Biomedical subjects

Amit Joshi

Publications and source records attributed to Amit Joshi.

8 recordsLinked to original sources

PubMed2006

Plane-wave fluorescence tomography with adaptive finite elements.

We present three-dimensional fluorescence yield tomography of a tissue phantom in a noncontact reflectance imaging setup. The method employs planar illumination with modulated light and frequency domain fluorescence measurements made on the illumination plane. An adaptive finite-element algorithm is used to handle the ill-posed and computationally demanding inverse image reconstruction problem. Tomographic images of fluorescent targets buried at 1-2 cm depths from the illumination surface demonstrate the feasibility of fluorescence tomography from reflectance tomography in clinically relevant tissue volumes.

Algorithms↗

PubMed2006

Synthesis of copolymers containing an active ester of methacrylic acid by RAFT: controlled molecular weight scaffolds for biofunctionalization.

We report the controlled radical copolymerization of N-(2-hydroxypropyl)methacrylamide (HPMA) with a monomer containing an active ester, N-methacryloyloxysuccinimide (NMS), by reversible addition fragmentation chain transfer (RAFT). The large difference in the reactivity ratios of HPMA and NMS resulted in significant variations in copolymer composition with increasing conversion during batch copolymerization. The use of a semi-batch copolymerization method, involving the gradual addition of the more reactive NMS, allowed uniformity of copolymer composition to be maintained during the polymerization. We synthesized polymers in a wide range of molecular weights (M(n) = 3000-50,000 Da) with low polydispersities (1.1-1.3). The effect of the ratio of monomer to chain transfer agent (CTA) on the molecular weight of the polymer was investigated. Given the numerous applications of poly(HPMA)-based conjugates in designing polymeric therapeutics, these controlled molecular weight activated polymers represent attractive scaffolds for biofunctionalization. As a demonstration, we attached a peptide to the activated polymer backbone to synthesize a potent controlled molecular weight polyvalent inhibitor of anthrax toxin.

Biopolymers↗

PubMed2006

Synthesis of polyvalent inhibitors of controlled molecular weight: structure-activity relationship for inhibitors of anthrax toxin.

We describe a novel method to synthesize activated polymers of controlled molecular weight and apply this method to investigate the relationship between the structure and activity of polyvalent inhibitors of anthrax toxin. In particular, we observe an initial sharp increase in potency with increasing ligand density, followed by a plateau where potency is independent of ligand density. Our simple strategy for designing polyvalent inhibitors of controlled molecular weight and ligand density will be broadly applicable for designing inhibitors for a variety of pathogens and toxins, and for elucidating structure-activity relationships in these systems. Our results also demonstrate a role for kinetics in influencing inhibitory potency in polyvalent systems. Finally, our work presents a synthetic route to polyvalent inhibitors that are more structurally defined and effective in vivo. This control over inhibitor composition will be generally useful for the optimization of inhibitor potency and pharmacokinetics, and for the eventual application of these molecules in vivo.

Animals↗

PubMed2006

Fully adaptive FEM based fluorescence optical tomography from time-dependent measurements with area illumination and detection.

Using an area-illumination and area-detection scheme, we acquire fluorescence frequency domain measurements from a tissue phantom with an embedded fluorescent target and obtain tomographic reconstructions of the interior fluorescence absorption map with an adaptive finite element based scheme. The tissue phantom consisted of a clear acrylic cubic box (512 ml) filled with 1% Liposyn solution, while the fluorescent targets were 5 mm diameter glass bulbs filled with 1 microM Indocyanine Green dye solution in 1% Liposyn. Frequency domain area illumination and detection employed a planar excitation source using an expanded intensity modulated (100 MHz) 785 nm diode laser light and a gain modulated image intensified charge coupled device camera, respectively. The excitation pattern was characterized by isolating the singly scattered component with cross polarizers and was input into a dual adaptive finite element-based scheme for three dimensional reconstructions of fluorescent targets embedded beneath the phantom surface. Adaptive mesh refinement techniques allowed efficient simulation of the incident excitation light and the reconstruction of fluorescent targets buried at the depths of 1 and 2 cm. The results demonstrate the first clinically relevant noncontact fluorescence tomography with adaptive finite element methods.

Algorithms↗

PubMed2003

Study of the spread of a cold instantaneous heavy gas release with surface heat transfer and variable entrainment.

Air quality models help in developing relationships between the amount of pollutant released into the ambient atmosphere by a source and the corresponding incremental contribution in the atmospheric concentration. Of the various dispersion models, the heavy gas models help in predicting the concentrations due to release of gases heavier than air and the risks associated with the increased concentrations. Several differences exist among the various models developed to study the heavy-gas dispersion phenomena. These differences mainly arise because of the varied treatment given to physical processes involved in the dispersion mechanism. One of these processes, which have not been fully considered in many of the existing models, is the effect of ground heating on the movement of a cloud under windy conditions. In this study, the box model developed by Kunsch and Fannelop (J. Hazard. Mater. 43 (1995) 169) is extended to incorporate variable air entrainment on the dispersion of a heavy gas cloud spreading in a channel under windy conditions. The air entrainment was assumed to be proportional to the cloud frontal velocity. The semi-analytical equations developed were then solved by numerical methods to provide a heavy gas cloud dispersion profile. The popular Runge-Kutta fourth order technique was adopted to solve the differential equations numerically. The model was applied on a cold cloud released instantaneously and the results indicated that the model behavior follows closely the expected dispersion trends and observed cloud characteristics reported in a laboratory study. The trial run carried out in order to model the scenario of no heat transfer, by equating the source temperature to the ambient temperature, followed variations observed in the field. The analysis of cloud behavior indicated that the cloud length is strongly influenced by source density and initial cloud temperature.

Air Movements↗

PubMed2002

Sonicated transdermal drug transport.

The following review explores the promise shown by sonicated transdermal drug transport as a novel drug delivery system in great detail. It elucidates the advantages of transdermal drug transport (TDT) over the currently prevalent modes of drug administration and then goes on to explain why despite these obvious advantages TDT is so sparingly used. This discussion includes the problems posed by the impregnable barrier--our skin, or more precisely the stratum corneum (SC), and how sonicated TDT breaches this barrier. A succinct definition of sonophoresis is included along with a description of the experimental setup and a discussion of the results. The mechanism of sonophoresis with particular emphasis on the role of cavitation (both inside and outside the skin), thermal effects, convective transport, and mechanical stresses is also included. The paper also includes a discussion on the variation of sonophoretic enhancement from drug to drug along with a recent mathematical model explaining this. The paper concludes with a section detailing possible applications of sonicated TDT in the near future.

Administration, Cutaneous↗

PubMedDate not supplied

Synthesis of potent inhibitors of anthrax toxin based on poly-L-glutamic acid.

We report the synthesis of biodegradable polyvalent inhibitors of anthrax toxin based on poly-L-glutamic acid (PLGA). These biocompatible polyvalent inhibitors are at least 4 orders of magnitude more potent than the corresponding monovalent peptides in vitro and are comparable in potency to polyacrylamide-based inhibitors of anthrax toxin assembly. We have elucidated the influence of peptide density on inhibitory potency and demonstrated that these inhibitory potencies are limited by kinetics, with even higher activities seen when the inhibitors are preincubated with the heptameric receptor-binding subunit of anthrax toxin prior to exposure to cells. These polyvalent inhibitors are also effective at neutralizing anthrax toxin in vivo and represent attractive leads for designing biocompatible anthrax therapeutics.

Absorbable Implants↗

PubMedDate not supplied

Improved excitation light rejection enhances small-animal fluorescent optical imaging.

Small-animal fluorescence-enhanced imaging involves the detection of weak fluorescent signals emanating from nanomolar to picomolar concentrations of exogenous or endogenously produced fluorophore concurrent with the rejection of an overwhelmingly large component of backscattered excitation light. The elimination of the back-reflected excitation light of the collected signal remains a major and often unrecognized challenge for further reducing the noise floor and increasing sensitivity of small-animal fluorescence imaging. Herein, we show that the combination of three-cavity interference and holographic super notch filters with appropriate imaging lenses to collimate light improves rejection of excitation light, enabling more accurate imaging. To assess excitation leakage, the "out-of-band (S(lambda x))" to "in-band (S(lambda m) - S(lambda x))" signal ratio from phantom studies and the target-to-background ratio (TBR) from in vivo animal imaging was acquired with and without collimating optics. The addition of collimating optics resulted in a 51% to 75% reduction in the ratio of (S(lambda x))/(S(lambda m) - S(lambda x)) for the phantom studies and an improvement of TBR from 11% to 31% and of signal-to-noise ratio from 11% to 142% for an integrin-targeting conjugate in human glioma xenografts.

Animals↗