Puncture mechanics of cnidarian cnidocysts: a natural actuator

<p>Abstract</p> <p>Background</p> <p>Cnidocysts isolated from cnidarian organisms are attractive as a drug-delivery platform due to their fast, efficient delivery of toxins. The cnidocyst could be utilized as the means to deliver therapeutics in a wearable drug-delivery patch. Cnidocysts have been previously shown to discharge upon stimulation via electrical, mechanical, and chemical pathways. Cnidocysts isolated from the Portuguese Man O' War jellyfish (<it>Physalia physalis</it>) are attractive for this purpose because they possess relatively long threads, are capable of puncturing through hard fish scales, and are stable for years.</p> <p>Results</p> <p>As a first step in using cnidocysts as a functional component of a drug delivery system, the puncture mechanics of the thread were characterized. Tentacle-contained cnidocysts were used as a best-case scenario due to physical immobilization of the cnidocysts within the tentacle. <it>Ex vivo </it>tentacle-contained cnidocysts from <it>Physalia </it>possessed an elastic modulus puncture threshold of approximately 1-2 MPa, based on puncture tests of materials with a gamut of hardness. Also, a method for inducing discharge of isolated cnidocysts was found, utilizing water as the stimulant. Preliminary lectin-binding experiments were performed using fluorophore-conjugated lectins as a possible means to immobilize the isolated cnidocyst capsule, and prevent reorientation upon triggering. Lectins bound homogeneously to the surface of the capsule, suggesting the lectins could be used for cnidocyst immobilization but not orientation.</p> <p>Conclusion</p> <p>Cnidocysts were found to puncture materials up to 1 MPa in hardness, can be discharged in a dry state using water as a stimulant, and bind homogeneously to lectins, a potential means of immobilization. The information gained from this preliminary work will aid in determining the materials and design of the patch that could be used for drug delivery.</p

Microfluidic device for drug delivery

A microfluidic device is provided for delivering a drug to an individual. The microfluidic device includes a body that defines a reservoir for receiving the drug therein. A valve interconnects the reservoir to an output needle that is insertable into the skin of an individual. A pressure source urges the drug from the reservoir toward the needle. The valve is movable between a closed position preventing the flow of the drug from the reservoir to the output needle and an open position allowing for the flow of the drug from the reservoir to the output needle in response to a predetermined condition in the physiological fluids of the individual

Micro-Fluidic Device for Drug Delivery

A microfluidic device is provided for delivering a drug to an individual. The microfluidic device includes a body that defines a reservoir for receiving the drug therein. A valve interconnects the reservoir to an output needle that is insertable into the skin of an individual. A pressure source urges the drug from the reservoir toward the needle. The valve is movable between a closed position preventing the flow of the drug from the reservoir to the output needle and an open position allowing for the flow of the drug from the reservoir to the output needle in response to a predetermined condition in the physiological fluids of the individual

Statistical Dynamics of Flowing Red Blood Cells by Morphological Image Processing

Blood is a dense suspension of soft non-Brownian cells of unique importance. Physiological blood flow involves complex interactions of blood cells with each other and with the environment due to the combined effects of varying cell concentration, cell morphology, cell rheology, and confinement. We analyze these interactions using computational morphological image analysis and machine learning algorithms to quantify the non-equilibrium fluctuations of cellular velocities in a minimal, quasi-two-dimensional microfluidic setting that enables high-resolution spatio-temporal measurements of blood cell flow. In particular, we measure the effective hydrodynamic diffusivity of blood cells and analyze its relationship to macroscopic properties such as bulk flow velocity and density. We also use the effective suspension temperature to distinguish the flow of normal red blood cells and pathological sickled red blood cells and suggest that this temperature may help to characterize the propensity for stasis in Virchow\u27s Triad of blood clotting and thrombosis

The velocity distribution of nearby stars from Hipparcos data I. The significance of the moving groups

We present a three-dimensional reconstruction of the velocity distribution of nearby stars (<~ 100 pc) using a maximum likelihood density estimation technique applied to the two-dimensional tangential velocities of stars. The underlying distribution is modeled as a mixture of Gaussian components. The algorithm reconstructs the error-deconvolved distribution function, even when the individual stars have unique error and missing-data properties. We apply this technique to the tangential velocity measurements from a kinematically unbiased sample of 11,865 main sequence stars observed by the Hipparcos satellite. We explore various methods for validating the complexity of the resulting velocity distribution function, including criteria based on Bayesian model selection and how accurately our reconstruction predicts the radial velocities of a sample of stars from the Geneva-Copenhagen survey (GCS). Using this very conservative external validation test based on the GCS, we find that there is little evidence for structure in the distribution function beyond the moving groups established prior to the Hipparcos mission. This is in sharp contrast with internal tests performed here and in previous analyses, which point consistently to maximal structure in the velocity distribution. We quantify the information content of the radial velocity measurements and find that the mean amount of new information gained from a radial velocity measurement of a single star is significant. This argues for complementary radial velocity surveys to upcoming astrometric surveys

The Period Changes of the Cepheid RT Aurigae

Observations of the light curve for the 3.7-day Cepheid RT Aur both before and since 1980 indicate that the variable is undergoing an overall period increase, amounting to +0.082 +-0.012 s/yr, rather than a period decrease, as implied by all observations prior to 1980. Superposed on the star's O-C variations is a sinusoidal trend that cannot be attributed to random fluctuations in pulsation period. Rather, it appears to arise from light travel time effects in a binary system. The derived orbital period for the system is P = 26,429 +-89 days (72.36 +-0.24 years). The inferred orbital parameters from the O-C residuals differ from those indicated by existing radial velocity data. The latter imply the most reasonable results, namely a1 sin i = 9.09 (+-1.81) x 10^8 km and a minimum secondary mass of M2 = 1.15 +-0.25 Msun. Continued monitoring of the brightness and radial velocity changes in the Cepheid are necessary to confirm the long-term trend and to provide data for a proper spectroscopic solution to the orbit.Comment: Accepted for publication in PASP (November 2007

Multiphysics simulation of a microfluidic perfusion chamber for brain slice physiology

Understanding and optimizing fluid flows through in vitro microfluidic perfusion systems is essential in mimicking in vivo conditions for biological research. In a previous study a microfluidic brain slice device (μBSD) was developed for microscale electrophysiology investigations. The device consisted of a standard perfusion chamber bonded to a polydimethylsiloxane (PDMS) microchannel substrate. Our objective in this study is to characterize the flows through the μBSD by using multiphysics simulations of injections into a pourous matrix to identify optimal spacing of ports. Three-dimensional computational fluid dynamic (CFD) simulations are performed with CFD-ACE + software to model, simulate, and assess the transport of soluble factors through the perfusion bath, the microchannels, and a material that mimics the porosity, permeability and tortuosity of brain tissue. Additionally, experimental soluble factor transport through a brain slice is predicted by and compared to simulated fluid flow in a volume that represents a porous matrix material. The computational results are validated with fluorescent dye experiments

High-Redshift QSOs in the SWIRE Survey and the z~3 QSO Luminosity Function

We use a simple optical/infrared (IR) photometric selection of high-redshift QSOs that identifies a Lyman Break in the optical photometry and requires a red IR color to distinguish QSOs from common interlopers. The search yields 100 z~3 (U-dropout) QSO candidates with 19<r'<22 over 11.7 deg^2 in the ELAIS-N1 (EN1) and ELAIS-N2 (EN2) fields of the Spitzer Wide-area Infrared Extragalactic (SWIRE) Legacy Survey. The z~3 selection is reliable, with spectroscopic follow-up of 10 candidates confirming they are all QSOs at 2.83<z<3.44. We find that our z~4$ (g'-dropout) sample suffers from both unreliability and incompleteness but present 7 previously unidentified QSOs at 3.50<z<3.89. Detailed simulations show our z~3 completeness to be ~80-90% from 3.0<z<3.5, significantly better than the ~30-80% completeness of the SDSS at these redshifts. The resulting luminosity function extends two magnitudes fainter than SDSS and has a faint end slope of beta=-1.42 +- 0.15, consistent with values measured at lower redshift. Therefore, we see no evidence for evolution of the faint end slope of the QSO luminosity function. Including the SDSS QSO sample, we have now directly measured the space density of QSOs responsible for ~70% of the QSO UV luminosity density at z~3. We derive a maximum rate of HI photoionization from QSOs at z~3.2, Gamma = 4.8x10^-13 s^-1, about half of the total rate inferred through studies of the Ly-alpha forest. Therefore, star-forming galaxies and QSOs must contribute comparably to the photoionization of HI in the intergalactic medium at z~3.Comment: Accepted for publication in ApJ. emulateapj format. 23 pages, 17 figure

Signal Transmission in the Auditory System

Contains table of contents for Section 3, an introduction, and reports on seven research projects.National Institutes of Health Grant 5 R01 DC00194National Institutes of Health Grant P01 DC00119National Institutes of Health Grant F32 DC00073National Institutes of Health Grant 5 R01 DC00473National Institutes of Health Grant 2 R01 DC00238National Institutes of Health Grant 2 R01 DC00235National Institutes of Health Grant 5 P01 DC00361National Institutes of Health Grant T32 DC00006Whitaker Health Sciences Fun