2002 — 2006 |
Depireux, Didier A |
R01Activity Code Description: To support a discrete, specified, circumscribed project to be performed by the named investigator(s) in an area representing his or her specific interest and competencies. |
Encoding of Dynamic Spectrum in Auditory Cortex @ University of Maryland Baltimore
DESCRIPTION (provided by applicant): Our research proposes to investigate the response properties and functional organization of primary auditory cortex and neighboring areas, in the awake ferret: specifically, the study seeks to determine how timbre, i.e. the shape of the acoustic spectrum, is represented in the single-unit responses in these areas. Our study starts with tones and clicks to characterize cortical neurons and compare their response properties and the maps they form to the results we and others have already obtained in the anesthetized preparation. Nxt, we use broadband stimuli with sinusoidally modulated spectral envelopes (also called ripples), to characterize the purely temporal and purely spectral properties of cells' responses to broadband sounds. The response of cells to these ripples, together with the response to response to combinations of orthogonal ripples are analyzed by data analysis methods based on systems theory which yield auditory units response fields and fully characterize the linear part of their spectral and temporal properties. These methods are founded on the assumption that the auditory responses are linear with respect to the stimulus spectral envelope and its dynamics. Therefore, a fundamental objective of the proposed investigations is to examine the degree of response linearity by determining whether unit responses to complex sounds such as speech can be predicted from their responses to simple ripples. A second objective is to delineate the origin and extent of various types of response nonlinearities such as threshold, halt-wave rectification, saturation, and various forms of adaptation. The separability of the spectral and temporal aspects of the response fields can also be evaluated by comparing the cells response to the different types of sounds. The results that will emerge from this study will enhance our understanding of the encoding of complex acoustic spectra such as speech and music in auditory cortex. More generally, however, they will place auditory cortical processing within the larger framework of visual and other sensory processing in the brain because of the abstract nature of the stimuli and of the theoretical concepts behind them.
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0.972 |
2014 — 2015 |
Depireux, Didier A Masri, Radi [⬀] |
R21Activity Code Description: To encourage the development of new research activities in categorical program areas. (Support generally is restricted in level of support and in time.) |
Magnetic Delivery of Therapeutic Nanoparticles to the Dental Pulp @ University of Maryland Baltimore
DESCRIPTION (provided by applicant): Inflammation of the dental pulp, or pulpitis, is a common, painful, and costly global public health problem that affects quality of life of patients. n most cases, pulpitis is a consequence of moderate or advanced dental caries (tooth decay), the most common chronic disease in the world. Pulpitis can also result from repeated thermal insults to a sensitive tooth, tooth attrition, trauma, microleakage of dental restorations, and periodontitis (inflammation of tissues supporting the teeth). Pulpitis is characterized by sharp shooting pain evoked by thermal stimuli (reversible pulpitis) or debilitating, dull, throbbing pain that occurs spontaneously or can be evoked by mechanical or thermal stimuli and lingers after cessation of the stimulus, necessitating emergency care (irreversible pulpitis). The quality and severity of the pain correlates with the extent of irritation from bacteria and other etiologies. Diagnosis can be complicated because the pain can be referred to other orofacial structures, or to adjacent teeth. We recently invented a new technique to deliver therapeutic agents to the pulp without affecting the integrity of the pulp chamber. To do so, we take advantage of naturally occurring dentinal tubules (~0.3 - 2 ?m diameter channels in dentin), and use magnetic forces to direct therapeutic magnetic particles into the tooth pulp. Preliminary experiments demonstrated efficient delivery of 100-500 nm starch-coated particles to the pulp chamber of extracted human teeth in approximately 30 minutes, using magnet arrays of our design. In this application, we seek funds to allow us to develop this innovative technique and to test its effect on pulpal tissues and tissues surrounding the teeth. We aim: Aim 1. To test the magneto-dynamics and pharmacokinetics of biocompatible nanoparticles guided to the pulp through dentinal tubules. We will use an in vitro preparation of freshly extracted human teeth and investigate: (1) The optimum particle size for delivery into the pulp; (2) The effect of polysaccharide coating (starch vs. chitosan) on the delivery of particles to the pulp; and (3) The amount of therapeutic medication (prednisolone or ofloxacin) that can be delivered to the pulp and the rate of sustained release of these therapeutic agents after magnetic force application is stopped. Nanoparticle concentrations will be determined using inductively coupled plasma atomic emission spectroscopy (ICP-AES), and drug levels will be quantified using high performance liquid chromatography coupled with mass spectrometry. Aim 2. To quantify delivery of drug-conjugated nanoparticles to the pulp in vivo, and to evaluate the effects of these nanoparticles on pulpal tissues under normal and pathologic conditions. We will prepare cavities of various depths in the molar teeth of rats. We will apply nanoparticles coated with polysaccharides or conjugated to prednisolone, or ofloxacin (particle size will be based on results from Aim 1) and: (1) Assess changes in pulpal biology and surrounding dental tissues after the application of polysaccharide-coated nanoparticles to experimentally prepared cavities in rat molars; and (2) Test the effect of drug-conjugated nanoparticles (prednisolone, and ofloxacin) on directly or indirectly injured pulp. We will use histological examination to test for changes in pulpal biology, inflammatory cell infiltration in the pulp and tissues surrounding the tooth, thickness of periodontal ligament (tissues surrounding the tooth). We will also use ICP-AES to determine nanoparticle concentration within the teeth.
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0.972 |