The chemistry of high-performance magnetic resonance imaging contrast agents remains an active area of research. In this work, we demonstrate that the potassium permanganate-based oxidative chemical procedures used to synthesize graphite oxide or graphene nanoparticles leads to the confinement (intercalation) of trace amounts of Mn2+ ions between the graphene sheets, and that these manganese intercalated graphitic and graphene structures show disparate structural, chemical and magnetic properties, and high relaxivity (up to 2 order) and distinctly different nuclear magnetic resonance dispersion profiles compared to paramagnetic chelate compounds. The results taken together with other published reports on confinement of paramagnetic metal ions within single-walled carbon nanotubes (a rolled up graphene sheet) show that confinement (encapsulation or intercalation) of paramagnetic metal ions within graphene sheets, and not the size, shape or architecture of the graphitic carbon particles is the key determinant for increasing relaxivity, and thus, identifies nano confinement of paramagnetic ions as novel general strategy to develop paramagnetic metal-ion graphitic-carbon complexes as high relaxivity MRI contrast agents.

We report the magnetic behavior, relaxometry, phantom magnetic resonance imaging (MRI), and near-infrared (NIR) photoluminescence spectroscopy of gadolinium (Gd) catalyzed single-walled carbon nanotubes (Gd-SWCNTs). Gd-SWCNTs are paramagnetic with an effective magnetic moment of 7.29 l B . Gd-SWCNT solutions show high r 1 and r 2 relaxivities at very low (0.01 MHz) to clinically relevant (61 MHz) magnetic fields (). Analysis of nuclear magnetic resonance dispersion profiles using Solomon, Bloembergen, and Morgan equations suggests that multiple structural and dynamic parameters such as rotational correlation time s R , rate of water exchange s M , and the number of fast-exchanging water molecules within the inner sphere q may be responsible for the increase in r 1 and r 2 relaxivity. The T 1 weighted MRI signal intensity (gradient echo sequence; repetition time (TR) ¼ 66 ms, echo time (TE) ¼ 3 ms, flop angle ¼ 108 ) of Gd-SWCNT phantom solution is 14 times greater than the Gd-based clinical MRI contrast agent Magnevist. Additionally, these nanotubes exhibit near infrared fluorescence with distinct E 11 transitions of several semiconducting SWCNTs. Taken together, these results demonstrate that Gd-SWCNTs have potential as a novel, highly efficacious, multimodal MRI-NIR optical imaging contrast agent. V C 2013 American Institute of Physics. [http://dx

The light-dependent decrease in cyclic guanosine monophosphate (cGMP) in the rod outer segment is produced by a phosphodiesterase (PDE6), consisting of catalytic α and β subunits and two inhibitory γ subunits. The molecular mechanism of PDE6γ regulation of the catalytic subunits is uncertain. To study this mechanism in vivo, we introduced a modified Pde6g gene for PDE6γ into a line of Pde6gtm1/Pde6gtm1 mice that does not express PDE6γ. The resulting ILE86TER mice have a PDE6γ that lacks the two final carboxyl-terminal Ile86 and Ile87 residues, a mutation previously shown in vitro to reduce inhibition by PDE6γ. ILE86TER rods showed a decreased sensitivity and rate of activation, probably the result of a decreased level of expression of PDE6 in ILE86TER rods. More importantly, they showed a decreased rate of decay of the photoresponse, consistent with decreased inhibition of PDE6 α and β by PDE6γ. Furthermore, ILE86TER rods had a higher rate of spontaneous activation of PDE6 than WT rods. Circulating current in ILE86TER rods that also lacked both guanylyl cyclase activating proteins (GCAPs) could be increased several fold by perfusion with 100 µM of the PDE6 inhibitor 3-isobutyl-1-methylxanthine (IBMX), consistent with a higher rate of dark PDE6 activity in the mutant photoreceptors. In contrast, IBMX had little effect on the circulating current of WT rods, unlike previous results from amphibians. Our results show for the first time that the Ile86 and Ile87 residues are necessary for normal inhibition of PDE6 catalytic activity in vivo, and that increased basal activity of PDE can be partially compensated by GCAP-dependent regulation of guanylyl cyclase.

No abstract

Amplitude comodulation is the phenomenon that for many types of sound sources, all of the individual frequency components emitted will be amplitude modulated in a related manner, i.e., they will all start/stop and rise/fall together. It is known from various psychophysical studies that comodulation plays an important role in perceptual grouping of sound components. In this work, amplitude comodulation is examined for possible use as a basis for auditory source separation. A derivation is presented of the equations governing a comodulated system for the case of constant frequency sources. A theorem is proved giving necessary and sufficient conditions for uniquely decomposing a sound mixture into its constituent sources. A by-product of these conditions is an understanding of the importance of common onsets and offsets in source separation. An algorithm is presented for computing the unique solution in those cases where one exists. Finally, possible future extensions to the case of frequency varying sources are discussed. [Work supported by NIH Training Grant No. 5T32 DC00038.]

In previous work, amplitude comodulation was investigated as a basis for monaural source separation. Amplitude comodulation refers to similarities in amplitude envelopes of individual spectral components emitted by particular types of sources. In many types of musical instruments, amplitudes of all resonant modes rise/fall, and start/stop together during the course of normal playing. We found that under certain well-defined conditions, a mixture of constant frequency, amplitude comodulated sources can unambiguously be decomposed into its constituents on the basis of these similarities. In this work, system performance was improved by relaxing the constant frequency requirement. String instruments, for example, which are normally played with vibrato, are both amplitude and frequency comodulated sources, and could not be properly tracked under the constant frequency assumption upon which our original algorithm was based. Frequency comodulation refers to similarities in frequency variations of individual harmonics emitted by these types of sources. The analytical difficulty is in defining a representation of the source which properly tracks frequency varying components. A simple, fixed filter bank can only track an individual spectral component for the duration in which it is within the passband of one of the filters. Alternatives are therefore explored which are amenable to real-time implementation.

In previous work we created a mathematical model and identified a major source of distortion in Cochlear Implant(CI) processing which manifests itself in three forms, all of which are due to the nonlinear envelope processing algorithms which are widely used in some form or another in many current models. The first are spectral gaps or dead zones within the claimed frequency coverage range. This means that there exist regions of the spectrum for which there is no possible input that can produce an output at those frequencies. The second are frequency transformations which convert input tones of one frequency to tones of another frequency. Because this is a many-to-one transformation, it renders following a melody impossible, as the fundamental frequency of two different notes may be mapped to the same output frequency. This makes them impossible to distinguish, (although there may be differences in higher order harmonics that we will discuss). The third type of distortion are intermodulation products between input tones which yield additional output tones that were not present in either input. In the case of multiple talkers, these will compound the comprehension difficulty, as not only are the original spectral components of each speaker transformed, but additional nonexistent components have been added into the mix. This accounts for the great difficulty of CI users in noise. In this work, we extend our earlier work in three ways. First, we clarify our description of spectral gaps which a number of readers pointed out was unclear, in that it implied that certain input tones will produce no response at all. In fact, all input tones will produce a response, but in most cases, the output will be frequency-transformed to a different frequency which the CI is capable of producing. Second, we graphically illustrate the input/output frequency transformation, so that the reader can clearly see at a glance how each frequency is altered. The form of this transformation is a staircase over most of the usable range, meaning that for single, pure tones all frequencies in the passband of a particular channel are mapped to a single frequency--the center frequency of that channel. As frequency continues to increase, all frequencies in the passband of the next channel become mapped to the center frequency of that channel, and so on. The exception is in the low frequencies, for reasons that we discuss. Third, in our earlier work we analyzed the simple case of only two pure tones within a single channel. Here we extend to the more realistic case of mixtures of complex tones, such as musical notes or the vowels of speech which may each have multiple harmonics extending throughout much of the audible frequency range. We find that, as expected, the output components of a source within a single channel often clash (are dissonant) with each other, and with those output components of that source (higher harmonics) which fall within other channels. So that instead of there being a harmonic or integral relationship among the output spectral components of each source, these components are no longer related to each other harmonically as they were at the input, thus producing a dissonant and grating percept. Furthermore, in the case two or more complex tones, additional intermodulation components are produced that further distort the sound. All these assertions are derived from theoretical considerations, and also noted from the author's own listening experience, and further confirmed from correspondence with other CI users.