetric activation because the two RLNs were synergistic in decreasing F0, glottal width, and strain. Phonation onset pressure increased and airflow decreased with symmetric RLN activation. Conclusion Asymmetric laryngeal activation from RLN paresis and paralysis has consistent effects on vocal fold vibration, acoustics, and aerodynamics. This information may be useful in diagnosis and management of vocal fold paresis. PMID:24913182

  12. A short latency vestibular evoked potential (VsEP) produced by bone-conducted acoustic stimulation

    NASA Astrophysics Data System (ADS)

    McAngus Todd, Neil P.; Rosengren, Sally M.; Colebatch, James G.

    2003-12-01

    In this paper data are presented from an experiment which provides evidence for the existence of a short latency, acoustically evoked potential of probable vestibular origin. The experiment was conducted in two phases using bone-conducted acoustic stimulation. In the first phase subjects were stimulated with 6-ms, 500-Hz tone bursts in order to obtain the threshold VT for vestibular evoked myogenic potentials (VEMP). It was confirmed that the difference between bone-conducted auditory and acoustic vestibular thresholds was slightly over 30 dB. The estimated threshold was then used as a reference value in the second part of the experiment to stimulate subjects over a range of intensities from -6 to +18 dB (re:VT). Averaged EEG recordings were made with eight Ag/AgCl electrodes placed on the scalp at Fpz, F3, F4, F7, F8, Cz, T3, and T4 according to the 10-20 system. Below VT auditory midlatency responses (MLRs) were observed. Above VT two additional potentials appeared: a positivity at about 10 ms (P10) which was maximal at Cz, and a negativity at about 15 ms (N15) which was maximal at Fpz. Extrapolation of the growth functions for the P10 and N15 indicated a threshold close to VT, consistent with a vestibular origin of these potentials. Given the low threshold of vestibular acoustic sensitivity it is possible that this mode may make a contribution to the detection of and affective responses to loud low frequency sounds. The evoked potentials may also have application as a noninvasive and nontraumatic test of vestibular projections to the cortex.

  13. Imipenem represses CRISPR-Cas interference of DNA acquisition through H-NS stimulation in Klebsiella pneumoniae.

    PubMed

    Lin, Tzu-Lung; Pan, Yi-Jiun; Hsieh, Pei-Fang; Hsu, Chun-Ru; Wu, Meng-Chuan; Wang, Jin-Town

    2016-01-01

    Analysis of the genome of Klebsiella pneumoniae NTUH-K2044 strain revealed the presence of two clustered regularly interspaced short palindromic repeats (CRISPR) arrays separated with CRISPR-associated (cas) genes. Carbapenem-resistant K. pneumoniae isolates were observed to be less likely to have CRISPR-Cas than sensitive strains (5/85 vs. 22/132). Removal of the transcriptional repressor, H-NS, was shown to prevent the transformation of plasmids carrying a spacer and putative proto-spacer adjacent motif (PAM). The CRISPR-Cas system also decreased pUC-4K plasmid stability, resulting in plasmid loss from the bacteria with acquisition of new spacers. Analysis of the acquired proto-spacers in pUC-4K indicated that 5'-TTN-3' was the preferred PAM in K. pneumoniae. Treatment of cells by imipenem induced hns expression, thereby decreasing cas3 expression and consequently repressed CRISPR-Cas activity resulted in increase of plasmid stability. In conclusion, NTUH-K2044 CRISPR-Cas contributes to decrease of plasmid transformation and stability. Through repression of CRISPR-Cas activity by induced H-NS, bacteria might be more able to acquire DNA to confront the challenge of imipenem. PMID:27531594

  14. Imipenem represses CRISPR-Cas interference of DNA acquisition through H-NS stimulation in Klebsiella pneumoniae

    PubMed Central

    Lin, Tzu-Lung; Pan, Yi-Jiun; Hsieh, Pei-Fang; Hsu, Chun-Ru; Wu, Meng-Chuan; Wang, Jin-Town

    2016-01-01

    Analysis of the genome of Klebsiella pneumoniae NTUH-K2044 strain revealed the presence of two clustered regularly interspaced short palindromic repeats (CRISPR) arrays separated with CRISPR-associated (cas) genes. Carbapenem-resistant K. pneumoniae isolates were observed to be less likely to have CRISPR-Cas than sensitive strains (5/85 vs. 22/132). Removal of the transcriptional repressor, H-NS, was shown to prevent the transformation of plasmids carrying a spacer and putative proto-spacer adjacent motif (PAM). The CRISPR-Cas system also decreased pUC-4K plasmid stability, resulting in plasmid loss from the bacteria with acquisition of new spacers. Analysis of the acquired proto-spacers in pUC-4K indicated that 5′-TTN-3′ was the preferred PAM in K. pneumoniae. Treatment of cells by imipenem induced hns expression, thereby decreasing cas3 expression and consequently repressed CRISPR-Cas activity resulted in increase of plasmid stability. In conclusion, NTUH-K2044 CRISPR-Cas contributes to decrease of plasmid transformation and stability. Through repression of CRISPR-Cas activity by induced H-NS, bacteria might be more able to acquire DNA to confront the challenge of imipenem. PMID:27531594

  15. Acoustic Stimulation of Colloid Behavior at the Pore and Core Scales

    NASA Astrophysics Data System (ADS)

    Roberts, P. M.

    2006-12-01

    Acoustic waves can influence the attachment and/or detachment of colloids at solid/liquid interfaces. They can also induce colloid-colloid interactions leading to colloid trapping or clustering. Subsequent accumulation or release of colloids in a porous medium can alter its permeability. This can cause either good or bad effects on porous fluid-flow behavior in the Earth and geomaterials. Prior experiments using a microscopic, video image- processing system focused on a glass flow-visualization cell indicated that 0.5 to 5 MHz acoustic energy can induce attachment and detachment of sub-micron-size polystyrene microspheres at solid/liquid interfaces. New experiments were performed to investigate the effect of particle size, concentration (volume fraction), ionic strength, and acoustic energy on the deposition and removal kinetics of colloidal particles onto different solid surfaces. Additional experiments demonstrated that acoustically excited particles can attract other particles and cause them to orbit each other in directions that depend on the acoustic frequency. Other prior experiments on centimeter-size sandstone cores showed that 50 Hz mechanical stress oscillations can mobilize trapped in-situ colloids as well as injected 300-nm polystyrene microspheres. A unique core-holder apparatus that mechanically strains 2.54-cm-diameter porous rock samples during constant-rate fluid flow was used for those experiments. To investigate the effect of particle size on trapping and acoustic release of colloids, new experiments were performed by injecting 1-micron microspheres suspended in deionized water and 0.1M NaCl solution. The larger size microspheres were trapped at both high and low ionic strengths, unlike the smaller 300-nm microspheres which were only trapped at high ionic strength. Stress stimulation at less than 100 Hz caused enhanced release of the trapped microspheres at a rate much higher than the average background production rate during water flow alone

  16. 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

  17. Acoustic sensing of the initial adhesion of chemokine-stimulated cancer cells.

    PubMed

    Wei, Xiao-Lan; Zhang, Jing; Zhao, Na

    2013-11-01

    Chemokines together with their receptors play important roles in tumor metastasis. Intracellular signals stimulated by chemokines regulate the initial adhesion of cancer cells, which controls the subsequent cell spreading and migration. Until now, the nature of initial cell adhesion has been understood very poorly, since conventional assays are static and could not provide dynamic information. In order to address this issue, we adopt an acoustic sensor, quartz crystal microbalance (QCM), to monitor the attachment of chemokine-stimulated cancer cells in real-time. As a model, the chemokine CXCL12 was used to stimulate three human breast cancer cell lines expressing different levels of its receptor CXCR4, which triggers intracellular signaling pathways that activate integrins across cell membrane. Interaction between cellular integrins and adhesion molecules (CAMs) pre-coated on sensor surfaces were in situ monitored by QCM of which the frequency was sensitive to the mechanical connection of cells to the sensor surface. The ratio of frequency shift under stimulation to that without stimulation indicated the number and strength of integrin-CAM binding stimulated by the chemokine. The cell-surface binding was found to be enhanced by CXCL12, which depends on the CAM type and levels of chemokine and receptor, and was significantly inhibited by a blocker of the chemokine pathway. The binding of integrin with intercellular adhesion molecule was also found to be strong and in good correlated with the chemotactic indexes obtained by the classical Boyden chamber assay. This research suggests that acoustic sensing of initial cell adhesion could provide a dynamic insight into cell interfacial phenomena. PMID:23911626

  18. 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

  19. Two-bubble acoustic tweezing cytometry for biomechanical probing and stimulation of cells.

    PubMed

    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

  20. A measure of acoustic noise generated from transcranial magnetic stimulation coils.

    PubMed

    Dhamne, Sameer C; Kothare, Raveena S; Yu, Camilla; Hsieh, Tsung-Hsun; Anastasio, Elana M; Oberman, Lindsay; Pascual-Leone, Alvaro; Rotenberg, Alexander

    2014-01-01

    The intensity of sound emanating from the discharge of magnetic coils used in repetitive transcranial magnetic stimulation (rTMS) can potentially cause acoustic trauma. Per Occupational Safety and Health Administration (OSHA) standards for safety of noise exposure, hearing protection is recommended beyond restricted levels of noise and time limits. We measured the sound pressure levels (SPLs) from four rTMS coils with the goal of assessing if the acoustic artifact levels are of sufficient amplitude to warrant protection from acoustic trauma per OSHA standards. We studied the SPLs at two frequencies (5 and 10 Hz), three machine outputs (MO) (60, 80 and 100%), and two distances from the coil (5 and 10 cm). We found that the SPLs were louder at closer proximity from the coil and directly dependent on the MO. We also found that in all studied conditions, SPLs were lower than the OSHA permissible thresholds for short (<15 min) acoustic exposure, but at extremes of use, may generate sufficient noise to warrant ear protection with prolonged (>8 h) exposure. PMID:24582370

  1. Electromotile hearing: Acoustic tones mask psychophysical response to high-frequency electrical stimulation of intact guinea pig cochleaea)

    PubMed Central

    Le Prell, Colleen G.; Kawamoto, Kohei; Raphael, Yehoash; Dolan, David F.

    2011-01-01

    When sinusoidal electric stimulation is applied to the intact cochlea, a frequency-specific acoustic emission can be recorded in the ear canal. Acoustic emissions are produced by basilar membrane motion, and have been used to suggest a corresponding acoustic sensation termed “electromotile hearing.” Electromotile hearing has been specifically attributed to electric stimulation of outer hair cells in the intact organ of Corti. To determine the nature of the auditory perception produced by electric stimulation of a cochlea with intact outer hair cells, we tested guinea pigs in a psychophysical task. First, subjects were trained to report detection of sinusoidal acoustic stimuli and dynamic range was assessed using response latency. Subjects were then implanted with a ball electrode placed into scala tympani. Following the surgical implant procedure, subjects were transferred to a task in which acoustic signals were replaced by sinusoidal electric stimulation, and dynamic range was assessed again. Finally, the ability of acoustic pure-tone stimuli to mask the detection of the electric signals was assessed. Based on the masking effects, we conclude that sinusoidal electric stimulation of the intact cochlea results in perception of a tonal (rather than a broad-band or noisy) sound at a frequency of 8 kHz or above. PMID:17225416

  2. Vibro-acoustography: An imaging modality based on ultrasound-stimulated acoustic emission

    PubMed Central

    Fatemi, Mostafa; Greenleaf, James F.

    1999-01-01

    We describe theoretical principles of an imaging modality that uses the acoustic response of an object to a highly localized dynamic radiation force of an ultrasound field. In this method, named ultrasound-stimulated vibro-acoustography (USVA), ultrasound is used to exert a low-frequency (in kHz range) force on the object. In response, a portion of the object vibrates sinusoidally in a pattern determined by its viscoelastic properties. The acoustic emission field resulting from object vibration is detected and used to form an image that represents both the ultrasonic and low-frequency (kHz range) mechanical characteristics of the object. We report the relation between the emitted acoustic field and the incident ultrasonic pressure field in terms of object parameters. Also, we present the point-spread function of the imaging system. The experimental images in this report have a resolution of about 700 μm, high contrast, and high signal-to-noise ratio. USVA is sensitive enough to detect object motions on the order of nanometers. Possible applications include medical imaging and material evaluation. PMID:10359758

  3. Suppressibility of the 2f1-f2 stimulated acoustic emissions in gerbil and man.

    PubMed

    Brown, A M; Kemp, D T

    1984-01-01

    The suppression tuning properties of the oto-acoustic distortion product emission, 2f1-f2 have been measured in the ear canal of gerbil and man. The results show the acoustic response to be suppressible in a similar, frequency-dependent manner in both species. Frequencies near to those of the stimulating tones are most effective in suppressing the response. Derived iso-suppression tuning curves have Q10dB values of between 1 and 6. Suppressor tones having frequencies near to f2 (the higher frequency stimulus) make a contribution to the tuning curve which is largely independent of the stimulus intensity and the frequency ratio between the two primary tones. Suppressors having f1-associated frequencies produce a variable amount of suppression depending on the stimulus parameters chosen. No specific suppression feature could be associated with suppressors near to 2f1-f2. The frequency selectivity of the acoustic DP generation mechanism shown by this study indicates a close association with the transduction mechanism. The demonstration of comparable signals in gerbil and man facilitates the direct transfer of laboratory results to the study of human ears. PMID:6706860

  4. Acoustotaxis -in vitro stimulation in a wound healing assay employing surface acoustic waves.

    PubMed

    Stamp, M E M; Brugger, M S; Wixforth, A; Westerhausen, C

    2016-07-21

    A novel, ultrasound based approach for the dynamic stimulation and promotion of tissue healing processes employing surface acoustic waves (SAW) on a chip is presented for the example of osteoblast-like SaOs-2 cells. In our investigations, we directly irradiate cells with SAW on a SiO2 covered piezoelectric LiNbO3 substrate. Observing the temporal evolution of cell growth and migration and comparing non-irradiated to irradiated areas on the chip, we find that the SAW-treated cells exhibit a significantly increased migration as compared to the control samples. Apart from quantifying our experimental findings on the cell migration stimulation, we also demonstrate the full bio compatibility and bio functionality of our SAW technique by using LDH assays. We safely exclude parasitic side effects such as a SAW related increased substrate temperature or nutrient flow by thoroughly monitoring the temperature and the flow field using infrared microscopy and micro particle image velocimetry. Our results show that the SAW induced dynamic mechanical and electrical stimulation obviously directly promotes the cell growth. We conclude that this stimulation method offers a powerful platform for future medical treatment, e.g. being implemented as a implantable biochip with wireless extra-corporal power supply to treat deeper tissue. PMID:27138623

  5. Spatio-temporal source modeling of evoked potentials to acoustic and cochlear implant stimulation.

    PubMed

    Ponton, C W; Don, M; Waring, M D; Eggermont, J J; Masuda, A

    1993-01-01

    Spatio-temporal source modeling (STSM) of event-related potentials was used to estimate the loci and characteristics of cortical activity evoked by acoustic stimulation in normal hearing subjects and by electrical stimulation in cochlear implant (CI) subjects. In both groups of subjects, source solutions obtained for the N1/P2 complex were located in the superior half of the temporal lobe in the head model. Results indicate that it may be possible to determine whether stimulation of different implant channels activates different regions of cochleotopically organized auditory cortex. Auditory system activation can be assessed further by examining the characteristics of the source wave forms. For example, subjects whose cochlear implants provided auditory sensations and normal hearing subjects had similar source activity. In contrast, a subject in whom implant activation evoked eyelid movements exhibited different source wave forms. STSM analysis may provide an electrophysiological technique for guiding rehabilitation programs based on the capabilities of the individual implant user and for disentangling the complex response patterns to electrical stimulation of the brain. PMID:7694834

  6. Ultrasound-Stimulated Acoustic Emission in Thermal Image-Guided HIFU Therapy: A Phantom Study

    SciTech Connect

    Jiang, C. P.; Lin, W. T.; Chen, W. S.

    2006-05-08

    Magnetic resonance image (MRI) is a promising monitoring tool for non-invasive real-time thermal guidance in high intensity focused ultrasound (HIFU) during thermal ablation surgery. However, this approach has two main drawbacks: 1) majority of components need to be redesigned to be MR compatible in order to avoid effecting MR images, and 2) the cost of operating MRI facilities is high. Alternately, ultrasound-stimulated acoustic emission (USAE) method has been applied for detecting thermal variations in tissues. An optical transparent phantom, made from polyacrylamide, containing thermal sensitive indicator protein (Bovine Serum Albumin), was prepared for observing the HIFU-induced denaturalization. A thermal-couple was set up for validation of temperature distribution. Experimental results show that thermal image can be captured clearly under stationary conditions.

  7. 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. PMID:25994712

  8. Development of a loudness normalisation strategy for combined cochlear implant and acoustic stimulation.

    PubMed

    Francart, Tom; McDermott, Hugh J

    2012-12-01

    Users of a cochlear implant together with a hearing aid in the non-implanted ear currently use devices that were developed separately and are often fitted separately. This results in very different growth of loudness with level in the two ears, potentially leading to decreased wearing comfort and suboptimal perception of interaural level differences. A loudness equalisation strategy, named 'SCORE bimodal', is proposed. It equalises loudness growth for the two modalities using existing models of loudness for acoustic and electric stimulation, and is suitable for implementation in wearable devices. Loudness balancing experiments were performed with six bimodal listeners to validate the strategy. In a first set of experiments, the function of each loudness model used was validated by balancing the loudness of four harmonic complexes of different bandwidths, ranging from 200 Hz to 1000 Hz, separately for each ear. Both the electric and acoustic loudness models predicted the data well. In a second set of experiments, binaural balancing was done for the same stimuli. It was found that SCORE significantly improved binaural balance. PMID:23000118

  9. 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

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

    PubMed

    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

  11. 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

  12. Stimulated acoustic emission: pseudo-Doppler shifts seen during the destruction of nonmoving microbubbles.

    PubMed

    Tiemann, K; Pohl, C; Schlosser, T; Goenechea, J; Bruce, M; Veltmann, C; Kuntz, S; Bangard, M; Becher, H

    2000-09-01

    The purpose of this study was to evaluate the appearance and the characteristics of stimulated acoustic emission (SAE) as an echo contrast-specific color Doppler phenomenon with impact on myocardial contrast echocardiography (MCE). Stationary microbubbles of the new contrast agent SH-U 563A (Schering AG) were embedded within a tissue-mimicking gel material. Harmonic power Doppler imaging (H-PDI), color Doppler and pulse-wave Doppler data were acquired using an HDI-5000 equipped with a phased-array transducer (1.67/3.3 MHz). In color Doppler mode, bubble destruction resulted in random noise like Doppler signals. PW-Doppler revealed short "pseudo-Doppler" shifts with a broadband frequency spectrum. Quantification of SAE events by H-PDI demonstrated an exponential decay of signal intensities over successive frames. A strong linear relationship was found between bubble concentration and the square root of the linearized H-PDI signal for a range of concentrations of more than two orders of magnitude (R = 0.993, p < 0.0001). Intensity of the H-PDI signals correlated well with emission power (R = 0.96, p = 0.0014). SAE results from disintegration of microbubbles and can be demonstrated by all Doppler imaging modalities, including H-PDI. Intensity of SAE signals is influenced by the applied acoustic power and correlates highly with the concentration of microbubbles. Because intensity of SAE signals correlates highly with echo contrast concentrations, analysis of SAE signals might be used for quantitative MCE. PMID:11053751

  13. Influence of pump wavelength and core size on stimulated Brillouin scattering spectra of acoustically antiguiding optical fibres

    SciTech Connect

    Likhachev, M E; Alekseev, V V; Bubnov, M M; Yashkov, M V; Vechkanov, N N; Gur'yanov, A N; Peyhambarian, N; Temyanko, V; Nagel, J

    2014-11-30

    Optical fibres having an acoustically antiguiding structure produced by alumina doping of their core have been fabricated and investigated. The stimulated Brillouin scattering (SBS) spectra of the fibres have been measured and calculated theoretically. The results demonstrate that the shape of the SBS spectrum of the acoustically antiguiding fibres strongly depends on the pump wavelength, core size and dopant profile across the fibre. A considerable broadening of the SBS gain spectrum is only possible at certain guidance parameters of the fibre and a fixed operating wavelength. (fibre and integrated-optical structures)

  14. 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

  15. Acoustics

    NASA Astrophysics Data System (ADS)

    The acoustics research activities of the DLR fluid-mechanics department (Forschungsbereich Stroemungsmechanik) during 1988 are surveyed and illustrated with extensive diagrams, drawings, graphs, and photographs. Particular attention is given to studies of helicopter rotor noise (high-speed impulsive noise, blade/vortex interaction noise, and main/tail-rotor interaction noise), propeller noise (temperature, angle-of-attack, and nonuniform-flow effects), noise certification, and industrial acoustics (road-vehicle flow noise and airport noise-control installations).

  16. 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. PMID:19955720

  17. 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.

  18. 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

    2016-04-01

    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. PMID:26964472

  19. LpMab-12 Established by CasMab Technology Specifically Detects Sialylated O-Glycan on Thr52 of Platelet Aggregation-Stimulating Domain of Human Podoplanin

    PubMed Central

    Kato, Yukinari; Ogasawara, Satoshi; Oki, Hiroharu; Goichberg, Polina; Honma, Ryusuke; Fujii, Yuki; Kaneko, Mika K.

    2016-01-01

    Podoplanin (PDPN), also known as Aggrus, possesses three tandem repeat of platelet aggregation-stimulating (PLAG) domains in its N-terminus. Among the PLAG domains, sialylated O-glycan on Thr52 of PLAG3 is essential for the binding to C-type lectin-like receptor-2 (CLEC-2) and the platelet-aggregating activity of human PDPN (hPDPN). Although various anti-hPDPN monoclonal antibodies (mAbs) have been generated, no specific mAb has been reported to target the epitope containing glycosylated Thr52. We recently established CasMab technology to develop mAbs against glycosylated membrane proteins. Herein, we report the development of a novel anti-glycopeptide mAb (GpMab), LpMab-12. LpMab-12 detected endogenous hPDPN by flow cytometry. Immunohistochemical analyses also showed that hPDPN-expressing lymphatic endothelial and cancer cells were clearly labeled by LpMab-12. The minimal epitope of LpMab-12 was identified as Asp49–Pro53 of hPDPN. Furthermore, LpMab-12 reacted with the synthetic glycopeptide of hPDPN, corresponding to 38–54 amino acids (hpp3854: 38-EGGVAMPGAEDDVVTPG-54), which carries α2–6 sialylated N-acetyl-D-galactosamine (GalNAc) on Thr52. LpMab-12 did not recognize non-sialylated GalNAc-attached glycopeptide, indicating that sialylated GalNAc on Thr52 is necessary for the binding of LpMab-12 to hPDPN. Thus, LpMab-12 could serve as a new diagnostic tool for determining whether hPDPN possesses the sialylation on Thr52, a site-specific post-translational modification critical for the hPDPN association with CLEC-2. PMID:27031228

  20. Sympathetic skin response following thermal, electrical, acoustic, and inspiratory gasp stimulation in familial dysautonomia patients and healthy persons.

    PubMed

    Hilz, M J; Azelrod, F B; Schweibold, G; Kolodny, E H

    1999-08-01

    To determine whether sympathetic skin response (SSR) testing evaluates afferent small or efferent sympathetic nerve fiber dysfunction, we studied SSR in patients with familial dysautonomia (FD) in whom both afferent small and efferent sympathetic fibers are largely reduced. We analyzed whether the response pattern to a combination of stimuli specific for large or small fiber activation allows differentiation between afferent and efferent small fiber dysfunction. In 52 volunteers and 13 FD patients, SSR was studied at palms and soles after warm, cold and heat as well as electrical, acoustic, and inspiratory gasp stimulation. In addition, thermal thresholds were assessed at four body sites using a Thermotest device (Somedic; Stockholm, Sweden). In volunteers, any stimulus induced reproducible SSRs. Only cold failed to evoke SSR in two volunteers. In all FD patients, electrical SSR was present, but amplitudes were reduced. Five patients had no acoustic SSR, four had no inspiratory SSR. Thermal SSR was absent in 10 patients with abnormal thermal perception and present in one patient with preserved thermal sensation. In two patients, thermal SSR was present only when skin areas with preserved temperature perception were stimulated. In patients with FD, preserved electrical SSR demonstrated the overall integrity of the SSR reflex but amplitude reduction suggested impaired sudomotor activation. SSR responses were dependent on the perception of the stimulus. In the presence of preserved electrical SSR, absent thermal SSR reflects afferent small fiber dysfunction. A combination of SSR stimulus types allows differentiation between afferent small or efferent sympathetic nerve fiber dysfunction. PMID:10574280

  1. 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.

  2. 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.

  3. The effects of bilateral electric and bimodal electric--acoustic stimulation on language development.

    PubMed

    Nittrouer, Susan; Chapman, Christopher

    2009-09-01

    There is no doubt that cochlear implants have improved the spoken language abilities of children with hearing loss, but delays persist. Consequently, it is imperative that new treatment options be explored. This study evaluated one aspect of treatment that might be modified, that having to do with bilateral implants and bimodal stimulation. A total of 58 children with at least one implant were tested at 42 months of age on four language measures spanning a continuum from basic to generative in nature. When children were grouped by the kind of stimulation they had at 42 months (one implant, bilateral implants, or bimodal stimulation), no differences across groups were observed. This was true even when groups were constrained to only children who had at least 12 months to acclimatize to their stimulation configuration. However, when children were grouped according to whether or not they had spent any time with bimodal stimulation (either consistently since their first implant or as an interlude to receiving a second) advantages were found for children who had some bimodal experience, but those advantages were restricted to language abilities that are generative in nature. Thus, previously reported benefits of simultaneous bilateral implantation early in a child's life may not extend to generative language. In fact, children may benefit from a period of bimodal stimulation early in childhood because low-frequency speech signals provide prosody and serve as an aid in learning how to perceptually organize the signal that is received through a cochlear implant. PMID:19713210

  4. 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

    2016-05-01

    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 five-fold. The goal of the study was to assess the impact of the stimulation by comparing pre- and post-stimulation logs and well-logging (temperature [T] log) 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.

  5. Amplification of light in a plasma by stimulated ion acoustic waves driven by multiple crossing pump beams.

    PubMed

    Kirkwood, R K; Michel, P; London, R A; Callahan, D; Meezan, N; Williams, E; Seka, W; Suter, L; Haynam, C; Landen, O

    2011-08-01

    Experiments demonstrate the amplification of 351 nm laser light in a hot dense plasma similar to those in inertial confinement fusion ignition experiments. A seed beam interacts with one or two counter-propagating pump beams, each with an intensity of 1.2×10(15) W/cm2 at 351 nm, crossing the seed at 24.8° at the position where the flow is Mach 1, allowing resonant stimulation of ion acoustic waves. Results show that the energy and power transferred to the seed are increased with two pumps beyond the level that occurs with a single pump, demonstrating that, under conditions similar to ignition experiments where each beam has a low gain exponent, the total scatter produced by the multiple beams can be significantly larger than that of the individual beams. It is further demonstrated that the amplification is greatly reduced when the pump polarization is orthogonal to the seed, as expected from models of stimulated scatter. PMID:21929115

  6. 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

  7. 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

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

    PubMed

    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 cochlea

  9. Inhibitory effect of A10 dopaminergic neurons of the ventral tegmental area on the orienting response evoked by acoustic stimulation in the cat.

    PubMed

    Crescimanno, G; Sorbera, F; Emmi, A; Amato, G

    1998-01-01

    The effect of bilateral electric stimulation of A10 dopaminergic neurons of the ventral tegmental area (80-300 microA, 20-50 Hz, 0.1-0.5 ms, 2 s duration) on latency and duration of the orienting response, evoked by acoustic stimuli (4500-8000 Hz, 2 s), was studied in the cat. A10 neuron stimulation, simultaneous with the acoustic one, was performed with threshold parameters inducing minimal behavioral signs (head searching movement, sniffing, increase in alertness). By means of a videoanalysis system, a statistically significant increase, both of latency and duration of the response, was observed. The possible role of dopamine was studied administrating sulpiride (20 mg/kg i.p.), a dopaminergic antagonist prevalently acting on the mesolimbic-mesocortical system. In this condition, the disappearance of A10 neuron effect occurred. Sulpiride injection did not affect the parameters of the orienting response to acoustic stimulus alone, suggesting a direct effect on A10 dopaminergic neurons. Moreover, when saline administration was carried out, no significant modification of the effects, obtained following A10 neuron activation, was observed. The data suggest that A10 dopaminergic neurons, origin of the mesolimbic-mesocortical system, may be involved in the control of the response to sensory stimuli, likely by influencing sensorimotor integration processes. An involvement in the inhibitory regulation of the switching of attention is also discussed. PMID:9434203

  10. Acoustic-frequency vibratory stimulation regulates the balance between osteogenesis and adipogenesis of human bone marrow-derived mesenchymal stem cells.

    PubMed

    Chen, Xi; He, Fan; Zhong, Dong-Yan; Luo, Zong-Ping

    2015-01-01

    Osteoporosis can be associated with the disordered balance between osteogenesis and adipogenesis of bone marrow-derived mesenchymal stem cells (BM-MSCs). Although low-frequency mechanical vibration has been demonstrated to promote osteogenesis, little is known about the influence of acoustic-frequency vibratory stimulation (AFVS). BM-MSCs were subjected to AFVS at frequencies of 0, 30, 400, and 800 Hz and induced toward osteogenic or adipogenic-specific lineage. Extracellular matrix mineralization was determined by Alizarin Red S staining and lipid accumulation was assessed by Oil Red O staining. Transcript levels of osteogenic and adipogenic marker genes were evaluated by real-time reverse transcription-polymerase chain reaction. Cell proliferation of BM-MSCs was promoted following exposure to AFVS at 800 Hz. Vibration at 800 Hz induced the highest level of calcium deposition and significantly increased mRNA expression of COL1A1, ALP, RUNX2, and SPP1. The 800 Hz group downregulated lipid accumulation and levels of adipogenic genes, including FABP4, CEBPA, PPARG, and LEP, while vibration at 30 Hz supported adipogenesis. BM-MSCs showed a frequency-dependent response to acoustic vibration. AFVS at 800 Hz was the most favorable for osteogenic differentiation and simultaneously suppressed adipogenesis. Thus, acoustic vibration could potentially become a novel means to prevent and treat osteoporosis. PMID:25738155

  11. 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

  12. 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

  13. [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…

  14. Multi-dimensional dynamics of stimulated Brillouin scattering in a laser speckle: Ion acoustic wave bowing, breakup, and laser-seeded two-ion-wave decay

    NASA Astrophysics Data System (ADS)

    Albright, B. J.; Yin, L.; Bowers, K. J.; Bergen, B.

    2016-03-01

    Two- and three-dimensional particle-in-cell simulations of stimulated Brillouin scattering (SBS) in laser speckle geometry have been analyzed to evaluate the relative importance of competing nonlinear processes in the evolution and saturation of SBS. It is found that ion-trapping-induced wavefront bowing and breakup of ion acoustic waves (IAW) and the associated side-loss of trapped ions dominate electron-trapping-induced IAW wavefront bowing and breakup, as well as the two-ion-wave decay instability over a range of Z Te/Ti conditions and incident laser intensities. In the simulations, the latter instability does not govern the nonlinear saturation of SBS; however, evidence of two-ion-wave decay is seen, appearing as a modulation of the ion acoustic wavefronts. This modulation is periodic in the laser polarization plane, anti-symmetric across the speckle axis, and of a wavenumber matching that of the incident laser pulse. A simple analytic model is provided for how spatial "imprinting" from a high frequency inhomogeneity (in this case, the density modulation from the laser) in an unstable system with continuum eigenmodes can selectively amplify modes with wavenumbers that match that of the inhomogeneity.

  15. 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.

  16. Sensitivity of the cochlear nerve to acoustic and electrical stimulation months after a vestibular labyrinthectomy in guinea pigs.

    PubMed

    Brown, D J; Mukherjee, P; Pastras, C J; Gibson, W P; Curthoys, I S

    2016-05-01

    Single-sided deafness patients are now being considered candidates to receive a cochlear implant. With this, many people who have undergone a unilateral vestibular labyrinthectomy for the treatment of chronic vertigo are now being considered for cochlear implantation. There is still some concern regarding the potential efficacy of cochlear implants in these patients, where factors such as cochlear fibrosis or nerve degeneration following unilateral vestibular labyrinthectomy may preclude their use. Here, we have performed a unilateral vestibular labyrinthectomy in normally hearing guinea pigs, and allowed them to recover for either 6 weeks, or 10 months, before assessing morphological and functional changes related to cochlear implantation. Light sheet fluorescence microscopy was used to assess gross morphology throughout the entire ear. Whole nerve responses to acoustic, vibrational, or electrical stimuli were used as functional measures. Mild cellular infiltration was observed at 6 weeks, and to a lesser extent at 10 months after labyrinthectomy. Following labyrinthectomy, cochlear sensitivity to high-frequency acoustic tone-bursts was reduced by 16 ± 4 dB, vestibular sensitivity was almost entirely abolished, and electrical sensitivity was only mildly reduced. These results support recent clinical findings that patients who have received a vestibular labyrinthectomy may still benefit from a cochlear implant. PMID:26873525

  17. 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. PMID:26680661

  18. 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.

  19. 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. PMID:26429474

  20. The role of Cas8 in type I CRISPR interference

    PubMed Central

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

    2015-01-01

    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. PMID:26182359

  1. 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

    2015-01-01

    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. PMID:26182359

  2. [The effect of electrical and acoustic stimulation in early ontogeny on the characteristics of higher nervous activity and on the nucleic acid content of the tissues in chum salmon fry].

    PubMed

    Tikhomirov, A M; Vitvitskaia, L V

    1991-01-01

    Stimulation of salmon larvae by electric current led further to unstable character of reactions in the open field. Acoustic stimulation both by tonal and musical signals favourably influenced the behaviour in the open field and the ability to elaborate conditioned reflexes. Changes of the content of nucleic acids were not found in the brain tissue but were found in the muscles, where they correlated with the growth speed and motor activity of the experimental fishes. The obtained data show the possibility of elaboration of applied methods of the control of CNS development and behaviour of young fishes at fishing plants. PMID:1714672

  3. Cas9 Functionally Opens Chromatin.

    PubMed

    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

  4. 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

  5. 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

  6. Acoustic neuroma

    MedlinePlus

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

  7. Stimulated scattering of space-charge waves in a relativistic electron beam by the ion acoustic wave of a plasma waveguide

    SciTech Connect

    Balakirev, V.A.; Buts, V.A.

    1982-05-01

    The interaction of a relativistic electron beam with a plasma waveguide whose density is modulated by an ion acoustic wave leads to the emission of electromagnetic radiation. The wavelength of the radiation is 2..gamma../sup 2/ times shorter than the ion acoustic wavelength. The emission is accompanied by the amplification of the ion acoustic wave. The maximum amplitudes of the excited waves are found.

  8. Targeted Gene Manipulation in Plants Using the CRISPR/Cas Technology.

    PubMed

    Zhang, Dandan; Li, Zhenxiang; Li, Jian-Feng

    2016-05-20

    The CRISPR/Cas technology is emerging as a revolutionary genome editing tool in diverse organisms including plants, and has quickly evolved into a suite of versatile tools for sequence-specific gene manipulations beyond genome editing. Here, we review the most recent applications of the CRISPR/Cas toolkit in plants and also discuss key factors for improving CRISPR/Cas performance and strategies for reducing the off-target effects. Novel technical breakthroughs in mammalian research regarding the CRISPR/Cas toolkit will also be incorporated into this review in hope to stimulate prospective users from the plant research community to fully explore the potential of these technologies. PMID:27165865

  9. Shifting the Operating Point of Cochlear Amplification?:. Impact of Low Frequency Biasing and Contralateral Sound Stimulation on Dpoae

    NASA Astrophysics Data System (ADS)

    Wittekindt, Anna; Abel, Cornelius; Kössl, Manfred

    2009-02-01

    The mammalian efferent medial olivo-cochlear system is known to modulate active amplification of low-level sound in the cochlea. We investigated the effect of contralateral acoustic stimulation (CAS), known to elicit efferent activity, on distortion product otoacoustic emissions (DPOAEs) in the gerbil and, in second approach, biased the position of the cochlear partition and hence the operating point of the cochlear amplifier periodically by a low frequency tone (5 Hz). The study focussed on the quadratic distortion product f2-f1 that is sensitive to changes in the operating point of the amplifier transfer function. During CAS, a significant increase of the amplitude of f2-f1 was found while 2f1-f2 was less affected. Biasing by the low frequency tone resulted in a phase related amplitude modulation of f2-f1. This modulation pattern was changed pronouncedly during CAS, in dependence on the CAS-level. The current results suggest that efferent effects on DPOAEs might be produced by changes in the operating point of the cochlear amplifier and were in good agreement with a simple model based on a Boltzman function.

  10. 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. PMID:26950513

  11. 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.

  12. Cas3 is a single-stranded DNA nuclease and ATP-dependent helicase in the CRISPR/Cas immune system.

    PubMed

    Sinkunas, Tomas; Gasiunas, Giedrius; Fremaux, Christophe; Barrangou, Rodolphe; Horvath, Philippe; Siksnys, Virginijus

    2011-04-01

    Clustered regularly interspaced short palindromic repeat (CRISPR) is a recently discovered adaptive prokaryotic immune system that provides acquired immunity against foreign nucleic acids by utilizing small guide crRNAs (CRISPR RNAs) to interfere with invading viruses and plasmids. In Escherichia coli, Cas3 is essential for crRNA-guided interference with virus proliferation. Cas3 contains N-terminal HD phosphohydrolase and C-terminal Superfamily 2 (SF2) helicase domains. Here, we provide the first report of the cloning, expression, purification and in vitro functional analysis of the Cas3 protein of the Streptococcus thermophilus CRISPR4 (Ecoli subtype) system. Cas3 possesses a single-stranded DNA (ssDNA)-stimulated ATPase activity, which is coupled to unwinding of DNA/DNA and RNA/DNA duplexes. Cas3 also shows ATP-independent nuclease activity located in the HD domain with a preference for ssDNA substrates. To dissect the contribution of individual domains, Cas3 separation-of-function mutants (ATPase(+)/nuclease(-) and ATPase(-)/nuclease(+)) were obtained by site-directed mutagenesis. We propose that the Cas3 ATPase/helicase domain acts as a motor protein, which assists delivery of the nuclease activity to Cascade-crRNA complex targeting foreign DNA. PMID:21343909

  13. 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 ...

  14. 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.

  15. 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.

  16. Exploiting CRISPR/Cas systems for biotechnology

    PubMed Central

    Sampson, Timothy R.; Weiss, David S.

    2015-01-01

    The Cas9 endonuclease is the central component of the Type II CRISPR/Cas system, a prokaryotic adaptive restriction system against invading nucleic acids, such as those originating from bacteriophages and plasmids. Recently, this RNA-directed DNA endonuclease has been harnessed to target DNA sequences of interest. Here, we review the development of Cas9 as an important tool to not only edit the genomes of a number of different prokaryotic and eukaryotic species, but also as an efficient system for site-specific transcriptional repression or activation. Additionally, a specific Cas9 protein has been observed to target an RNA substrate, suggesting that Cas9 may have the ability to be programmed to target RNA as well. Cas proteins from other CRISPR/Cas subtypes may also be exploited in this regard. Thus, CRISPR/Cas systems represent an effective and versatile biotechnological tool, which will have significant impact on future advancements in genome engineering. PMID:24323919

  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. "CAS" Statement of Shared Ethical Principles

    ERIC Educational Resources Information Center

    Council for the Advancement of Standards in Higher Education, 2006

    2006-01-01

    The Council for the Advancement of Standards in Higher Education (CAS) has served as a voice for quality assurance and promulgation of standards in higher education for over 25 years. CAS was established to promote inter-association efforts to address quality assurance, student learning, and professional integrity. CAS includes membership of over…

  19. Silencing of p130Cas in Ovarian Carcinoma: A Novel Mechanism for Tumor Cell Death

    PubMed Central

    Nick, Alpa M.; Stone, Rebecca L.; Armaiz-Pena, Guillermo; Ozpolat, Bulent; Tekedereli, Ibrahim; Graybill, Whitney S.; Landen, Charles N.; Villares, Gabriel; Vivas-Mejia, Pablo; Bottsford-Miller, Justin; Kim, Hye Sun; Lee, Ju-Seog; Kim, Soo Mi; Baggerly, Keith A.; Ram, Prahlad T.; Deavers, Michael T.; Coleman, Robert L.; Lopez-Berestein, Gabriel

    2011-01-01

    reduction in tumor growth compared with control siRNA therapy (92%–95% reduction in tumor growth; P < .001 for all). Compared with control siRNA therapy, p130cas siRNA-DOPC reduced SKOV3ip1 cell proliferation (31% reduction, P < .001) and increased apoptosis (143% increase, P < .001) in vivo. Increased tumor cell apoptosis may have persisted despite pan-caspase inhibition by the induction of autophagy and related signaling pathways. Conclusions Increased p130cas expression is associated with poor clinical outcome in human ovarian carcinoma, and p130cas gene silencing decreases tumor growth through stimulation of apoptotic and autophagic cell death. PMID:21957230

  20. Next Generation Prokaryotic Engineering: The CRISPR-Cas Toolkit.

    PubMed

    Mougiakos, Ioannis; Bosma, Elleke F; de Vos, Willem M; van Kranenburg, Richard; van der Oost, John

    2016-07-01

    The increasing demand for environmentally friendly production processes of green chemicals and fuels has stimulated research in microbial metabolic engineering. CRISPR-Cas-based tools for genome editing and expression control have enabled fast, easy, and accurate strain development for established production platform organisms, such as Escherichia coli and Saccharomyces cerevisiae. However, the growing interest in alternative production hosts, for which genome editing options are generally limited, requires further developing such engineering tools. In this review, we discuss established and emerging CRISPR-Cas-based tools for genome editing and transcription control of model and non-model prokaryotes, and we analyse the possibilities for further improvement and expansion of these tools for next generation prokaryotic engineering. PMID:26944793

  1. Topological Acoustics

    NASA Astrophysics Data System (ADS)

    Yang, Zhaoju; Gao, Fei; Shi, Xihang; Lin, Xiao; Gao, Zhen; Chong, Yidong; Zhang, Baile

    2015-03-01

    The manipulation of acoustic wave propagation in fluids has numerous applications, including some in everyday life. Acoustic technologies frequently develop in tandem with optics, using shared concepts such as waveguiding and metamedia. It is thus noteworthy that an entirely novel class of electromagnetic waves, known as "topological edge states," has recently been demonstrated. These are inspired by the electronic edge states occurring in topological insulators, and possess a striking and technologically promising property: the ability to travel in a single direction along a surface without backscattering, regardless of the existence of defects or disorder. Here, we develop an analogous theory of topological fluid acoustics, and propose a scheme for realizing topological edge states in an acoustic structure containing circulating fluids. The phenomenon of disorder-free one-way sound propagation, which does not occur in ordinary acoustic devices, may have novel applications for acoustic isolators, modulators, and transducers.

  2. Topological acoustics.

    PubMed

    Yang, Zhaoju; Gao, Fei; Shi, Xihang; Lin, Xiao; Gao, Zhen; Chong, Yidong; Zhang, Baile

    2015-03-20

    The manipulation of acoustic wave propagation in fluids has numerous applications, including some in everyday life. Acoustic technologies frequently develop in tandem with optics, using shared concepts such as waveguiding and metamedia. It is thus noteworthy that an entirely novel class of electromagnetic waves, known as "topological edge states," has recently been demonstrated. These are inspired by the electronic edge states occurring in topological insulators, and possess a striking and technologically promising property: the ability to travel in a single direction along a surface without backscattering, regardless of the existence of defects or disorder. Here, we develop an analogous theory of topological fluid acoustics, and propose a scheme for realizing topological edge states in an acoustic structure containing circulating fluids. The phenomenon of disorder-free one-way sound propagation, which does not occur in ordinary acoustic devices, may have novel applications for acoustic isolators, modulators, and transducers. PMID:25839273

  3. Acoustic neuroma

    MedlinePlus

    Vestibular schwannoma; Tumor - acoustic; Cerebellopontine angle tumor; Angle tumor ... 177. Battista RA. Gamma knife radiosurgery for vestibular schwannoma. Otolaryngol Clin North Am . 2009;42:635-654. ...

  4. 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.

  5. CAS-1 lunar soil simulant

    NASA Astrophysics Data System (ADS)

    Zheng, Yongchun; Wang, Shijie; Ouyang, Ziyuan; Zou, Yongliao; Liu, Jianzhong; Li, Chunlai; Li, Xiongyao; Feng, Junming

    2009-02-01

    Lunar soil simulant is a geochemical reproduction of lunar regolith, and is needed for lunar science and engineering researches. This paper describes a new lunar soil simulant, CAS-1, prepared by the Chinese Academy of Sciences, to support lunar orbiter, soft-landing mission and sample return missions of China’s Lunar Exploration Program, which is scheduled for 2004 2020. Such simulants should match the samples returned from the Moon, all collected from the lunar regolith rather than outcrops. The average mineral and chemical composition of lunar soil sample returned from the Apollo 14 mission, which landed on the Fra Mauro Formation, is chosen as the model for the CAS-1 simulant. Source material for this simulant was a low-Ti basaltic scoria dated at 1600 years from the late Quaternary volcanic area in the Changbai Mountains of northeast China. The main minerals of this rock are pyroxene, olivine, and minor plagioclase, and about 20 40% modal glass. The scoria was analyzed by XRF and found to be chemically similar to Apollo 14 lunar sample 14163. It was crushed in an impact mill with a resulting median particle size 85.9 μm, similar to Apollo soils. Bulk density, shear resistance, complex permittivity, and reflectance spectra were also similar to Apollo 14 soil. We conclude that CAS-1 is an ideal lunar soil simulant for science and engineering research of future lunar exploration program.

  6. 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

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

    PubMed

    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

  8. 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.

  9. Acoustic Neuroma

    MedlinePlus

    ... slow growing tumor which arise primarily from the vestibular portion of the VIII cranial nerve and lie ... you have a "brain tumor" called acoustic neuroma (vestibular schwannoma). You think you are the only one ...

  10. Underwater Acoustics

    NASA Astrophysics Data System (ADS)

    Kuperman, William A.; Roux, Philippe

    It is well underwater established that sound waves, compared to electromagnetic waves, propagate long distances in the ocean. Hence, in the ocean as opposed to air or a vacuum, one uses sound navigation and ranging (SONAR) instead navigation and ranging (SONAR) of radar, acoustic communication instead of radio, and acoustic imaging and tomography instead of microwave or optical imaging or X-ray tomography. Underwater acoustics is the science of sound in water (most commonly in the ocean) and encompasses not only the study of sound propagation, but also the masking of sound signals by interfering phenomenon and signal processing for extracting these signals from interference. This chapter we will present the basics physics of ocean acoustics and then discuss applications.

  11. 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)

  12. 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.

  13. 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

  14. 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. PMID:27365040

  15. 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

  16. 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.

  17. 48 CFR 9903.201-2 - Types of CAS coverage.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 48 Federal Acquisition Regulations System 7 2014-10-01 2014-10-01 false Types of CAS coverage... ACCOUNTING STANDARDS CONTRACT COVERAGE CAS Program Requirements 9903.201-2 Types of CAS coverage. (a) Full coverage. Full coverage requires that the business unit comply with all of the CAS specified in part...

  18. 48 CFR 9903.201-2 - Types of CAS coverage.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 48 Federal Acquisition Regulations System 7 2010-10-01 2010-10-01 false Types of CAS coverage... ACCOUNTING STANDARDS CONTRACT COVERAGE CAS Program Requirements 9903.201-2 Types of CAS coverage. (a) Full coverage. Full coverage requires that the business unit comply with all of the CAS specified in part...

  19. 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... ACCOUNTING STANDARDS CONTRACT COVERAGE CAS Program Requirements 9903.201-2 Types of CAS coverage. (a) Full coverage. Full coverage requires that the business unit comply with all of the CAS specified in part...

  20. Assisting Students' Cognitive Strategies with the Use of CAS

    ERIC Educational Resources Information Center

    Sarvari, Csaba; Lavicza, Zsolt; Klincsik, Mihaly

    2010-01-01

    This paper examines various cognitive strategies applied while CAS (Computer Algebra System) are used in undergraduate-level engineering mathematics teaching and learning. We posed some questions in relation to such CAS use: What kind of tools can CAS offer to enhance different cognitive strategies of students? How can the use of CAS widen the…

  1. 48 CFR 9903.201-2 - Types of CAS coverage.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 48 Federal Acquisition Regulations System 7 2012-10-01 2012-10-01 false Types of CAS coverage... ACCOUNTING STANDARDS CONTRACT COVERAGE CAS Program Requirements 9903.201-2 Types of CAS coverage. (a) Full coverage. Full coverage requires that the business unit comply with all of the CAS specified in part...

  2. 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...

  3. 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.

  4. 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.

  5. V723 Cas a borderline classical nova

    NASA Astrophysics Data System (ADS)

    Friedjung, M.; Iijima, T.

    2002-11-01

    V723 Cas had a light curve similar to that of HR Del before maximum, with a very slow pre-maximum rise, explained according to [2] by the presence of an optically thin wind before maximum unlike the optically thick wind generally seen for classical novae after maximum. Examination of the Fe II emission lines by the SAC method, is compatible with this also having been the case for V723 Cas.

  6. Characterization of Cas9-Guide RNA Orthologs.

    PubMed

    Braff, Jonathan L; Yaung, Stephanie J; Esvelt, Kevin M; Church, George M

    2016-01-01

    In light of the multitude of new Cas9-mediated functionalities, the ability to carry out multiple Cas9-enabled processes simultaneously and in a single cell is becoming increasingly valuable. Accomplishing this aim requires a set of Cas9-guide RNA (gRNA) pairings that are functionally independent and insulated from one another. For instance, two such protein-gRNA complexes would allow for concurrent activation and editing at independent target sites in the same cell. The problem of establishing orthogonal CRISPR systems can be decomposed into three stages. First, putatively orthogonal systems must be identified with an emphasis on minimizing sequence similarity of the Cas9 protein and its associated RNAs. Second, the systems must be characterized well enough to effectively express and target the systems using gRNAs. Third, the systems should be established as orthogonal to one another by testing for activity and cross talk. Here, we describe the value of these orthogonal CRISPR systems, outline steps for selecting and characterizing potentially orthogonal Cas9-gRNA pairs, and discuss considerations for the desired specificity in Cas9-coupled functions. PMID:27140923

  7. Medical Acoustics

    NASA Astrophysics Data System (ADS)

    Beach, Kirk; 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.

  8. 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.}

  9. 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…

  10. 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.

  11. 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 ...

  12. 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.

  13. 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.

  14. 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

  15. 48 CFR 970.3002 - CAS program requirements.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 48 Federal Acquisition Regulations System 5 2012-10-01 2012-10-01 false CAS program requirements. 970.3002 Section 970.3002 Federal Acquisition Regulations System DEPARTMENT OF ENERGY AGENCY....3002 CAS program requirements....

  16. 48 CFR 970.3002 - CAS program requirements.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 48 Federal Acquisition Regulations System 5 2013-10-01 2013-10-01 false CAS program requirements. 970.3002 Section 970.3002 Federal Acquisition Regulations System DEPARTMENT OF ENERGY AGENCY....3002 CAS program requirements....

  17. 48 CFR 970.3002 - CAS program requirements.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 48 Federal Acquisition Regulations System 5 2011-10-01 2011-10-01 false CAS program requirements. 970.3002 Section 970.3002 Federal Acquisition Regulations System DEPARTMENT OF ENERGY AGENCY....3002 CAS program requirements....

  18. 48 CFR 970.3002 - CAS program requirements.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 48 Federal Acquisition Regulations System 5 2014-10-01 2014-10-01 false CAS program requirements. 970.3002 Section 970.3002 Federal Acquisition Regulations System DEPARTMENT OF ENERGY AGENCY....3002 CAS program requirements....

  19. 48 CFR 970.3002 - CAS program requirements.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 48 Federal Acquisition Regulations System 5 2010-10-01 2010-10-01 false CAS program requirements. 970.3002 Section 970.3002 Federal Acquisition Regulations System DEPARTMENT OF ENERGY AGENCY....3002 CAS program requirements....

  20. CRISPR-Cas: Revolutionising genome engineering.

    PubMed

    Nicholson, Samantha Anne; Pepper, Michael Sean

    2016-09-01

    The ability to permanently alter or repair the human genome has been the subject of a number of science fiction films, but with the recent advent of several customisable sequence-specific endonuclease technologies, genome engineering looks set to become a clinical reality in the near future. This article discusses recent advancements in the technology called 'clustered regularly interspaced palindromic repeat (CRISPR)-associated genes' (CRISPR-Cas), the potential of CRISPR-Cas to revolutionise molecular medicine, and the ethical and regulatory hurdles facing its application. PMID:27601107

  1. Engineered CRISPR-Cas9 nucleases with altered PAM specificities

    PubMed Central

    Kleinstiver, Benjamin P.; Prew, Michelle S.; Tsai, Shengdar Q.; Topkar, Ved; Nguyen, Nhu T.; Zheng, Zongli; Gonzales, Andrew P.W.; Li, Zhuyun; Peterson, Randall T.; Yeh, Jing-Ruey Joanna; Aryee, Martin J.; Joung, J. Keith

    2015-01-01

    Although CRISPR-Cas9 nucleases are widely used for genome editing1, 2, the range of sequences that Cas9 can recognize is constrained by the need for a specific protospacer adjacent motif (PAM)3–6. As a result, it can often be difficult to target double-stranded breaks (DSBs) with the precision that is necessary for various genome editing applications. The ability to engineer Cas9 derivatives with purposefully altered PAM specificities would address this limitation. Here we show that the commonly used Streptococcus pyogenes Cas9 (SpCas9) can be modified to recognize alternative PAM sequences using structural information, bacterial selection-based directed evolution, and combinatorial design. These altered PAM specificity variants enable robust editing of endogenous gene sites in zebrafish and human cells not currently targetable by wild-type SpCas9, and their genome-wide specificities are comparable to wild-type SpCas9 as judged by GUIDE-Seq analysis7. In addition, we identified and characterized another SpCas9 variant that exhibits improved specificity in human cells, possessing better discrimination against off-target sites with non-canonical NAG and NGA PAMs and/or mismatched spacers. We also found that two smaller-size Cas9 orthologues, Streptococcus thermophilus Cas9 (St1Cas9) and Staphylococcus aureus Cas9 (SaCas9), function efficiently in the bacterial selection systems and in human cells, suggesting that our engineering strategies could be extended to Cas9s from other species. Our findings provide broadly useful SpCas9 variants and, more importantly, establish the feasibility of engineering a wide range of Cas9s with altered and improved PAM specificities. PMID:26098369

  2. Engineered CRISPR-Cas9 nucleases with altered PAM specificities.

    PubMed

    Kleinstiver, Benjamin P; Prew, Michelle S; Tsai, Shengdar Q; Topkar, Ved V; Nguyen, Nhu T; Zheng, Zongli; Gonzales, Andrew P W; Li, Zhuyun; Peterson, Randall T; Yeh, Jing-Ruey Joanna; Aryee, Martin J; Joung, J Keith

    2015-07-23

    Although CRISPR-Cas9 nucleases are widely used for genome editing, the range of sequences that Cas9 can recognize is constrained by the need for a specific protospacer adjacent motif (PAM). As a result, it can often be difficult to target double-stranded breaks (DSBs) with the precision that is necessary for various genome-editing applications. The ability to engineer Cas9 derivatives with purposefully altered PAM specificities would address this limitation. Here we show that the commonly used Streptococcus pyogenes Cas9 (SpCas9) can be modified to recognize alternative PAM sequences using structural information, bacterial selection-based directed evolution, and combinatorial design. These altered PAM specificity variants enable robust editing of endogenous gene sites in zebrafish and human cells not currently targetable by wild-type SpCas9, and their genome-wide specificities are comparable to wild-type SpCas9 as judged by GUIDE-seq analysis. In addition, we identify and characterize another SpCas9 variant that exhibits improved specificity in human cells, possessing better discrimination against off-target sites with non-canonical NAG and NGA PAMs and/or mismatched spacers. We also find that two smaller-size Cas9 orthologues, Streptococcus thermophilus Cas9 (St1Cas9) and Staphylococcus aureus Cas9 (SaCas9), function efficiently in the bacterial selection systems and in human cells, suggesting that our engineering strategies could be extended to Cas9s from other species. Our findings provide broadly useful SpCas9 variants and, more importantly, establish the feasibility of engineering a wide range of Cas9s with altered and improved PAM specificities. PMID:26098369

  3. 48 CFR 30.201-1 - CAS applicability.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... CONTRACTING REQUIREMENTS COST ACCOUNTING STANDARDS ADMINISTRATION CAS Program Requirements 30.201-1 CAS applicability. See 48 CFR 9903.201-1 (FAR appendix). ... 48 Federal Acquisition Regulations System 1 2012-10-01 2012-10-01 false CAS applicability....

  4. 48 CFR 30.201-2 - Types of CAS coverage.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... CONTRACTING REQUIREMENTS COST ACCOUNTING STANDARDS ADMINISTRATION CAS Program Requirements 30.201-2 Types of CAS coverage. See 48 CFR 9903.201-2 (FAR appendix). ... 48 Federal Acquisition Regulations System 1 2014-10-01 2014-10-01 false Types of CAS coverage....

  5. 48 CFR 30.201-1 - CAS applicability.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... CONTRACTING REQUIREMENTS COST ACCOUNTING STANDARDS ADMINISTRATION CAS Program Requirements 30.201-1 CAS applicability. See 48 CFR 9903.201-1 (FAR appendix). ... 48 Federal Acquisition Regulations System 1 2013-10-01 2013-10-01 false CAS applicability....

  6. 48 CFR 30.201-2 - Types of CAS coverage.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... CONTRACTING REQUIREMENTS COST ACCOUNTING STANDARDS ADMINISTRATION CAS Program Requirements 30.201-2 Types of CAS coverage. See 48 CFR 9903.201-2 (FAR appendix). ... 48 Federal Acquisition Regulations System 1 2012-10-01 2012-10-01 false Types of CAS coverage....

  7. 48 CFR 9903.201-1 - CAS applicability.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 48 Federal Acquisition Regulations System 7 2012-10-01 2012-10-01 false CAS applicability. 9903... ACCOUNTING STANDARDS CONTRACT COVERAGE CAS Program Requirements 9903.201-1 CAS applicability. (a) This subsection describes the rules for determining whether a proposed contract or subcontract is exempt from...

  8. 48 CFR 30.201-2 - Types of CAS coverage.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... CONTRACTING REQUIREMENTS COST ACCOUNTING STANDARDS ADMINISTRATION CAS Program Requirements 30.201-2 Types of CAS coverage. See 48 CFR 9903.201-2 (FAR appendix). ... 48 Federal Acquisition Regulations System 1 2013-10-01 2013-10-01 false Types of CAS coverage....

  9. 48 CFR 9903.201-1 - CAS applicability.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 48 Federal Acquisition Regulations System 7 2010-10-01 2010-10-01 false CAS applicability. 9903... ACCOUNTING STANDARDS CONTRACT COVERAGE CAS Program Requirements 9903.201-1 CAS applicability. (a) This subsection describes the rules for determining whether a proposed contract or subcontract is exempt from...

  10. 48 CFR 30.201-2 - Types of CAS coverage.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... CONTRACTING REQUIREMENTS COST ACCOUNTING STANDARDS ADMINISTRATION CAS Program Requirements 30.201-2 Types of CAS coverage. See 48 CFR 9903.201-2 (FAR appendix). ... 48 Federal Acquisition Regulations System 1 2011-10-01 2011-10-01 false Types of CAS coverage....

  11. 48 CFR 30.201-1 - CAS applicability.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... CONTRACTING REQUIREMENTS COST ACCOUNTING STANDARDS ADMINISTRATION CAS Program Requirements 30.201-1 CAS applicability. See 48 CFR 9903.201-1 (FAR appendix). ... 48 Federal Acquisition Regulations System 1 2011-10-01 2011-10-01 false CAS applicability....

  12. 48 CFR 9903.201-1 - CAS applicability.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 48 Federal Acquisition Regulations System 7 2014-10-01 2014-10-01 false CAS applicability. 9903... ACCOUNTING STANDARDS CONTRACT COVERAGE CAS Program Requirements 9903.201-1 CAS applicability. (a) This subsection describes the rules for determining whether a proposed contract or subcontract is exempt from...

  13. 48 CFR 30.201-1 - CAS applicability.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... CONTRACTING REQUIREMENTS COST ACCOUNTING STANDARDS ADMINISTRATION CAS Program Requirements 30.201-1 CAS applicability. See 48 CFR 9903.201-1 (FAR appendix). ... 48 Federal Acquisition Regulations System 1 2014-10-01 2014-10-01 false CAS applicability....

  14. 48 CFR 9903.201-1 - CAS applicability.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 48 Federal Acquisition Regulations System 7 2013-10-01 2012-10-01 true CAS applicability. 9903.201... ACCOUNTING STANDARDS CONTRACT COVERAGE CAS Program Requirements 9903.201-1 CAS applicability. (a) This subsection describes the rules for determining whether a proposed contract or subcontract is exempt from...

  15. 48 CFR 30.201-2 - Types of CAS coverage.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... CONTRACTING REQUIREMENTS COST ACCOUNTING STANDARDS ADMINISTRATION CAS Program Requirements 30.201-2 Types of CAS coverage. See 48 CFR 9903.201-2 (FAR appendix). ... 48 Federal Acquisition Regulations System 1 2010-10-01 2010-10-01 false Types of CAS coverage....

  16. 48 CFR 30.201-1 - CAS applicability.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... CONTRACTING REQUIREMENTS COST ACCOUNTING STANDARDS ADMINISTRATION CAS Program Requirements 30.201-1 CAS applicability. See 48 CFR 9903.201-1 (FAR appendix). ... 48 Federal Acquisition Regulations System 1 2010-10-01 2010-10-01 false CAS applicability....

  17. 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.

  18. 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.

  19. Acoustic hemostasis

    NASA Astrophysics Data System (ADS)

    Crum, L.; Andrew, M.; Bailey, M.; Beach, K.; Brayman, A.; Curra, F.; Kaczkowski, P.; Kargl, S.; Martin, R.; Vaezy, S.

    2003-04-01

    Over the past several years, the Center for Industrial and Medical Ultrasound (CIMU) at the Applied Physics Laboratory in the University of Washington has undertaken a broad research program in the general area of High Intensity Focused Ultrasound (HIFU). Our principal emphasis has been on the use of HIFU to induce hemostasis; in particular, CIMU has sought to develop a small, lightweight, portable device that would use ultrasound for both imaging and therapy. Such a technology is needed because nearly 50% of combat casualty mortality results from exsanguinations, or uncontrolled bleeding. A similar percentage occurs for civilian death due to trauma. In this general review, a presentation of the general problem will be given, as well as our recent approaches to the development of an image-guided, transcutaneous, acoustic hemostasis device. [Work supported in part by the USAMRMC, ONR and the NIH.

  20. 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.

  1. 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. PMID:26929403

  2. Historic light curve of V890 Cas

    NASA Astrophysics Data System (ADS)

    Nesci, R.

    2016-05-01

    The variability of V890 Cas is studied with 87 -band plates of the Asiago archive. The star shows variations of about 5 mag with an average magnitude =13 and a period of 486 days. An 5.0 color index is also derived near the maximum luminosity.

  3. 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.

  4. Lessons Learned on Management of CAS Development.

    ERIC Educational Resources Information Center

    Boyadjieff, Kiril

    1995-01-01

    Computer-assisted studies (CAS) attract foreign language professionals' attention due to the reliability of personal computers, the decreasing cost of available technology, and the new generation of students for whom electronic media are a familiar habitat. This article focuses on a project of the Defense Language Institute that produced over…

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

    PubMed

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

    2016-08-19

    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

  6. 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.

  7. 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. PMID:26269544

  8. Acoustical coupling of lizard eardrums.

    PubMed

    Christensen-Dalsgaard, Jakob; Manley, Geoffrey A

    2008-12-01

    Lizard ears are clear examples of two-input pressure-difference receivers, with up to 40-dB differences in eardrum vibration amplitude in response to ipsi- and contralateral stimulus directions. The directionality is created by acoustical coupling of the eardrums and interaction of the direct and indirect sound components on the eardrum. The ensuing pressure-difference characteristics generate the highest directionality of any similar-sized terrestrial vertebrate ear. The aim of the present study was to measure the gain of the direct and indirect sound components in three lizard species: Anolis sagrei and Basiliscus vittatus (iguanids) and Hemidactylus frenatus (gekkonid) by laser vibrometry, using either free-field sound or a headphone and coupler for stimulation. The directivity of the ear of these lizards is pronounced in the frequency range from 2 to 5 kHz. The directivity is ovoidal, asymmetrical across the midline, but largely symmetrical across the interaural axis (i.e., front-back). Occlusion of the contralateral ear abolishes the directionality. We stimulated the two eardrums with a coupler close to the eardrum to measure the gain of the sound pathways. Within the frequency range of maximal directionality, the interaural transmission gain (compared to sound arriving directly) is close to or even exceeds unity, indicating a pronounced acoustical transparency of the lizard head and resonances in the interaural cavities. Our results show that the directionality of the lizard ear is caused by the acoustic interaction of the two eardrums. The results can be largely explained by a simple acoustical model based on an electrical analog circuit. PMID:18648878

  9. Acoustical Coupling of Lizard Eardrums

    PubMed Central

    Manley, Geoffrey A.

    2008-01-01

    Lizard ears are clear examples of two-input pressure-difference receivers, with up to 40-dB differences in eardrum vibration amplitude in response to ipsi- and contralateral stimulus directions. The directionality is created by acoustical coupling of the eardrums and interaction of the direct and indirect sound components on the eardrum. The ensuing pressure-difference characteristics generate the highest directionality of any similar-sized terrestrial vertebrate ear. The aim of the present study was to measure the gain of the direct and indirect sound components in three lizard species: Anolis sagrei and Basiliscus vittatus (iguanids) and Hemidactylus frenatus (gekkonid) by laser vibrometry, using either free-field sound or a headphone and coupler for stimulation. The directivity of the ear of these lizards is pronounced in the frequency range from 2 to 5 kHz. The directivity is ovoidal, asymmetrical across the midline, but largely symmetrical across the interaural axis (i.e., front–back). Occlusion of the contralateral ear abolishes the directionality. We stimulated the two eardrums with a coupler close to the eardrum to measure the gain of the sound pathways. Within the frequency range of maximal directionality, the interaural transmission gain (compared to sound arriving directly) is close to or even exceeds unity, indicating a pronounced acoustical transparency of the lizard head and resonances in the interaural cavities. Our results show that the directionality of the lizard ear is caused by the acoustic interaction of the two eardrums. The results can be largely explained by a simple acoustical model based on an electrical analog circuit. PMID:18648878

  10. 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

  11. 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

  12. Structure and Engineering of Francisella novicida Cas9.

    PubMed

    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

    2016-02-25

    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 the FnCas9-ribonucleoprotein complex can be microinjected into mouse zygotes to edit endogenous sites with the 5'-YG-3' PAM, thus expanding the target space of the CRISPR-Cas9 toolbox. PMID:26875867

  13. Photoactivatable CRISPR-Cas9 for optogenetic genome editing.

    PubMed

    Nihongaki, Yuta; Kawano, Fuun; Nakajima, Takahiro; Sato, Moritoshi

    2015-07-01

    We describe an engineered photoactivatable Cas9 (paCas9) that enables optogenetic control of CRISPR-Cas9 genome editing in human cells. paCas9 consists of split Cas9 fragments and photoinducible dimerization domains named Magnets. In response to blue light irradiation, paCas9 expressed in human embryonic kidney 293T cells induces targeted genome sequence modifications through both nonhomologous end joining and homology-directed repair pathways. Genome editing activity can be switched off simply by extinguishing the light. We also demonstrate activation of paCas9 in spatial patterns determined by the sites of irradiation. Optogenetic control of targeted genome editing should facilitate improved understanding of complex gene networks and could prove useful in biomedical applications. PMID:26076431

  14. Bimodal stimulation: benefits for music perception and sound quality.

    PubMed

    Sucher, Catherine M; McDermott, Hugh J

    2009-01-01

    With recent expansions in cochlear implantation candidacy criteria, increasing numbers of implantees can exploit their remaining hearing by using bimodal stimulation (combining electrical stimulation via the implant with acoustic stimulation via hearing aids). This study examined the effect of bimodal stimulation on music perception and perceived sound quality. The perception of music and sound quality by nine post-lingually deafened adult implantees was examined in three conditions: implant alone, hearing aid alone and bimodal stimulation. On average, bimodal stimulation provided the best results for music perception and perceived sound quality when compared with results obtained with electrical stimulation alone. Thus, for implantees with usable acoustic hearing, bimodal stimulation may be advantageous when listening to music and other non-speech sounds. PMID:19230032

  15. Acoustic hemostasis

    NASA Astrophysics Data System (ADS)

    Crum, Lawrence; Beach, Kirk; Carter, Stephen; Chandler, Wayne; Curra, Francesco; Kaczkowski, Peter; Keilman, George; Khokhlova, Vera; Martin, Roy; Mourad, Pierre; Vaezy, Shahram

    2000-07-01

    In cases of severe injury, physicians speak of a "golden hour"—a brief grace period in which quickly applied, proper therapy can save the life of the patient. Much of this mortality results from exsanguination, i.e., bleeding to death—often from internal hemorrhage. The inability of a paramedic to treat breaches in the vascular system deep within the body or to stem the loss of blood from internal organs is a major reason for the high level of mortality associated with blunt trauma. We have undertaken an extensive research program to treat the problem of internal bleeding. Our approach is as follows: (a) We use scanning ultrasound to identify internal bleeding and hemorrhage, (b) we use ultrasound imaging to locate specific breaches in the vascular system, both from damaged vessels and gross damage to the capillary bed, and (c) we use High Intensity Focused Ultrasound (HIFU) to treat the damaged region and to induce hemostasis. We present a general review of this research with some emphasis on the role of nonlinear acoustics.

  16. Unification of Cas protein families and a simple scenario for the origin and evolution of CRISPR-Cas systems

    PubMed Central

    2011-01-01

    Background The CRISPR-Cas adaptive immunity systems that are present in most Archaea and many Bacteria function by incorporating fragments of alien genomes into specific genomic loci, transcribing the inserts and using the transcripts as guide RNAs to destroy the genome of the cognate virus or plasmid. This RNA interference-like immune response is mediated by numerous, diverse and rapidly evolving Cas (CRISPR-associated) proteins, several of which form the Cascade complex involved in the processing of CRISPR transcripts and cleavage of the target DNA. Comparative analysis of the Cas protein sequences and structures led to the classification of the CRISPR-Cas systems into three Types (I, II and III). Results A detailed comparison of the available sequences and structures of Cas proteins revealed several unnoticed homologous relationships. The Repeat-Associated Mysterious Proteins (RAMPs) containing a distinct form of the RNA Recognition Motif (RRM) domain, which are major components of the CRISPR-Cas systems, were classified into three large groups, Cas5, Cas6 and Cas7. Each of these groups includes many previously uncharacterized proteins now shown to adopt the RAMP structure. Evidence is presented that large subunits contained in most of the CRISPR-Cas systems could be homologous to Cas10 proteins which contain a polymerase-like Palm domain and are predicted to be enzymatically active in Type III CRISPR-Cas systems but inactivated in Type I systems. These findings, the fact that the CRISPR polymerases, RAMPs and Cas2 all contain core RRM domains, and distinct gene arrangements in the three types of CRISPR-Cas systems together provide for a simple scenario for origin and evolution of the CRISPR-Cas machinery. Under this scenario, the CRISPR-Cas system originated in thermophilic Archaea and subsequently spread horizontally among prokaryotes. Conclusions Because of the extreme diversity of CRISPR-Cas systems, in-depth sequence and structure comparison continue to

  17. 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.

  18. Acoustic Holography

    NASA Astrophysics Data System (ADS)

    Kim, Yang-Hann

    One of the subtle problems that make noise control difficult for engineers is the invisibility of noise or sound. A visual image of noise often helps to determine an appropriate means for noise control. There have been many attempts to fulfill this rather challenging objective. Theoretical (or numerical) means for visualizing the sound field have been attempted, and as a result, a great deal of progress has been made. However, most of these numerical methods are not quite ready for practical applications to noise control problems. In the meantime, rapid progress with instrumentation has made it possible to use multiple microphones and fast signal-processing systems. Although these systems are not perfect, they are useful. A state-of-the-art system has recently become available, but it still has many problematic issues; for example, how can one implement the visualized noise field. The constructed noise or sound picture always consists of bias and random errors, and consequently, it is often difficult to determine the origin of the noise and the spatial distribution of the noise field. Section 26.2 of this chapter introduces a brief history, which is associated with sound visualization, acoustic source identification methods and what has been accomplished with a line or surface array. Section 26.2.3 introduces difficulties and recent studies, including de-Dopplerization and de-re verberation methods, both essential for visualizing a moving noise source, such as occurs for cars or trains. This section also addresses what produces ambiguity in realizing real sound sources in a room or closed space. Another major issue associated with sound/noise visualization is whether or not we can distinguish between mutual dependencies of noise in space (Sect. 26.2.4); for example, we are asked to answer the question, Can we see two birds singing or one bird with two beaks?

  19. Acoustic Holography

    NASA Astrophysics Data System (ADS)

    Kim, Yang-Hann

    One of the subtle problems that make noise control difficult for engineers is the invisibility of noise or sound. A visual image of noise often helps to determine an appropriate means for noise control. There have been many attempts to fulfill this rather challenging objective. Theoretical (or numerical) means for visualizing the sound field have been attempted, and as a result, a great deal of progress has been made. However, most of these numerical methods are not quite ready for practical applications to noise control problems. In the meantime, rapid progress with instrumentation has made it possible to use multiple microphones and fast signal-processing systems. Although these systems are not perfect, they are useful. A state-of-the-art system has recently become available, but it still has many problematic issues; for example, how can one implement the visualized noise field. The constructed noise or sound picture always consists of bias and random errors, and consequently, it is often difficult to determine the origin of the noise and the spatial distribution of the noise field. Section 26.2 of this chapter introduces a brief history, which is associated with "sound visualization," acoustic source identification methods and what has been accomplished with a line or surface array. Section 26.2.3 introduces difficulties and recent studies, including de-Dopplerization and de-reverberation methods, both essentialfor visualizing a moving noise source, such as occurs for cars or trains. This section also addresses what produces ambiguity in realizing real sound sources in a room or closed space. Another major issue associated with sound/noise visualization is whether or not we can distinguish between mutual dependencies of noise in space (Sect. 26.2.4); for example, we are asked to answer the question, "Can we see two birds singing or one bird with two beaks?"

  20. What Is an Acoustic Neuroma

    MedlinePlus

    ... Acoustic Neuroma An acoustic neuroma, also called a vestibular schwannoma, is a rare benign tumor of the ... Acoustic Neuroma? An acoustic neuroma, known as a vestibular schwannoma, is a benign (non-cancerous) growth that ...

  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. Substrate generation for endonucleases of CRISPR/cas systems.

    PubMed

    Zoephel, Judith; Dwarakanath, Srivatsa; Richter, Hagen; Plagens, André; Randau, Lennart

    2012-01-01

    The interaction of viruses and their prokaryotic hosts shaped the evolution of bacterial and archaeal life. Prokaryotes developed several strategies to evade viral attacks that include restriction modification, abortive infection and CRISPR/Cas systems. These adaptive immune systems found in many Bacteria and most Archaea consist of clustered regularly interspaced short palindromic repeat (CRISPR) sequences and a number of CRISPR associated (Cas) genes (Fig. 1) (1-3). Different sets of Cas proteins and repeats define at least three major divergent types of CRISPR/Cas systems (4). The universal proteins Cas1 and Cas2 are proposed to be involved in the uptake of viral DNA that will generate a new spacer element between two repeats at the 5' terminus of an extending CRISPR cluster (5). The entire cluster is transcribed into a precursor-crRNA containing all spacer and repeat sequences and is subsequently processed by an enzyme of the diverse Cas6 family into smaller crRNAs (6-8). These crRNAs consist of the spacer sequence flanked by a 5' terminal (8 nucleotides) and a 3' terminal tag derived from the repeat sequence (9). A repeated infection of the virus can now be blocked as the new crRNA will be directed by a Cas protein complex (Cascade) to the viral DNA and identify it as such via base complementarity(10). Finally, for CRISPR/Cas type 1 systems, the nuclease Cas3 will destroy the detected invader DNA (11,12) . These processes define CRISPR/Cas as an adaptive immune system of prokaryotes and opened a fascinating research field for the study of the involved Cas proteins. The function of many Cas proteins is still elusive and the causes for the apparent diversity of the CRISPR/Cas systems remain to be illuminated. Potential activities of most Cas proteins were predicted via detailed computational analyses. A major fraction of Cas proteins are either shown or proposed to function as endonucleases (4). Here, we present methods to generate crRNAs and precursor-cRNAs for

  3. Protein engineering of Cas9 for enhanced function

    PubMed Central

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

    2015-01-01

    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 complimentary 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 directly into 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. PMID:25398355

  4. CRISPR-Cas9-assisted recombineering in Lactobacillus reuteri.

    PubMed

    Oh, Jee-Hwan; van Pijkeren, Jan-Peter

    2014-01-01

    Clustered regularly interspaced palindromic repeats (CRISPRs) and the CRISPR-associated (Cas) nuclease protect bacteria and archeae from foreign DNA by site-specific cleavage of incoming DNA. Type-II CRISPR-Cas systems, such as the Streptococcus pyogenes CRISPR-Cas9 system, can be adapted such that Cas9 can be guided to a user-defined site in the chromosome to introduce double-stranded breaks. Here we have developed and optimized CRISPR-Cas9 function in the lactic acid bacterium Lactobacillus reuteri ATCC PTA 6475. We established proof-of-concept showing that CRISPR-Cas9 selection combined with single-stranded DNA (ssDNA) recombineering is a realistic approach to identify at high efficiencies edited cells in a lactic acid bacterium. We show for three independent targets that subtle changes in the bacterial genome can be recovered at efficiencies ranging from 90 to 100%. By combining CRISPR-Cas9 and recombineering, we successfully applied codon saturation mutagenesis in the L. reuteri chromosome. Also, CRISPR-Cas9 selection is critical to identify low-efficiency events such as oligonucleotide-mediated chromosome deletions. This also means that CRISPR-Cas9 selection will allow identification of recombinant cells in bacteria with low recombineering efficiencies, eliminating the need for ssDNA recombineering optimization procedures. We envision that CRISPR-Cas genome editing has the potential to change the landscape of genome editing in lactic acid bacteria, and other Gram-positive bacteria. PMID:25074379

  5. Costs of CRISPR-Cas-mediated resistance in Streptococcus thermophilus

    PubMed Central

    Vale, Pedro F.; Lafforgue, Guillaume; Gatchitch, Francois; Gardan, Rozenn; Moineau, Sylvain; Gandon, Sylvain

    2015-01-01

    CRISPR-Cas is a form of adaptive sequence-specific immunity in microbes. This system offers unique opportunities for the study of coevolution between bacteria and their viral pathogens, bacteriophages. A full understanding of the coevolutionary dynamics of CRISPR-Cas requires knowing the magnitude of the cost of resisting infection. Here, using the gram-positive bacterium Streptococcus thermophilus and its associated virulent phage 2972, a well-established model system harbouring at least two type II functional CRISPR-Cas systems, we obtained different fitness measures based on growth assays in isolation or in pairwise competition. We measured the fitness cost associated with different components of this adaptive immune system: the cost of Cas protein expression, the constitutive cost of increasing immune memory through additional spacers, and the conditional costs of immunity during phage exposure. We found that Cas protein expression is particularly costly, as Cas-deficient mutants achieved higher competitive abilities than the wild-type strain with functional Cas proteins. Increasing immune memory by acquiring up to four phage-derived spacers was not associated with fitness costs. In addition, the activation of the CRISPR-Cas system during phage exposure induces significant but small fitness costs. Together these results suggest that the costs of the CRISPR-Cas system arise mainly due to the maintenance of the defence system. We discuss the implications of these results for the evolution of CRISPR-Cas-mediated immunity. PMID:26224708

  6. Expanding the catalog of cas genes with metagenomes.

    PubMed

    Zhang, Quan; Doak, Thomas G; Ye, Yuzhen

    2014-02-01

    The CRISPR (clusters of regularly interspaced short palindromic repeats)-Cas adaptive immune system is an important defense system in bacteria, providing targeted defense against invasions of foreign nucleic acids. CRISPR-Cas systems consist of CRISPR loci and cas (CRISPR-associated) genes: sequence segments of invaders are incorporated into host genomes at CRISPR loci to generate specificity, while adjacent cas genes encode proteins that mediate the defense process. We pursued an integrated approach to identifying putative cas genes from genomes and metagenomes, combining similarity searches with genomic neighborhood analysis. Application of our approach to bacterial genomes and human microbiome datasets allowed us to significantly expand the collection of cas genes: the sequence space of the Cas9 family, the key player in the recently engineered RNA-guided platforms for genome editing in eukaryotes, is expanded by at least two-fold with metagenomic datasets. We found genes in cas loci encoding other functions, for example, toxins and antitoxins, confirming the recently discovered potential of coupling between adaptive immunity and the dormancy/suicide systems. We further identified 24 novel Cas families; one novel family contains 20 proteins, all identified from the human microbiome datasets, illustrating the importance of metagenomics projects in expanding the diversity of cas genes. PMID:24319142

  7. 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

  8. Efficient Mitochondrial Genome Editing by CRISPR/Cas9

    PubMed Central

    Jo, Areum; Ham, Sangwoo; Lee, Gum Hwa; Lee, Yun-Il; Kim, SangSeong; Lee, Yun-Song; Shin, Joo-Ho; Lee, Yunjong

    2015-01-01

    The Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)/Cas9 system has been widely used for nuclear DNA editing to generate mutations or correct specific disease alleles. Despite its flexible application, it has not been determined if CRISPR/Cas9, originally identified as a bacterial defense system against virus, can be targeted to mitochondria for mtDNA editing. Here, we show that regular FLAG-Cas9 can localize to mitochondria to edit mitochondrial DNA with sgRNAs targeting specific loci of the mitochondrial genome. Expression of FLAG-Cas9 together with gRNA targeting Cox1 and Cox3 leads to cleavage of the specific mtDNA loci. In addition, we observed disruption of mitochondrial protein homeostasis following mtDNA truncation or cleavage by CRISPR/Cas9. To overcome nonspecific distribution of FLAG-Cas9, we also created a mitochondria-targeted Cas9 (mitoCas9). This new version of Cas9 localizes only to mitochondria; together with expression of gRNA targeting mtDNA, there is specific cleavage of mtDNA. MitoCas9-induced reduction of mtDNA and its transcription leads to mitochondrial membrane potential disruption and cell growth inhibition. This mitoCas9 could be applied to edit mtDNA together with gRNA expression vectors without affecting genomic DNA. In this brief study, we demonstrate that mtDNA editing is possible using CRISPR/Cas9. Moreover, our development of mitoCas9 with specific localization to the mitochondria should facilitate its application for mitochondrial genome editing. PMID:26448933

  9. Breaking-Cas-interactive design of guide RNAs for CRISPR-Cas experiments for ENSEMBL genomes.

    PubMed

    Oliveros, Juan C; Franch, Mònica; Tabas-Madrid, Daniel; San-León, David; Montoliu, Lluis; Cubas, Pilar; Pazos, Florencio

    2016-07-01

    The CRISPR/Cas technology is enabling targeted genome editing in multiple organisms with unprecedented accuracy and specificity by using RNA-guided nucleases. A critical point when planning a CRISPR/Cas experiment is the design of the guide RNA (gRNA), which directs the nuclease and associated machinery to the desired genomic location. This gRNA has to fulfil the requirements of the nuclease and lack homology with other genome sites that could lead to off-target effects. Here we introduce the Breaking-Cas system for the design of gRNAs for CRISPR/Cas experiments, including those based in the Cas9 nuclease as well as others recently introduced. The server has unique features not available in other tools, including the possibility of using all eukaryotic genomes available in ENSEMBL (currently around 700), placing variable PAM sequences at 5' or 3' and setting the guide RNA length and the scores per nucleotides. It can be freely accessed at: http://bioinfogp.cnb.csic.es/tools/breakingcas, and the code is available upon request. PMID:27166368

  10. Acoustic particle palpation for measuring tissue elasticity

    PubMed Central

    Koruk, Hasan; El Ghamrawy, Ahmed

    2015-01-01

    We propose acoustic particle palpation—the use of sound to press a population of acoustic particles against an interface—as a method for measuring the qualitative and quantitative mechanical properties of materials. We tested the feasibility of this method by emitting ultrasound pulses across a tunnel of an elastic material filled with microbubbles. Ultrasound stimulated the microbubble cloud to move in the direction of wave propagation, press against the distal surface, and cause deformations relevant for elasticity measurements. Shear waves propagated away from the palpation site with a velocity that was used to estimate the material's Young's modulus. PMID:26869723

  11. Acoustic particle palpation for measuring tissue elasticity

    NASA Astrophysics Data System (ADS)

    Koruk, Hasan; El Ghamrawy, Ahmed; Pouliopoulos, Antonios N.; Choi, James J.

    2015-11-01

    We propose acoustic particle palpation—the use of sound to press a population of acoustic particles against an interface—as a method for measuring the qualitative and quantitative mechanical properties of materials. We tested the feasibility of this method by emitting ultrasound pulses across a tunnel of an elastic material filled with microbubbles. Ultrasound stimulated the microbubble cloud to move in the direction of wave propagation, press against the distal surface, and cause deformations relevant for elasticity measurements. Shear waves propagated away from the palpation site with a velocity that was used to estimate the material's Young's modulus.

  12. 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 ...

  13. 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.

  14. 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).

  15. 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. PMID:26470680

  16. Inducible in vivo genome editing with CRISPR/Cas9

    PubMed Central

    O'Rourke, Kevin P; Muley, Ashlesha; Kastenhuber, Edward R; Livshits, Geulah; Tschaharganeh, Darjus F; Socci, Nicholas D; Lowe, Scott W

    2015-01-01

    CRISPR/Cas9-based genome editing enables the rapid genetic manipulation of any genomic locus without the need for gene targeting by homologous recombination. Here we describe a conditional transgenic approach that allows temporal control of CRISPR/Cas9 activity for inducible genome editing in adult mice. We show that doxycycline-regulated Cas9 induction enables widespread gene disruption in multiple tissues and that limiting the duration of Cas9 expression or using a Cas9D10A (Cas9n) variant, can regulate the frequency and size of target gene modifications, respectively. Further, we show that the inducible CRISPR (iCRISPR) system can be used effectively to create biallelic mutation in multiple target loci and thus, provides a flexible and fast platform to study loss of function phenotypes in vivo. PMID:25690852

  17. Evaporated CaS thin films for AC electroluminescence devices

    NASA Astrophysics Data System (ADS)

    Kobayashi, H.; Tanaka, S.; Shanker, V.; Shiiki, M.; Deguchi, H.

    1985-08-01

    The growth behavior of evaporated CaS thin films has been investigated to achieve bright electroluminescence. The crystallinity of CaS films is improved with substrate temperature and for temperatures higher than 300°C, the films orient to the (200) plane. Sulfur coevaporation further helps to form a more perfect film even at lower temperatures. A CaS: Ce,Cl electroluminescent thin film device has been fabricated with a brightness of 650 cd/m 2.

  18. 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

  19. 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

  20. 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. PMID:26503043

  1. Cas9 as a versatile tool for engineering biology

    PubMed Central

    Mali, Prashant; Esvelt, Kevin M; Church, George M

    2014-01-01

    RNA-guided Cas9 nucleases derived from clustered regularly interspaced short palindromic repeats (CRISPR)-Cas systems have dramatically transformed our ability to edit the genomes of diverse organisms. We believe tools and techniques based on Cas9, a single unifying factor capable of colocalizing RNA, DNA and protein, will grant unprecedented control over cellular organization, regulation and behavior. Here we describe the Cas9 targeting methodology, detail current and prospective engineering advances and suggest potential applications ranging from basic science to the clinic. PMID:24076990

  2. Optical Control of CRISPR/Cas9 Gene Editing

    PubMed Central

    Hemphill, James; Borchardt, Erin K.; Brown, Kalyn; Asokan, Aravind; Deiters, Alexander

    2016-01-01

    The CRISPR/Cas9 system has emerged as an important tool in biomedical research for a wide range of applications, with significant potential for genome engineering and gene therapy. In order to achieve conditional control of the CRISPR/Cas9 system, a genetically encoded light-activated Cas9 was engineered through the site-specific installation of a caged lysine amino acid. Several potential lysine residues were identified as viable caging sites that can be modified to optically control Cas9 function, as demonstrated through optical activation and deactivation of both exogenous and endogenous gene function. PMID:25905628

  3. 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.

  4. 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

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

    PubMed Central

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

    2014-01-01

    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. PMID:24748663

  6. 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.

  7. 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. PMID:25301567

  8. 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.

  9. Controllable optical transparency using an acoustic standing-wave device

    NASA Astrophysics Data System (ADS)

    Moradi, Kamran; El-Zahab, Bilal

    2015-09-01

    In this paper, a suspended-particle device with controllable light transmittance was developed based on acoustic stimuli. Using a glass compartment and carbon particle suspension in an organic solvent, the device responded to acoustic stimulation by alignment of particles. The alignment of light-absorbing carbon particles afforded an increase in light transmittance as high as 84.5% and was controllable based on the control of the frequency and amplitude of the acoustic waves. The device also demonstrated alignment memory rendering it energy-efficient.

  10. 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.

  11. Achieving Electric-Acoustic Benefit with a Modulated Tone

    PubMed Central

    Brown, Christopher A.; Bacon, Sid P.

    2013-01-01

    Objective When either real or simulated electric stimulation from a cochlear implant (CI) is combined with low-frequency acoustic stimulation (electric-acoustic stimulation [EAS]), speech intelligibility in noise can improve dramatically. We recently showed that a similar benefit to intelligibility can be observed in simulation when the low-frequency acoustic stimulation (low-pass target speech) is replaced with a tone that is modulated both in frequency with the fundamental frequency (F0) of the target talker and in amplitude with the amplitude envelope of the low-pass target speech (Brown & Bacon 2009). The goal of the current experiment was to examine the benefit of the modulated tone to intelligibility in CI patients. Design Eight CI users who had some residual acoustic hearing either in the implanted ear, the unimplanted ear, or both ears participated in this study. Target speech was combined with either multitalker babble or a single competing talker and presented to the implant. Stimulation to the acoustic region consisted of no signal, target speech, or a tone that was modulated in frequency to track the changes in the target talker’s F0 and in amplitude to track the amplitude envelope of target speech low-pass filtered at 500 Hz. Results All patients showed improvements in intelligibility over electric-only stimulation when either the tone or target speech was presented acoustically. The average improvement in intelligibility was 46 percentage points due to the tone and 55 percentage points due to target speech. Conclusions The results demonstrate that a tone carrying F0 and amplitude envelope cues of target speech can provide significant benefit to CI users and may lead to new technologies that could offer EAS benefit to many patients who would not benefit from current EAS approaches. PMID:19546806

  12. CRISPR-Cas9 Genome Engineering in Saccharomyces cerevisiae Cells.

    PubMed

    Ryan, Owen W; Poddar, Snigdha; Cate, Jamie H D

    2016-01-01

    This protocol describes a method for CRISPR-Cas9-mediated genome editing that results in scarless and marker-free integrations of DNA into Saccharomyces cerevisiae genomes. DNA integration results from cotransforming (1) a single plasmid (pCAS) that coexpresses the Cas9 endonuclease and a uniquely engineered single guide RNA (sgRNA) expression cassette and (2) a linear DNA molecule that is used to repair the chromosomal DNA damage by homology-directed repair. For target specificity, the pCAS plasmid requires only a single cloning modification: replacing the 20-bp guide RNA sequence within the sgRNA cassette. This CRISPR-Cas9 protocol includes methods for (1) cloning the unique target sequence into pCAS, (2) assembly of the double-stranded DNA repair oligonucleotides, and (3) cotransformation of pCAS and linear repair DNA into yeast cells. The protocol is technically facile and requires no special equipment. It can be used in any S. cerevisiae strain, including industrial polyploid isolates. Therefore, this CRISPR-Cas9-based DNA integration protocol is achievable by virtually any yeast genetics and molecular biology laboratory. PMID:27250940

  13. Interacting Parallel Constructions of Knowledge in a CAS Context

    ERIC Educational Resources Information Center

    Kidron, Ivy; Dreyfus, Tommy

    2010-01-01

    We consider the influence of a CAS context on a learner's process of constructing a justification for the bifurcations in a logistic dynamical process. We describe how instrumentation led to cognitive constructions and how the roles of the learner and the CAS intertwine, especially close to the branching and combining of constructing actions. The…

  14. Semiotic and Discursive Variables in CAS-Based Didactical Engineering.

    ERIC Educational Resources Information Center

    Winslow, Carl

    2003-01-01

    Presents a semiotic analysis of the potential of computer algebra systems (CAS) for enabling mathematical activity on a conceptual level higher than usual. Illustrates examples of theoretical points from a development project in the context of a first year university course in calculus. Discusses how CAS may be used in a didactical analysis and in…

  15. 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.

  16. 48 CFR 970.3002-1 - CAS applicability.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ....3002-1 CAS applicability. The provisions of 48 CFR part 30 and 48 CFR chapter 99 (FAR Appendix) shall... 48 Federal Acquisition Regulations System 5 2010-10-01 2010-10-01 false CAS applicability. 970.3002-1 Section 970.3002-1 Federal Acquisition Regulations System DEPARTMENT OF ENERGY...

  17. 48 CFR 970.3002-1 - CAS applicability.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ....3002-1 CAS applicability. The provisions of 48 CFR part 30 and 48 CFR chapter 99 (FAR Appendix) shall... 48 Federal Acquisition Regulations System 5 2011-10-01 2011-10-01 false CAS applicability. 970.3002-1 Section 970.3002-1 Federal Acquisition Regulations System DEPARTMENT OF ENERGY...

  18. 48 CFR 970.3002-1 - CAS applicability.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ....3002-1 CAS applicability. The provisions of 48 CFR part 30 and 48 CFR chapter 99 (FAR Appendix) shall... 48 Federal Acquisition Regulations System 5 2014-10-01 2014-10-01 false CAS applicability. 970.3002-1 Section 970.3002-1 Federal Acquisition Regulations System DEPARTMENT OF ENERGY...

  19. 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…

  20. 48 CFR 970.3002-1 - CAS applicability.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ....3002-1 CAS applicability. The provisions of 48 CFR part 30 and 48 CFR chapter 99 (FAR Appendix) shall... 48 Federal Acquisition Regulations System 5 2013-10-01 2013-10-01 false CAS applicability. 970.3002-1 Section 970.3002-1 Federal Acquisition Regulations System DEPARTMENT OF ENERGY...

  1. 48 CFR 970.3002-1 - CAS applicability.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ....3002-1 CAS applicability. The provisions of 48 CFR part 30 and 48 CFR chapter 99 (FAR Appendix) shall... 48 Federal Acquisition Regulations System 5 2012-10-01 2012-10-01 false CAS applicability. 970.3002-1 Section 970.3002-1 Federal Acquisition Regulations System DEPARTMENT OF ENERGY...

  2. 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…

  3. 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. PMID:27340770

  4. Simplified CRISPR-Cas genome editing for Saccharomyces cerevisiae.

    PubMed

    Generoso, Wesley Cardoso; Gottardi, Manuela; Oreb, Mislav; Boles, Eckhard

    2016-08-01

    CRISPR-Cas has become a powerful technique for genetic engineering of yeast. Here, we present an improved version by using only one single plasmid expressing Cas9 and one or two guide-RNAs. A high gene deletion efficiency was achieved even with simultaneous recombination cloning of the plasmid and deletion in industrial strains. PMID:27327211

  5. Recent Progress in CRISPR/Cas9 Technology.

    PubMed

    Mei, Yue; Wang, Yan; Chen, Huiqian; Sun, Zhong Sheng; Ju, Xing-Da

    2016-02-20

    The clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9 system, a simple and efficient tool for genome editing, has experienced rapid progress in its technology and applicability in the past two years. Here, we review the recent advances in CRISPR/Cas9 technology and the ways that have been adopted to expand our capacity for precise genome manipulation. First, we introduce the mechanism of CRISPR/Cas9, including its biochemical and structural implications. Second, we highlight the latest improvements in the CRISPR/Cas9 system, especially Cas9 protein modifications for customization. Third, we review its current applications, in which the versatile CRISPR/Cas9 system was employed to edit the genome, epigenome, or RNA of various organisms. Although CRISPR/Cas9 allows convenient genome editing accompanied by many benefits, we should not ignore the significant ethical and biosafety concerns that it raises. Finally, we discuss the prospective applications and challenges of several promising techniques adapted from CRISPR/Cas9. PMID:26924689

  6. Infant Stimulation.

    ERIC Educational Resources Information Center

    International Children's Centre, Paris (France).

    This set of documents consists of English, French, and Spanish translations of four pamphlets on infant stimulation. The pamphlets provide information designed for lay persons, educators and primary care personnel, academics and professionals, and for health administrators and family-planning organizations. The contents cover infant needs; infant…

  7. Nonlinear Acoustics in Fluids

    NASA Astrophysics Data System (ADS)

    Lauterborn, Werner; Kurz, Thomas; Akhatov, Iskander

    At high sound intensities or long propagation distances at in fluids sufficiently low damping acoustic phenomena become nonlinear. This chapter focuses on nonlinear acoustic wave properties in gases and liquids. The origin of nonlinearity, equations of state, simple nonlinear waves, nonlinear acoustic wave equations, shock-wave formation, and interaction of waves are presented and discussed. Tables are given for the nonlinearity parameter B/A for water and a range of organic liquids, liquid metals and gases. Acoustic cavitation with its nonlinear bubble oscillations, pattern formation and sonoluminescence (light from sound) are modern examples of nonlinear acoustics. The language of nonlinear dynamics needed for understanding chaotic dynamics and acoustic chaotic systems is introduced.

  8. 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

  9. Conditional Control of CRISPR/Cas9 Function.

    PubMed

    Zhou, Wenyuan; Deiters, Alexander

    2016-04-25

    The recently discovered CRISPR/Cas9 endonuclease system, comprised of a guide RNA for the recognition of a DNA target and the Cas9 nuclease protein for binding and processing the target, has been extensively studied and has been widely applied in genome editing, synthetic biology, and transcriptional modulation in cells and animals. Toward more precise genomic modification and further expansion of the CRISPR/Cas9 system as a spatiotemporally controlled gene regulatory system, several approaches of conditional activation of Cas9 function using small molecules and light have recently been developed. These methods have led to improvements in the genome editing specificity of the CRISPR/Cas9 system and enabled its activation with temporal and spatial precision. PMID:26996256

  10. Acoustic metamaterial design and applications

    NASA Astrophysics Data System (ADS)

    Zhang, Shu

    The explosion of interest in metamaterials is due to the dramatically increased manipulation ability over light as well as sound waves. This material research was stimulated by the opportunity to develop an artificial media with negative refractive index and the application in superlens which allows super-resolution imaging. High-resolution acoustic imaging techniques are the essential tools for nondestructive testing and medical screening. However, the spatial resolution of the conventional acoustic imaging methods is restricted by the incident wavelength of ultrasound. This is due to the quickly fading evanescent fields which carry the subwavelength features of objects. By focusing the propagating wave and recovering the evanescent field, a flat lens with negative-index can potentially overcome the diffraction limit. We present the first experimental demonstration of focusing ultrasound waves through a flat acoustic metamaterial lens composed of a planar network of subwavelength Helmholtz resonators. We observed a tight focus of half-wavelength in width at 60.5 KHz by imaging a point source. This result is in excellent agreement with the numerical simulation by transmission line model in which we derived the effective mass density and compressibility. This metamaterial lens also displays variable focal length at different frequencies. Our experiment shows the promise of designing compact and light-weight ultrasound imaging elements. Moreover, the concept of metamaterial extends far beyond negative refraction, rather giving enormous choice of material parameters for different applications. One of the most interesting examples these years is the invisible cloak. Such a device is proposed to render the hidden object undetectable under the flow of light or sound, by guiding and controlling the wave path through an engineered space surrounding the object. However, the cloak designed by transformation optics usually calls for a highly anisotropic metamaterial, which

  11. 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…

  12. Localized acoustic surface modes

    NASA Astrophysics Data System (ADS)

    Farhat, Mohamed; Chen, Pai-Yen; Bağcı, Hakan

    2016-04-01

    We introduce the concept of localized acoustic surface modes. We demonstrate that they are induced on a two-dimensional cylindrical rigid surface with subwavelength corrugations under excitation by an incident acoustic plane wave. Our results show that the corrugated rigid surface is acoustically equivalent to a cylindrical scatterer with uniform mass density that can be represented using a Drude-like model. This, indeed, suggests that plasmonic-like acoustic materials can be engineered with potential applications in various areas including sensing, imaging, and cloaking.

  13. 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.

  14. Acoustic dispersive prism.

    PubMed

    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

  15. 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

  16. 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.

  17. 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

  18. 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

  19. Characterization of Acoustic Droplet Vaporization Using MRI

    NASA Astrophysics Data System (ADS)

    Li, David; Allen, Steven; Hernandez-Garcia, Luis; Bull, Joseph

    2013-11-01

    Acoustic droplet vaporization (ADV) is the selective vaporization of liquid droplets to form larger gas bubbles. The ADV process is currently being researched for biomedical applications such as gas embolotherapy, drug delivery, and phase-change contrast agents. In this study an albumin encapsulated dodecafluoropentane (DDFP, CAS: 678-26-2) microdroplet suspension was vaporized using a single element focused (f/2, D = 19 mm) 3.5 MHz transducer (Panametrics A321S, Olympus, Waltham, MA). The resulting DDFP bubble clouds were imaged using both bright field microscopy and MRI (Varian 7T, Agilent Technologies Inc., Santa Clara, CA). Field distortions due to DDFP bubble generation were characterized against the bright field images as a function of acoustic power and bubble cloud size. Experimentally a direct correlation between bubble cloud dimensions generated and field distortions seen in the MRI was observed. Additionally, MR velocimetry was used to measure the flow field resulting from ADV. The field distortions due to the bubbles were further characterized by modeling Maxwell's equations using COMSOL (COMSOL Inc., Burlington, MA). The ability to characterize ADV with alternative imaging modalities may prove useful in further development of ADV based biomedical therapies.

  20. 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...

  1. 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…

  2. p130Cas Is Required for Mammary Tumor Growth and Transforming Growth Factor-β-mediated Metastasis through Regulation of Smad2/3 Activity*

    PubMed Central

    Wendt, Michael K.; Smith, Jason A.; Schiemann, William P.

    2009-01-01

    During breast cancer progression, transforming growth factor-β (TGF-β) switches from a tumor suppressor to a pro-metastatic molecule. Several recent studies suggest that this conversion in TGF-β function depends upon fundamental changes in the TGF-β signaling system. We show here that these changes in TGF-β signaling are concomitant with aberrant expression of the focal adhesion protein, p130Cas. Indeed, elevating expression of either the full-length (FL) or just the carboxyl terminus (CT) of p130Cas in mammary epithelial cells (MECs) diminished the ability of TGF-β1 to activate Smad2/3, but increased its coupling to p38 MAPK. This shift in TGF-β signaling evoked (i) resistance to TGF-β-induced growth arrest, and (ii) acinar filling upon three-dimensional organotypic cultures of p130Cas-FL or -CT expressing MECs. Furthermore, rendering metastatic MECs deficient in p130Cas enhanced TGF-β-stimulated Smad2/3 activity, which restored TGF-β-induced growth inhibition both in vitro and in mammary tumors produced in mice. Additionally, whereas elevating TβR-II expression in metastatic MECs had no affect on their phosphorylation of Smad2/3, this event markedly enhanced their activation of p38 MAPK, leading to increased MEC invasion and metastasis. Importantly, depleting p130Cas expression in TβR-II-expressing metastatic MECs significantly increased their activation of Smad2/3, which (i) reestablished the physiologic balance between canonical and noncanonical TGF-β signaling, and (ii) reversed cellular invasion and early mammary tumor cell dissemination stimulated by TGF-β. Collectively, our findings identify p130Cas as a molecular rheostat that regulates the delicate balance between canonical and noncanonical TGF-β signaling, a balance that is critical to maintaining the tumor suppressor function of TGF-β during breast cancer progression. PMID:19822523

  3. 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

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

    PubMed Central

    Schwartz, Christine; Gao, Huirong; Falco, S. Carl; Cigan, A. Mark

    2015-01-01

    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. PMID:26269544

  5. CRISPR/Cas9 in Genome Editing and Beyond.

    PubMed

    Wang, Haifeng; La Russa, Marie; Qi, Lei S

    2016-06-01

    The Cas9 protein (CRISPR-associated protein 9), derived from type II CRISPR (clustered regularly interspaced short palindromic repeats) bacterial immune systems, is emerging as a powerful tool for engineering the genome in diverse organisms. As an RNA-guided DNA endonuclease, Cas9 can be easily programmed to target new sites by altering its guide RNA sequence, and its development as a tool has made sequence-specific gene editing several magnitudes easier. The nuclease-deactivated form of Cas9 further provides a versatile RNA-guided DNA-targeting platform for regulating and imaging the genome, as well as for rewriting the epigenetic status, all in a sequence-specific manner. With all of these advances, we have just begun to explore the possible applications of Cas9 in biomedical research and therapeutics. In this review, we describe the current models of Cas9 function and the structural and biochemical studies that support it. We focus on the applications of Cas9 for genome editing, regulation, and imaging, discuss other possible applications and some technical considerations, and highlight the many advantages that CRISPR/Cas9 technology offers. PMID:27145843

  6. 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. PMID:27072635

  7. 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.

  8. 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. PMID:26949040

  9. Acoustics Critical Readiness Review

    NASA Technical Reports Server (NTRS)

    Ballard, Kenny

    2010-01-01

    This presentation reviews the status of the acoustic equipment from the medical operations perspective. Included is information about the acoustic dosimeters, sound level meter, and headphones that are planned for use while on orbit. Finally there is information about on-orbit hearing assessments.

  10. The challenge of acoustics

    NASA Astrophysics Data System (ADS)

    Lord, P.

    1981-01-01

    The various applications of acoustics, including sonar, ultrasonic examination of unborn foetuses and architectural applications, are briefly reviewed. Problems in traffic and industrial noise, auditorium design and explosive noise are considered in more detail. The educational aspects of acoustical science and technology are briefly considered.

  11. 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. PMID:25479838

  12. 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

  13. Highly directional acoustic receivers.

    PubMed

    Cray, Benjamin A; Evora, Victor M; Nuttall, Albert H

    2003-03-01

    The theoretical directivity of a single combined acoustic receiver, a device that can measure many quantities of an acoustic field at a collocated point, is presented here. The formulation is developed using a Taylor series expansion of acoustic pressure about the origin of a Cartesian coordinate system. For example, the quantities measured by a second-order combined receiver, denoted a dyadic sensor, are acoustic pressure, the three orthogonal components of acoustic particle velocity, and the nine spatial gradients of the velocity vector. The power series expansion, which can be of any order, is cast into an expression that defines the directivity of a single receiving element. It is shown that a single highly directional dyadic sensor can have a directivity index of up to 9.5 dB. However, there is a price to pay with highly directive sensors; these sensors can be significantly more sensitive to nonacoustic noise sources. PMID:12656387

  14. Ocean acoustic hurricane classification.

    PubMed

    Wilson, Joshua D; Makris, Nicholas C

    2006-01-01

    Theoretical and empirical evidence are combined to show that underwater acoustic sensing techniques may be valuable for measuring the wind speed and determining the destructive power of a hurricane. This is done by first developing a model for the acoustic intensity and mutual intensity in an ocean waveguide due to a hurricane and then determining the relationship between local wind speed and underwater acoustic intensity. From this it is shown that it should be feasible to accurately measure the local wind speed and classify the destructive power of a hurricane if its eye wall passes directly over a single underwater acoustic sensor. The potential advantages and disadvantages of the proposed acoustic method are weighed against those of currently employed techniques. PMID:16454274

  15. 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.

  16. 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

  17. 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.

  18. 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.

  19. Arabidopsis Histone Methylase CAU1/PRMT5/SKB1 Acts as an Epigenetic Suppressor of the Calcium Signaling Gene CAS to Mediate Stomatal Closure in Response to Extracellular Calcium[W

    PubMed Central

    Fu, Yan-Lei; Zhang, Guo-Bin; Lv, Xin-Fang; Guan, Yuan; Yi, Hong-Ying; Gong, Ji-Ming

    2013-01-01

    Elevations in extracellular calcium ([Ca2+]o) are known to stimulate cytosolic calcium ([Ca2+]cyt) oscillations to close stomata. However, the underlying mechanisms regulating this process remain largely to be determined. Here, through the functional characterization of the calcium underaccumulation mutant cau1, we report that the epigenetic regulation of CAS, a putative Ca2+ binding protein proposed to be an external Ca2+ sensor, is involved in this process. cau1 mutant plants display increased drought tolerance and stomatal closure. A mutation in CAU1 significantly increased the expression level of the calcium signaling gene CAS, and functional disruption of CAS abolished the enhanced drought tolerance and stomatal [Ca2+]o signaling in cau1. Map-based cloning revealed that CAU1 encodes the H4R3sme2 (for histone H4 Arg 3 with symmetric dimethylation)-type histone methylase protein arginine methytransferase5/Shk1 binding protein1. Chromatin immunoprecipitation assays showed that CAU1 binds to the CAS promoter and modulates the H4R3sme2-type histone methylation of the CAS chromatin. When exposed to elevated [Ca2+]o, the protein levels of CAU1 decreased and less CAU1 bound to the CAS promoter. In addition, the methylation level of H4R3sme2 decreased in the CAS chromatin. Together, these data suggest that in response to increases in [Ca2+]o, fewer CAU1 protein molecules bind to the CAS promoter, leading to decreased H4R3sme2 methylation and consequent derepression of the expression of CAS to mediate stomatal closure and drought tolerance. PMID:23943859

  20. 41 CFR 102-33.435 - What CAS cost and utilization data must we report?

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 41 Public Contracts and Property Management 3 2012-01-01 2012-01-01 false What CAS cost and... Services (cas) Cost and Utilization Data § 102-33.435 What CAS cost and utilization data must we report? You must report the costs and flying hours for each CAS aircraft you hire. You must also report...

  1. 41 CFR 102-33.130 - If we hire CAS, what are our management responsibilities?

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 41 Public Contracts and Property Management 3 2010-07-01 2010-07-01 false If we hire CAS, what are... § 102-33.130 If we hire CAS, what are our management responsibilities? If you hire CAS, you are... agreements; (b) Accounting for the cost of your aircraft and services hired as CAS; (c) Accounting for use...

  2. 41 CFR 102-33.440 - Who must report CAS cost and utilization data?

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 41 Public Contracts and Property Management 3 2014-01-01 2014-01-01 false Who must report CAS cost... (cas) Cost and Utilization Data § 102-33.440 Who must report CAS cost and utilization data? Executive agencies, except the Armed Forces and U.S. intelligence agencies, must report CAS cost and utilization...

  3. 41 CFR 102-33.130 - If we hire CAS, what are our management responsibilities?

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 41 Public Contracts and Property Management 3 2011-01-01 2011-01-01 false If we hire CAS, what are... § 102-33.130 If we hire CAS, what are our management responsibilities? If you hire CAS, you are... agreements; (b) Accounting for the cost of your aircraft and services hired as CAS; (c) Accounting for use...

  4. 41 CFR 102-33.435 - What CAS cost and utilization data must we report?

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 41 Public Contracts and Property Management 3 2014-01-01 2014-01-01 false What CAS cost and... Services (cas) Cost and Utilization Data § 102-33.435 What CAS cost and utilization data must we report? You must report the costs and flying hours for each CAS aircraft you hire. You must also report...

  5. 41 CFR 102-33.440 - Who must report CAS cost and utilization data?

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 41 Public Contracts and Property Management 3 2013-07-01 2013-07-01 false Who must report CAS cost... (cas) Cost and Utilization Data § 102-33.440 Who must report CAS cost and utilization data? Executive agencies, except the Armed Forces and U.S. intelligence agencies, must report CAS cost and utilization...

  6. 41 CFR 102-33.435 - What CAS cost and utilization data must we report?

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 41 Public Contracts and Property Management 3 2010-07-01 2010-07-01 false What CAS cost and... Services (cas) Cost and Utilization Data § 102-33.435 What CAS cost and utilization data must we report? You must report the costs and flying hours for each CAS aircraft you hire. You must also report...

  7. 41 CFR 102-33.130 - If we hire CAS, what are our management responsibilities?

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 41 Public Contracts and Property Management 3 2013-07-01 2013-07-01 false If we hire CAS, what are... § 102-33.130 If we hire CAS, what are our management responsibilities? If you hire CAS, you are... agreements; (b) Accounting for the cost of your aircraft and services hired as CAS; (c) Accounting for use...

  8. 41 CFR 102-33.440 - Who must report CAS cost and utilization data?

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 41 Public Contracts and Property Management 3 2010-07-01 2010-07-01 false Who must report CAS cost... (cas) Cost and Utilization Data § 102-33.440 Who must report CAS cost and utilization data? Executive agencies, except the Armed Forces and U.S. intelligence agencies, must report CAS cost and utilization...

  9. 41 CFR 102-33.435 - What CAS cost and utilization data must we report?

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 41 Public Contracts and Property Management 3 2013-07-01 2013-07-01 false What CAS cost and... Services (cas) Cost and Utilization Data § 102-33.435 What CAS cost and utilization data must we report? You must report the costs and flying hours for each CAS aircraft you hire. You must also report...

  10. 41 CFR 102-33.440 - Who must report CAS cost and utilization data?

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 41 Public Contracts and Property Management 3 2011-01-01 2011-01-01 false Who must report CAS cost... (cas) Cost and Utilization Data § 102-33.440 Who must report CAS cost and utilization data? Executive agencies, except the Armed Forces and U.S. intelligence agencies, must report CAS cost and utilization...

  11. 41 CFR 102-33.130 - If we hire CAS, what are our management responsibilities?

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 41 Public Contracts and Property Management 3 2012-01-01 2012-01-01 false If we hire CAS, what are... § 102-33.130 If we hire CAS, what are our management responsibilities? If you hire CAS, you are... agreements; (b) Accounting for the cost of your aircraft and services hired as CAS; (c) Accounting for use...

  12. 41 CFR 102-33.435 - What CAS cost and utilization data must we report?

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 41 Public Contracts and Property Management 3 2011-01-01 2011-01-01 false What CAS cost and... Services (cas) Cost and Utilization Data § 102-33.435 What CAS cost and utilization data must we report? You must report the costs and flying hours for each CAS aircraft you hire. You must also report...

  13. 41 CFR 102-33.440 - Who must report CAS cost and utilization data?

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 41 Public Contracts and Property Management 3 2012-01-01 2012-01-01 false Who must report CAS cost... (cas) Cost and Utilization Data § 102-33.440 Who must report CAS cost and utilization data? Executive agencies, except the Armed Forces and U.S. intelligence agencies, must report CAS cost and utilization...

  14. 41 CFR 102-33.130 - If we hire CAS, what are our management responsibilities?

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 41 Public Contracts and Property Management 3 2014-01-01 2014-01-01 false If we hire CAS, what are... § 102-33.130 If we hire CAS, what are our management responsibilities? If you hire CAS, you are... agreements; (b) Accounting for the cost of your aircraft and services hired as CAS; (c) Accounting for use...

  15. Determination of the Physical Dimensions of μ Cas

    NASA Astrophysics Data System (ADS)

    Bach, K.; Kang, W.

    2015-07-01

    We investigate the physical properties of the nearby astrometric binary μ Cas based on a spectroscopic analysis and evolutionary calculations. The chemical composition of the μ Cas system has been determined based on high resolution spectroscopy from BOES. Combining our spectroscopic analysis with observations from Hipparcos and CHARA, we determine the evolutionary status of μ Cas. With well-constrained stellar parameters, the internal structure and frequency modes have also been calculated. The ultimate goal of this study is to describe the physical processes inside stars through a comprehensive modeling.

  16. 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

  17. Introducing the TI-Nspire CAS Learning Technology

    NASA Astrophysics Data System (ADS)

    Osbourne, Michael

    2008-03-01

    Engage your students! In this hands-on workshop, we will demonstrate how TI's newest graphing technology can be integrated into the physics classroom. Come experience both the TI-NspireT CAS Handheld and the TI- NspireT CAS Computer Software. The new TI-Nspire learning technology has been developed to allow students to explore physics and to better understand concepts through the manipulation of complex formulas,graphing, spreadsheets, data analysis, and simulations. During the workshop you will receive an overview of the technology, sample activities, along with the opportunity to experience how TI-Nspire CAS can be effectively integrated into the physics classroom. Limited to 20 participants.

  18. The Short Time Scale Events of Acoustic Droplet Vaporization

    NASA Astrophysics Data System (ADS)

    Li, David S.; Kripfgans, Oliver D.; Fowlkes, J. Brian; Bull, Joseph L.

    2012-11-01

    The conversion of a liquid microdroplets to gas bubbles initiated by an acoustic pulse, known as acoustic droplet vaporization (ADV), has been proposed as a method to selectively generate gas emboli for therapeutic purposes (gas embolotherapy), specifically for vascularized tumors. In this study we focused on the first 10 microseconds of the ADV process, namely the gas nucleation site formation and bubble evolution. BSA encapsulated dodecafluoropentane (CAS: 678-26-2) microdroplets were isolated at the bottom of a degassed water bath held at 37°C. Microdroplets, diameters ranging from 5-65 microns, were vaporized using a single pulse (4-16 cycles) from a 7.5 MHz focused single element transducer ranging from 2-5 MPa peak negative pressure and images of the vaporization process were recorded using an ultra-high speed camera (SIM802, Specialised Imaging Ltd). It was observed that typically two gas nuclei were formed in series with one another on axis with ultrasound pulse. However, relative positioning of the nucleation sites within the droplet depended on droplet diameter. Additionally, depending on acoustic parameters the bubble could deform into a toroidal shape. Such dynamics could suggest acoustic parameters that may result in tissue damage. This work is supported by NIH grant R01EB006476.

  19. Selectivity of optical stimulation in the auditory system

    NASA Astrophysics Data System (ADS)

    Izzo, Agnella D.; Pathria, Jyoti; Suh, Eul; Walsh, Joseph T., Jr.; Whitlon, Donna S.; Jansen, E. D.; Richter, Claus-Peter

    2006-02-01

    It is known that electrical current injected from cochlear implant contacts spreads within the cochlea, causing overlapping stimulation fields and possibly limiting the performance of cochlear implant users. We have investigated an alternative mechanism to stimulate auditory neurons in the gerbil cochlea using a laser, rather than electrical current. With the laser, it is possible to direct the light to a selected, known volume of tissue that is smaller than the electrically stimulated population of cells. In the present experiments, a transiently expressed transcription factor, c-FOS, was used to stain activated nerve cells. Immunohistochemical staining for c-FOS in the cochlea shows a small area of optical stimulation, which occurs directly opposite to the optical fiber. Additionally, masking data indicate that the laser can stimulate a small population of cells similar to an acoustic toneburst. Smaller populations of stimulated cells could reduce the amount of overlap in stimulation fields and allow more stimulation contacts in a neuroprothesis.

  20. Ocean seismo-acoustics. Low-frequency underwater acoustics

    SciTech Connect

    Akal, T.; berkson, J.M.

    1986-01-01

    This book presents information on seismo-acoustic propagation in seawater and sea beds that includes theoretical developments, modelling and experiments, and fluctuations. Boundary scatteiring, seismo-acoustic waves and seismo-acoustic noise are discussed. Technology and new approaches in seismo-acoustic measurements are presented.

  1. 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. PMID:20482059

  2. 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.

  3. 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.

  4. 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.

  5. The Structural Biology of CRISPR-Cas Systems

    PubMed Central

    Jiang, Fuguo; Doudna, Jennifer A.

    2015-01-01

    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. PMID:25723899

  6. CAS Standards and Guidelines for Student Services/Development Programs.

    ERIC Educational Resources Information Center

    NACADA Journal, 1986

    1986-01-01

    The Council for the Advancement of Standards for Student Services/Development Programs (CAS) developed and adopted standards and interpretive guidelines for specific functional areas of student services/development programs within postsecondary educational institutions. These guidelines are presented. (MLW)

  7. CRISPR-Cas9-Guided Genome Engineering in C. elegans.

    PubMed

    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 have 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, as well as injection methods required for delivering Cas9, sgRNAs, and repair template DNA into the C. elegans germline. © 2016 by John Wiley & Sons, Inc. PMID:27366893

  8. Methods for Optimizing CRISPR-Cas9 Genome Editing Specificity.

    PubMed

    Tycko, Josh; Myer, Vic E; Hsu, Patrick D

    2016-08-01

    Advances in the development of delivery, repair, and specificity strategies for the CRISPR-Cas9 genome engineering toolbox are helping researchers understand gene function with unprecedented precision and sensitivity. CRISPR-Cas9 also holds enormous therapeutic potential for the treatment of genetic disorders by directly correcting disease-causing mutations. Although the Cas9 protein has been shown to bind and cleave DNA at off-target sites, the field of Cas9 specificity is rapidly progressing, with marked improvements in guide RNA selection, protein and guide engineering, novel enzymes, and off-target detection methods. We review important challenges and breakthroughs in the field as a comprehensive practical guide to interested users of genome editing technologies, highlighting key tools and strategies for optimizing specificity. The genome editing community should now strive to standardize such methods for measuring and reporting off-target activity, while keeping in mind that the goal for specificity should be continued improvement and vigilance. PMID:27494557

  9. 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. PMID:24685391

  10. 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. PMID:24766887

  11. CRISPR-Cas systems: prokaryotes upgrade to adaptive immunity

    PubMed Central

    Barrangou, Rodolphe; Marraffini, Luciano A.

    2014-01-01

    Summary 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. PMID:24766887

  12. An updated evolutionary classification of CRISPR-Cas systems.

    PubMed

    Makarova, Kira S; Wolf, Yuri I; Alkhnbashi, Omer S; Costa, Fabrizio; Shah, Shiraz A; Saunders, Sita J; Barrangou, Rodolphe; Brouns, Stan J J; Charpentier, Emmanuelle; Haft, Daniel H; Horvath, Philippe; Moineau, Sylvain; Mojica, Francisco J M; Terns, Rebecca M; Terns, Michael P; White, Malcolm F; Yakunin, Alexander F; Garrett, Roger A; van der Oost, John; Backofen, Rolf; Koonin, Eugene V

    2015-11-01

    The evolution of CRISPR-cas loci, which encode adaptive immune systems in archaea and bacteria, involves rapid changes, in particular numerous rearrangements of the locus architecture and horizontal transfer of complete loci or individual modules. These dynamics complicate straightforward phylogenetic classification, but here we present an approach combining the analysis of signature protein families and features of the architecture of cas loci that unambiguously partitions most CRISPR-cas loci into distinct classes, types and subtypes. The new classification retains the overall structure of the previous version but is expanded to now encompass two classes, five types and 16 subtypes. The relative stability of the classification suggests that the most prevalent variants of CRISPR-Cas systems are already known. However, the existence of rare, currently unclassifiable variants implies that additional types and subtypes remain to be characterized. PMID:26411297

  13. Some Problems of modern acoustics

    NASA Technical Reports Server (NTRS)

    Stan, A.

    1974-01-01

    The multidisciplinary and interdisciplinary character of acoustics is considered and its scientific, technological, economical and social implications, as well as the role of acoustics in creating new machines and equipment and improving the quality of products are outlined. Research beyond audible frequencies, as well as to extremely high acoustic intensities, which requires the development of a nonlinear acoustics is elaborated.

  14. 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.

  15. Acoustic rotation control

    NASA Technical Reports Server (NTRS)

    Elleman, D. D.; Croonquist, A. P.; Wang, T. G. (Inventor)

    1983-01-01

    A system is described for acoustically controlled rotation of a levitated object, which avoids deformation of a levitated liquid object. Acoustic waves of the same wavelength are directed along perpendicular directions across the object, and with the relative phases of the acoustic waves repeatedly switched so that one wave alternately leads and lags the other by 90 deg. The amount of torque for rotating the object, and the direction of rotation, are controlled by controlling the proportion of time one wave leads the other and selecting which wave leads the other most of the time.

  16. 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.

  17. 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.

  18. 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.

  19. Comparison of Cas9 activators in multiple species.

    PubMed

    Chavez, Alejandro; Tuttle, Marcelle; Pruitt, Benjamin W; Ewen-Campen, Ben; Chari, Raj; Ter-Ovanesyan, Dmitry; Haque, Sabina J; Cecchi, Ryan J; Kowal, Emma J K; Buchthal, Joanna; Housden, Benjamin E; Perrimon, Norbert; Collins, James J; Church, George

    2016-07-01

    Several programmable transcription factors exist based on the versatile Cas9 protein, yet their relative potency and effectiveness across various cell types and species remain unexplored. Here, we compare Cas9 activator systems and examine their ability to induce robust gene expression in several human, mouse, and fly cell lines. We also explore the potential for improved activation through the combination of the most potent activator systems, and we assess the role of cooperativity in maximizing gene expression. PMID:27214048

  20. 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. PMID:26535798

  1. Target specificity of the CRISPR-Cas9 system

    PubMed Central

    Wu, Xuebing; Kriz, Andrea J.; Sharp, Phillip A.

    2015-01-01

    The CRISPR-Cas9 system, naturally a defense mechanism in prokaryotes, has been repurposed as an RNA-guided DNA targeting platform. It has been widely used for genome editing and transcriptome modulation, and has shown great promise in correcting mutations in human genetic diseases. Off-target effects are a critical issue for all of these applications. Here we review the current status on the target specificity of the CRISPR-Cas9 system. PMID:25722925

  2. Rational design of a split-Cas9 enzyme complex

    DOE PAGESBeta

    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 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

  3. Internal guide RNA interactions interfere with Cas9-mediated cleavage.

    PubMed

    Thyme, Summer B; Akhmetova, Laila; Montague, Tessa G; Valen, Eivind; Schier, Alexander F

    2016-01-01

    The CRISPR/Cas system uses guide RNAs (gRNAs) to direct sequence-specific DNA cleavage. Not every gRNA elicits cleavage and the mechanisms that govern gRNA activity have not been resolved. Low activity could result from either failure to form a functional Cas9-gRNA complex or inability to recognize targets in vivo. Here we show that both phenomena influence Cas9 activity by comparing mutagenesis rates in zebrafish embryos with in vitro cleavage assays. In vivo, our results suggest that genomic factors such as CTCF inhibit mutagenesis. Comparing near-identical gRNA sequences with different in vitro activities reveals that internal gRNA interactions reduce cleavage. Even though gRNAs containing these structures do not yield cleavage-competent complexes, they can compete with active gRNAs for binding to Cas9. These results reveal that both genomic context and internal gRNA interactions can interfere with Cas9-mediated cleavage and illuminate previously uncharacterized features of Cas9-gRNA complex formation. PMID:27282953

  4. CRISPR-Cas9 Based Engineering of Actinomycetal Genomes.

    PubMed

    Tong, Yaojun; Charusanti, Pep; Zhang, Lixin; Weber, Tilmann; Lee, Sang Yup

    2015-09-18

    Bacteria of the order Actinomycetales are one of the most important sources of pharmacologically active and industrially relevant secondary metabolites. Unfortunately, many of them are still recalcitrant to genetic manipulation, which is a bottleneck for systematic metabolic engineering. To facilitate the genetic manipulation of actinomycetes, we developed a highly efficient CRISPR-Cas9 system to delete gene(s) or gene cluster(s), implement precise gene replacements, and reversibly control gene expression in actinomycetes. We demonstrate our system by targeting two genes, actIORF1 (SCO5087) and actVB (SCO5092), from the actinorhodin biosynthetic gene cluster in Streptomyces coelicolor A3(2). Our CRISPR-Cas9 system successfully inactivated the targeted genes. When no templates for homology-directed repair (HDR) were present, the site-specific DNA double-strand breaks (DSBs) introduced by Cas9 were repaired through the error-prone nonhomologous end joining (NHEJ) pathway, resulting in a library of deletions with variable sizes around the targeted sequence. If templates for HDR were provided at the same time, precise deletions of the targeted gene were observed with near 100% frequency. Moreover, we developed a system to efficiently and reversibly control expression of target genes, deemed CRISPRi, based on a catalytically dead variant of Cas9 (dCas9). The CRISPR-Cas9 based system described here comprises a powerful and broadly applicable set of tools to manipulate actinomycetal genomes. PMID:25806970

  5. Rational design of a split-Cas9 enzyme complex

    PubMed Central

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

    2015-01-01

    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. PMID:25713377

  6. Internal guide RNA interactions interfere with Cas9-mediated cleavage

    PubMed Central

    Thyme, Summer B.; Akhmetova, Laila; Montague, Tessa G.; Valen, Eivind; Schier, Alexander F.

    2016-01-01

    The CRISPR/Cas system uses guide RNAs (gRNAs) to direct sequence-specific DNA cleavage. Not every gRNA elicits cleavage and the mechanisms that govern gRNA activity have not been resolved. Low activity could result from either failure to form a functional Cas9–gRNA complex or inability to recognize targets in vivo. Here we show that both phenomena influence Cas9 activity by comparing mutagenesis rates in zebrafish embryos with in vitro cleavage assays. In vivo, our results suggest that genomic factors such as CTCF inhibit mutagenesis. Comparing near-identical gRNA sequences with different in vitro activities reveals that internal gRNA interactions reduce cleavage. Even though gRNAs containing these structures do not yield cleavage-competent complexes, they can compete with active gRNAs for binding to Cas9. These results reveal that both genomic context and internal gRNA interactions can interfere with Cas9-mediated cleavage and illuminate previously uncharacterized features of Cas9–gRNA complex formation. PMID:27282953

  7. 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.

  8. 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.

  9. Highly specific targeted mutagenesis in plants using Staphylococcus aureus Cas9

    PubMed Central

    Kaya, Hidetaka; Mikami, Masafumi; Endo, Akira; Endo, Masaki; Toki, Seiichi

    2016-01-01

    The CRISPR/Cas9 system is an efficient and convenient tool for genome editing in plants. Cas9 nuclease derived from Streptococcus pyogenes (Sp) is commonly used in this system. Recently, Staphylococcus aureus Cas9 (SaCas9)-mediated genome editing was reported in human cells and Arabidopsis. Because SaCas9 (1053 a.a.) is smaller than SpCas9 (1368 a.a.), SaCas9 could have substantial advantages for delivering and expressing Cas9 protein, especially using virus vectors. Since the protospacer adjacent motif (PAM) sequence of SaCas9 (5′-NNGRRT-3′) differs from that of SpCas9 (5′-NGG-3′), the use of this alternative Cas9 nuclease could expand the selectivity at potential cleavage target sites of the CRISPR/Cas9 system. Here we show that SaCas9 can mutagenize target sequences in tobacco and rice with efficiencies similar to those of SpCas9. We also analyzed the base preference for ‘T’ at the 6th position of the SaCas9 PAM. Targeted mutagenesis efficiencies in target sequences with non-canonical PAMs (5′-NNGRRV-3′) were much lower than those with a canonical PAM (5′-NNGRRT-3′). The length of target sequence recognized by SaCas9 is one or two nucleotides longer than that recognized by SpCas9. Taken together, our results demonstrate that SaCas9 has higher sequence recognition capacity than SpCas9 and is useful for reducing off-target mutations in crop. PMID:27226350

  10. Highly specific targeted mutagenesis in plants using Staphylococcus aureus Cas9.

    PubMed

    Kaya, Hidetaka; Mikami, Masafumi; Endo, Akira; Endo, Masaki; Toki, Seiichi

    2016-01-01

    The CRISPR/Cas9 system is an efficient and convenient tool for genome editing in plants. Cas9 nuclease derived from Streptococcus pyogenes (Sp) is commonly used in this system. Recently, Staphylococcus aureus Cas9 (SaCas9)-mediated genome editing was reported in human cells and Arabidopsis. Because SaCas9 (1053 a.a.) is smaller than SpCas9 (1368 a.a.), SaCas9 could have substantial advantages for delivering and expressing Cas9 protein, especially using virus vectors. Since the protospacer adjacent motif (PAM) sequence of SaCas9 (5'-NNGRRT-3') differs from that of SpCas9 (5'-NGG-3'), the use of this alternative Cas9 nuclease could expand the selectivity at potential cleavage target sites of the CRISPR/Cas9 system. Here we show that SaCas9 can mutagenize target sequences in tobacco and rice with efficiencies similar to those of SpCas9. We also analyzed the base preference for 'T' at the 6th position of the SaCas9 PAM. Targeted mutagenesis efficiencies in target sequences with non-canonical PAMs (5'-NNGRRV-3') were much lower than those with a canonical PAM (5'-NNGRRT-3'). The length of target sequence recognized by SaCas9 is one or two nucleotides longer than that recognized by SpCas9. Taken together, our results demonstrate that SaCas9 has higher sequence recognition capacity than SpCas9 and is useful for reducing off-target mutations in crop. PMID:27226350

  11. Acoustic Neuroma Association

    MedlinePlus

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

  12. 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.

  13. 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.

  14. 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.

  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. 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.

  17. 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.

  18. 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

    2014-01-01

    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. PMID:25418084

  19. Acoustic communication by ants

    NASA Astrophysics Data System (ADS)

    Hickling, Robert

    2002-05-01

    Many ant species communicate acoustically by stridulating, i.e., running a scraper over a washboard-like set of ridges. Ants appear to be insensitive to airborne sound. Consequently, myrmecologists have concluded that the stridulatory signals are transmitted through the substrate. This has tended to diminish the importance of acoustic communication, and it is currently believed that ant communication is based almost exclusively on pheromones, with acoustic communication assigned an almost nonexistent role. However, it can be shown that acoustic communication between ants is effective only if the medium is air and not the substrate. How, then, is it possible for ants to appear deaf to airborne sound and yet communicate through the air? An explanation is provided in a paper [R. Hickling and R. L. Brown, ``Analysis of acoustic communication by ants,'' J. Acoust. Soc. Am. 108, 1920-1929 (2000)]. Ants are small relative to the wavelengths they generate. Hence, they create a near field, which is characterized by a major increase in sound velocity (particle velocity of sound) in the vicinity of the source. Hair sensilla on the ants' antennae respond to sound velocity. Thus, ants are able to detect near-field sound from other ants and to exclude extraneous airborne sound.

  20. Acoustic detection of pneumothorax

    NASA Astrophysics Data System (ADS)

    Mansy, Hansen A.; Royston, Thomas J.; Balk, Robert A.; Sandler, Richard H.

    2003-04-01

    This study aims at investigating the feasibility of using low-frequency (<2000 Hz) acoustic methods for medical diagnosis. Several candidate methods of pneumothorax detection were tested in dogs. In the first approach, broadband acoustic signals were introduced into the trachea during end-expiration and transmitted waves were measured at the chest surface. Pneumothorax was found to consistently decrease pulmonary acoustic transmission in the 200-1200-Hz frequency band, while less change was observed at lower frequencies (p<0.0001). The ratio of acoustic energy between low (<220 Hz) and mid (550-770 Hz) frequency bands was significantly different in the control (healthy) and pneumothorax states (p<0.0001). The second approach measured breath sounds in the absence of an external acoustic input. Pneumothorax was found to be associated with a preferential reduction of sound amplitude in the 200- to 700-Hz range, and a decrease of sound amplitude variation (in the 300 to 600-Hz band) during the respiration cycle (p<0.01 for each). Finally, chest percussion was implemented. Pneumothorax changed the frequency and decay rate of percussive sounds. These results imply that certain medical conditions may be reliably detected using appropriate acoustic measurements and analysis. [Work supported by NIH/NHLBI #R44HL61108.

  1. 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. PMID:26723303

  2. 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. PMID:26921652

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

    PubMed Central

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

    2016-01-01

    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. PMID:26817415

  4. 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

    2016-01-01

    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. PMID:26817415

  5. CRISPR-Cas9-mediated gene knockout in primary human airway epithelial cells reveals a proinflammatory role for MUC18.

    PubMed

    Chu, H W; Rios, C; Huang, C; Wesolowska-Andersen, A; Burchard, E G; O'Connor, B P; Fingerlin, T E; Nichols, D; Reynolds, S D; Seibold, M A

    2015-10-01

    Targeted knockout of genes in primary human cells using CRISPR-Cas9-mediated genome-editing represents a powerful approach to study gene function and to discern molecular mechanisms underlying complex human diseases. We used lentiviral delivery of CRISPR-Cas9 machinery and conditional reprogramming culture methods to knockout the MUC18 gene in human primary nasal airway epithelial cells (AECs). Massively parallel sequencing technology was used to confirm that the genome of essentially all cells in the edited AEC populations contained coding region insertions and deletions (indels). Correspondingly, we found mRNA expression of MUC18 was greatly reduced and protein expression was absent. Characterization of MUC18 knockout cell populations stimulated with TLR2, 3 and 4 agonists revealed that IL-8 (a proinflammatory chemokine) responses of AECs were greatly reduced in the absence of functional MUC18 protein. Our results show the feasibility of CRISPR-Cas9-mediated gene knockouts in AEC culture (both submerged and polarized), and suggest a proinflammatory role for MUC18 in airway epithelial response to bacterial and viral stimuli. PMID:26043872

  6. Acoustic calibration apparatus for calibrating plethysmographic acoustic pressure sensors

    NASA Technical Reports Server (NTRS)

    Zuckerwar, Allan J. (Inventor); Davis, David C. (Inventor)

    1995-01-01

    An apparatus for calibrating an acoustic sensor is described. The apparatus includes a transmission material having an acoustic impedance approximately matching the acoustic impedance of the actual acoustic medium existing when the acoustic sensor is applied in actual in-service conditions. An elastic container holds the transmission material. A first sensor is coupled to the container at a first location on the container and a second sensor coupled to the container at a second location on the container, the second location being different from the first location. A sound producing device is coupled to the container and transmits acoustic signals inside the container.

  7. Acoustic neuromodulation from a basic science prospective.

    PubMed

    Sassaroli, Elisabetta; Vykhodtseva, Natalia

    2016-01-01

    We present here biophysical models to gain deeper insights into how an acoustic stimulus might influence or modulate neuronal activity. There is clear evidence that neural activity is not only associated with electrical and chemical changes but that an electro-mechanical coupling is also involved. Currently, there is no theory that unifies the electrical, chemical, and mechanical aspects of neuronal activity. Here, we discuss biophysical models and hypotheses that can explain some of the mechanical aspects associated with neuronal activity: the soliton model, the neuronal intramembrane cavitation excitation model, and the flexoelectricity hypothesis. We analyze these models and discuss their implications on stimulation and modulation of neuronal activity by ultrasound. PMID:27213044

  8. 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

  9. Tuning CAS Application using AIMS: An Automated Instrumentation and Monitoring System

    NASA Technical Reports Server (NTRS)

    Mehra, P.; Sarukkai, S.; Schmidt, M.; Schulbach, C.; VanVoorst, B.; Yan, Jerry; Woodrow, Thomas (Technical Monitor)

    1994-01-01

    To bring together NASA's scientists and engineers and their counterparts in industry, other government agencies, and academia working in the Computational AeroSciences (CAS) field. This workshop is part of the technology transfer plan of the High Performance Computing and Communications Program (HPCCP). Specific objectives of this Workshop are to: (1) communicate the goals and objectives of HPCCP in the area of CAS; (2) promote and disseminate CAS technology within the appropriate technical communities, including NASA, industry, academia, and other government labs; (3) help promote synergy among CAS scientists; and (4) permit feedback from peer researchers in issues pacing the CAS field in general and the HPCCP CAS program in particular.

  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. Thomson-Scattering Study of the Subharmonic Decay of Ion-Acoustic Waves Driven by the Brillouin Instability

    NASA Astrophysics Data System (ADS)

    Bandulet, H. C.; Labaune, C.; Lewis, K.; Depierreux, S.

    2004-07-01

    Thomson scattering (TS) has been used to investigate the two-ion decay instability of ion acoustic waves generated by stimulated Brillouin scattering in an underdense CH plasma. Two complementary TS diagnostics, spectrally and spatially resolved, demonstrate the occurrence of the subharmonic decay of the primary ion acoustic wave into two secondary waves. The study of the laser intensity dependence shows that the secondary ion acoustic waves are correlated with the SBS reflectivity saturation, at a level of a few percent.

  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. Repurposing CRISPR/Cas9 for in situ functional assays

    PubMed Central

    Malina, Abba; Mills, John R.; Cencic, Regina; Yan, Yifei; Fraser, James; Schippers, Laura M.; Paquet, Marilène; Dostie, Josée; Pelletier, Jerry

    2013-01-01

    RNAi combined with next-generation sequencing has proven to be a powerful and cost-effective genetic screening platform in mammalian cells. Still, this technology has its limitations and is incompatible with in situ mutagenesis screens on a genome-wide scale. Using p53 as a proof-of-principle target, we readapted the CRISPR (clustered regularly interspaced short palindromic repeats)/Cas9 (CRISPR associated 9) genome-editing system to demonstrate the feasibility of this methodology for targeted gene disruption positive selection assays. By using novel “all-in-one” lentiviral and retroviral delivery vectors heterologously expressing both a codon-optimized Cas9 and its synthetic guide RNA (sgRNA), we show robust selection for the CRISPR-modified Trp53 locus following drug treatment. Furthermore, by linking Cas9 expression to GFP fluorescence, we use an “all-in-one” system to track disrupted Trp53 in chemoresistant lymphomas in the Eμ-myc mouse model. Deep sequencing analysis of the tumor-derived endogenous Cas9-modified Trp53 locus revealed a wide spectrum of mutants that were enriched with seemingly limited off-target effects. Taken together, these results establish Cas9 genome editing as a powerful and practical approach for positive in situ genetic screens. PMID:24298059

  14. 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. PMID:20843716

  15. Measurement of Flux Density of Cas A at Low Frequencies

    NASA Astrophysics Data System (ADS)

    Patil, Ajinkya; Fisher, R.

    2012-01-01

    Cas A is used as a flux calibrator throughout the radio spectrum. Therefore it is important to know the spectral and secular variations in its flux density. Earlier observations by Scott et. al. (1969) and Baars et. al. (1972) suggested a secular decrease in flux density of Cas A at a rate of about 1% per year at all frequencies. However later observations by Erickson & Perley (1975) and Read (1977) indicated anomalously high flux from Cas A at 38 MHz. Also, these observations suggested that the original idea of faster decay of the flux density rate at low frequencies may be in error or that something more complex than simple decay is affecting the flux density at low frequencies. The source changes at 38 MHz still remains a mystery. We intend to present the results of follow up observations made from 1995 to 1998 with a three element interferometer in Green Bank operating in frequency range 30 to 120 MHz. We will discuss the problems at such low frequencies due to large beamwidth and unstable ionosphere. We will also discuss the strategies we have used so far to to find the flux density of Cas A by calculating the ratio of flux density of Cas A to that of Cyg A, assuming flux density of Cyg A to be constant. Above mentioned work was performed in summer student program sponsored by National Radio Astronomy Observatory.

  16. General pharmacology of the four gastrointestinal motility stimulants bethanechol, metoclopramide, trimebutine, and cisapride.

    PubMed

    Megens, A A; Awouters, F H; Niemegeers, C J

    1991-06-01

    The pharmacological profile of bethanechol (CAS 674-38-4), metoclopramide (CAS 364-62-5), trimebutine (CAS 39133-31-8) and cisapride (CAS 81098-60-4) was studied in a series of simple pharmacological tests in rats and dogs. Bethanechol stimulated both gastric emptying and intestinal propulsion but displayed also the well-known behavioral effects of a direct muscarinic acetylcholine receptor agonist. Metoclopramide showed the profile of a centrally active dopamine D2 antagonist. In addition, metoclopramide displayed a stimulant effect on spontaneous gastric emptying in rats, an effect that could not be related to dopamine D2 antagonism. The only effect observed with trimebutine was protection from castor oil diarrhea, probably due to its reported interaction with peripheral opiate receptors. Cisapride was a potent stimulant of gastric emptying in rats, 7 times more potent than metoclopramide. Cisapride was also a very specific gastrokinetic, over a large dose range (specificity ratio: greater than or equal to 20) devoid of effects indicative for direct interaction with dopamine or acetylcholine receptors. The relationship between the differential activity profiles of the compounds in the present study and differences in their mechanism of action and side-effect liability is discussed. PMID:1930352

  17. 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.

  18. Scanning Tomographic Acoustic Microscopy

    NASA Astrophysics Data System (ADS)

    Wade, G.; Meyyappan, A.

    1988-07-01

    The technology for "seeing" with sound has an important and interesting history. Some of nature's creatures have been using sound waves for many millenia to image otherwise unobservable objects. The human species, lacking this natural ability, have overcome this deficiency by developing several different ultrasonic imaging techniques. acoustic microscopy is one such technique, which produces high resolution images of detailed structure of small objects in a non-destructive fashion. Two types of acoustic microscopes have evolved for industrial exploitation. They are the scanning laser acoustic microscope (SLAM) and the scanning acoustic microscope (SAM). In this paper, we review the principles of SLAM and describe how we use elements of SLAM to realize the scanning tomographic acoustic microscope (STAM). We describe the data acquisition process and the image reconstruction procedure. We also describe techniques to obtain projection data from different angles of wave incidence enabling us to reconstruct different planes of a complex specimen tomo-graphically. Our experimental results show that STAM is capable of producing high-quality high-resolution subsurface images.

  19. Displacement of p130Cas from focal adhesions links actomyosin contraction to cell migration.

    PubMed

    Machiyama, Hiroaki; Hirata, Hiroaki; Loh, Xia Kun; Kanchi, Madhu Mathi; Fujita, Hideaki; Tan, Song Hui; Kawauchi, Keiko; Sawada, Yasuhiro

    2014-08-15

    Cell adhesion complexes provide platforms where cell-generated forces are transmitted to the extracellular matrix (ECM). Tyrosine phosphorylation of focal adhesion proteins is crucial for cells to communicate with the extracellular environment. However, the mechanisms that transmit actin cytoskeletal motion to the extracellular environment to drive cell migration are poorly understood. We find that the movement of p130Cas (Cas, also known as BCAR1), a mechanosensor at focal adhesions, correlates with actin retrograde flow and depends upon actomyosin contraction and phosphorylation of the Cas substrate domain (CasSD). This indicates that CasSD phosphorylation underpins the physical link between Cas and the actin cytoskeleton. Fluorescence recovery after photobleaching (FRAP) experiments reveal that CasSD phosphorylation, as opposed to the association of Cas with Src, facilitates Cas displacement from adhesion complexes in migrating cells. Furthermore, the stabilization of Src-Cas binding and inhibition of myosin II, both of which sustain CasSD phosphorylation but mitigate Cas displacement from adhesion sites, retard cell migration. These results indicate that Cas promotes cell migration by linking actomyosin contractions to the adhesion complexes through a dynamic interaction with Src as well as through the phosphorylation-dependent association with the actin cytoskeleton. PMID:24928898

  20. 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…

  1. Acoustic energy shaping

    NASA Technical Reports Server (NTRS)

    Wang, T. G.; Elleman, D. D. (Inventor)

    1977-01-01

    A suspended mass is shaped by melting all or a selected portion of the mass and applying acoustic energy in varying amounts to different portions of the mass. In one technique for forming an optical waveguide slug, a mass of oval section is suspended and only a portion along the middle of the cross-section is heated to a largely fluid consistency. Acoustic energy is applied to opposite edges of the oval mass to press the unheated opposite edge portions together so as to form bulges at the middle of the mass. In another technique for forming a ribbon of silicon for constructing solar cells, a cylindrical thread of silicon is drawn from a molten mass of silicon, and acoustic energy is applied to opposite sides of the molten thread to flatten it into a ribbon.

  2. 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.

  3. Surface Acoustic Wave Microfluidics

    NASA Astrophysics Data System (ADS)

    Yeo, Leslie Y.; Friend, James R.

    2014-01-01

    Fluid manipulations at the microscale and beyond are powerfully enabled through the use of 10-1,000-MHz acoustic waves. A superior alternative in many cases to other microfluidic actuation techniques, such high-frequency acoustics is almost universally produced by surface acoustic wave devices that employ electromechanical transduction in wafer-scale or thin-film piezoelectric media to generate the kinetic energy needed to transport and manipulate fluids placed in adjacent microfluidic structures. These waves are responsible for a diverse range of complex fluid transport phenomena - from interfacial fluid vibration and drop and confined fluid transport to jetting and atomization - underlying a flourishing research literature spanning fundamental fluid physics to chip-scale engineering applications. We highlight some of this literature to provide the reader with a historical basis, routes for more detailed study, and an impression of the field's future directions.

  4. Latticed pentamode acoustic cloak

    PubMed Central

    Chen, Yi; Liu, Xiaoning; Hu, Gengkai

    2015-01-01

    We report in this work a practical design of pentamode acoustic cloak with microstructure. The proposed cloak is assembled by pentamode lattice made of a single-phase solid material. The function of rerouting acoustic wave round an obstacle has been demonstrated numerically. It is also revealed that shear related resonance due to weak shear resistance in practical pentamode lattices punctures broadband feature predicted based on ideal pentamode cloak. As a consequence, the latticed pentamode cloak can only conceal the obstacle in segmented frequency ranges. We have also shown that the shear resonance can be largely reduced by introducing material damping, and an improved broadband performance can be achieved. These works pave the way for experimental demonstration of pentamode acoustic cloak. PMID:26503821

  5. Seamount acoustic scattering

    NASA Astrophysics Data System (ADS)

    Boehlert, George W.

    The cover of the March 1 issue of Eos showed a time series of acoustic scattering above Southeast Hancock Seamount (29°48‧N, 178°05‧E) on July 17-18, 1984. In a comment on that cover Martin Hovland (Eos, August 2, p. 760) argued that gas or “other far reaching causes” may be involved in the observed acoustic signals. He favors a hypothesis that acoustic scattering observed above a seeping pockmark in the North Sea is a combination of bubbles, stable microbubbles, and pelagic organisms and infers that this may be a more general phenomenon and indeed plays a role in the attraction of organisms to seamounts

  6. Highly efficient primed spacer acquisition from targets destroyed by the Escherichia coli type I-E CRISPR-Cas interfering complex

    PubMed Central

    Semenova, Ekaterina; Savitskaya, Ekaterina; Musharova, Olga; Strotskaya, Alexandra; Vorontsova, Daria; Datsenko, Kirill A.; Logacheva, Maria D.; Severinov, Konstantin

    2016-01-01

    Prokaryotic clustered regularly interspaced short palindromic repeat (CRISPR)-CRISPR associated (Cas) immunity relies on adaptive acquisition of spacers—short fragments of foreign DNA. For the type I-E CRISPR-Cas system from Escherichia coli, efficient “primed” adaptation requires Cas effector proteins and a CRISPR RNA (crRNA) whose spacer partially matches a segment (protospacer) in target DNA. Primed adaptation leads to selective acquisition of additional spacers from DNA molecules recognized by the effector–crRNA complex. When the crRNA spacer fully matches a protospacer, CRISPR interference—that is, target destruction without acquisition of additional spacers—is observed. We show here that when the rate of degradation of DNA with fully and partially matching crRNA targets is made equal, fully matching protospacers stimulate primed adaptation much more efficiently than partially matching ones. The result indicates that different functional outcomes of CRISPR-Cas response to two kinds of protospacers are not caused by different structures formed by the effector–crRNA complex but are due to the more rapid destruction of targets with fully matching protospacers. PMID:27325762

  7. Highly efficient primed spacer acquisition from targets destroyed by the Escherichia coli type I-E CRISPR-Cas interfering complex.

    PubMed

    Semenova, Ekaterina; Savitskaya, Ekaterina; Musharova, Olga; Strotskaya, Alexandra; Vorontsova, Daria; Datsenko, Kirill A; Logacheva, Maria D; Severinov, Konstantin

    2016-07-01

    Prokaryotic clustered regularly interspaced short palindromic repeat (CRISPR)-CRISPR associated (Cas) immunity relies on adaptive acquisition of spacers-short fragments of foreign DNA. For the type I-E CRISPR-Cas system from Escherichia coli, efficient "primed" adaptation requires Cas effector proteins and a CRISPR RNA (crRNA) whose spacer partially matches a segment (protospacer) in target DNA. Primed adaptation leads to selective acquisition of additional spacers from DNA molecules recognized by the effector-crRNA complex. When the crRNA spacer fully matches a protospacer, CRISPR interference-that is, target destruction without acquisition of additional spacers-is observed. We show here that when the rate of degradation of DNA with fully and partially matching crRNA targets is made equal, fully matching protospacers stimulate primed adaptation much more efficiently than partially matching ones. The result indicates that different functional outcomes of CRISPR-Cas response to two kinds of protospacers are not caused by different structures formed by the effector-crRNA complex but are due to the more rapid destruction of targets with fully matching protospacers. PMID:27325762

  8. 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)

  9. GENOME EDITING IN HUMAN CELLS USING CRISPR/CAS NUCLEASES

    PubMed Central

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

    2016-01-01

    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), the 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. Here we describe 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. PMID:26423589

  10. CRISPR-Cas9: A Revolutionary Tool for Cancer Modelling

    PubMed Central

    Torres-Ruiz, Raul; Rodriguez-Perales, Sandra

    2015-01-01

    The cancer-modelling field is now experiencing a conversion with the recent emergence of the RNA-programmable CRISPR-Cas9 system, a flexible methodology to produce essentially any desired modification in the genome. Cancer is a multistep process that involves many genetic mutations and other genome rearrangements. Despite their importance, it is difficult to recapitulate the degree of genetic complexity found in patient tumors. The CRISPR-Cas9 system for genome editing has been proven as a robust technology that makes it possible to generate cellular and animal models that recapitulate those cooperative alterations rapidly and at low cost. In this review, we will discuss the innovative applications of the CRISPR-Cas9 system to generate new models, providing a new way to interrogate the development and progression of cancers. PMID:26389881

  11. 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. PMID:26496751

  12. CRISPR-Cas9: A Revolutionary Tool for Cancer Modelling.

    PubMed

    Torres-Ruiz, Raul; Rodriguez-Perales, Sandra

    2015-01-01

    The cancer-modelling field is now experiencing a conversion with the recent emergence of the RNA-programmable CRISPR-Cas9 system, a flexible methodology to produce essentially any desired modification in the genome. Cancer is a multistep process that involves many genetic mutations and other genome rearrangements. Despite their importance, it is difficult to recapitulate the degree of genetic complexity found in patient tumors. The CRISPR-Cas9 system for genome editing has been proven as a robust technology that makes it possible to generate cellular and animal models that recapitulate those cooperative alterations rapidly and at low cost. In this review, we will discuss the innovative applications of the CRISPR-Cas9 system to generate new models, providing a new way to interrogate the development and progression of cancers. PMID:26389881

  13. Densitometry By Acoustic Levitation

    NASA Technical Reports Server (NTRS)

    Trinh, Eugene H.

    1989-01-01

    "Static" and "dynamic" methods developed for measuring mass density of acoustically levitated solid particle or liquid drop. "Static" method, unknown density of sample found by comparison with another sample of known density. "Dynamic" method practiced with or without gravitational field. Advantages over conventional density-measuring techniques: sample does not have to make contact with container or other solid surface, size and shape of samples do not affect measurement significantly, sound field does not have to be know in detail, and sample can be smaller than microliter. Detailed knowledge of acoustic field not necessary.

  14. 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.

  15. 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.

  16. Strong acoustic wave action

    NASA Astrophysics Data System (ADS)

    Gokhberg, M. B.

    1983-07-01

    Experiments devoted to acoustic action on the atmosphere-magnetosphere-ionosphere system using ground based strong explosions are reviewed. The propagation of acoustic waves was observed by ground observations over 2000 km in horizontal direction and to an altitude of 200 km. Magnetic variations up to 100 nT were detected by ARIEL-3 satellite near the epicenter of the explosion connected with the formation of strong field aligned currents in the magnetosphere. The enhancement of VLF emission at 800 km altitude is observed.

  17. 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.

  18. Acoustic and electromagnetic waves

    NASA Astrophysics Data System (ADS)

    Jones, Douglas Samuel

    Theoretical models of EM and acoustic wave propagation are presented in an introductory text intended for intermediate-level science and engineering students. Chapters are devoted to the mathematical representation of acoustic and EM fields, the special theory of relativity, radiation, resonators, waveguide theory, refraction, surface waves, scattering by smooth objects, diffraction by edges, and transient waves. The mathematical tools required for the analysis (Bessel, Legendre, Mathieu, parabolic-cylinder, and spheroidal functions; tensor calculus; and the asymptotic evaluation of integrals) are covered in appendices.

  19. Structural Acoustics and Vibrations

    NASA Astrophysics Data System (ADS)

    Chaigne, Antoine

    This 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.

  20. 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.

  1. Acoustic loading in straight pipes

    NASA Technical Reports Server (NTRS)

    El-Raheb, M.

    1980-01-01

    Based on linear one-dimensional acoustics, a geometrically perfect elastic waveguide would respond to an oscillatory internal pressure only in the presence of path deflectors (elbows and branches). In practice, a significant elasto-acoustic interaction results even in straight conduits as a result of manufacturing tolerances. A theoretical model of the linear acoustic loading in straight pipes is developed that considers the acoustic wave distortion due to perimeter, axial, and wall thickness nonuniformities.

  2. 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.

  3. 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

  4. Multidimensional scaling between acoustic and electric stimuli in cochlear implant users with contralateral hearing

    PubMed Central

    Vermeire, Katrien; Landsberger, David M.; Schleich, Peter; Van de Heyning, Paul H.

    2013-01-01

    This study investigated the perceptual relationship between acoustic and electric stimuli presented to CI users with functional contralateral hearing. Fourteen subjects with unilateral profound deafness implanted with a MED-EL CI scaled the perceptual differences between pure tones presented to the acoustic hearing ear and electric biphasic pulse trains presented to the implanted ear. The differences were analyzed with a multidimensional scaling (MDS) analysis. Additionally, speech performance in noise was tested using sentence material presented in different spatial configurations while patients listened with both their acoustic hearing and implanted ears. Results of alternating least squares scaling (ALSCAL) analysis consistently demonstrate that a change in place of stimulation is in the same perceptual dimension as a change in acoustic frequency. However, the relative perceptual differences between the acoustic and the electric stimuli varied greatly across subjects. A degree of perceptual separation between acoustic and electric stimulation (quantified by relative dimensional weightings from an INDSCAL analysis) was hypothesized that would indicate a change in perceptual quality, but also be predictive of performance with combined acoustic and electric hearing. Perceptual separation between acoustic and electric stimuli was observed for some subjects. However, no relationship between the degree of perceptual separation and performance was found. PMID:24055624

  5. Multidimensional scaling between acoustic and electric stimuli in cochlear implant users with contralateral hearing.

    PubMed

    Vermeire, Katrien; Landsberger, David M; Schleich, Peter; Van de Heyning, Paul H

    2013-12-01

    This study investigated the perceptual relationship between acoustic and electric stimuli presented to CI users with functional contralateral hearing. Fourteen subjects with unilateral profound deafness implanted with a MED-EL CI scaled the perceptual differences between pure tones presented to the acoustic hearing ear and electric biphasic pulse trains presented to the implanted ear. The differences were analyzed with a multidimensional scaling (MDS) analysis. Additionally, speech performance in noise was tested using sentence material presented in different spatial configurations while patients listened with both their acoustic hearing and implanted ears. Results of alternating least squares scaling (ALSCAL) analysis consistently demonstrate that a change in place of stimulation is in the same perceptual dimension as a change in acoustic frequency. However, the relative perceptual differences between the acoustic and the electric stimuli varied greatly across subjects. A degree of perceptual separation between acoustic and electric stimulation (quantified by relative dimensional weightings from an INDSCAL analysis) was hypothesized that would indicate a change in perceptual quality, but also be predictive of performance with combined acoustic and electric hearing. Perceptual separation between acoustic and electric stimuli was observed for some subjects. However, no relationship between the degree of perceptual separation and performance was found. PMID:24055624

  6. The Use of Ultrasonic Waves to Study and Stimulate the Coalescence of Oil Drops in Water.

    NASA Astrophysics Data System (ADS)

    Gardner, Edward Arthur

    The coalescence of oil drops in water are studied using acoustic levitation and stimulated with acoustic cavitation. The time required for two drops to coalesce, once they have been brought into proximity of one another, is one factor that affects emulsion stability. Unlike most earlier studies, which investigate the coalescence of a single drop with an initially planar interface, the use of acoustic radiation forces allows two drops to be brought into contact and allowed to coalesce. This acoustic technique has the advantage over other drop-drop coalescence systems in that the drops remain in contact until they coalesce without the use of solid supports to control them. Additionally, acoustic cavitation is observed to deposit sufficient energy in the oil-water interface to trigger the coalescence of a pair of 2 mm diameter drops. Some of the factors that affect spontaneous and stimulated coalescence are investigated.

  7. Variable-Position Acoustic Levitation

    NASA Technical Reports Server (NTRS)

    Barmatz, M. B.; Stoneburner, J. D.; Jacobi, N.; Wang, T. G.

    1983-01-01

    Method of acoustic levitation supports objects at positions other than acoustic nodes. Acoustic force is varied so it balances gravitational (or other) force, thereby maintaining object at any position within equilibrium range. Levitation method applicable to containerless processing. Such objects as table-tennis balls, hollow plastic spheres, and balsa-wood spheres levitated in laboratory by new method.

  8. Acoustical Environment of School Buildings.

    ERIC Educational Resources Information Center

    Fitzroy, Dariel; Reid, John L.

    A field study was made of the acoustical environment of schools designed for increased flexibility to meet the spatial requirements of new teaching methods. The object of the study was to define all the criteria for the acoustical design of this type of classroom including the determination of--(1) minimum acoustical separation required for…

  9. ACOUSTICAL ENVIRONMENT OF SCHOOL BUILDINGS.

    ERIC Educational Resources Information Center

    FITZROY, DARIEL; REID, JOHN L.

    A FIELD STUDY WAS MADE OF THE ACOUSTICAL ENVIRONMENT OF SCHOOLS DESIGNED FOR INCREASED FLEXIBILITY TO MEET THE SPATIAL REQUIREMENTS OF NEW TEACHING METHODS. THE OBJECT OF THE STUDY WAS TO DEFINE ALL THE CRITERIA FOR THE ACOUSTICAL DESIGN OF THIS TYPE OF CLASSROOM INCLUDING THE DETERMINATION OF--(1) MINIMUM ACOUSTICAL SEPARATION REQUIRED FOR…

  10. 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 ...

  11. 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

  12. High-throughput functional genomics using CRISPR-Cas9

    PubMed Central

    Shalem, Ophir; Sanjana, Neville E.; Zhang, Feng

    2015-01-01

    Forward genetic screens are powerful tools for the discovery and functional annotation of genetic elements. Recently, the RNA-guided CRISPR (clustered regularly interspaced short palindromic repeat)-associated Cas9 nuclease has been combined with genome-scale guide RNA libraries for unbiased, phenotypic screening. In this Review, we describe recent advances using Cas9 for genome-scale screens, including knockout approaches that inactivate genomic loci and strategies that modulate transcriptional activity. We discuss practical aspects of screen design, provide comparisons with RNA interference (RNAi) screening, and outline future applications and challenges. PMID:25854182

  13. 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

  14. 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

  15. 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. PMID:27612824

  16. 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.

  17. 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.

  18. V845 Cas - ein RRab-Stern mit Blazhko-Effekt

    NASA Astrophysics Data System (ADS)

    Maintz, Gisela

    2015-02-01

    CCD observations of V845 Cas (RA= 23 26 15.02, DE= +57 23 55.5 (2000)) were obtained at my private observatory. For V845 Cas 13 maxima were gained, showing a light curve, that varies from epoch to epoch. The irregularity of the lightcurves of V845 Cas is due to the Blazhko effect. Revised elements are given as: V845 Cas Max = 2456221.3450 + 0.570845 * E.

  19. Functional annotation of native enhancers with a Cas9-histone demethylase fusion.

    PubMed

    Kearns, Nicola A; Pham, Hannah; Tabak, Barbara; Genga, Ryan M; Silverstein, Noah J; Garber, Manuel; Maehr, René

    2015-05-01

    Understanding of mammalian enhancers is limited by the lack of a technology to rapidly and thoroughly test the cell type-specific function. Here, we use a nuclease-deficient Cas9 (dCas9)-histone demethylase fusion to functionally characterize previously described and new enhancer elements for their roles in the embryonic stem cell state. Further, we distinguish the mechanism of action of dCas9-LSD1 at enhancers from previous dCas9-effectors. PMID:25775043

  20. 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

  1. 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. PMID:26344044

  2. The Cas6e ribonuclease is not required for interference and adaptation by the E. coli type I-E CRISPR-Cas system

    PubMed Central

    Semenova, Ekaterina; Kuznedelov, Konstantin; Datsenko, Kirill A.; Boudry, Pierre M.; Savitskaya, Ekaterina E.; Medvedeva, Sofia; Beloglazova, Natalia; Logacheva, Maria; Yakunin, Alexander F.; Severinov, Konstantin

    2015-01-01

    CRISPR-Cas are small RNA-based adaptive prokaryotic immunity systems protecting cells from foreign DNA or RNA. Type I CRISPR-Cas systems are composed of a multiprotein complex (Cascade) that, when bound to CRISPR RNA (crRNA), can recognize double-stranded DNA targets and recruit the Cas3 nuclease to destroy target-containing DNA. In the Escherichia coli type I-E CRISPR-Cas system, crRNAs are generated upon transcription of CRISPR arrays consisting of multiple palindromic repeats and intervening spacers through the function of Cas6e endoribonuclease, which cleaves at specific positions of repeat sequences of the CRISPR array transcript. Cas6e is also a component of Cascade. Here, we show that when mature unit-sized crRNAs are provided in a Cas6e-independent manner by transcription termination, the CRISPR-Cas system can function without Cas6e. The results should allow facile interrogation of various targets by type I-E CRISPR-Cas system in E. coli using unit-sized crRNAs generated by transcription. PMID:26013814

  3. CRISPR/Cas-Mediated Site-Specific Mutagenesis in Arabidopsis thaliana Using Cas9 Nucleases and Paired Nickases.

    PubMed

    Schiml, Simon; Fauser, Friedrich; Puchta, Holger

    2016-01-01

    The CRISPR/Cas system has recently become the most important tool for genome engineering due to its simple architecture that allows for rapidly changing the target sequence and its applicability to organisms throughout all kingdoms of life. The need for an easy-to-use and reliable nuclease is especially high in plant research, as precise genome modifications are almost impossible to achieve by Agrobacterium-mediated transformation and the regeneration of plants from protoplast cultures is very labor intensive. Here, we describe the application of the Cas9 nuclease to Arabidopsis thaliana for the induction of heritable targeted mutations, which may also be used for other plant species. To cover the concern for off-target activity, we also describe the generation of stable mutants using paired Cas9 nickases. PMID:27557689

  4. 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.

  5. On the Integration of Computer Algebra Systems (CAS) by Canadian Mathematicians: Results of a National Survey

    ERIC Educational Resources Information Center

    Buteau, Chantal; Jarvis, Daniel H.; Lavicza, Zsolt

    2014-01-01

    In this article, we outline the findings of a Canadian survey study (N = 302) that focused on the extent of computer algebra systems (CAS)-based technology use in postsecondary mathematics instruction. Results suggest that a considerable number of Canadian mathematicians use CAS in research and teaching. CAS use in research was found to be the…

  6. 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…

  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. PMID:26423968

  8. 48 CFR 9904.412-64.1 - Transition Method for the CAS Pension Harmonization Rule.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... CAS Pension Harmonization Rule. 9904.412-64.1 Section 9904.412-64.1 Federal Acquisition Regulations... Transition Method for the CAS Pension Harmonization Rule. Contractors or subcontractors that become subject... through 7 Notes (Note 1) Actuarial Accrued Liability $2,470,500 $14,225,000 2 CAS Actuarial Value...

  9. 48 CFR 9904.412-64.1 - Transition Method for the CAS Pension Harmonization Rule.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... CAS Pension Harmonization Rule. 9904.412-64.1 Section 9904.412-64.1 Federal Acquisition Regulations... Transition Method for the CAS Pension Harmonization Rule. Contractors or subcontractors that become subject... through 7 Notes (Note 1) Actuarial Accrued Liability $2,470,500 $14,225,000 2 CAS Actuarial Value...

  10. 48 CFR 9904.412-60.1 - Illustrations-CAS Pension Harmonization Rule.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 48 Federal Acquisition Regulations System 7 2013-10-01 2012-10-01 true Illustrations-CAS Pension... AND COST ACCOUNTING STANDARDS COST ACCOUNTING STANDARDS 9904.412-60.1 Illustrations—CAS Pension... cost on or after the Applicability Date of the CAS Harmonization Rule. The illustrations present...

  11. 48 CFR 9904.412-60.1 - Illustrations-CAS Pension Harmonization Rule.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 48 Federal Acquisition Regulations System 7 2014-10-01 2014-10-01 false Illustrations-CAS Pension... AND COST ACCOUNTING STANDARDS COST ACCOUNTING STANDARDS 9904.412-60.1 Illustrations—CAS Pension... cost on or after the Applicability Date of the CAS Harmonization Rule. The illustrations present...

  12. 48 CFR 9904.412-60.1 - Illustrations-CAS Pension Harmonization Rule.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 48 Federal Acquisition Regulations System 7 2012-10-01 2012-10-01 false Illustrations-CAS Pension... AND COST ACCOUNTING STANDARDS COST ACCOUNTING STANDARDS 9904.412-60.1 Illustrations—CAS Pension... cost on or after the Applicability Date of the CAS Harmonization Rule. The illustrations present...

  13. 48 CFR 9904.413-64.1 - Transition Method for the CAS Pension Harmonization Rule.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... CAS Pension Harmonization Rule. 9904.413-64.1 Section 9904.413-64.1 Federal Acquisition Regulations... Transition Method for the CAS Pension Harmonization Rule. The transition method for the CAS Pension Harmonization Rule under this Standard shall be in accordance with 9904.412.64.1 Transition Method for...

  14. 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…

  15. 48 CFR 9904.413-64.1 - Transition Method for the CAS Pension Harmonization Rule.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... CAS Pension Harmonization Rule. 9904.413-64.1 Section 9904.413-64.1 Federal Acquisition Regulations... Transition Method for the CAS Pension Harmonization Rule. The transition method for the CAS Pension Harmonization Rule under this Standard shall be in accordance with 9904.412.64.1 Transition Method for...

  16. 48 CFR 9904.413-64.1 - Transition Method for the CAS Pension Harmonization Rule.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... CAS Pension Harmonization Rule. 9904.413-64.1 Section 9904.413-64.1 Federal Acquisition Regulations... Transition Method for the CAS Pension Harmonization Rule. The transition method for the CAS Pension Harmonization Rule under this Standard shall be in accordance with 9904.412.64.1 Transition Method for...

  17. The Impact on Student Achievement of When CAS Technology Is Introduced

    ERIC Educational Resources Information Center

    Driver, David

    2012-01-01

    When a Computer Algebra System (CAS) is used as a pedagogical and functional tool in class and as a functional tool in exams, its effect on student achievement can be quite profound. The timing of when students are first introduced to a CAS has an impact on gains in student achievement. In this action research project, the CAS calculator was…

  18. 48 CFR 9904.412-64.1 - Transition Method for the CAS Pension Harmonization Rule.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... CAS Pension Harmonization Rule. 9904.412-64.1 Section 9904.412-64.1 Federal Acquisition Regulations... Transition Method for the CAS Pension Harmonization Rule. Contractors or subcontractors that become subject... through 7 Notes (Note 1) Actuarial Accrued Liability $2,470,500 $14,225,000 2 CAS Actuarial Value...

  19. Guide RNAs: A Glimpse at the Sequences that Drive CRISPR-Cas Systems.

    PubMed

    Briner, Alexandra E; Barrangou, Rodolphe

    2016-01-01

    CRISPR-Cas systems provide adaptive immunity in bacteria and archaea. Although there are two main classes of CRISPR-Cas systems defined by gene content, interfering RNA biogenesis, and effector proteins, Type II systems have recently been exploited on a broad scale to develop next-generation genetic engineering and genome-editing tools. Conveniently, Type II systems are streamlined and rely on a single protein, Cas9, and a guide RNA molecule, comprised of a CRISPR RNA (crRNA) and trans-acting CRISPR RNA (tracrRNA), to achieve effective and programmable nucleic acid targeting and cleavage. Currently, most commercially available Cas9-based genome-editing tools use the CRISPR-Cas system from Streptococcus pyogenes (SpyCas9), although many orthogonal Type II systems are available for diverse and multiplexable genome engineering applications. Here, we discuss the biological significance of Type II CRISPR-Cas elements, including the tracrRNA, crRNA, Cas9, and protospacer-adjacent motif (PAM), and look at the native function of these elements to understand how they can be engineered, enhanced, and optimized for genome editing applications. Additionally, we discuss the basis for orthogonal Cas9 and guide RNA systems that would allow researchers to concurrently use multiple Cas9-based systems for different purposes. Understanding the native function of endogenous Type II CRISPR-Cas systems can lead to new Cas9 tool development to expand the genetic manipulation toolbox. PMID:27371605

  20. Microfiber interferometric acoustic transducers.

    PubMed

    Wang, Xiuxin; Jin, Long; Li, Jie; Ran, Yang; Guan, Bai-Ou

    2014-04-01

    Acoustic and ultrasonic transducers are key components in biomedical information technology, which has been applied in medical diagnosis, photoacoustic endoscopy and photoacoustic imaging. In this paper, an acoustic transducer based on Fabry-Perot interferometer (FPI) fabricated in a microscaled optical fiber is demonstrated. The transducer is fabricated by forming two wavelength-matched Bragg gratings into the microfiber by means of side illumination with a 193nm excimer laser. When placing the transducer in water, the applied acoustic signal periodically changes the refractive index (RI) of the surrounding liquid and modulates the transmission of the FPI based on the evanescent-field interaction between the liquid and the transmitting light. As a result, the acoustic signal can be constructed with a tunable laser whose output wavelength is located at the slope of the inteferometric fringes. The transducer presents a sensitivity of 10 times higher than the counterparts fabricated in conventional singlemode fibers and has great potential to achieve higher resolution for photoacoustic imaging due to its reduced diameter. PMID:24718189

  1. 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.

  2. 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…

  3. Teaching acoustics online

    NASA Astrophysics Data System (ADS)

    Morrison, Andrew; Rossing, Thomas D.

    2003-10-01

    We teach an introductory course in musical acoustics using a Blackboard. Students in this course can access audio and video materials as well as printed materials on our course website. All homework is submitted online, as are tests and examinations. The students also have the opportunity to use synchronous and asynchronous chat rooms to discuss the course with each other or with the instructors.

  4. 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.

  5. COMBUSTION ACOUSTICS DIAGNOSTICS

    EPA Science Inventory

    This is an Exploratory Research Project that was awarded by APPCD for research on developing an acoustic flame condition monitor. It will involve a bench scale experiment of 4-6 weeks duration to record adjacent audible energy of a Bunsen burner. The experiment will require a d...

  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. Acoustics- Version 1.0

    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, themore » sounds are removed, as a character forgets what it has heard.« less

  8. Apport de l'imagerie dans le diagnostic des sacroiliites infectieuses : à propos de 19 cas

    PubMed Central

    Abid, Hanen; Chaabouni, Salim; Frikha, Faten; Toumi, Nozha; Souissi, Basma; Lahiani, Dorra; Bahloul, Zouhir; Ben Mahfoudh, Khaireddine

    2014-01-01

    Les sacro-iliites infectieuses méritent d’être mieux connues. Leur diagnostic est souvent retardé en raison d'une symptomatologie trompeuse et des diffcultés d'exploration de l'articulation sacro-iliaque. Notre travail est basé sur une étude rétrospective portant sur les cas de SII, recueillis sur une période comprise entre 1997 et 2008 dans notre centre universitaire Sfax-Tunisie. Le diagnostic de sacro-iliite était retenu en présence d'arguments cliniques et radiologiques d'atteinte sacroiliaque. Nous rapportons dix neuf cas de sacroiliites infectieuses (10 hommes et 9 femmes), avec un âge moyen de 32 ans. L'atteinte était unilatérale dans tous les cas. Les radiographies standard faites dans tous les cas ont été suggestives dans 14 cas et normales dans les autres cas. La TDM faite dans 13 cas a montré, un abcès des parties molles dans 8 cas et un séquestre osseux dans 2 cas. L'IRM réalisée dans 8 cas, a objectivé une infiltration des parties molles dans tous les cas et un abcès dans 3 cas. Le germe a été identifié dans 9 cas (3 cas de tuberculose, 3 cas de brucellose, 2 sacro-iliites à pyogène et un cas de candidose). Cette identification était faite par biopsie dans 3 cas, hémocultures dans 2 cas, prélèvement au niveau de la porte d'entrée dans 1 cas et sérodiagnostic dans 3 cas. Pour les autres cas, l'origine pyogène a été retenue sur des arguments cliniques et biologiques. L'imagerie joue un rôle primordial dans le diagnostic précoce et l'orientation étiologique d'une sacroiliite infectieuse. PMID:25120884

  9. 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. PMID:26902348

  10. 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…

  11. 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…

  12. Research Needed on the Use of CAS Standards and Guidelines.

    ERIC Educational Resources Information Center

    Creamer, Don G.

    2003-01-01

    This article suggests research projects that would extend the knowledge base about the use of Council for the Advancement of Standards in Higher Education (CAS) standards and guidelines in useful ways. Included are five research questions and specific research methodologies to guide researchers. (Contains 20 references.) (Author)

  13. 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…

  14. Does CAS Use Disadvantage Girls in VCE Mathematics?

    ERIC Educational Resources Information Center

    Forgasz, Helen; Tan, Hazel

    2010-01-01

    In 2009, four mathematics subjects were offered at the year 12 level in the Victorian Certificate of Education (VCE). The two subjects at the intermediate level--Mathematical Methods and Mathematical Methods CAS--run in parallel, that is, a student can be enrolled in only one or the other, the choice being made at the school level. The curricular…

  15. Targeted mutagenesis in chicken using CRISPR/Cas9 system.

    PubMed

    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

  16. 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…

  17. CRISPR/Cas9-targeted mutagenesis in Caenorhabditis elegans.

    PubMed

    Waaijers, Selma; Portegijs, Vincent; Kerver, Jana; Lemmens, Bennie B L G; Tijsterman, Marcel; van den Heuvel, Sander; Boxem, Mike

    2013-11-01

    The generation of genetic mutants in Caenorhabditis elegans has long relied on the selection of mutations in large-scale screens. Directed mutagenesis of specific loci in the genome would greatly speed up analysis of gene function. Here, we adapt the CRISPR/Cas9 system to generate mutations at specific sites in the C. elegans genome. PMID:23979586

  18. 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. PMID:26707540

  19. 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

  20. Indispensable Manual Calculation Skills in a CAS Environment.

    ERIC Educational Resources Information Center

    Herget, Wilfried; Heugl, Helmut; Kutzler, Bernhard; Lehmann, Eberhard

    Which manual calculation skills are still needed when students use graphic/symbolic calculators or computers with computer algebra systems (CAS)? What should students be able to do manually, i.e. just using paper and pencil? This text is the outcome of a two-day discussion on these questions, held by the four authors. Our answers and proposals are…

  1. Some Reflections on CAS Assisted Proofs of Theorems

    ERIC Educational Resources Information Center

    Dana-Picard, Thierry

    2005-01-01

    A mathematician's work consists of proving theorems, calculating, and making mathematics understandable. An assistant for all three components is a Computer Algebra System. We describe and discuss various CAS-assisted processes for proving theorems, and discuss the constraints which can appear regarding efficiency, confidence in the result and…

  2. 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…

  3. Duchenne muscular dystrophy: CRISPR/Cas9 treatment.

    PubMed

    Mendell, Jerry R; Rodino-Klapac, Louise R

    2016-05-01

    A novel approach to gene correction by genome editing shows great promise as a treatment for Duchenne muscular dystrophy (DMD). CRISPR/Cas9 delivered by adeno-associated virus to a mouse model for DMD demonstrated improvement in function and histology. PMID:26926391

  4. 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…

  5. 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

  6. Maximizing mutagenesis with solubilized CRISPR-Cas9 ribonucleoprotein complexes.

    PubMed

    Burger, Alexa; Lindsay, Helen; Felker, Anastasia; Hess, Christopher; Anders, Carolin; Chiavacci, Elena; Zaugg, Jonas; Weber, Lukas M; Catena, Raul; Jinek, Martin; Robinson, Mark D; Mosimann, Christian

    2016-06-01

    CRISPR-Cas9 enables efficient sequence-specific mutagenesis for creating somatic or germline mutants of model organisms. Key constraints in vivo remain the expression and delivery of active Cas9-sgRNA ribonucleoprotein complexes (RNPs) with minimal toxicity, variable mutagenesis efficiencies depending on targeting sequence, and high mutation mosaicism. Here, we apply in vitro assembled, fluorescent Cas9-sgRNA RNPs in solubilizing salt solution to achieve maximal mutagenesis efficiency in zebrafish embryos. MiSeq-based sequence analysis of targeted loci in individual embryos using CrispRVariants, a customized software tool for mutagenesis quantification and visualization, reveals efficient bi-allelic mutagenesis that reaches saturation at several tested gene loci. Such virtually complete mutagenesis exposes loss-of-function phenotypes for candidate genes in somatic mutant embryos for subsequent generation of stable germline mutants. We further show that targeting of non-coding elements in gene regulatory regions using saturating mutagenesis uncovers functional control elements in transgenic reporters and endogenous genes in injected embryos. Our results establish that optimally solubilized, in vitro assembled fluorescent Cas9-sgRNA RNPs provide a reproducible reagent for direct and scalable loss-of-function studies and applications beyond zebrafish experiments that require maximal DNA cutting efficiency in vivo. PMID:27130213

  7. Genome Editing with CRISPR-Cas9: Can It Get Any Better?

    PubMed

    Haeussler, Maximilian; Concordet, Jean-Paul

    2016-05-20

    The CRISPR-Cas revolution is taking place in virtually all fields of life sciences. Harnessing DNA cleavage with the CRISPR-Cas9 system of Streptococcus pyogenes has proven to be extraordinarily simple and efficient, relying only on the design of a synthetic single guide RNA (sgRNA) and its co-expression with Cas9. Here, we review the progress in the design of sgRNA from the original dual RNA guide for S. pyogenes and Staphylococcus aureus Cas9 (SpCas9 and SaCas9). New assays for genome-wide identification of off-targets have provided important insights into the issue of cleavage specificity in vivo. At the same time, the on-target activity of thousands of guides has been determined. These data have led to numerous online tools that facilitate the selection of guide RNAs in target sequences. It appears that for most basic research applications, cleavage activity can be maximized and off-targets minimized by carefully choosing guide RNAs based on computational predictions. Moreover, recent studies of Cas proteins have further improved the flexibility and precision of the CRISPR-Cas toolkit for genome editing. Inspired by the crystal structure of the complex of sgRNA-SpCas9 bound to target DNA, several variants of SpCas9 have recently been engineered, either with novel protospacer adjacent motifs (PAMs) or with drastically reduced off-targets. Novel Cas9 and Cas9-like proteins called Cpf1 have also been characterized from other bacteria and will benefit from the insights obtained from SpCas9. Genome editing with CRISPR-Cas9 may also progress with better understanding and control of cellular DNA repair pathways activated after Cas9-induced DNA cleavage. PMID:27210042

  8. 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.

  9. Rigorous characterization of acoustic-optical interactions in silicon slot waveguides by full-vectorial finite element method.

    PubMed

    Sriratanavaree, S; Rahman, B M A; Leung, D M H; Kejalakshmy, N; Grattan, K T V

    2014-04-21

    For the first time detailed interactions between optical and acoustic modes in a silicon slot waveguide are presented. A new computer code has been developed by using a full-vectorial formulation to study the acoustic modes in optical waveguides. The results have shown that the acoustic modes in an optical slot waveguide are not purely longitudinal or transverse but fully hybrid in nature. The model allows the effects of Stimulated Brillouin Scattering and the associated frequency shift due to the interaction of these hybrid acoustic modes with the fully hybrid optical mode also to be presented. PMID:24787841

  10. 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…

  11. Production of genome-edited pluripotent stem cells and mice by CRISPR/Cas [Review].

    PubMed

    Horii, Takuro; Hatada, Izuho

    2016-03-31

    Clustered regularly at interspaced short palindromic repeats (CRISPR) and CRISPR-associated (Cas) nucleases, so-called CRISPR/Cas, was recently developed as an epoch-making genome engineering technology. This system only requires Cas9 nuclease and single-guide RNA complementary to a target locus. CRISPR/Cas enables the generation of knockout cells and animals in a single step. This system can also be used to generate multiple mutations and knockin in a single step, which is not possible using other methods. In this review, we provide an overview of genome editing by CRISPR/Cas in pluripotent stem cells and mice. PMID:26743444

  12. Mobile CRISPR/Cas-Mediated Bacteriophage Resistance in Lactococcus lactis

    PubMed Central

    Millen, Anne M.; Horvath, Philippe; Boyaval, Patrick; Romero, Dennis A.

    2012-01-01

    Lactococcus lactis is a biotechnological workhorse for food fermentations and potentially therapeutic products and is therefore widely consumed by humans. It is predominantly used as a starter microbe for fermented dairy products, and specialized strains have adapted from a plant environment through reductive evolution and horizontal gene transfer as evidenced by the association of adventitious traits with mobile elements. Specifically, L. lactis has armed itself with a myriad of plasmid-encoded bacteriophage defensive systems to protect against viral predation. This known arsenal had not included CRISPR/Cas (clustered regularly interspaced short palindromic repeats/CRISPR-associated proteins), which forms a remarkable microbial immunity system against invading DNA. Although CRISPR/Cas systems are common in the genomes of closely related lactic acid bacteria (LAB), none was identified within the eight published lactococcal genomes. Furthermore, a PCR-based search of the common LAB CRISPR/Cas systems (Types I and II) in 383 industrial L. lactis strains proved unsuccessful. Here we describe a novel, Type III, self-transmissible, plasmid-encoded, phage-interfering CRISPR/Cas discovered in L. lactis. The native CRISPR spacers confer resistance based on sequence identity to corresponding lactococcal phage. The interference is directed at phages problematic to the dairy industry, indicative of a responsive system. Moreover, targeting could be modified by engineering the spacer content. The 62.8-kb plasmid was shown to be conjugally transferrable to various strains. Its mobility should facilitate dissemination within microbial communities and provide a readily applicable system to naturally introduce CRISPR/Cas to industrially relevant strains for enhanced phage resistance and prevention against acquisition of undesirable genes. PMID:23240053

  13. 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. PMID:26086867

  14. Anti-cas spacers in orphan CRISPR4 arrays prevent uptake of active CRISPR-Cas I-F systems.

    PubMed

    Almendros, Cristóbal; Guzmán, Noemí M; García-Martínez, Jesús; Mojica, Francisco J M

    2016-01-01

    Archaea and bacteria harbour clustered regularly interspaced short palindromic repeats (CRISPR) loci. These arrays encode RNA molecules (crRNA), each containing a sequence of a single repeat-intervening spacer. The crRNAs guide CRISPR-associated (Cas) proteins to cleave nucleic acids complementary to the crRNA spacer, thus interfering with targeted foreign elements. Notably, pre-existing spacers may trigger the acquisition of new spacers from the target molecule by means of a primed adaptation mechanism. Here, we show that naturally occurring orphan CRISPR arrays that contain spacers matching sequences of the cognate (absent) cas genes are able to elicit both primed adaptation and direct interference against genetic elements carrying those genes. Our findings show the existence of an anti-cas mechanism that prevents the transfer of a fully equipped CRISPR-Cas system. Hence, they suggest that CRISPR immunity may be undesired by particular prokaryotes, potentially because they could limit possibilities for gaining favourable sequences by lateral transfer. PMID:27573106

  15. Observation d'un minimum plat pour RZ Cas [Observation of a flat minimum of RZ Cas

    NASA Astrophysics Data System (ADS)

    Dumont, M.

    1995-07-01

    We observed a minimum of RZ Cas during the night 15/16 august 1991 with the 76 cm telescope of the Fungfraujoch Observatory. We found: Min = HJD 2,448,484.50062 and observed a flat minimum during 10 minutes.

  16. Structural Basis for the Altered PAM Specificities of Engineered CRISPR-Cas9.

    PubMed

    Hirano, Seiichi; Nishimasu, Hiroshi; Ishitani, Ryuichiro; Nureki, Osamu

    2016-03-17

    The RNA-guided endonuclease Cas9 cleaves double-stranded DNA targets bearing a PAM (protospacer adjacent motif) and complementarity to the guide RNA. A recent study showed that, whereas wild-type Streptococcus pyogenes Cas9 (SpCas9) recognizes the 5'-NGG-3' PAM, the engineered VQR, EQR, and VRER SpCas9 variants recognize the 5'-NGA-3', 5'-NGAG-3', and 5'-NGCG-3' PAMs, respectively, thus expanding the targetable sequences in Cas9-mediated genome editing applications. Here, we present the high-resolution crystal structures of the three SpCas9 variants in complexes with a single-guide RNA and its altered PAM-containing, partially double-stranded DNA targets. A structural comparison of the three SpCas9 variants with wild-type SpCas9 revealed that the multiple mutations synergistically induce an unexpected displacement in the phosphodiester backbone of the PAM duplex, thereby allowing the SpCas9 variants to directly recognize the altered PAM nucleotides. Our findings explain the altered PAM specificities of the SpCas9 variants and establish a framework for further rational engineering of CRISPR-Cas9. PMID:26990991

  17. 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. PMID:26857072

  18. 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.

  19. 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.

  20. 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.

  1. 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.

  2. 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.

  3. Acoustic tractor beam.

    PubMed

    Démoré, Christine E M; Dahl, Patrick M; Yang, Zhengyi; Glynne-Jones, Peter; Melzer, Andreas; Cochran, Sandy; MacDonald, Michael P; Spalding, Gabriel C

    2014-05-01

    Negative radiation forces act opposite to the direction of propagation, or net momentum, of a beam but have previously been challenging to definitively demonstrate. We report an experimental acoustic tractor beam generated by an ultrasonic array operating on macroscopic targets (>1 cm) to demonstrate the negative radiation forces and to map out regimes over which they dominate, which we compare to simulations. The result and the geometrically simple configuration show that the effect is due to nonconservative forces, produced by redirection of a momentum flux from the angled sides of a target and not by conservative forces from a potential energy gradient. Use of a simple acoustic setup provides an easily understood illustration of the negative radiation pressure concept for tractor beams and demonstrates continuous attraction towards the source, against a net momentum flux in the system. PMID:24836252

  4. Acoustic Tractor Beam

    NASA Astrophysics Data System (ADS)

    Démoré, Christine E. M.; Dahl, Patrick M.; Yang, Zhengyi; Glynne-Jones, Peter; Melzer, Andreas; Cochran, Sandy; MacDonald, Michael P.; Spalding, Gabriel C.

    2014-05-01

    Negative radiation forces act opposite to the direction of propagation, or net momentum, of a beam but have previously been challenging to definitively demonstrate. We report an experimental acoustic tractor beam generated by an ultrasonic array operating on macroscopic targets (>1 cm) to demonstrate the negative radiation forces and to map out regimes over which they dominate, which we compare to simulations. The result and the geometrically simple configuration show that the effect is due to nonconservative forces, produced by redirection of a momentum flux from the angled sides of a target and not by conservative forces from a potential energy gradient. Use of a simple acoustic setup provides an easily understood illustration of the negative radiation pressure concept for tractor beams and demonstrates continuous attraction towards the source, against a net momentum flux in the system.

  5. Alaskan river environmental acoustics

    NASA Astrophysics Data System (ADS)

    Dahl, Peter H.; Pfisterer, Carl; Geiger, Harold J.

    2005-04-01

    Sonars are used by the Alaska Department of Fish and Game (ADF&G) to obtain daily and hourly estimates of at least four species of migratory salmon during their seasonal migration which lasts from June to beginning of September. Suspended sediments associated with a river's sediment load is an important issue for ADF&G's sonar operations. Acoustically, the suspended sediments are a source of both volume reverberation and excess attenuation beyond that expected in fresh water. Each can impact daily protocols for fish enumeration via sonar. In this talk, results from an environmental acoustic study conducted in the Kenai River (June 1999) using 420 kHz and 200 kHz side looking sonars, and in the Yukon River (July 2001) using a 120 kHz side looking sonar, are discussed. Estimates of the volume scattering coefficient and attenuation are related to total suspended sediments. The relative impact of bubble scattering and sediment scattering is also discussed.

  6. 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.

  7. 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. PMID:27586767

  8. Books on acoustics

    NASA Astrophysics Data System (ADS)

    Shaw, Neil A.

    2001-05-01

    The legacy of a man is not limited to just his projects. His writings in many cases are a more lasting, and a definitely more accessible, monument. For 60 years, Leo L. Beranek has produced books on acoustics, acoustic measurements, sound control, music and architecture, noise and vibration control, concert halls, and opera houses in addition to teaching and consulting. His books are standard references and still cited in other books and in technical and professional articles. Many of his books were among, if not, the first comprehensive modern treatment of the subject and many are still foremost. A review of Dr. Beranek's many books as well as some anecdotes about the circumstances and consequences of same will be presented.

  9. Effect of acoustic fine structure cues on the recognition of auditory-only and audiovisual speech.

    PubMed

    Meister, Hartmut; Fuersen, Katrin; Schreitmueller, Stefan; Walger, Martin

    2016-06-01

    This study addressed the hypothesis that an improvement in speech recognition due to combined envelope and fine structure cues is greater in the audiovisual than the auditory modality. Normal hearing listeners were presented with envelope vocoded speech in combination with low-pass filtered speech. The benefit of adding acoustic low-frequency fine structure to acoustic envelope cues was significantly greater for audiovisual than for auditory-only speech. It is suggested that this is due to complementary information of the different acoustic and visual cues. The results have potential implications for the assessment of bimodal cochlear implant fittings or electroacoustic stimulation. PMID:27369134

  10. Theory on acoustic sources

    NASA Technical Reports Server (NTRS)

    Wright, S. E.

    1978-01-01

    A theory is described for the radiation emission emission from acoustic multipole sources. The sources can be stationary or moving at speeds including supersonic and experience stationary or moving disturbances. The effect of finite source distributions and disturbances is investigated as well as the manner in which they interact. Distinction is made between source distributions that responsed as a function of time and those that respond as a function of space.

  11. 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.

  12. 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.

  13. 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.

  14. 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

  15. Fast wideband acoustical holography.

    PubMed

    Hald, Jørgen

    2016-04-01

    Patch near-field acoustical holography methods like statistically optimized near-field acoustical holography and equivalent source method are limited to relatively low frequencies, where the average array-element spacing is less than half of the acoustic wavelength, while beamforming provides useful resolution only at medium-to-high frequencies. With adequate array design, both methods can be used with the same array. But for holography to provide good low-frequency resolution, a small measurement distance is needed, whereas beamforming requires a larger distance to limit sidelobe issues. The wideband holography method of the present paper was developed to overcome that practical conflict. Only a single measurement is needed at a relatively short distance and a single result is obtained covering the full frequency range. The method uses the principles of compressed sensing: A sparse sound field representation is assumed with a chosen set of basis functions, a measurement is taken with an irregular array, and the inverse problem is solved with a method that enforces sparsity in the coefficient vector. Instead of using regularization based on the 1-norm of the coefficient vector, an iterative solution procedure is used that promotes sparsity. The iterative method is shown to provide very similar results in most cases and to be computationally much more efficient. PMID:27106299

  16. 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.

  17. Scanning tomographic acoustic microscopy

    NASA Astrophysics Data System (ADS)

    Lee, Hua

    2002-11-01

    This paper provides an overview of the design and development of the scanning tomographic acoustic microscopy (STAM). This research effort spans over a period of more than 12 years, which successfully elevated the acoustic microscopy from the traditional intensity-mapping mode to the level of holographic and tomographic imaging. The tomographic imaging capability of STAM was developed on the platform of the scanning laser acoustic microscope (SLAM), which operates in a coherent transmission mode with plane-wave illumination and scanning laser wavefield detection. The image formation techniques were based on the backward propagation method implemented in the plane-to-plane format. In this paper, the key elements of the design and development, including the modification of the data-acquisition hardware, implementation of image reconstruction algorithms for multiple-frequency and multiple-angle tomography, and the high-precision phase-correction and image registration techniques for the superposition of coherent sub-images, will be discussed. Results of full-scale experiments will also be included to demonstrate the capability of holographic and tomographic image formation in microscopic scale.

  18. 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. PMID:26827343

  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. Spatiotemporally resolved granular acoustics

    NASA Astrophysics Data System (ADS)

    Owens, Eli; Daniels, Karen

    2011-03-01

    Acoustic techniques provide a non-invasive method of characterizing granular material properties; however, there are many challenges in formulating accurate models of sound propagation due to the inherently heterogeneous nature of granular materials. In order to quantify acoustic responses in space and time, we perform experiments in a photoelastic granular material in which the internal stress pattern (in the form of force chains) is visible. We utilize two complementary methods, high-speed imaging and piezoelectric transduction, to provide particle-scale measurements of the amplitude of the acoustic wave. We observe that the average wave amplitude is largest within particles experiencing the largest forces. The force-dependence of this amplitude is in qualitative agreement with a simple Hertzian-like model for contact area. In addition, we investigate the power spectrum of the propagating signal using the piezoelectric sensors. For a Gaussian wave packet input, we observe a broad spectrum of transmitted frequencies below the driving frequency, and we quantify the characteristic frequencies and corresponding length scales of our material as the system pressure is varied.

  1. BCAR3/AND-34 can signal independent of complex formation with CAS family members or the presence of p130Cas

    PubMed Central

    Borre, Pierre Vanden; Near, Richard I.; Makkinje, Anthony; Mostoslavsky, Gustavo; Lerner, Adam

    2011-01-01

    BCAR3 binds to the carboxy-terminus of p130Cas, a focal adhesion adapter protein. Both BCAR3 and p130Cas have been linked to resistance to anti-estrogens in breast cancer, Rac activation and cell motility. Using R743A BCAR3, a point mutant that has lost the ability to bind p130Cas, we find that BCAR3-p130Cas complex formation is not required for BCAR3-mediated anti-estrogen resistance, Rac activation or discohesion of epithelial breast cancer cells. Complex formation was also not required for BCAR3-induced lamellipodia formation in BALB/c-3T3 fibroblasts but was required for optimal BCAR3-induced motility. Although both wildtype and R743A BCAR3 induced phosphorylation of p130Cas and the related adapter protein HEF1/NEDD9, chimeric NSP3:BCAR3 experiments demonstrate that such phosphorylation does not correlate with BCAR3-induced anti-estrogen resistance or lamellipodia formation. Wildtype but not R743A BCAR3 induced lamellipodia formation and augmented cell motility in p130Cas-/- murine embryonic fibroblasts (MEFs), suggesting that while p130Cas itself is not strictly required for these endpoints, complex formation with other CAS family members is, at least in cells lacking p130Cas. Overall, our work suggests that many, but not all, BCAR3-mediated signaling events in epithelial and mesenchymal cells are independent of p130Cas association. These studies also indicate that disruption of the BCAR3-p130Cas complex is unlikely to reverse BCAR3-mediated anti-estrogen resistance. PMID:21262352

  2. Acoustic properties of triggered lightning

    NASA Astrophysics Data System (ADS)

    Dayeh, M. A.; Evans, N.; Ramaekers, J.; Trevino, J.; Rassoul, H.; Lucia, R. J.; Dwyer, J. R.; Uman, M. A.; Jordan, D. M.

    2014-12-01

    Acoustic signatures from rocket-triggered lightning are measured by a 15m long, one-dimensional microphone array consisting of 16 receivers situated 90 meters from the lightning channel. Measurements were taken at the International Center for Lightning Research and Testing (ICLRT) in Camp Blanding, FL during the summer of 2014. The linear array was oriented in an end-fire position so that the peak acoustic reception pattern can be steered vertically along the channel with a frequency-dependent spatial resolution, enabling us to sample the acoustic signatures from different portions along the lightning channel. We report on the characteristics of acoustic signatures associated with several return strokes in 6 measured flashes (total of 29 return strokes). In addition, we study the relationship between the amplitude, peak frequency, and inferred energy input of each stroke acoustic signature and the associated measured lightning parameters. Furthermore, challenges of obtaining acoustic measurements in thunderstorm harsh conditions and their countermeasures will also be discussed.

  3. 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

  4. 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

  5. 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.

  6. Acoustic nonlinearity in dispersive solids

    NASA Technical Reports Server (NTRS)

    Cantrell, John H.; Yost, William T.

    1991-01-01

    An investigation to consider the effects of dispersion on the generation of the static acoustic wave component is presented. It is considered that an acoustic toneburst may be modeled as a modulated continuous waveform and that the generated initial static displacement pulse may be viewed as a modulation-confined disturbance. A theoretical model for the generation of the acoustic modulation solitons evolved is developed and experimental evidence in samples of vitreous silica demonstrating the essential validity of the model is provided.

  7. 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.

  8. Optical Stimulation of Neurons

    PubMed Central

    Thompson, Alexander C.; Stoddart, Paul R.; Jansen, E. Duco

    2014-01-01

    Our capacity to interface with the nervous system remains overwhelmingly reliant on electrical stimulation devices, such as electrode arrays and cuff electrodes that can stimulate both central and peripheral nervous systems. However, electrical stimulation has to deal with multiple challenges, including selectivity, spatial resolution, mechanical stability, implant-induced injury and the subsequent inflammatory response. Optical stimulation techniques may avoid some of these challenges by providing more selective stimulation, higher spatial resolution and reduced invasiveness of the device, while also avoiding the electrical artefacts that complicate recordings of electrically stimulated neuronal activity. This review explores the current status of optical stimulation techniques, including optogenetic methods, photoactive molecule approaches and infrared neural stimulation, together with emerging techniques such as hybrid optical-electrical stimulation, nanoparticle enhanced stimulation and optoelectric methods. Infrared neural stimulation is particularly emphasised, due to the potential for direct activation of neural tissue by infrared light, as opposed to techniques that rely on the introduction of exogenous light responsive materials. However, infrared neural stimulation remains imperfectly understood, and techniques for accurately delivering light are still under development. While the various techniques reviewed here confirm the overall feasibility of optical stimulation, a number of challenges remain to be overcome before they can deliver their full potential. PMID:26322269

  9. Electrophysiological channel interactions using focused multipolar stimulation for cochlear implants

    NASA Astrophysics Data System (ADS)

    George, Shefin S.; Shivdasani, Mohit N.; Wise, Andrew K.; Shepherd, Robert K.; Fallon, James B.

    2015-12-01

    Objective. Speech intelligibility with existing multichannel cochlear implants (CIs) is thought to be limited by poor spatial selectivity and interactions between CI channels caused by overlapping activation with monopolar (MP) stimulation. Our previous studies have shown that focused multipolar (FMP) and tripolar (TP) stimulation produce more restricted neural activation in the inferior colliculus (IC), compared to MP stimulation. Approach. This study explored interactions in the IC produced by simultaneous stimulation of two CI channels. We recorded multi-unit neural activity in the IC of anaesthetized cats with normal and severely degenerated spiral ganglion neuron populations in response to FMP, TP and MP stimulation from a 14 channel CI. Stimuli were applied to a ‘fixed’ CI channel, chosen toward the middle of the cochlear electrode array, and the effects of simultaneously stimulating a more apical ‘test’ CI channel were measured as a function of spatial separation between the two stimulation channels and stimulus level of the fixed channel. Channel interactions were quantified by changes in neural responses and IC threshold (i.e., threshold shift) elicited by simultaneous stimulation of two CI channels, compared to stimulation of the test channel alone. Main results. Channel interactions were significantly lower for FMP and TP than for MP stimulation (p < 0.001), whereas no significant difference was observed between FMP and TP stimulation. With MP stimulation, threshold shifts increased with decreased inter-electrode spacing and increased stimulus levels of the fixed channel. For FMP and TP stimulation, channel interactions were found to be similar for different inter-electrode spacing and stimulus levels of the fixed channel. Significance. The present study demonstrates how the degree of channel interactions in a CI can be controlled using stimulation configurations such as FMP and TP; such knowledge is essential in enhancing CI function in complex

  10. Truck acoustic data analyzer system

    DOEpatents

    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.

  11. 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.

  12. Guided acoustic wave inspection system

    DOEpatents

    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.

  13. ACTH (cosyntropin) stimulation test

    MedlinePlus

    ... The ACTH stimulation test measures how well the adrenal glands respond to adrenocorticotropic hormone ( ACTH ). ACTH is a ... produced in the pituitary gland that stimulates the adrenal glands to release a hormone called cortisol. How the ...

  14. 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. PMID:27208253

  15. An Effective Strategy for Reliably Isolating Heritable and Cas9-Free Arabidopsis Mutants Generated by CRISPR/Cas9-Mediated Genome Editing1[OPEN

    PubMed Central

    Gao, Xiuhua; Chen, Jilin; Dai, Xinhua; Zhang, Da

    2016-01-01

    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. PMID:27208253

  16. Broadening Staphylococcus aureus Cas9 Targeting Range by Modifying PAM Recognition

    PubMed Central

    Kleinstiver, Benjamin P.; Prew, Michelle S.; Tsai, Shengdar Q.; Nguyen, Nhu T.; Topkar, Ved V.; Zheng, Zongli; Joung, J. Keith

    2015-01-01

    CRISPR-Cas9 nucleases are primarily guided by RNA-DNA interactions but also require Cas9-mediated recognition of a protospacer adjacent motif (PAM). While potentially advantageous for specificity, extended PAM sequences limit the targeting range of Cas9 orthologues for genome editing. One possible strategy to relieve this restriction is to relax specificities for certain positions within the PAM. Here we used molecular evolution to modify the NNGRRT PAM specificity of Staphylococcus aureus Cas9 (SaCas9). One variant we identified, referred to as KKH SaCas9, shows robust genome editing activities at endogenous human target sites with NNNRRT PAMs. Importantly, using GUIDE-seq, we show that both wild-type and KKH SaCas9 induce comparable numbers of off-target effects in human cells. KKH SaCas9 increased the targeting range of SaCas9 by nearly two- to four-fold. Our molecular evolution strategy does not require structural information and therefore should be applicable to a wide range of Cas9 orthologues. PMID:26524662

  17. Nucleosomes impede Cas9 access to DNA in vivo and in vitro.

    PubMed

    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. PMID:26987018

  18. 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

  19. 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

  20. 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

    2016-01-01

    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

  1. Force Sensing by Extension of the Src Family Kinase Substrate, p130Cas

    PubMed Central

    Sawada, Yasuhiro; Tamada, Masako; Dubin-Thaler, Benjamin J.; Cherniavskaya, Oksana; Sakai, Ryuichi; Tanaka, Sakae; Sheetz, Michael P.

    2009-01-01

    SUMMARY Physical force is implicated in many cell functions. However, the molecular mechanisms of force sensing are poorly understood. Here, we show that mechanical extension of p130Cas (Cas) in vitro and in vivo causes phosphorylation by Src family kinases with no apparent change in Src kinase activity and that Cas phosphorylation is involved in stretch-dependent activation of the small GTPase, Rap1. In vitro, we mechanically extended bacterially expressed Cas substrate domain (CasSD) and found a remarkable enhancement of phosphorylation by specific kinases. Using an antibody that recognized extended CasSD in vitro, Cas extension in intact cells was observed in the peripheral regions of spreading cells where higher traction forces are expected and phosphorylated Cas was detected, suggesting that the in vitro extension and phosphorylation of CasSD is relevant to physiological force transduction. Thus, Cas acts as a primary force-sensor through extension of the substrate domain, which primes it for phosphorylation. PMID:17129785

  2. Highly efficient targeted chromosome deletions using CRISPR/Cas9.

    PubMed

    He, Zuyong; Proudfoot, Chris; Mileham, Alan J; McLaren, David G; Whitelaw, C Bruce A; Lillico, Simon G

    2015-05-01

    The CRISPR/Cas9 system has emerged as an intriguing new technology for genome engineering. It utilizes the bacterial endonuclease Cas9 which, when delivered to eukaryotic cells in conjunction with a user-specified small guide RNA (gRNA), cleaves the chromosomal DNA at the target site. Here we show that concurrent delivery of gRNAs designed to target two different sites in a human chromosome introduce DNA double-strand breaks in the chromosome and give rise to targeted deletions of the intervening genomic segment. Predetermined genomic DNA segments ranging from several-hundred base pairs to 1 Mbp can be precisely deleted at frequencies of 1-10%, with no apparent correlation between the size of the deleted fragment and the deletion frequency. The high efficiency of this technique holds promise for large genomic deletions that could be useful in generation of cell and animal models with engineered chromosomes. PMID:25362885

  3. 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. PMID:26874259

  4. Application of CRISPR/Cas9 Technology to HBV

    PubMed Central

    Lin, Guigao; Zhang, Kuo; Li, Jinming

    2015-01-01

    More than 240 million people around the world are chronically infected with hepatitis B virus (HBV). Nucleos(t)ide analogs and interferon are the only two families of drugs to treat HBV currently. However, none of these anti-virals directly target the stable nuclear covalently closed circular DNA (cccDNA), which acts as a transcription template for viral mRNA and pre-genomic RNA synthesis and secures virus persistence. Thus, the fact that only a small number of patients treated achieve sustained viral response (SVR) or cure, highlights the need for new therapies against HBV. The clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9 gene editing system can specifically target the conserved regions of the HBV genome. This results in robust viral suppression and provides a promising tool for eradicating the virus. In this review, we discuss the function and application of the CRISPR/Cas9 system as a novel therapy for HBV. PMID:26540039

  5. 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

  6. 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.

  7. 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.

  8. Dissociation of CAS phase in the uppermost lower mantle

    NASA Astrophysics Data System (ADS)

    Ishibashi, Kazufusa; Hirose, Kei; Sata, Nagayoshi; Ohishi, Yasuo

    2008-05-01

    The high-pressure stability limit of calcium aluminosilicate (CAS) phase has been examined in its end-member CaAl4Si2O11 composition at 18 39 GPa and 1,670 2,300 K in a laser-heated diamond-anvil cell (LHDAC). The in-situ synchrotron X-ray diffraction measurements revealed that the CAS phase decomposes into three-phase assemblage of cubic Al-bearing CaSiO3 perovskite, Al2O3 corundum, and SiO2 stishovite above 30 GPa and 2,000 K with a positive pressure temperature slope. Present results have important implications for the subsolidus mineral assemblage of subducted sediment and the melting phase relation of basalt in the lower mantle.

  9. Plasmocytome costal solitaire: à propos d'un cas

    PubMed Central

    Razafimanjato, Narindra Njarasoa Mihaja; Ravoatrarilandy, Manjakaniaina; Rakotoarisoa, Andriamihaja Jean Claude; Hasiniatsy, Rodrigue; Hunald, Allen Francis; Rakototiana, Auberlin Felantsoa; Rafaramino, Florine; Rakotovao, Hanitrala Jean Louis

    2014-01-01

    Les auteurs rapportent un cas de plasmocytome solitaire particulière par leur localisation costale. Le diagnostic est basé sur la mise en évidence d'une tumeur localisée, constituée de cellules plasmocytaires monoclonales cytologiquement identiques à celles du myélome multiple, en l'absence d'autres signes en faveur d'une forme disséminée. Nous rapportons un cas de plasmocytome solitaire à localisation costale et nous discutons les aspects diagnostiques et thérapeutiques de cette affection potentiellement menacée dans son évolution par la transformation en myélome multiple. PMID:25419306

  10. 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.

  11. Ares I Scale Model Acoustic Test Lift-Off Acoustics

    NASA Technical Reports Server (NTRS)

    Counter, Douglas D.; Houston, Janie D.

    2011-01-01

    The lift-off acoustic (LOA) environment is an important design factor for any launch vehicle. For the Ares I vehicle, the LOA environments were derived by scaling flight data from other launch vehicles. The Ares I LOA predicted environments are compared to the Ares I Scale Model Acoustic Test (ASMAT) preliminary results.

  12. Inactivation of Cancer Mutations Utilizing CRISPR/Cas9.

    PubMed

    Gebler, Christina; Lohoff, Tim; Paszkowski-Rogacz, Maciej; Mircetic, Jovan; Chakraborty, Debojyoti; Camgoz, Aylin; Hamann, Martin V; Theis, Mirko; Thiede, Christian; Buchholz, Frank

    2017-01-01

    Although whole-genome sequencing has uncovered a large number of mutations that drive tumorigenesis, functional ratification for most mutations remains sparse. Here, we present an approach to test functional relevance of tumor mutations employing CRISPR/Cas9. Combining comprehensive sgRNA design and an efficient reporter assay to nominate efficient and selective sgRNAs, we establish a pipeline to dissect roles of cancer mutations with potential applicability to personalized medicine and future therapeutic use. PMID:27576906

  13. Motions of alloying additions in the CAS steelmaking operations

    NASA Astrophysics Data System (ADS)

    Mazumdar, D.; Guthrie, R. I. L.

    1993-08-01

    Water model studies in a pilot scale ladle ( D = 1.12 m and L = 0.93 m) were carried out to investigate the subsurface motion of both buoyant and sinking additions during the CAS (com-position adjustment by sealed argon bubbling systems) alloy addition procedure in steelmaking. This technique involves placing a refractory baffle around a rising gas/liquid plume within a stirred ladle of steel. Alloy additions are then made by projecting them into the slag-free region of steel within the baffled region. It was found that such particles while moving through the upwelling two-phase plume region can experience a significant reduction in drag forces, causing buoyant particles to penetrate more deeply than anticipated for a homogeneous fluid. Therefore, considering reduced drag on particles penetrating the upwelling gas liquid plume region, predictions were made for the trajectories of spherical-shaped particles using Newton’s law of motion. Predictions were in very reasonable agreement with those measured. Incorporating the velocity fields in industrial size vessels already reported by the present authors, trajectories of spherical-shaped additions (diameter ˜ 80 mm) in a 150-ton ladle during CAS operations were then predicted. The industrial implications of such trajectories, together with the alloy’s dissolution and dispersion behavior, were also analyzed. Finally, advantages of the CAS alloy addition procedure over conventional methods, in terms of the recovery rates of buoyant additions, are discussed.

  14. Targeted mutagenesis using CRISPR/Cas system in medaka

    PubMed Central

    Ansai, Satoshi; Kinoshita, Masato

    2014-01-01

    ABSTRACT Clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated (Cas) system-based RNA-guided endonuclease (RGEN) has recently emerged as a simple and efficient tool for targeted genome editing. In this study, we showed successful targeted mutagenesis using RGENs in medaka, Oryzias latipes. Somatic and heritable mutations were induced with high efficiency at the targeted genomic sequence on the DJ-1 gene in embryos that had been injected with the single guide RNA (sgRNA) transcribed by a T7 promoter and capped RNA encoding a Cas9 nuclease. The sgRNAs that were designed for the target genomic sequences without the 5′ end of GG required by the T7 promoter induced the targeted mutations. This suggests that the RGEN can target any sequence adjacent to an NGG protospacer adjacent motif (PAM) sequence, which occurs once every 8 bp. The off-target alterations at 2 genomic loci harboring double mismatches in the 18-bp targeting sequences were induced in the RGEN-injected embryos. However, we also found that the off-target effects could be reduced by lower dosages of sgRNA. Taken together, our results suggest that CRISPR/Cas-mediated RGENs may be an efficient and flexible tool for genome editing in medaka. PMID:24728957

  15. Embolie de liquide amniotique: à propos de deux cas

    PubMed Central

    Elbahraoui, Houda; Bouziane, Hanane; Elghanmi, Adil; Lakhdar, Amina; Elhanchi, Zaki; Ferhati, Driss

    2012-01-01

    L’embolie de liquide amniotique (ELA) est une complication imprévisible de l’accouchement, souvent fatale, associant un collapsus cardiovasculaire sévère, un syndrome de détresse respiratoire aiguë et une hémorragie avec coagulation intra vasculaire disséminée (CIVD). Dès l’évocation du diagnostic, la prise en charge doit être multidisciplinaire et intensive. ELA est responsable d’une mortalité maternelle et néonatale importante, son incidence est extrêmement variable selon les études et le taux de mortalité maternelle varie entre 26 et 86 % selon les études. Ces dix dernières années, le pronostic materno-fœtal semble en amélioration grâce aux progrès de prise en charge standardisée multidisciplinaire sur les lieux d’accouchement. Nous rapportons deux cas d’embolie de liquide amniotique. Le premier cas s’est manifesté au cours du travail et le deuxième cas est survenu dans les suites immédiates de l’accouchement. PMID:22655108

  16. CRISPR-Cas systems for genome editing, regulation and targeting

    PubMed Central

    Sander, Jeffry D.; Joung, J. Keith

    2014-01-01

    Targeted genome editing using engineered nucleases has rapidly transformed from a niche technology to a mainstream method used by many biological researchers. This widespread adoption has been largely fueled by the emergence of the clustered regularly interspaced short palindromic repeat (CRISPR) technology, an important new platform for generating RNA-guided nucleases (RGNs), such as Cas9, with customizable specificities. RGN-mediated genome editing is facile, rapid and has enabled the efficient modification of endogenous genes in a wide variety of biomedically important cell types and novel organisms that have traditionally been challenging to manipulate genetically. Furthermore, a modified version of the CRISPR-Cas9 system has been developed to recruit heterologous domains that can regulate endogenous gene expression or label specific genomic loci in living cells. Although the genome-wide specificities of CRISPR-Cas9 systems remain to be fully defined, the capabilities of these systems to perform targeted, highly efficient alterations of genome sequence and gene expression will undoubtedly transform biological research and spur the development of novel molecular therapeutics for human disease. PMID:24584096

  17. 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

  18. Dynamic acoustic tractor beams

    NASA Astrophysics Data System (ADS)

    Mitri, F. G.

    2015-03-01

    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.

  19. 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

  20. 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.